THE DEVELOPMENT OF EXTRACORPOREAL TECHNlQUES AND OVEN‘HEART SURGERY 2N THE. DOG Thesis for the Degree of M. 8.. WSHESAN STATE UNNERSSTY GEORGE E. EYSTER 1 9 68 1p V935 LIRF 1RY MlChlgi ‘\ SUN Univrnity .5 BINSING av 7’ A HMS 8: SHNS' 800K WNUERY INC. """‘ BINDERS ABSTRACT THE DEVELOPMENT OF EXTRACORPOREAL TECHNIQUES AND OPEN-HEART SURGERY IN THE DOG by George E. Eyster Approximately 1 of every 12 dogs is affected with cardiovascular disease.1 Some of these conditions are amenable to surgery, but until the present time open-heart surgery has been reported only on the experimental animal. An extracorporeal circulation system has been deve10ped using old Sigma finger pumps and disposable Travenol oxygenator bags. These systems were mated by an inexpensive, pump table designed and develOped by our surgical team. Open-heart surgery was performed on research and privately owned dogs. Right lateral thoracotomy was performed with the use of electro- cautery to expose the heart. The anterior and posterior vena cavae were cannulated through the right atrium for venous return to the pump. The left femoral artery was cannulated and connected to the arterial return line. Numerous Open-heart surgical procedures were done on the dogs, including: right and left atriotomy; right ventriculotomy; mitral chordae tendinotomy; creation of atrial septal defect, pulmonic stenosis, pulmonic insufficiency and ventricular septal defect, correction of pulmonic stenosis; auto-transplant; and removal of Dirofilaria immitis. George E. Eyster The animals were monitored throughout surgery by electrocardio- graphy and by the determination of arterial and venous pressures, blood pH, partial pressure oxygen, partial pressure carbon dioxide, arterial oxygen saturation, and red cell fragility. It was demonstrated that Open-heart surgery can be performed on the clinic dog. The equipment, which can be purchased for less than $500, performed admirably, particularly on surgery of the right side of the heart. Moderate success was obtained in the surgical procedures, especially on repeated experiments for a particular procedure. Final success of the project culminated with successful surgical corrections of cardiac abnormalities in dogs presented to the Veterinary Clinic. 1Detweiler, D. K.: Canine Medicine, 2nd ed. American Veteri— nary Publications, Inc., Santa Barbara, Calif., 1962. THE DEVELOPMENT OF EXTRACORPOREAL TECHNIQUES AND OPEN-HEART SURGERY IN THE DOG By I _. {V George EJLEyster A THESIS Submitted to Michigan State University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Department of Veterinary Surgery and Medicine 1968 This work is dedicated to those overworked, underpaid clinicians at Michigan State University who gave an additional night each week and to the senior students whose interest in this project made possible this team effort. ii ACKNOWLEDGEMENTS The author wishes to thank Dr. Gabel Conner; his committee, Dr. W. D. Collings, Dr. Waldo Keller, Dr. Wade Brinker and, especially, Dr. Robert Schirmer; and his wife, who guided the deveIOpment and counseled the preparation of this thesis. In addition, I wish to thank the cardiovascular surgery team at Ingham Medical Hospital, without whose training I could not have pre- pared for the surgical procedures. Among the many who helped in my training from Ingham Medical Hospital were Dr. Scong Chi, Dr. Arthur Stanley, Dr. Calvin Blair, Dr. William Weber, Bob Cole, Karen Seelof and Charles Thomas. Lastly, I wish to thank the clinicians and students at Michigan State University Veterinary Clinic, without whose many long nights of sometimes discouraging surgery these techniques could not have been developed. Included are Dr. Richard Bennett, Dr. Robert Bull, Dave DeYoung, Dr. Emil Dolensek, Dr. Gretchen Flo, Dr. Ken Gertsen, Dr. waldo Keller, Dr. Robert Rosenthal, Diane Shelberg, Dr. Paul Tillotson, Dr. Robert Whipple, Dr. Randy Wysong, and Dr. William Kelch on the pump. This was a team effort. iii TABLE OF CONTENTS INTRODUCTION 0 O O O O O O O O O O O 0 O O O O O 0 REVIEW OF THE LITERATURE. . . . . . . . . . . . MATERIALS AND METHODS . . . . . . . . . . . . . . A. B. DISCUSSION. SUMMARY AND The Heart-Lung Pump System . . . . . . Anesthesia for Cardiac Surgery . . . . Monitoring the Open-Heart Surgery Procedure. The Experimental Animals . . . . . . . The Basic Open-Heart Surgery Procedure 1. Preparation. . . . . . . . . . . . 2. Thoracic surgery . . . . . . . . . 3. Perfusion. . . . . . . . . . . . . 4. The perfusate. . . . . . . . . . . Intracardiac Surgical Procedures . . . Development of Open-Heart Surgery. . . Surgical Results . . . . . . . . . . . The Prime Solution . . . . . . . . . . Laboratory Results . . . . . . . . . . CONCLUSIONS . . . . . . . . . . . . . BIBLIOGRAPHY O O O O O O O O O O O O O O O O O O 0 APPENDICES. iv Page 12 12 14 15 15 16 17 18 21 24 . 24 24 26 26 29 32 33 36 LIST OF TABLES Table Page 1 Surgical procedures and the outcome. . . . . . . . . . . . . . 25 Figure LIST OF FIGURES The pump table, front view. The low table with metal bag frame attached. In the frame is hung an oxygenator bag. 0 O I I O O O O O O O O O O O O . O O O O O O O O O O The pump table, rear view. Resting on the pump table are the 3 pumps. To the front is the disposable oxygenator bag I O O I O I O I Q O O O O O O O O I O O O O O O O O O 0 Block diagram of the pump oxygenator system. . . . . . . . The DR8 Recorder 0 O O O O O O O O O O O O O O O O O O O O The Radiometer Gas Monitor and American Optical Micro- OXimeter O O O O O O 0 O O O O O O O O O O O O O O O O O O Venous connection. The assembled venous cannulae with connection to the venous return line . . . . . . . . . . . Close view of the right atrium with the venous cannulae in place 0 O O I O 0 O O O I O O O O O O O O O O O O O O O The oxygenator in use. The bubbles of oxygenated blood can be seen rising in the left of the bag. The blood then collects in the debubbling helix to go to the pump . . . . vi Page 10 10 11 13 14 17 17 18 LIST OF APPENDICES Appendix Page I Data Not Submitted for Statistical Analysis . . . . . . . . 36 II Open-Heart Surgery Conducted at Ingham Medical Hospital . . 43 III Catheterization Data on Live Dogs, Postoperative. . . . . . 46 IV Postmortem on Unsuccessful Open-Heart Surgery Dogs. . . . . 48 V Equipment and Drugs . . . . . . . . . . . . . . . . . . . . 54 vii INTRODUCTION Approximately 8% of all dogs have some heart disease. One out of every 10 dogs over 5 years of age has mitral valve disease, while in closely observed colonies l in 250 dogs is born with a congenital heart disorder. The most common congenital conditions are patent ductus arteriosus (PDA), pulmonic stenosis (PS), and atrial septal defect (ASD). Ventricular septal defect (VSD), tetralogy of Fallot, and aortic stenosis (AS) are less commonly observed.11» Not all of these conditions are amenable to Open-heart surgery: for example, only in severe cases of mitral insufficiency is surgical intervention considered the treatment of choice. For the last decade open-heart surgery has been an accepted thera- peutic regimen for some cardiac conditions in man. Throughout these 10 years, techniques have been develOped that now allow successful extracorporeal perfusions for up to 8 hours, climaxing with successful transplantation of the heart. Open-heart surgical procedures are routine in some medical centers and are carried out daily on human patients. In the majority of surgical techniques, the experimentation has been on the canine. Many medical centers today use the dog for a prac- tice animal. The survival rate of these laboratory dogs is low, but their usefulness in developing the procedures has been satisfactory. fIhe reasons for poor survival rates include inexperienced surgeons, [Door selection of surgical animals, poor after care, unfamiliarity with 2 anatomy, inherent weakness of the canine to extracorporeal circulation, and blood incompatibilities. As sophisticated techniques evolved, better equipment became neces- sary. With saphistication came expense. The cost of a complete extra- corporeal heart-lung preparation ranges up to $10,000. In addition, monitoring devices for Open-heart surgery can cost between $10,000 and $20,000. This expense made the develOpment of the equipment for veteri- nary use prohibitive. We proposed to deve10p a simple, inexpensive extracorporeal circu— lation system that would be applicable to the clinic case in veterinary medicine. In order to accomplish this, an inexpensive pump and a pump system that would accommodate a disposable oxygenator was needed. A surgical and heart-lung monitor team would need to be trained. By accomplishing the development of an extracorporeal circulation system for use in veterinary medicine, 3 important manifestations would result. First, the patient could be helped. In the applicable case, Open—heart surgical correction could be accomplished and the life of the patient lengthened. Second, the surgical intervention would provide a unique opportunity to observe the disease process directly. In some cases hereditary disease might be corrected and the patient preserved for propagation of a colony of animals with the particular disease. Third, the surgical techniques that were heretofore unavailable to veterinary medicine would be brought into our sphere of study. The procedures of open-heart surgery, which medical surgeons have dominated, could be shared by veterinary surgeons. REVIEW OF THE LITERATURE Richard Lower, in 1666, first recognized the effect of air (oxygen) on venous blood. He was able to oxygenate venous blood with air contact. In several precocious experiments, Lower became the first person to per— fuse organs with the rather unique perfusate, beer. Sidney Ringer later kept amphibian hearts alive and beating by placing them in saline solu— tions made from non-distilled water. By adding trace elements to dis- tilled water, further experiments demonstrated the requirement of the living heart for calcium, potassium, and other ions that are today known to be present in blood and necessary for cardiac muscle contraction.