Tuesday Morning, April 9, 1963

8:30 A.M. Scientific Session: THORACIC SURGERY FORUM

Emerald Room

14. Major Airway Collapsibility in the Pathogenesis of Obstructive Emphysema

W. Gerald Rainer, David Hutchison, James Newby,

Roger Hamstra, and John R. Durrance (all by invitation), Denver, Colo.

Sponsored by Henry Swan

Contrary to the time-honored concept that the pathology in obstructive emphysema is limited to the bronchiole-alveolar level, the generalized destructive process could be explained more readily if central airway obstruction could be demonstrated. Methods: Forty subjects (10 normal volunteers and 30 with varying degrees of emphysema) were subjected to cinefluorographic study of the trachea and main bronchi. In twenty of these subjects, additional synchronous determinations of intratracheal and intraesophageal pressure changes, and spirometric and pneumotachygraphic values were recorded for correlation with the cinefluorographic studies. Airway deformation and effects on airflow were studied under conditions of various intrathoracic pressures. Major airway collapse accompanying forced expiration and cough in emphysema is demonstrated. Pressure-flow data show high intrabronchial pressures below the point of tracheal collapse associated with severe reduction of expiratory airflow. On the basis of these studies, it is felt that, although the origin of emphysema is in the smaller branches of the tracheo-bronchial tree, the destructive effects of prolonged intermittent increases in intrathroacic pressure produce severe changes in the trachea and major bronchi that are responsible for the severe airway obstruction and consequent alveolar destruction characteristic of chronic obstructive emphysema.

15. Evaluation of the Functional Anatomy of the Thoracic Duct by Lymphangiography

Marvin Pomerantz, Jean R. L. Herdt, David S. Rockoff, and

Alfred S. Ketcham (all by invitation), Bethesda, Md.

Sponsored by Will C. Sealy

Utilizing lymphangiography the anatomy and fluid dynamics of the thoracic duct has been studied. The thoracic ducts of 70 patients without thoracic disease and 30 patients with thoracic disease have been evaluated. Twenty-five patients had cinefluorography of their thoracic ducts under varying conditions. Five patients had studies prior to and following cervical thoracic duct ligation incidental to radical neck dissection. Five dogs had cervical ligation of their thoracic ducts and an additional five dogs had intrathoracic division of their thoracic ducts. Serial lymphangiograms were performed on these animals. These findings were correlated with human studies. The numerous variations in the anatomy of the thoracic duct reported from cadaver studies has been substantiated by these functional lymphangiographic studies. Thoracic duct displacement was found in two patients, one with a benign, the other with a malignant mediastinal neoplasm. Cinefluorography revealed a lack of intrinsic peristalsis, ampullary filling with inspiration, and emptying with coughing or the Valsalva maneuver. Following cervical ligation ether some degree of thoracic duct lymph stasis was present or lymph returned to the blood vascular system through collateral channels. This study demonstrates visually the numerous functional anatomical variations of the thoracic duct and the dynamics of flow within the duct.

16. The Use of Plastic Adhesive in Pulmonary Surgery

Robert J. Wilder, Herman Playforth, Michael Bryant

(all by invitation), and Mark M. Ravitch, Baltimore, Md.

To determine the value of rapidly polymerizing adhesive in pulmonary surgery, seventy animal experiments have thus far been performed. In the first group of dogs, bronchial closures and bronchial anastomoses were made with Eastman 910 Monomer. In a second group, the pulmonary apex was amputated and the raw surface sealed either with adhesive alone or with adhesive and a free pericardial graft. In a group, the security of the bronchial closure was evaluated using (a) silk sutures, (b) tantalum staples, (c) and Eastman 910 Monomer after standard inoculation of the bronchial stump with staphylococcus aureus. The results demonstrate that with plastic adhesive alone, the dog bronchus can be satisfactorily closed or anastomosed. In addition, the raw transected lung surface is easily sealed either with pericardium and adhesive or with adhesive alone. A comparison of the three methods used for closing the bronchial stump in the face of heavy bacterial contamination has demonstrated no significant difference in fistula and death rates between silk suture, tantalum staples or adhesive closures in 30 experiments.

17. Pulmonary Function Studies in Canine Lung Transplantations

Keith Reemtsma, Robert E. Rogers (by invitation),

John F. Lucas, Jr. (by invitation), Frank E. Schmidt (by invitation),

Frank H. Davis, Jr. (by invitation), and

Oscar Creech, Jr. New Orleans, La.

