WEDNESDAY MORNING, APRIL 8, 1970

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

International Ballroom Center

34. Synthetic Blood

Leland C. Clark, Jr.,* Samuel Kaplan,* and Fernando Becattini,*

Cincinnati, Ohio

Sponsored by James A. Helmsworth

The discovery by Clark that silicone oils and certain perfluorinated liquids can transfer enough oxygen and carbon dioxide to sustain the life of animals breathing them suggests that they may serve in some form as valuable intracorporeal gas transfer agents. Such preparations may be useful in organ preservation, perfusion experiments, and even as emergency blood because, besides being able to contain at least 20 volumes % oxygen, they may be stored and they can be autoclaved. Emulsions of inert perfluorinated organics prepared by sonication of the fluorocarbon in Ringer's and other isotonic solutions containing surfactants, separately proven to be non-toxic, were shown to be excellent substitutes or adjuvants for natural blood. It is theoretically and experimentally demonstrable that such emulsions increase mixed venous and tissue oxygen tensions and are able to sustain life. The fate and half-life of the artificial blood will be reported together with experiments where these emulsions were given to mice, cats, and dogs while blood gas, tissue oxygen tension changes, and survival were tested. There was no problem with carbon dioxide transport and mixed venous pCO₂ tensions as high as 300 mm. could be obtained.

35. Negligible Hemolysis in Lande'-Edwards Membrane Oxygenator, Especially at Physiological Gas Tensions

Albert Vervloet,* Miles J. Edwards,* and M. Lowell Edwards,*

Portland, Ore.

Sponsored by Albert Starr

Blood damage has limited the use of external gas exchangers. Blood and gas are separated by membranes of silicon rubber in the Lande'-Edwards oxygenator. We tested a small prototype of this oxygenator at flows of 250 ml/min using 250 ml of fresh heparinized human blood at 37°C for 24 hours in vitro. We compared three gas mixtures: (1) 21% 0₂ and 6% C0₂ ("PHYS" O₂-CO₂); (2) 94% O₂ and 6% CO₂ (HIGH 02); (3) 21% O₂ and 0% CO₂ (LOW CO₂). At 8 hours, the per cent hemolysis was (mean ± S.D.): "PHYS" O₂-CO₂ = 0.36 ± 0.09 (n = 4); HIGH O₂ = 0.59 ± 0.15 (n = 4); LOW CO₂ = 0.69 ± 0.16 (n = 3). Hemolysis with "PHYS" O₂-CO₂ only slightly exceeded the 0.28% expected in vivo and was significantly less than with either HIGH O₂ or LOW CO₂ (P<0.01). On microscopy, there was much greater damage to both erythrocytes and leukocytes with HIGH O₂ or LOW CO₂ than with "PHYS" O₂-CO₂. This oxygenator causes little apparent blood cell damage Prolonged exposure to either high O₂ or low CO₂ damages blood.

36. Partial Cardiopulmonary Bypass Lasting up to Seven Days in Alert Lambs with Membrane Lung Blood Oxygenation

Theodor Kolobow,* Robert L. Sigman,* Warren M. Zapol,*

and Joseph Pierce, Bethesda, Md.

Sponsored by Robert L. Reis

Alert, unsedated, tethered 7-12 kg. lambs were subject to continuous 5-7 day veno-arterial perfusion with membrane lung blood oxygenation, with survival. Blood was drained from the inferior vena cava and right atrium into a closed reservoir through a non-kinking, large bore polyure-(hane catheter; it was then pumped by a non-occlusive roller pump through a fixed prime volume spiral silicone membrane oxygenator and returned to the common carotid artery. Heparin was infused at 1.5 mg/ (kg)(hr). Extracorporeal blood flow averaged 35-65 cc/(kg) (min). Plasma free hemoglobin remained below 5 mg%. Blood hemoglobin decreased by 1 gm% per day due to blood sampling. Platelet counts averaged 400.000/mm³. WBG counts averaged 13.000/mm³. Venous pH, pCO₂ and pO₂ remained at control values throughout. Cardiac output with pump temporarily off remained at control values of about 200 cc/(kg) (min). LVEDP after prolonged pumping ranged between 5 and 10 mm. Hg. Central venous pressure was always less than 5 mm. Hg. Institution of bypass slowed the heart by 20-30% with a transient 10-20 mm. Hg. rise in mean BP. Heart, lungs, and other internal organs of perfused animals grossly appeared normal. We conclude that in alert lambs continuous partial non-pulsatile long-term cardiopulmonary bypass with silicone membrane blood oxygenation is possible without producing cardiac, pulmonary, or hematologic impairment.