* But LeGallois in 1813, as cited by Rossi,35 was the first to sug- gest-that an artificial pump could replace heart action. The SOphisticated mechanical equipment and the understanding of the basic physiologic principles necessary for significant research in extracorporeal circulation were not available until the early 20th cen— tury. Until this equipment became available, LeGallois and other con- cerned researchers could only speculate as to the possibility of actual experiments in heart bypass. The present concepts of extracorporeal circulation were deve10ped in the 19303 by Gibbon.18 working with cats, he was able to perform 2 cardiac bypass. In 1952, Andreasen and Watson used blood from the azygous vein for partial bypass. Even the small amount of azygous *Hoff, H. E.: Personal communication, Baylor University, Houston, Texas, July, 1967. 4 blood when oxygenated and distributed to the brain and heart allowed 30- minute perfusions. Dodrill §£_§l,13 in 1952 first used total bypass for correction of pulmonic stenosis. By 1953 Gibbon17 succeeded in closing an atrial septal defect by direct vision, the first successful intracardiac procedure in man. Since the mid-19503 much has been accomplished, and tremendous insight into the intricacies of extracorporeal circulation has been gained. Better understanding of the physiology of bypass, of pumps and pump sys- tems, of oxygenators, anticoagulants, surgical procedures, anesthesia and monitoring, and of postoPerative care have come into general knowledge. Galletti and Brecher14 described the following qualities of a good pump system: It must move the blood in a pulsatile manner; have a volume flow from 2000-5000 m1./min.; be able to work against a pressure range up to 180 mm. mercury; operate easily; and have low flow velocities. In addition, Bernstein.§£_§l,5 demonstrated that pumping caused sublethal. damage to red blood cells and therefore the pump system should be one that has minimal red blood cell change. In general, pump systems have evolved along 2 lines. The finger pump which massages blood through a distendable tube by consecutive synchronous occlusion of metal fingers was the first efficient system. But this system has received less usage recently due to its noise and 28 feels the most the trauma it produces to red blood cells.35 Neville pOpular system used today is the roller pump. This mechanismlconsists of double rollers that each move the blood by pinching the blood tube against the pump head for a 180° turn. The rollers are housed in the center of the pump head that is arranged as a semicircle slightly over 180°. This arrangement of the roller head complex is situated such that 5 before one roller disengages the compressible tube the opposite roller compresses the tube for the next stroke. Oxygenation of blood has been accomplished in several ways. The simplest method is to bubble oxygen through venous blood. Until Clark §£_al,,7 in 1950, demonstrated that silicone compounds act as defoaming agents in blood, small oxygen bubbles in the oxygenated blood caused gas embolism. By adding siliconized defoaming agents to bubble oxygenators, a very popular method of oxygenation was introduced.3’9 Several commer- cial companies now have disposable units in production that, in addition to ease of handling, allow for very small priming volumes. A blood-gas interface can be obtained by allowing a film of blood to come in contact with oxygen. The stationary screen and rotating disc oxygenators are examples of this type. The stationary screen, as the name implies, allows blood to run down a screen in contact with oxygen. The blood falls down the screen slowly by gravity and is oxygenated. In the rotating disc oxygenator, multiple discs rotate in a pool of blood above which is an oxygen atmosphere. As each disc moves through the blood it picks up a small blood film, rotates into the oxygen atmosphere and oxygenates the blood film. These units have the advantage that they do very little damage to red blood cells and cause no foam, but the dis- advantage that they require large priming volumes and are very difficult to clean. The ideal oxygenator is one that functions like the lung (i.e., there is no direct contact between oxygen and red blood cells). The membrane oxygenator acts in this way. There is no trauma to red blood cells, but the extremely large priming volume makes this unit very expensive to operate and maintain. Gerbode 35 31.16 described the 6 development of a membrane oxygenator, but noted that at the present time no synthetic material has been produced that approaches the alveoli of the lung as a diffusion membrane. Polyethylene and teflon have been tried but are not totally successful. Because of the 12:1 ratio of partial pressure of oxygen to carbon dioxide (600:50) a membrane 12 times as permeable to C02 as oxygen is needed. Since one is not avail- able 12 times as much surface area is needed to reduce hypercarbia. With improved pumps and oxygenators, improved accessory instruments have been develOped. Hypothermia, in addition to reducing body demands 39 Thus, hypothermic units were for oxygen, protected red blood cells. added to many pump systems. Electrocardiography, improved pressure moni- toring, and faster pH and blood gas analysis allowed the surgeons and anesthesiologists more control over the patient. The drastic physio- logical changes in blood pH, gas concentration and ions that can occur in short periods of time, especially in dilution perfusion, were outlined by Linderggflabz4 These changes must be recognized quickly in order that immediate steps may be taken to restore normal physiologic balance. Carbon dioxide tension must be kept low during perfusion, especially if membrane oxygenators are in use. If respiratory acidosis from carbon dioxide retention becomes severe, the patient will succumb. The new blood-gas analyzers allow the surgical team to evaluate carbon dioxide and pH of the patient under perfusion quickly and repeatedly. In addi- tion, oxygen tension determinations and oxymetry using spectrophotometric methods allow constant check of partial pressure of oxygen and the blood oxygen saturation that is being accomplished by the artificial lung. Oxygen saturation of blood by the machine should not fall below 90% during a perfusion. 7 In order that extracorporeal circulation can be accomplished, the blood must be made incoagulable. Gilbert g£_§1,19 summarized the addi- tional problems of postoperative bleeding associated with the use of heparin. Killen and Edwards23 demonstrated the particularly prolonged effect of heparin in the dog. Protamine and hexadimethrine bromide have generally been used for heparin neutralization, but some evidence indicates that because they are electrOpositive they reduce the electro- negative charge of red blood cells and cause increased cell aggregation. In addition, heparin neutralization causes severe lowering of fibrinogen and circulating platelets to occur.15 However, without neutralization, bleeding would certainly continue, and death would ensue. It was in large part due to the bleeding tendency of the dog after open-heart surgery that Glenn remarked, "If dog survival was the criterion of successful open-heart surgery, we would not be doing it in peOple today."* Perhaps the most significant improvement in the development of Open- heart surgery, as summarized by Hara g£_al,?1 was the concept of hemo- dilution. Early in the 1960s Cooley ggngl.,8 Long g£_al,,25 and DeWall et 1.12 performed open—heart surgery without using blood as the priming solution. Dextrose (5%) in water,3’4’8’24’29930 low molecular weight 25,30 1,32 and electrolyte solutionslo'zz‘927’30 in place dextran, mannito of blood as the priming solution have been extremely successful in extracorporeal procedures. Neville ggnal.27 have demonstrated that clot mechanisms, blood urea nitrogen, urine output, and pH stayed near normal and returned to normal more rapidly with balanced electrolyte prime than in similar procedures with blood priming solution. In addition *Glen, W. L.: Personal communication, Yale University, New Haven, Conn., June, 1966. 