The functional status of the transplanted canine lung usually has been assessed by the survival period and x-ray appearance. In the present series of 32 lung transplants serial determinations of oxygen consumption, minute ventilation and pulmonary blood flow were performed on the normal and transplanted canine lung. Left lung homotransplantation was performed with anastomoses of the left pulmonary artery, left bronchus and left atrium. Following insertion of a bronchospirometric tube, simultaneous determinations of oxygen consumption and minute ventilation were obtained for each lung. Using the Fick principle as modified by Fishman, differential pulmonary blood flows were calculated for each lung. In the immediate post-transplantation period, oxygen consumption by the transplanted lung was markedly depressed, although minute ventilation of the transplanted lung approached that of the normal lung. Serial determinations usually showed good ventilatory function of the transplant until shortly before death, persistence of impaired oxygen transfer by the transplanted lung throughout the post-transplantation period, and moderate variation in the blood flow through the transplant. These studies suggest that the oxygen transfer by the transplanted lung is markedly impaired despite reasonably well-maintained ventilation and blood flow.

18. Physiological Alterations of Cardiopulmonary Function in Dogs Living One and One-half Years on Only a Reim-planted Right Lung

Salvatore L. Nigro, Richard H. Evans, John R. Benfield

(all by invitation), and William E. Adams Chicago, Ill.

Previous reports have shown that dogs can survive after reimplantation of one lung, but usually die when the contralateral lung is removed. Twenty dogs were subjected to complete removal and immediate reimplantation of the right lung. On removal, the lung was perfused with heparin-normal saline solution, chilled to 10° C and then reimplanted. Of the twenty dogs operated upon, fourteen survived. Angiocardiograms were done to demonstrate the patency of the pulmonary vascular pattern. Mean pulmonary artery pressures varied from 11 to 8 mm Hg. By bronchospirometric studies, it was found that the transplanted lung had a reduction in ventilatory function of about 10%, while the oxygen uptake was depressed by some 25%. Pulmonary compliance was decreased about 20%. When an animal thus prepared was subjected to a total left pneumonectomy, fatal pulmonary hypertension was produced with pulmonary artery pressure 55/25 and mean 33. Therefore, staged pulmonary resections combined with bronchial stenosis on the opposite side were substituted for one-stage pneumonectomy. Some of these dogs have survived on the reimplanted lung alone for one and one-half years and are living and healthy. In these dogs, the pulmonary artery pressures are elevated. The results of these completed studies, including histologic studies of the lung, will be presented and their significance discussed.

19. Autoimplantation and Homotransplantation of the Lung: Further Studies

James D. Hardy, (and by invitation) Martin L. Dalton, Jr.,

Sadan Eraslan, and Fikri Alican, Jackson, Miss.

Successful homotransplantation of the lung would of course provide a therapeutic weapon of great value in the management of a wide variety of lung diseases which produce respiratory insufficiency. The present series of studies was designed to explore technical, physiologic and immunologic factors in lung transplantation. Initially lung autoimplantation, immediate or delayed, was performed in a series of over 100 dogs to evaluate effects upon respiratory reflexes, the reimplanted lung and the animal generally. The effects of late contralateral pulmonary artery ligation, contralateral pneumonectomy, contralateral pneumonectomy and reimplantation and contralateral multiple lobectomies were recorded. Respiratory reflexes originating in at least a portion of the contralateral lung must be preserved. Denervation of a lung often diminished respiratory efficiency. To prolong lung homograft takes (130 dogs) the following drugs or maneuvers have been evaluated: BW 57-322 (Imuran), BW 57-322 plus Actinomycin C, methotrexate, 6-mercaptopurine, and drugs plus mother-to-grown offspring homotransplants as well as offspring-to-mother homotransplants. The BW 57-322 proved to be the most effective of the drugs in prolonging homograft survival in dogs.

20. Prolonged Survival of Orthotopic Homotransplants of the Heart in Animals Treated with Methotrexate

David A. Blumenstock (by invitation), Cooperstown, N.Y.,

Herbert B. Hechtman (by invitation), New York, N.Y.,

Alfred Jaretzki, III,James D. Hosbein (by invitation) Cooperstown, N.Y.,

Walter Zingc (by invitation), Winnipeg, Manitoba, Canada,

and John H. Powers (by invitation), Cooperstown, N.Y.