37. Prolonged Partial Cardiopulmonary Bypass and the Integrity of Small Blood Vessels: Role of Serotonin and of Platelet Transfusion

Peter Wisselink,* Mario Feola,* Clarence P. Alfrey,*

Minoru Suzuki,* J. N. Ross, Jr.,* and John H. Kennedy,

Houston, Texas

While short-term circulatory support by means of a heart lung machine may be useful, prolonged perfusion is usually attended by increasing vascular resistance, rising perfusion pressures, decreasing flow rates, and edema. This is caused by obstruction of the microcirculation by cellular aggregates and emboli. Gimbrone et al. have demonstrated that vascular resistance and fluid accumulation were significantly lower during perfusions with platelet-rich plasma than with platelet-poor plasma in isolated organ perfusion. Preliminary experiments by one of the authors (JHK) have suggested that the Serotonin-binding capacity of platelets may be involved in their nurturing effect on vascular integrity. In 32 dogs Cardiopulmonary bypass for five hours with platelet-rich plasma and with platelet-poor plasma was carried out in normal and in splenectomized dogs. The parameters studied were: platelet counts, blood Serotonin, peripheral vascular resistance, light and electron microscopy of kidney and skin vascular endothelium. Thrombocytopnia of 50% after one hour was regularly seen in bypass controls, but not in anesthesia controls, and was accompanied by a rise in systemic vascular resistance, but a progressive decrease in Serotonin. Platelet transfusion reversed these effects. The possibility that platelet transfusion may be of benefit for clinical assisted circulation or for organ perfusion is considered.

38. Peristaltic Bypass-Type Heart Assist Device

Hisateru Takano,* Hiroyuki Takagi,* Charles A. Farish,*

and Tetsuzo Akutsu,* Jackson, Miss.

Sponsored by James D. Hardy

In order to eliminate thrombus formation, a new bypass-type heart assist device has been designed without using a conventional type valve. The device consists of six-air driven chambers which function like a moving valve. This device can be filled simultaneously as it pumps. Synchronized pumping was done being triggered by the R-wave of the EGG. The device was implanted between the left atrium and the descending aorta. Eleven consecutive acute experiments demonstrated that this device effectively changed left ventricular pressure, femoral arterial pressure, left atrial pressure, the bypass flow, aortic root flow, and left ventricular work. Maximum bypass flow was 4.24 liters/min. The maximum decrease in aortic root flow was 105.4 per cent of control measurements. The left ventricular work, expressed by the tension-time index, was dramatically decreased. The maximum decrease was 100 per cent, being indicated by completely flat left ventricular pressure curve. Regulation of bypass flow was achieved either by changing the trigger ratio from 1:1 through 5:1 or by changing the number of pumping chambers used from six through three. When all six chambers were used at 1:1 trigger ratio, complete atrialization of the left ventrical was achieved.

39. Physiological Observations During Partial and Total Left Heart Bypass

William F. Bernhard, C. G. Lafarge,* M. Husain,* N. Yamamura,*

and T. C. Robinson,* Boston, Mass.

A previous report from this laboratory indicated that prolonged left heart bypass was possible in calves at flows up to 3.0 liters/minute. Subsequent investigations, using a larger pump (stroke volume 100 mls), were undertaken at higher flow rates (4.0-8.0 liters/minute) and continued for periods of one to four months. Prior to surgical implantation, the pump lining was primed with bovine collagen and seeded with cultured, fetal (bovine) fibroblasts. Physiological observations in these animals were made by cardiac catheterization: at rest, in left ventricular failure, and during treadmill exercise. At rest, left ventricular pressure could be reduced to zero mmHg., and end-diastolic volume decreased; in addition, cardiac output, left ventricular stroke volume, and ejection fraction were increased. Similar results were obtained during transient left ventricular failure induced by balloon-cuff coronary occlusion. During exercise, implanted electromagnetic flow probes reflected a doubling of cardiac output, with maintenance of bypass at eight liters/minute. Erythrocyte survival studies (D.F.³²P.) returned to normal in 12 calves after one month of by-pass, and examination of the blood-pump interface (by light and electron microscopy) disclosed viable fibroblasts and abundant collagen fibrils (up to 130 days).

40. A Comparative Study of Arterio-Arterial and Intra-Aortic Balloon Counterpulsation in the Therapy of Cardiogenic Shock

William H. Fleming,* and Gene V. Aaby,* Washington, D. C.