8 there is no possibility of primer blood incompatibility. In the dog with many and frequent untyped blood factors, this problem is even more severe. The additional foreign protein reactions that may occur from microfilaria in the dog (blood) are nonexistent with nonhemic prime.20 The postoperative care of the Open—heart patient has also been improved in the last 5 years. Coronary care units have allowed constant monitoring of the patient. The stabilization of the lysosome membrane with corticosteroids improves survival rate.33 Cardiac output can be improved after surgery by intravenous digitalization and alkalyzing agents.26 Regardless of the improved surgical and postOperative techniques, complications are still too common. Kahn.g£.§l,,22 in 1965, still reported severe massive pulmonary collapse. Jaundice, due mostly to red blood cell destruction, occurs in from 1/10 to 2/3 of all patients subjected to extracorporeal circulation.34’37 The variation in jaundice depends on the procedure and, to a greater extent, the length of the perfusion. The occurrence of intravascular sludging and microembolism, although still present, is definitely on the decrease.]"36 In general, due to tremendous advancements in surgical techniques and accessory equipment, most of the acquired and some of the congenital cardiac conditions in man are now amenable to surgery. In addition, better understanding of the physiology of bypass and improved care of the postOperative patient have given the patient an excellent chance for successful return to active life. Certainly few fields of endeavor have made such vast improvement in so few years. MATERIALS AND METHODS A. The Heart-Lung Pump System In order to develop open-heart surgery for the canine patient, improvisations were necessary in many areas. The pump had to be of suf- ficient quality to deliver the required blood flow rates without severe damage to red blood cells. We obtained a used Sigma 2-head finger pump (Appendix V) to be used for the arterial line and the primary suction. In addition, a Sigma coronary sinus finger pump (Appendix V) was ob- tained to serve as a coronary sinus return. Three pump heads severely limit some techniques but are sufficient for most procedures performed on the right side of the heart. A Travenol Miniprime Disposable Oxygenator (Appendix V) that was resterilized 2 or 3 times was chosen as the oxygenator system. The cost of the oxygenator ranged from $35 to $75, depending on the size of the patient. Resterilization was accomplished by the use of 702 ethyl alcohol contact for 24 hours and wash with sterile distilled water. In order to mate the heart pump and lung oxygenator systems inex- pensively, a pump cart using l—inch metal tubing and a cut-down stain— less steel table was designed. The cost of the cart and accessory framework was less than $50. The pump cart consisted of a low table 8 inches above the floor, upon which the pumps rested. Extending to a height of 6 feet from the front edge of the cart was a metal frame on which the oxygenator bag holder was hung. The bag holder was attached by a pulley from the top 9 10 of the frame and allowed movement of the bag from 8 inches to 6 feet above the floor (Figures 1 and 2). ~o gr . .3 {fiat - - -_ I C - I f ‘5 '.&-\ Figure 2. The pump table, rear view. Resting on the pump table are the 3 pumps. To the front is the disposable oxygena- tor bag. Figure l. The pump table, front view. The low table with metal bag frame attached. In the frame is hung an oxygenator bag. 11 The venous return line entered the oxygenator bag at the bottom of the oxygenator column. In addition, suction return lines entered the oxygenator column at the same point. Blood was oxygenated, defoamed and debubbled, and it flowed by gravity to the pump for pulsatile pres- sure. From the pump the blood was forced into a tygon cylinder. This acted as a bubble trap. The blood left the trap at the bottom by way of the arterial line and was returned to the dog by the femoral artery (Figure 3). Filter Defoamer ' ‘ (’3 u :€?95V23 tic/A17» A . ”3.1.416 Oxygenaho Debubbler Bubble trap ' 0 enous return line 2 Pump ‘////"‘\\ Femoral artery uc ion Dog return line Figure 3. Block diagram of the pump oxygenator system. 12 The additional pumps served as suction lines. This made it possible after heparinization to return all bleeding to the system. Vacuum was created by the pumps, thus allowing hemorrhage to be returned through a filter attached above the level of the oxygenator bag. From the filter the blood returned to the oxygenator bag by gravity. B. Anesthesia for Cardiac Surgery The anesthesia for surgery was supplied through an Ohio Heidbrink anesthetic machine (Appendix V) with a sidearm vernitrol. The vernitrol is a precise temperature compensated gas vaporizer. This machine allowed close monitoring of the levels of nitrous oxide, 02, halothane, and methoxyflurane (Appendix V). The anesthetic gas usually chosen was halothane, 02, and N02. Induction was by cephalic intravenous injection of sodium thiamylal (Appendix V) followed immediately by endotracheal intubation and 4% halothane and oxygen. After attaining surgical anes- thesia, the level of halothane was reduced to .5 to 1.52 in 20% N02 and 80% 02. Halothane was selected in spite of its hypotensive tendency, because of its tendency to allow good organ perfusion with blood and low partition coefficient. When necessary during cardiac bypass, sodium thiamylal was given intravenously. C. Monitoring the Open-Heart Surgery Procedure All patients for cardiac surgery were examined preoperatively and were found to be in apparent good health. Complete blood counts (CBC), blood urea nitrogen (BUN) and platelet counts were performed. During surgery and in the immediate postOperative period, the patient's electro- cardiograms (ECG) were continuously monitored. The arterial and venous pressures were monitored throughout surgery by means of a DR8 Recorder 13 (Appendix V) and Statham P23Db pressure transducers (Appendix V) (Figure 4). Figure 4. The DR8 Recorder. Early in the program, only venous pressures were monitored using a direct coupled water manometer. Oxygen saturations were determined during the perfusion by using the American Optical micro-oximeter (Appendix V). Oxygen saturations were obtained using only 0.2 cc. arterial blood and read-out was obtained within 15 seconds. Oxygen, carbon dioxide gas partial pressures, and pH of arterial bloods were continuously monitored during bypass and in the immediate postoperative period with the Radiometer Micro Gas Monitor (Appendix V) (Figure 5). :1 Figure 5. The Radiometer Gas Monitor and American Optical Micro—oximeter. These procedures used only 0.1 cc. of blood each, and read-out was com- plete in 2 minutes. Red cell fragility determinations were performed periodically during the bypass procedure. Like arterial and venous pres- sure monitoring, oxygen saturation, pH, partial pressure oxygen (P02), partial pressure of carbon dioxide (PC02) and red blood cell fragility were accomplished only in the later experiments and were taken approxi- mately every 5 minutes. D. The Experimental Animals Experimental dogs used for the surgical procedures were generally young mongrels weighing between 50 and 60 pounds. They were examined clinically and determined to be in good health, had been vaccinated for distemper and hepatitis, and had no cardiac pathology. However, several dogs were found at surgery to have Dirofilaria immitis. The only excep- tions to the general research dog were the clinic cases in which surgery was performed. These animals were in varying states of health, depending on the cardiac pathology. 15 E. The Basic Open-Heart Surgery Procedure 1. Preparation a. The animal was atrOpinized with 1/120 gr. atropine sulfate/5 Kg. body weight intramuscularly 15 minutes before onset of anesthesia. The dog was anesthetized with sodium thiamylal administered by way of the cephalic vein to a level that would allow endotracheal intubation. The gas anesthetic mixture was started at 42 fluothane and 02 and was quickly reduced to 12 fluothane in 20% N02 and 80% 02. b. A slow intravenous drip of 52 dextrose in water or 1/6 molar sodium lactate was started in the cephalic vein. This venipuncture would be used for future drug administrations that were not added to the oxy- genator bag. c. The dog was placed in left lateral recumbency, with the rear legs apart and right leg tied over and back exposing both femoral groove areas. d. Needle electrode leads for the ECG were attached to the limbs and continuous standard lead II ECG was monitored. e. The right thorax and groin were clipped and scrubbed with povidine-iodine (Appendix V). f. Cutdown was completed on the right femoral groove. The femoral artery and vein were exposed and occluded distally with 00 silk sutures. The vessels were distended and opened. Cannulae were introduced into each vessel, threaded into the posterior vena cava and thoracic aorta, respectively, and tied into place with 00 silk. These cannulae were connected to the Statham pressure transducers and thus to the DR8 recorder for continuous arterial and venous pressure monitoring. 