The survival of homografts of skin, spleen, and lung has been prolonged by treating the recipient animal with methotrexate. The effect of this drug upon orthotopic homotransplants of the heart has been studied. The hearts of 36 dogs were excised and replaced with homografts from unrelated donors. The recipient animal was given methotrexate, 0.2 mg./kg. on the day following operation and 0.1 mg./kg. on alternate days thereafter. Thirty-one animals died during the first 24 hours after transplantation. Five animals survived and were sustained 2, 10, 17, 26, and 42 days solely by the transplanted heart. The usual survival of a heart placed in an untreated animal is four to six days. These results indicate significant supression of rejection of the transplanted heart by methotrexate. Histologic and electrocardiographic studies of these animals will be presented.

21. Combined Gas and Heat Exchange in Extracorporeal Circulation

Nicholas P.D. Smyth (by invitation), and Brian Blades,

Washington, D.C.

In extracorporeal circulation there would seem to be obvious advantages in combining the functions of gas and heat exchange in one unit, since each requires the dispersion of blood over a large surface area. Priming volume of the system would be reduced, and also the length of tubing and the number of connections used. We selected the vertical screen oxygenator for modification, firstly because of its known efficiency, and secondly because its absence of moving parts made the task theoretically easier. In the proposed modification the wire screens of the oxygenator would be replaced by thin metal plates, through the center of which the heat exchange fluid would circulate, and on the surface of which the blood would be filmed for gas and heat exchange. Using a single 30 x 45 cm. test plate, heat exchange was studied by circulating heparinized dogs' blood across the plate in a closed system. Inlet and outlet temperatures for blood and heat exchange fluid were measured serially at various flow rates. Gas exchange was studied using partial bypass in an anesthestized dog. Arterio-venous oxygen difference across the plate was measured at various flow rates. Data showing satisfactory gas and heat exchange will be presented.

22. Capillary Membrane Oxygenator

Bruce R. Bodell, James M. Head, Louis R. Head,

Anthony J. Formolo (all by invitation), and Jerome R. Head

Chicago, Ill.

In the past few years it has been recognized that an ideal oxygenator for use in extracorporeal circulation systems is one in which a membrane (permeable to CO₂ and O₂)separates blood from gas. This paper reports initial experiments in extracorporeal circulation using a fixed blood volume, closed system, membrane oxygenator of new design and concept employing silastic capillary tubing (0.012" X 0.025") as a gas transport to the blood pool. The oxygenator is an assembly of disposable units which can be mass produced and distributed in presterilized packages. Cardiac bypass perfusions were carried out on ten 85 lb. sheep at flow rates of 2-3L/min. All but one animal survived the perfusions. Blood pH, pCO₂, and pO₂ determinations were made at intervals over 45 minutes of bypass. Oxygen saturations of 99% were maintained in all animals. A problem of COs retention was encountered. By altering design to increase gas flow in the capillary tubing, it was possible to reduce the pCO₂ at 45 min. from 120 mm Hg to 70 mm Hg. Further alterations of design are in progress to enhance CO₂ elimination and reduce priming volume from 2000 cc. to 1000 cc.

23. The Feasibility of Hypothermic Perfusion Under Hyperbaric Conditions in the Surgical Management of Infants with Cyanotic Congenital Heart Disease

W. F. Bernhard, E. S. Tank (by invitation), and Robert E. Gross

Boston, Mass.

Experience in our laboratory indicates that administration of oxygen at an environmental pressure of 35-39 p.s.i. greatly increases the arterial O₂ saturation of cyanotic infants. Although the clinical improvement is temporary in nature, the possibility of performing palliative or corrective surgery during pressure therapy seemed worthy of investigation. Studies were performed in a large compression chamber which accommodated a team of five investigators. Utilizing a miniature pump-oxygenator, hypothermic perfusions were carried out in 40 dogs (3.0-8.0 Kg.) at a pressure of 35 p.s.i. Certain biochemical parameters were monitored during perfusion, which ranged in length from 60-180 minutes; pO₂, pCO₂, pH, CO₂ combining power, plasma lactate, pyruvate and free hemoglobin. Arterial pressure, venous pressure, and EKG tracings were also recorded. Oxygen consumption (under pressure) was calculated at 37^°C. and at reduced temperatures (37°-15° C).These experiments indicated that the oxygen in physical solution (6.0-8.0 vols.%), along with reduced metabolic requirements, permitted either prolonged, low-flow, perfusions (5-15 cc/Kg./min.) or extended intervals of total circulatory arrest without evidence of hypoxia or acidosis. Cardiac surgery for infants, performed in a compression chamber, with low-flow perfusion at reduced temperature, appear to be feasible.