Sponsored by Judson G. Randolph

Cardiogenic shock was produced in 30 dogs by ligation of coronary artery branches to the left ventricle, with decreases in aortic, left ventricular and coronary perfusion pressures, cardiac output by the direct Fick technique, and left ventricular work as measured by tension time index. Left ventricular end diastolic pressure and total peripheral resistance, increased. In all ten control animals these changes became increasingly severe until death within 20 hours. Treatment for one hour with arterio-arterial counterpulsation produced a reversal of all of these changes, both immediately and for 30 days thereafter. Counterpulsation by intra-aortic balloon showed the same reversal of the shock process, and the magnitude of change was very similar. This model was uniformly fatal without therapy, but there was marked improvement in pressures, cardiac output, and survival following therapy by counterpulsation by either the arterio-arterial or intra-aortic balloon technique, with most animals surviving for over 30 days.

41. Prosthetic Tracheal Replacement

John Borrie,* Dunedin, New Zealand

Sponsored by Hiram T. Langston

Principles governing tracheal reconstruction are reviewed against a 15-year experience of replacing long tracheal defects (5 cms or more). Such methods as (1) excision and suture alone, (2) suturing with lateral relieving incisions, (3) using ribbed Dacron or (4) Marlex mesh prostheses have all been tested and rejected. The first method produced strictures, the second usually necrosis and strictures. Dacron or Marlex prostheses either collapsed or developed fatal tracheo-prosthetic suture line stenosis, usually within 28 days. A 5 cm long Silastic and Dacron mesh prosthesis, with terminal Dacron suturing cuffs, gave an average of 42 days survival before fatal stenosis occurred, again at the tracheo-prosthetic suture line. As clinically, tracheal strictures in infants can be successfully held dilated by indwelling polythene stents, the Silastic prosthesis was modified by recessing the Dacron suture-cuff one centimeter from each end of the prosthesis. Of six experiments, all survived beyond 100 days. There were two late deaths, (1) after 108 days - peri-prosthetic abscess, (2) after 152 days - intratracheal haemorrhage. Two developed some granulation at one end of the prosthesis, controlled by bronchoscopy and silver nitrate cauterisation. Two remain uncomplicated. Further prostheses, 10 cm. cuff-to-cuff, are now being tested. This ‘Dunedin-Model' Silastic prosthesis, with sub-terminal Dacron suturing cuffs has been the most promising ‘Ersatz-trachea' yet tested.

42. Experimental Evaluation of a Radioisotope-Powered Cardiac Pacemaker

Andrew G. Morrow, Sidney Levitsky,* Charles L. McIntosh,,*

Victor Parsonnett,* and Peter L. Frommer,* Bethesda, Md.

With the cooperation and support of the Atomic Energy Commission a nuclear-powered pacemaker has been constructed. It has a potential operating life of 11 to 20 years. The fuel, ²³⁸plutonium, serves as a heat source (250C.). A thermopile, consisting of glass tapes incorporating metallic thermocouple wires, provides direct thermo-electric conversion; 200 microwatts are supplied to the pacemaker circuit. The fuel itself is triply encapsulated, and provided with thermal and radiation shields; there is insignificant heat and radioactivity externally. The entire unit is enclosed in an evacuated, hermetically-sealed titanium case, which is the anode. The unipolar stimulating electrode (cathode) is connected via a ceramic-to-metal feedthrough. The unit weighs 100 g., and is comparable in size to conventional pacemakers. Three prototype units have been implanted in dogs for periods up to 6 months. There have been no changes in rate or stimulus artifact amplitude and configuration, and pacing has been maintained continuously. Early clinical application of the device is anticipated.

43. Quantitation of Red Blood Cell Destruction Associated with Valvular Disease and Prosthetic Valves

Herbert W. Wallace,* and William S. Blakemore, Philadelphia, Pa.

A new technique of quantitating intravascular and extravascular hemolysis was applied to a study of 21 patients with aortic valvular disease who underwent open heart surgery. This method involves measurements of endogenous carbon monoxide production (Vco), which has been correlated quantitatively with heme catabplism. Plasma hemoglobin concentrations do not reflect true RBG destruction. Of 11 patients studied preoperatively, nine patients with aortic stenosis had a mean Vco of 0.91 ml/hr (normal ≤ 0.5 ml/hr), and one of two patients with severe aortic insufficiency had an elevated Vco (1.02 ml/hr). Postoperative studies were performed on four patients with malfunctioning aortic prosthetic valves and 11 patients with normally-functioning prosthetic valves. Without exception, the patients with malfunctioning valves had a markedly elevated Vco (mean, 1.88 ml/hr), but only one had an elevated plasma hemoglobin. Six or more months postoperatively, the mean Vco of the patients with normally-functioning prostheses was 0.5 ml/hr, although three had above normal values. Carbon monoxide production may be related to pressure gradient or stroke volume/systolic emptying period. Thus malfunctioning valves can induce marked RBC destruction, which may be detected by this technique. This methodology should also be helpful in evaluating new designs for prosthetic valves and artificial hearts.