16 The left femoral artery was similarly exposed for 2 cm. to be used later for arterial blood return. 2. Thoracic surgery a. A long right lateral thoracotomy incision was made in the 4th or 5th costal interspace.31 The latissimus dorsi muscle was cut, the serratus ventralis muscle devided, and the intercostal muscles were cut. Hemostasis was accomplished with electrocoagulation, and the chest was entered. b. The azygous vein was isolated and tied with 00 silk. c. Both anterior and posterior vena cavae were looped with umbili- cal tape outside the pericardium and a 5-inch-long, l/4—inch plastic tube placed on the loops. Care was taken not to include the vagus nerves. d. Using an electric scalpel, the pericardium was incised above the phrenic nerve and sutured to the skin with 00 silk to make a peri- cardial basket. In addition to lifting the heart into better view, this effectively retracted the lungs from the surgical site. e. The patients were heparinized with sodium heparin 350 u/Kg. body weight by the intravenous route. f. The right atrial appendage was grasped in a satinsky clamp near the juncture with the body of the atrium. A 00 silk purse-string suture was placed around the appendage approximately 1.5 cm. from the end. The tip of the appendage was cut off. g. A plastic vena cava cannula of sufficient size (Appendix V) was placed through the hole in the appendage in the center of the purse-string and pushed through the atrium and down into the posterior vena cava. The purse-string was tightened and secured while an additional 00 silk tie was made around the tube and appendage. 17 h. The center of the right atrium was grasped with the satinsky clamp and a similar catheterization was carried out, but into the anterior vena cava. These tubes were allowed to fill with blood, then were clamped and conjoined with a Y adapter (Figures 6 and 7). Figure 6. Venous connection. The assembled venous cannulae with connection to the venous return line. 5 _ _ I. V 15‘; '. Figure 7. Close view of the right atrium with the venous can- nulae in place. 'A-‘l ; _\ j 3. Perfusion a. The left femoral artery previously exposed was tied off distally with 00 silk. The artery was distended and Opened. A femoral return cannula (Appendix V) ranging from 4 to 5.5 mm. in diameter was intro- duced into the artery and sutured in place with 00 silk. In addition, the cannula was sutured to the leg with 00 silk. 18 b. The arterial and venous cannulae were connected to the arterial and venous lines from the heart-lung machine. c. With removal of the clamps on the cannulae, partial bypass was begun. The oxygenator bag was lowered. By tightening the ligature on the anterior and posterior vena cavae around the cannulae, total bypass was begun. Artificial respirations were stOpped. All venous blood save from the coronary sinus was shunted to the oxygenator bag by gravity flow and thus to the pump and back to the dog under pulsatile pressure (Figure 8). Figure 8. The oxygenator in use. The bubbles of oxygenated blood can be seen rising in the left of the bag. The blood then collects in the debubbling helix to go to the pump. 4. The perfusate a. In all perfusions a priming volume of approximately 1000 cc. lactated Ringer's solution was used (Appendix V). b. To this was added 0.5 Gm. tetracycline hydrochloride (Appendix V) or 1 Gm. chloramphenicol (Appendix V). c. Attempted flow rate was 70 cc./Kg. body weight/min., and this was maintained by the heart pump controller. 19 d. On long perfusions, dextrose (2.5%) in half-strength Ringer's solution was added to the oxygenator bag when additional flow volume was needed. e. Oxygen was bubbled freely into the oxygenator column of blood at 3 liters 02/liter blood flow. f. In some procedures atrOpine, calcium, or epinephrin were added to the bag to increase heart rate or improve heart strength or function if needed. 5. The appropriate procedures designed for surgery were accomplished. 6. Closure: a. Upon completion of the intracardiac procedure the ligatures on the vena cavae were released and partial bypass was again initiated. Manual respirations were again instituted. b. The oxygenator bag was raised until venous pressure in the bag forced more blood through the heart, commencing normal body function. When this function appeared good, the pump lines were clamped and bypass was concluded, total function being returned to the animal's heart and lungs. c. If the venous pressure remained low (no heart failure), the posterior vena cava tube was removed and the purse-string in the atrial appendage tightened and tied. An additional 00 silk ligature was placed on the appendage tip. d. If still no evidence of failure developed, the anterior vena cava cannula was removed and the appendage closed in the same manner. e. Protamine sulfate 1%, l mg./85 units heparin was given intra- venously over a lO-minute period to counteract the heparinization (Appendix V). 20 f. One-third total digitalization dose (.02 mg. digoxin/Kg. body weight) was administered by the intravenous route (Appendix V). g. The blood left in the oxygenator was slowly returned to the dog over a period of 1/2 hour by the femoral arterial cannula. h. 10 cc./Kg. body weight of 15% mannitol (Appendix V) was commenced in the cephalic vein. i. The pericardium was loosely closed with 00 silk interrupted sutures. j. A chest suction cannula was placed in the chest wall at the 7th rib. The tube was sutured to the skin. A negative 20—mm. mercury pres- sure was maintained to remove blood that would continue to ooze from the numerous incisions. This also served to evacuate air from the chest. k. The ribs were closed with 4 to 6 00 silk simple interrupted sutures. The chest muscles were closed with 3 rows of continuous lock suture of 00 silk or 00 chromic gut. The first row consisted of the serratus ventralis and intercostal muscles. The second row included the latissimus dorsi muscle. The third row of sutures included the cutaneous trunci when present and the subcutaneous tissues. The skin was closed with continuous lock suture of 00 silk. 1. The left femoral artery cannula was removed, the artery occluded with 00 silk ligature, and the femoral incision closed with 00 silk. m. The right femoral artery and vein were similarly occluded and the incision closed. n. Prednisolone up to l mg./Kg. and occasionally blood were ad- ministered intravenously if the animal was in shock (Appendix V). 0. When bleeding from the thorax became less than 25 cc. per hour, the chest drainage tube was removed. 21 F. Intracardiac Surgical Procedures The cardiac procedures attempted by the surgical team were: (1) simple perfusion, (2) right ventriculotomy, (3) left atriotomy, (4) right atriotomy, (5) creation of pulmonic insufficiency (PI), (6) crea- tion of pulmonic stenosis (PS), (7) repair of pulmonic stenosis, (8) creation of atrial septal defect (ASD), (9) creation of ventricular septal defect, (10) mitral chorade tendinotomy, (ll) auto-transplant, and (12) removal of Dirofilaria immitis. 1. The creation of VSD, PI, and PS, the correction of PS, and removal of Dirofilaria were performed through right ventriculotomy. A long inci- sion was made high in the pulmonary conus. The pulmonic valve leaflets were lifted and incised with scissors to create PI. The infundibular PS was created by removal of a l-cm.-wide portion of pulmonary conus. Correction of PS was accomplished by placing a double elliptical venous graft in the pulmonary conus. Dirofilaria were removed from the right ventricle and pulmonary artery through the ventriculotomy. For the VSD, a stab incision wound was made in the septa and a plastic cannula placed in this hole. The right ventriculotomy was closed with a double row of simple continuous 00 silk sutures. 2. The right atriotomy was made just below the vena cava cannulae. The ASD was created on the septal wall at the position of the foramen ovale by removal of a 1-cm.-diameter portion of the septum. The atriotomy was closed by l or 2 rows of simple continuous 00 silk sutures. 22 3. Mitral chordae tendinotomy was accomplished through the left atriotomy. A thin fibrous line at the base of the heart marks the division of the right and left atrium as seen from the right side. An incision was made just to the left above this line but below the pulmonary veins and the left atrium was Opened. The mitral valve was lifted and its chordae tendinae were cut. Closure after total evacuation of air was accomplished by a double row of simple continuous 00 silk sutures. 