24. Fat Embolization with Cardiotomy Using Cardiopulmonary Bypass

Feodor Caguin (by invitation), and M. G. Carter, New Haven, Conn.

The occurrence of symptoms indicating central nervous system damage following cardiac surgery with extracorporeal circulation led us to study a group of 92 patients undergoing 93 heart operations during the period April 1958 to January 1962. Five of the first 48 patients exhibited varying degrees of delirium, hallucinations, amnesia and tremors without localizing neurological signs. All patients recovered. Air, calcium and antifoam embolism and electrolyte changes were all deemed most unlikely causes. Fat embolism from blood aspirated via the cardiac sucker seemed a possible explanation. A second group of 45 patients were studied with 24 hour urine samples examined for fat globules before and after cardiotomy. Ten of these developed lipuria and all 10 had some or all of the neurological findings previously observed. Mental changes were not seen in 35 patients without lipuria. Fifteen random non-cardiac thoracotomy patients were similarly studied with negative findings. These data suggested that fat embohzation probably was responsible for the reversible neurologic damage. Since this study, great care has been taken to discard all blood spilling from the interior of the heart into either the pericardium or thorax and no further cases with mental changes or lipuria have been observed.

25. Hemorrhage due to Fibrinolysis Occurring with Open Heart Operations

David A. Tice, George E. Reed, Roy H. Clauss, and

Melvin H. Worth (all by invitation), New York, N.Y.

Sponsored by Walter W. Fischer

Hemorrhage due to fibrinolysis occurred in nine of the last fifty-five patients undergoing open heart surgery with cardiopulmonary bypass. Fibrinolytic activity was determined by a rapid method (reconstituted whole blood clot lysis) previously described. Fibrinolysis was significantly reduced and hemorrhage controlled in all patients by treatment with Epsilon Amino Caproic Acid or Trasylol. Death occurred in four of the nine patients; three due to heart failure with low cardiac output and one due to cerebral complications (air embolism). Lysis was associated with eight hypothermic and one normothermic perfusions. Three patients had less than 70 minutes and three had more than 130 minutes of perfusion. Metabolic acidosis was graded one to four plus using a nomogram previously described. No definite association of degree of acidosis with fibrinolytic activity was observed. All hypothermic patients received low molecular weight dextran (Rheomacrodex), constituting 15% of the priming volume of the pump oxygenator. Preliminary findings in ten recent patients suggest that fibrinolytic activity is associated with a rise in circulating lysosomal enzymes, acid phosphatase and beta glucuronidase.

26. Acidosis as a Cause of Renal Shutdown During Extra-corporeal Circulation: Its Correction by the Use of Tham

John E. Connolly (and by invitation) Samuel L. Kountz, and

James M. Guernsey, Palo Alto, Calif.

Renal shutdown persists as a serious complication that may accompany cardiopulmonary bypass, particularly if prolonged. In an attempt to clarify the etiology of such renal failure, we have measured renal blood flow under varying conditions. In eight experiments, dogs were connected to an oxygenator primed with fresh blood. The animal's right renal artery was encircled with an electromagnetic flowmeter providing continuous recording of renal blood flow. Frequent blood pH and pCO₂ determinations were made. The effects of low flow and high flow, total and partial cardiopulmonary bypass on renal blood flow were determined. Surprisingly renal blood flow paralleled blood pH, falling rapidly with development of acidosis. As others have shown, low bypass flow rates resulted in metabolic acidosis. However, acidosis with markedly depressed renal blood flow was seen with high flow rates when acidosis was induced by adding excess CO₂ to the oxygenator or lactic acid to the animal. THAM given during bypass rapidly corrected the acidosis returning renal flow to normal. These experiments indicate that acidosis is a cause of reduced renal blood flow and renal failure under certain conditions of cardiopulmonary bypass. Renal blood flow will remain in normal ranges if normal blood pH is maintained during bypass.