44. Replacement of Pulmonary Artery with a Pulmonary Arterial Homograft

S. Seki,* J. L. Titus,* and G. C. Rastelli,* Washington, D.C.

Sponsored by Dwight C. McGoon

Truncus arteriosus, transposition of the great arteries with subpulmonary stenosis, and pulmonary atresia have been successfully corrected using aortic homografts. Calcification in the elastic tissue of these homografts has developed postoperatively. Alternative grafts with which to replace the pulmonary artery and in which calcification might not occur are being investigated. The rationale of using a pulmonary homograft is that the pulmonary artery seldom becomes calcified from age or disease and that it contains less elastin and calcium than does the aorta. The pulmonary artery was ligated and excised in 25 dogs and replaced with a homograft consisting of the pulmonary valve, the main pulmonary artery, and right and left branches which were split longitudinally and sutured together so as to produce a tubular graft of the required length. Seventeen fresh grafts and eight frozen, irradiated grafts were implanted under cardiopulmonary bypass. Fifteen dogs are currently alive 2 weeks to 6 months after operation. Histologically these homografts are free of calcification 6 months after operation. This contrasts with the fate of aortic homografts which were used to replace the canine pulmonary artery and in which medial calcification had occurred by this time. Follow-up studies including hemodynamic data will be presented.

45. Immediate Function with Survival Following Left Lung Autotransplantation and Contralateral Pulmonary Artery Ligation in the Baboon

William L. Joseph,* and Donald L. Morton,* Bethesda, Md.

Sponsored by Paul C. Adkins

Until recently there have been no survivors after lung transplantation in the dog followed immediately by Contralateral pneumonectomy or ligation of the opposite pulmonary artery (PA). However, in clinical transplantation immediate function of the grafted lung will be necessary. Recently, Veith has reported a few survivors in dogs with angioplastic reconstruction of the pulmonary artery anastomosis to prevent subsequent PA hypertension. Left lung autotransplants without angioplastic reconstruction of the PA and with immediate Contralateral PA ligation were performed in 16 baboons. Postoperative differential bronchospirometry showed good function on the left; none on the right. Four died postoperatively while 12 are still alive at up to 10 weeks. Systemic arterial blood gas studies following transplantation (average: Po₂ 87 mm.Hg; pCO₂ 35 mm.Hg.) showed little change from preoperative values. Serial PA pressures showed a minimal rise in 6 baboons (average: 31/11 mm.Hg.) but all returned to normal within 14 days. Six had almost no change (average postoperative value 24/11 mmHg.). Lung autotransplantation with immediate function and survival is possible without the development of a sustained elevated PA pressure. The baboon appears to be a better animal for use in physiologic lung transplantation studies since it is probably more representative of man than the dog.

46. The Significance of the Bronchial Arterial Circulation in Lung Transplantation

Noel L. Mills,* Arthur D. Boyd,* and Charun Gherunpono,*

New York, N.Y.

Sponsored by Frank C. Spencer

This study was prompted by the uncertain consequences of interrupting the bronchial circulation at the time of lung transplantation. In reported experimental series without reconstitution of the bronchial arteries, the bronchial anastomosis complication rate has been 20 per cent or higher. If the incidence of significant bronchial complications in human lung allografts is as high and unpredictable as in dogs, bronchial circulatory reconstitution will be needed. In 50 postmortem dogs the anatomic patterns of the bronchial arterial supply to the left lung were classified by location and injection studies were performed. With this background, left lung allotransplantation was performed in 21 dogs in whom rejection was suppressed with Imuran. In 10 animals the bronchial circulation was reestablished while in 11 control animals it was not. In 82% of the control group bronchial complications, including ulceration (64%), stenosis (9%), and disruption (27%) occurred. This included disruption of the anastomosis in one animal (bronchial artery occluded) and ulceration in another. A review of the experiences with human lung transplantation with reference to bronchial complications will be included in the report.

*By Invitation