4. In all open-heart procedures the coronary bleeding and coronary sinus flow were controlled by suction from the pump and the blood was filtered and returned to the oxygenator bag. For this reason, after hepariniza- tion no blood was lost to the system. For the auto-transplant, one of the 2 auction lines from the pump system was used to perfuse the coronary arteries. This was accomplished by reversing the flow through the pump head. The right atrial wall, atrial septum and left atrial wall were cut just above the coronary sinus and just below the atrial appendage and vena cava cannula. The heart was rotated up and back, and the pulmonary artery and aorta were separated. The pulmonary artery was cut 1 cm. from the pulmonary valve. A coronary artery cannula was sutured in the small opening made in the aorta 1 cm. from the aortic valves. The aorta was clamped and cut between the clamps and the ligature around the coronary artery cannula. The perfused beating heart was lifted free of the dog. Coronary artery pressures were maintained below 60 mm. of mercury. Replacement of the heart was in the reversed order of its removal. The aorta was joined and sutured with simple continuous 6—0 silk suture. 23 The pulmonary artery was anastomosed with simple continuous 5-0 silk suture. The left atrium, atrial septum, and right atrial wall were sutured with simple continuous 000 silk suture in that order. RESULTS A. DevelOpment of Open—Heart Surgery We were able to successfully combine the finger pump system to the disposable oxygenator and perform open—heart surgery in the dog. B. Surgical Results The one clinic case (113014) on which an open-heart surgical pro- cedure was performed was successful. On the experimental animals, the success rate depended on several factors. Procedures that were attempted a second and third time generally gave better results than on the first attempt. The experience of the person operating the pump seemed to be the most important factor in increasing survival rate. To a lesser extent, the experience and skill of the chief surgeon influenced survival. Fifteen animals were submitted to Open-heart surgery at the Michigan State University Veterinary Clinic. Of these, 33.3% survived and 33.32 regained consciousness only to die in the postoperative period. Those designated as survival animals lived through the postoperative period and were euthanatized or destroyed by other means at least 1 week after surgery. To be classified as an animal that died in the postoperative period the animal was required to regain consciousness, reach sternal recumbency, be aware of its surroundings, regain its reflexes, and be somewhat alert. The surgical procedures and the results are listed in Table 1. 24 Table 1. —‘—_ 25 Surgical procedures and the outcome Post— Case operative Surgical Number Procedure Survival Death Death 111533 Pump run X 116767 Right ventriculotomy X 111765 Procedure to create X pulmonic stenosis 111765 Repair pulmonic X stenosis None Create ventricular X septal defect 113014 Heartworm removal X 114513 Create mitral insuf— ficiency (mitral X chordae tendinotomy) 116610 Auto—transplant X 116828 Create pulmonic X insufficiency 116606 Create pulmonic X insufficiency 116831 lCreate atrial septal X defect 116999 Create atrial septal X defect 116998 Heartworm removal X 117000 Create ventricular X septal defect 117373 Create mitral insuf— ficiency (mitral X chordae tendinotomy) 26 Causes of death during and after surgery ranged from surgical mis- takes to chronic nephritis and acute distemper (Appendix IV). C. The Prime Solution By using lactated Ringer's as a priming solution, blood with its inherent problems and incompatibilities was excluded. Lactated Ringer's is a balanced electrolyte that liberates free base when metabolized by the liver. In the long surgical procedures (over 30 minutes pump time), shock develOped. This might be expected in the use of nonhemic prime. The water in the solution is slowly (over 30 to 40 minutes) lost to the tissue space. In these long procedures supplementation of the perfusion volume with dextran, additional lactated Ringer's, osmitrol, or on rare occasions, blood was necessary. During short perfusion no shock developed; i.e., flow rates and venous return were consistently high. D. Laboratory Results In later surgeries P02, P002, pH, 02 saturations, and red blood cell fragility studies were conducted. The oxygen saturations were almost always over 902 during the surgery. 0n the 2 brief exceptions, increase in oxygen flow in the oxygenator immediately returned oxygen saturation to the normal range. In the post— bypass period, occasional oxygen saturation below 90% was recorded. Immedi- ate increase in oxygen percentage in the anesthetic gas mixture brought the level of oxygen back to normal. Oxygen saturations were accomplished on the last 5 cases (Appendix I-A). Throughout the bypass procedures, PO2 remained in or above the normal range. High flow rates of oxygen in the oxygenator and high oxygen per- centages in the anesthetic gas mixture were considered reasons for the 27 occasional higher than normal P02. In the last 3 cases P02's were recorded (Appendix I-B). In no case did the PC02 rise above normal levels during bypass. The high flow rate in the oxygenator and C02 absorber in the closed anesthetic system was considered the reason for the excellent low PC02. In the last 5 cases PCOZ's were recorded (Appendix I-C). In the last 6 cases pH was monitored. The pH in all cases drapped as the surgery proceeded. During routine surgery in the dog, pH drops quickly, and severely in long and difficult surgery.* The metabolic acidoses that were experienced were no more severe than for routine canine surgery; however, upon completion of the bypass procedure, acidosis became more severe. When left untreated, a pH of 7.05 immediately after the conclusion of surgery was found in 1 case. Extensive efforts were made to maintain pH at 7.2—7.4 range. By constant monitoring and sodium bicarbonate administration after the pH dropped to 7.25, it was possible to maintain the pH in a desirable range. The slow administration of 1/6 molar sodium lactate intravenously during surgery was believed to have helped maintain a higher pH throughout. The 1/6 molar lactated Ringer's prime solution is capable of releasing 28 mEq. of base per liter after metabolization by the liver38 (Appendix I-D). Since the finger pump has been considered very harmful to red blood cells, in the last 6 cases we were fortunate to be able to study red blood cell fragility. In early procedures, before red blood cell fragility was studied in bypass procedures lasting 45 minutes or more, surviving dogs develOped hemoglobinuria in the first 3 postOperative days. In the first *Unpublished data, Bennett, R. R., and Eyster, G. E., Michigan State University, East Lansing, Michigan, 1968. 28 procedure in which red blood cell fragility was determined, bypass time lasted 2 hours and 40 minutes. This was in the auto-transplant procedure. During the long bypass time, the red blood cell fragility increased dra- matically after 45 minutes. The decision was made whenever possible to limit all our procedures to 30 minutes or less. The results indicated that red blood cells were unaffected by short pumping time. In 1 animal (117000), hemolysis occurred after a 20~minute bypass. Postsurgically, the dog urinated twice with much hemoglobinuria. It was felt the hemolysis was due more to the pathology (VSD) (Appendix IV), since much turbulence was observed at surgery, when blood was shunted through the implanted plastic tube. In addition, extensive high vacuum suction was used to control the blood loss through the artificially created ventricular sep- tal defect. Although harmful to cells in bypass of 45 minutes or more, the pumping method was not a problem in the short (30 minutes or less) pump runs (Appendix I-E). DISCUSSION The heart pump system performed admirably, in that it was possible to accomplish the procedures attempted on the right side of the heart. Left side procedures, especially those involving the aortic valve, were beyond the scope of the system. Procedures that lasted over 1/2 hour generally had a poor success rate. The dogs showed marked postsurgical hemoglobinuria for 3 to 4 days. Red blood cell fragility studies indicated that the pump was extremely harmful to the cells after 30 minutes of extracorporeal circu— lation. The oxygenator, as would be expected, worked well and mated well with our system. Oxygen saturations were above 90% throughout pump bypass procedures. We accomplished surgical procedures on the right side of the heart successfully. In general these lasted 30 minutes or less. As more pro- ficiency was gained, the survival rate increased and surgery time decreased. Cause of death ranged from poor surgical technique through chronic renal disease 1 day postoperatively (Appendix IV). Although data were not extensive enough to submit to statistical analysis, some trends developed. Without exception, oxygen saturation, pH, and blood P02 and PCO2 stayed in normal range when on total bypass. Oxygen saturation, a good criterion of success of oxygenation, was consistently above 90%. Blood pH, P02 and PC02 were consistently in a range compatible with life during the pump run, but in most all cases 29 30 altered quickly once the patient's heart function was returned. The partial pressure of oxygen and, to a greater degree, pH began to fall shortly after cessation of perfusion. At the same time, PCO2 increased slightly. These abnormalities were generally easily controlled by in- creasing oxygen in the anesthetic gas mixture and more vigorous respira- tion. In addition, sodium bicarbonate was given intravenously to return pH to its normal range. As pumping time exceeded 30 minutes, red blood cell fragilities increased dramatically. The finger pump system has been considered by Neville28 and Rossi35 to be harmful to red blood cells, and our pump proved to be no exception. It is believed that the development of Open-heart surgery for the veterinary school clinic is not only feasible but is advisable from the standpoint of educational value. The techniques used were kept simple but were useful procedures for application to common cardiac disease. The general cost of the equipment is low. Expensive monitoring equip- ment was helpful but certainly not necessary for most techniques. Time and effort were expended to develop a competent surgical team. Practice was needed for familiarization with the techniques as well as the ana- tomic landmarks. In addition, a long period of time was needed to develop an understanding of the pumping system and its effects on the animal physiology. The qualified manpower available at a veterinary school certainly aided in the final successful surgical outcome. We feel the minimum number of people necessary for surgery makes this procedure impractical except at a large clinic. Most right—sided procedures required 2 or 3 surgeons, one scrub nurse, one anesthesiologist, one pump controller, 31 one person monitoring pH and blood gases, one person in general moni- toring, and one person for general Operating room assistance. SUMMARY AND CONCLUSIONS Open-heart surgery can be successfully performed on the canine clinical patient. Fourteen experimental dogs and 1 clinic patient were submitted to Open—heart surgery for various procedures. Of these, 5 survived, 5 died in the postoperative period, and 5 died surgical deaths. Included in the surviving animals was the clinic patient. With moderate expense (less than $1000, even with purchase of new equipment) and limited monitoring equipment, surgical procedures can be routinely performed on the right side of the heart. Left side pro- cedures, especially those of the aortic valve, would require more involved equipment. Minimal equipment necessary would include: 2 simple pump systems, disposable oxygenator bags, a technique to mate the pump and oxygenator, a venous pressure monitor, and an electrocardiographic monitor. In most veterinary clinics this would require less than $500 in additional pur- chases. The frequency of occurrence of congenital and acquired cardiac dis- ease would seem to make the application of open—heart surgery techniques worthwhile in university veterinary clinics. In addition, the large number of qualified veterinarians presents a supply of surgeons that are needed for the Open—heart surgical team. In an Open-heart operation, 3 surgeons, an anesthesiologist, a pump controller, and a technician are necessary for successful completion of the procedure. This team must work together to develop pump techniques before open-heart surgery should be applied to the clinic dog. 32 10. ll. 12. BIBLIOGRAPHY Allardyce, D. B., Yoshida, S. H., and Ashmore, P. G.: The Importance of Microembolism in the Pathogenesis of Organ Dysfunction Caused by Prolonged Use of the Pump Oxygenator. J. Thoracic and Cardio- vas. Surg., 52, (1966): 706-715, 720-724. Andreassen, A. T., and Watson, F.: Experimental Cardiovascular Surgery. Brit. J. Surg., 39, (1952): 548-551. Baffes, T. G., and Monelis, J.: A Disposable Bubble Oxygenator for Open Heart Operations. J. Int. Coll. Surg., 41, (1964): 250-256. Beall, A. C., Jr., Yow, E. M., Bloodwell, R. D., Hallman, G. L., and Cooley, D. A.: Open Heart Surgery Without Blood Transfusion. Arch. Surg., 14, (1967): 567—570. Bernstein, E. F., Indeglia, R. A., Shea, M. A., and Varco, R. L.: Sublethal Damage to the Red Blood Call from Pumping. Circ., Supplement I to 35 and 36, (1967): 1226—I233. Castaneda, A. R.: Must Heparin Be Neutralized Following Open-Heart Operations? I. Thoracic Cardiovas. Surg., 52, (1966): 716-719. Clark, L. C., Jr., Gollan, F., and Gupta, V. B.: The Oxygenation of Blood by Gas Dispersion. Science, 3, (1950): 85—87. Cooley, D. A., Beall, A. C., Jr., and Grondin, P.: Open-Heart Operations with Disposable Oxygenators, 5 Per-Cent Dextrose Prime, and Normothermia. Surgery, 52, (1962): 713—719. Cooley, D. A., and Beall, A. C., Jr.: Results of Open Heart Surgery by a Simplified Technic. West J. Surg., Obst. and Gynec., 72, (1964): 12-15. Cruz, A. B., and Callaghan, J. G.: Hemodilution in Extracorporeal Circulation: Large or Small Non-Blood Prime? J. Thoracic and Cardiovas. Surg., 52, (1966): 690—697, 720-724. Detweiler, D. R.: Canine Medicine, 2nd ed. American Veterinary Publi- cations, Inc., Santa Barbara, Calif., 1962. DeWall, R. A., Lillehei, R. C., and Sellers, R. D.: Hemodilution Perfusions for Open-Heart Surgery. New Eng. J. Med., 266, (1962): 1078—1084. 33 13. 14. 15. l6. 17. 18. 19. 20. 21. 22. 23. 24. 25. 34 Dodrill, F. D., Hill, E., Gerisch, R. A., and Johnson, A.: Pulmonary Valvuloplasty Under Direct Vision Using Mechanical Heart for a Com- plete Bypass of Right Heart in a Patient with Congenital Pulmonary Stenosis. J. Thoracic Surg., 26, (1953): 584—597. Galletti, P. M., and Brecher, G. A.: Heart Lung Bypass: Principles and Techniques of Extracorporeal Circulation. Grune and Stratton, Inc., New York, 1962. Gans, H., and Castaneda, A. R.: Problems in Hemostasis During Open Heart Surgery. Ann. Surg., 165, (1967): 551-556. Gerbode, F., Osborn, J. J., and Branson, M. L.: Experiences in the Development of a Membrane Heart—Lung Machine. Ann. J. Surg., 114, (1967): l6-23. Gibbon, J. H., Jr.: The Application of a Mechanical Heart and Lung Apparatus in Cardiac Surgery. Minn. Med., 37, (1954): 171-181. Gibbon, T. M., Jr.: Artificial Maintenance of Circulation During Experimental Occlusion of Pulmonary Artery. Arch. Surg., 34, (1937): 1105-1131. Gilbert, J. W., Bronson, W. R., and Brecher, G.: Incidence of Bleed— ing in Cardiac Surgery With Extracorporeal Circulation. Ann. N. Y. Acad. Sci., 115, (1964): 302—304. Godfrey, W. D., Neely, W., Elliott, R., and Grogan, J.: Canine Heartworms in Experimental Cardiac and Pulmonary Surgery. J. Surg. Res., 6, (1966): 331—336. Hara, M., Maris, M., Crumpler, J., Corn, B., and Perkins, W.: Effect Of Various Priming Solutions Upon Red Cell Mass, Plasma Volume, and Extracellular Fluid Volume of Dogs Following Hemodilution Technique of Extracorporeal Circulation. J. Thoracic and Cardio- vas. Surg., 53, (1967): 353—359. Kahn, D. R., Corssen, G., and Sloan, H.: Massive Pulmonary Collapse During Open-Heart Surgery. J. Thoracic and Cardiovas. Surg., 49, (1965): 840-843. Killen, D. A., and Edwards, R. H.: Systemic Heparinization of the Dog. J. Surg. Res., 7, (1967): 427-429. Linder, E., Sakai, Y., and Patton, B. P.: Electrolyte Changes During Dilution Perfusion. Arch. Surg., 88, (1964): 175-180. Long, D. M., Jr., Sanchez, L., Varco, R. L., and Lillehei, C. W.: The Use of Low Molecular Weight Dextran and Serum Albumin as Plasma Expanders in Extracorporeal Circulation. Surgery, 50, (1961): 12-28 0 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 35 Moffit, E. A., Sessler, A. D., and Kirklin, J. W.: Postoperative Care in Open—Heart Surgery. J.A.M.A., 199, (1967): 161-163. Neville, W. E., Colby, C., Peacock, H., and Kronkowski, T.: Superi- ority of Buffered Ringer's Lactate to Heparinized Blood as Total Prime of the Large Volume Disc Oxygenator. Ann. Surg., 165, (1967): 206—216. Neville, W. E.: Extracorporeal Circulation. Year Book Medical Publishers, Inc., Chicago, Ill., 1967. Patton, B. C.: Extracorporeal Circulation Without Blood. Rocky Mountain Med., 60, (1963): 25—29. Patton, B. C., and Rosenkrantz, J.: Non—Hemic Priming Fluids for Extracorporeal Circulation. Dis. Ches., 48, (1965): 311-320. Pettit, G. D.: Principles of Thoracic Surgery. J.A.V.M.A., (1965): 1424-1431. Porter, G. A., Starr, A., Kimsey, J., and Lenertz, H.: Mannitol Hemodilution-Perfusion: The Kinetics of Mannitol Distribution and Excretion During CardiOpulmonary Bypass. J. Surg. Res., 7, (1967): 447-456. Replogle, R. L., Gazzaniga, A. B., and Gross, R. E.: Use of Cortico- steroids During CardiOpulmonary Bypass: Possible Lysosome Stabi- lization. Circulation, Supplement to 33 and 34, (1966): 186-191. Robinson, J. S., Cole, F. R., Gibson, P., and Simpson, J. A.: Jaundice Following CardiOpulmonary Bypass. Thorax, 22, (1967): 232-237. Rossi, W. P.: Heart Lung Bypass. J. Lancet, 87, (1967): 89-96. Sachs, D., Derry, G. H., Krumhaar, D., Lee, W. H., Jr., and Maloney, J. V., Jr.: Chemical and Hypothermic Inhibition of Intravascular Sludging in Extracorporeal Circulation. Ann. Surg., 160, (1964): 183-188. Sanderson, R. C., Ellison, J. H., Benson, J. A., and Starr, A.: Jaundice Following Open-Heart Surgery. Ann. Surg., 165, (1967): 217-224. Trudnowski, R. J., Goel, S. B., and Lan, F. T.: Effect of Ringer's Lactate Solution and Sodium Bicarbonate on Surgical Acidosis. Surg. Gynecol. Obstet., 125, (1967): 807-814. Wilder, R. J., Rush, B. F., Jr., and Ravitch, M. M.: Protective Effect of Hypothermia on Canine Whole Blood During Extracorporeal Circulation. Ann. Surg., 160, (1964): 1057-1061. APPENDIX I Data Not Submitted for Statistical Analysis 36 37 APPENDIX I Data Not Submitted for Statistical Analysis Oxygen saturation The American Optical micro-oximeter measures oxygen saturation of unhemolyzed blood by determining light intensity diffusely back- scattered at 2 wave lengths. Two wave lengths eliminate error by hemolysis and packed cell volume differences. The instrument is correct to i;l% in the normal operating range. Blood for sample was withdrawn periodically from the femoral artery pressure cannula for oxygen saturations. Heparinized blood (.2 cc.) was injected to the cuvette. A stirrer was placed in the cuvette and the blood oxygen saturation was measured. Normal oxygen satura- tion (arterial) is 95%. In the low metabolic hypothermic state of extracorporeal circulation, 90% is entirely satisfactory. Graph I-A demonstrates the results of the oxygenation accomplished by our oxygenator system. The machine was very efficient in supplying needed gas to the red blood cells. Partial pressure of oxygen The gas tension of oxygen in mm. of mercury was obtained by the Radiometer gas monitor with the P02 electrode. A platinum electrode placed close to the cuvette membrane registers the oxygen that dif- fuses through the membrane by reduction of the oxygen. The oxidative reduction reaction produces a current in the electrode that is read on the meter. Because partial pressure oxygen is the motive force of the diffusion the response is prOportional to the pressure, and the electrode has linear response. Periodically .1 mm. blood samples were drawn through the femoral artery pressure cannula. Few POz's were done, since oxygen satura- tions, pH, and PC02'S were monitored. P02 is quite variable and tends to be high after using a bubble oxygenator. The P02 during perfusion seemed to be good; in fact, it increased during perfusion (Graph I-B). The P02 and 02 saturations paralleled each other during the perfusion. Partial pressure carbon dioxide PCOZ's in mm. of mercury tension were Obtained by use of the radiometer gas monitor and the PC02 electrode. The electrode Operates on the principle of the relationship of pH and C02 concentration and bicar- bonate concentration in sodium bicarbonate solution. At equilibrium pH and log of PC02 have linear dependence. In the radiometer elec- trode equilibrium is attained by diffusion through a teflon membrane and the PC02 is recorded by a precise pH measurement at that point. 38 Graph I-A & B. Oxygen Fuction Graph I-A. 02 saturation during cardiOpulmonary bypass 100% . l l l L l _. r 15 20 25 30 Time in Minutes 0 U1-1u— H 0 Graph I-B. Arterial PO2 during cardiOpulmonary bypass 500 T 400 -. PO 1.2 300 . mm. Hg 200 ‘ 100 ‘ 0 ' . : e :7 5 -4 o 5 10 15 20 25 30 Time in Minutes Case Number Code Ca§g_Nnmhex_ Code 116998 116831 ______ 117000 116999 117373 39 Periodically .1 mm. blood samples were obtained from the femoral' artery pressure cannula. Normal range for PCO (arterial) in man is approximately 30-45 mm. mercury. In the bu ble oxygenator PCOZ generally remains low. The high velocity bubbling of free oxygen at high flow rates allows sufficient oxygen blood interface to exchange for C02. The PCO during our perfusions were low in the normal range. They stayed below the range for that animal as compared to pre- and postperfusion, indicating good exchange of oxygen for C02 (Graph I-C). pH pH was measured by the radiometer micro-electrode pH meter. The electrode consists of a pH sensitive glass capillary electrode and a calomel electrode. Measurement occurs when the 2 electrodes are in contact by a salt bridge. Normal pH ranges between 7.35 and 7.4. However, Bennett and Eyster have indicated that during surgery acidosis is common, if not inevitable, in the canine. It should be noted that in most ani- mals on the study a slow intravenous drip of sodium lactate 1/6 molar solution was instituted from the start of surgery. Arterial blood .1 cc. was obtained through the femoral artery pres- sure cannula and examined periodically for pH (Graph I-D). The pH varied relatively little during the pump runs but in all cases dropped in the post-pump run period, to a point where therapy with sodium bicarbonate or sodium lactate was occasionally necessary. Red cell fragility Red cell fragility was measured by submitting samples of blood to decreasing osmotic concentrations of salt solutions. The normal RBC lyses at approximately .5% NaCl solution. If significant sub- lethal damage is done to the RBC, lysis will occur at higher (nearer physiologic) NaCl concentrations. Five cc. arterial blood was obtained through the femoral arterial pressure cannula before the pump run, just after the start of the pump run, periodically throughout the pump run, and after completion of the pump run. Results of the comparisons of sublethal damage are shown on Graph I-E. Red cell fragility did not change (with l exception, noted below) from the normal if the pump run was kept to a time less than 40 minutes. In 1 procedure lasting over 2 hours, over 30% of the cells were significantly altered. In-l procedure, creation of ventricu- lar septal defect, RBC fragilities increased in less than 30 minutes. This animal had a plastic tubing placed across his ventricular sep- tum and an additional aortic insufficiency created by the tube. Extensive turbulence was created by this means. In addition, 100 cc./min. blood was being aspirated by a high vacuum suction through- out the last 10 minutes of the procedure. 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I. r mm ma muowuzm unmosloomo weaken no .QIH sumac 42 mnmnaa ooo~aa om ' OHH 00H mo nuwooa ou monomeoo coaumuuomoooo Homz oamoaoammnm NON um OOfluHwamum Haoo pom mmmoHH ammoaa mmmoaa OHooHH "ooou pom nonasz Ommo mou=Oaa OH hummusm moansv mean so oEHH om on 00 on b D b S ‘ ow L ‘ \\ om meadow oawoa nofimmem \. N N2 2. mammq unmouom ease Howofim m wean: mmmomn %umooaflsmowvnmo mo oafiu .mIH names APPENDIX II Open-Heart Surgery Conducted at Ingham Medical Hospital 43 44 APPENDIX II Open-Heart Surgery Conducted at Ingham Medical Hospital Numerous experimental open-heart procedures were conducted in conjunction with the open-heart surgery team at Ingham Medical Hospital. These dog surgeries were used in a teaching procedure for the author and for the surgery team at Ingham Medical Hospital. It must be stressed that these were experimental, with the exception of 2 cases described below. 1. MSU Clinic Case 111142 (ll-9-66) 5-month-old male Great Pyrenees Diagnosis: pulmonic stenosis X ray - prominent pulmonary artery right ventricular hypertrOphy ECG - right ventricular hypertrOphy 270° axis shift Cardiac catheterization: valvular and subvalvular pulmonic stenosis by selective angiography, right ventricular pressures reaching 210 mm. mercury Surgery: a. Routine right lateral thoracotomy and cardiac bypass b. Right ventriculotomy c. Diseased pulmonary valve was removed d. Routine closure The animal recovered from anesthesia but died 5 hours post0peratively Pathology: a. Hemorrhage of the right thorax b. Fibrosis of the liver c. Apparently the animal had undergone ventricular arrythmia and death due to ventricular fibrillation MSU Clinic Case 111323 (ll-25-66) 3-year-Old male St. Bernard Diagnosis: atrial fibrillation and mitral insufficiency X ray - fluid in the pleural cavity pulmonary congestion enlarged left heart, especially the left atrium ECG - left side enlargement atrial fibrillation Cardiac catheterization: mitral insufficiency by selective angiography 45 Surgery: a. Routine right lateral thoracotomy and cardiac bypass b. Left atriotomy c. The diseased mitral valve was removed d. Cutter ball valve prosthesis placed in the mitral annulus e. Routine closure The animal recovered and improved. The dog is alive and active today. APPENDIX III Catheterization Data on Live Dogs, Postoperative 46 47 APPENDIX III Catheterization Data on Live Dogs, Postoperative MSU Clinic Case 116606 2-year-old male mixed breed Surgical procedure - removal of pulmonic valve (creation of pulmonary insufficiency) Surgery was successfully accomplished 2-15-68 Cardiac catheterization 3-7-68 Results of cardiac catheterization: a. X ray revealed insufficiency of pulmonic valves by selective angiography b. Pressure in pulmonary artery showed 25/4 mm. mercury; in the right ventricle 25/-4 mm. mercury. This pressure curve is diagnostic of insufficient pulmonic valve MSU Clinic Case 111323 3-year-Old male St. Bernard Surgical procedure (at Ingham Medical Hospital) - replacement of mitral valve with mitral prosthesis (repair, mitral insuf- ficiency) Surgery was successfully accomplished 1-5-67 Cardiac catheterization 2-3—67 Results of catheterization: a. The prosthetic mitral valve was functioning normally b. Cinemovies demonstrated no regurgitation c. Cardiac output had trippled since the presurgical studies APPENDIX IV Postmortem on Unsuccessful Open-Heart Surgery Dogs 48 49 APPENDIX IV Postmortem on Unsuccessful Open-Heart Surgery Dogs MSU Clinic Case 111533 (12-15-66) 5-year-old male Black Labrador Surgical procedure - lO-minute extracorporeal procedure Surgery appeared successful. The dog regained consciousness but died the following morning. Pathologic report: a. Extensive surgery on the right thorax b. Lungs reddened c. Intestine - small hemorrhages and hookworms d. Kidney - enlarged with whitish streaking Hisotpathologic report: a. Kidney - inflammation, fatty metamorphosis, mineraliza- tion of the epithelium of the cortex tubules b. Cardiac muscle - congestion c. Liver - central fibrosis d. Lungs - alveolar rupture Conclusions: Severe chronic mineralization of the kidney MSU Clinic Case 111765 (5-3-67) 3-year-old mixed breed female hound Previous creation of pulmonic stenosis by removal of a portion of pulmonic conus under open-heart surgery Surgical procedure - venous graft patch on pulmonary conus. The dog died after a tear developed in the upper right ventricle during surgery. ' Pathology: a. Extensive hemorrhage in the chest b. Extensive adhesions in the lung, pleura and pericardium on the right thorax c. Two surgical incisions on the right ventricle d. Cut in the left anterior upper section of the right ventricle, including major coronary branches Conclusions: Hemorrhage and myocardial ischemia due to surgical complications on right ventricle 50 No number (4-20-67) 4-year-Old male German Shepherd cross Surgical procedure - creation of a ventricular septal defect. Sur- gery was unsuccessful. Complete bundle branch block occurred when septum was cut. The animal died within 5 minutes. Pathology: a. Surgery in the chest and right heart b. Hemorrhage and trauma high in the ventricular septum, causing apparent destruction of bundle branches Conclusions: Death due to iatrogenic bundle branch block MSU Clinic Case 114513 (9-28-67) 6-month-Old female German Shepherd Surgical procedure - mitral chordae tendinotomy by left atrial approach. Surgery appeared successful, but the animal never regained consciousness. Pathology: a. Extensive hemorrhage in the right chest in the area of the surgery b. Hemopericardium c. Cut chordae tendinae of the mural leaflet of the mitral valve d. Hemorrhage and necrosis Of mitral annulus and left atrium Conclusions: Hemorrhage, hemOpericardium, and mitral insufficiency MSU Clinic Case 116610 (1-18-68) 5-year-Old male Black Labrador Surgical procedure - cardiac auto-transplant. Surgery was unsuccess- ful: air embolism during surgery caused death during the heart replacement portion of the procedure. Pathology: a. Extensive surgery in right thorax b. Hemorrhage in areas of the aorta, pulmonary artery, and atria where sutures had been placed c. Two small holes in the left atrium d. Grossly visible air emboli in the coronary arteries Conclusions: Air embolism in the arterial system 51 MSU Clinic Case 116828 (2-6-68) Surgical procedure - creation of pulmonic insufficiency. Surgical complications developed when the right ventricular wall was inadvertently cut near the pulmonic valve high to the left and forward. Ventricular fibrillation precipitated death. Pathology: a. Hemorrhage due to extensive surgery in the heart and right thorax b. Unrepaired cut in the right ventricular conus Conclusions: Death due to ventricular fibrillation caused by trauma and hemorrhage from the right ventricle and acute distemper MSU Clinic Case 116831 (3-7-68) 3-year-Old male Black Labrador Surgical procedure - creation of atrial septal defect. Surgery appeared‘successful. The dog regained consciousness but died the following morning. Pathology: a. Extensive surgery in the right chest and heart b. The animal had 24 heartworms in the right ventricle and pulmonary artery c. There was a small septal defect d. Congestion in the lungs Histopathology: a. Multiple large air emboli of kidney and suggestive in other tissues Conclusions: Heartworms and air embolism due to Open-heart surgery MSU Clinic Case 116999 (3-21-68) 2-year-old male Pointer cross Surgical procedure - creation Of atrial septal defect. Surgery appeared successful. The dog regained consciousness but died the following morning. Pathology: a. Extensive surgery in the right thorax b. Considerable free blood in the chest c. Three adhesions between the pericardium and right lung d. 8 mm. atrial septal defect 10. 52 HistOpathology: a. Thrombus in the lungs b. Evidence of liver ischemia Conclusions: Death due to extensive atrial septal defect and intrathoracic hemorrhage MSU Clinic Case 117000 (4-4-68) 6-year-old male German Shepherd cross Surgical procedure - creation of ventricular septal defect and suturing between the right and left ventricle a plastic tube. The hOpe of the procedure was that the animal might live 3 days. Surgery was successful. The dog regained consciousness but died the following day. Following placement of the tubing and closure of the heart, ECG reversed to right ventricular hypertrophy pattern as the right ventricle dilated. Pathology: a. Extensive surgery in the right thorax b. Large amount of free blood in the chest c. Swollen liver d. Dilated right ventricle e. Large ventricular septal defect with a 9-mm.-diameter plastic cannula sewn on the right ventricular side, creat- ing the defect f. Necrosis around the ventricular septal defect and plastic cannula HistOpathology: a. Necrosis of the ventricular septum b. Central fibrosis of the liver Conclusions: Death due to hemorrhage, right-sided failure and ventricular septal defect with cardiac necrosis MSU Clinic Case 117373 3-year-old female mixed breed Surgical procedure - creation of mitral insufficiency (mitral chordae tendinotomy). By the left atrial approach, the mitral valve was grasped and chordae tendinae cut. Surgery appeared successful, the dog regained consciousness and arose but died the following morning. Pathology: a. Extensive surgery in right thorax b. Suture line in left atrium c. Hemothorax d. Cut mitral chordae tendinae e. Atelectasis and emphysema of the lungs 53 HistOpathology: a. Atelectasis and emphysema of lungs b. Degeneration of liver suggestive of hypoxia Conclusions: Atelectasis of the lungs and liver degeneration APPENDIX V Equipment and Drugs 54 55 APPENDIX V Equipment and Drugs Sigma Two Head Finger Pump; Sigmamotor, Middleport, N.Y. Sigma Coronary Sinus Finger Pump TM4; Sigmamotor, Middleport, N.Y. Travenol Miniprime Disposable Oxygenator; Travenol Laboratories, Mbrton Grove, Ill. Ohio Heidbrink; Ohio Chemical Co., Madison, Wisc. Halothane (fluothane); Ayerst Laboratories, Inc., New York Methoxyflurane (metaphane); Dow, Pitman-Moore, Midland, Mich. Sodium Thiamylal (Surital); Parke, Davis & Co., Detroit, Mich. DR8 Recorder; Electronics for Medicine, White Plains, N.Y. Statham P23Db Pressure Transducer; Statham Laboratories, Inc., Hato Rey, Puerto Rico American Optical Micro-oximeter; American Optical, Bedford, Mass. Radiometer Micro Gas MOnitor; Radiometer, Copenhagen, Denmark Povidine-iodine (Betadine Surgical Scrub); Purdue Frederick Co., Yonkers, N.Y. Vena Cava Cannula; Ingram-Co., Detroit, Mich. Femoral Arterial Cannula; Sarns, Inc., Ann Arbor, Mich. Lactated Ringer's Solution; Abbott Laboratories, North Chicago, Ill. Per 1000 ml.: Sodium 130 mEq. Calcium 109 mEq. Lactate 28 mEq. Potassium 4 mEq. Chloride 109 mEq. Tetracycline hydrochloride (Achromycin); Lederle Co., Pearl River, N.Y. Chloramphenicol (chloromycetin); Parke, Davis & Co., Detroit, Mich. Protamine Sulfate, U.S.P. 1%; Eli Lilly Co., Indianapolis, Ind. Digoxin (Lonoxin); Burroughs Wellcome & Co., TuckahOe, N.Y. Mannitol (Osmitrol); Travenol Laboratories, Morton Grove, Ill. Prednisolone Sodium Succinate (Soludelta Cortef); Upjohn Co., Kalamazoo, Mich. --L~-~----~‘ “ ‘ W—h,”_ MICHIGAN STAT 3 129 I II UNIVERSITY LIBRARIES 03056 2866 l