Thursday Morning, May 12, 1960

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

Napoleon Room

14. The Subcoronary Implantation of a Flexible Tricuspid Aortic Valve Prosthesis.

Benson B. Roe, Mervyn F. Burke (by invitation), and

Harry Zehner (by invitation), San Francisco, Calif.

A satisfactory, low-resistance, totally competent, flexible tricuspid aortic valve prosthesis has been developed in our laboratories and was reported earlier. Its material and mechanical characteristics have undergone long-term testing in the ascending aorta of the experimental animal Despite many improvements in material and production, the valves implanted more than two years ago are continuing to function and have produced no clotting.

The cylindrical housing of the originally reported valve has been reduced to the shortest possible axial length and a plastic sponge jacket has been incorporated in the outside wall to promote tissue fusion with the endocardium. A satisfactory technique has been developed for placing this valve in the left ventricular outflow tract transaortically so that it is secured with accurately placed sutures below both coronary ostia. This maneuver now requires less than 25 minutes of extracorporeal circulation, including the time for total excision of the anatomic leaflets, three interruptions for intermittent coronary perfusion, and closure of the aortotomy. Twelve consecutive animals have recovered from the maneuver sufficiently to restore normal cardiac function with satisfactory systolic and diastolic pressures. Death has occurred between 6 and 12 hours from hemorrhage and shock, but in each instance the valve is seen to lie in a satisfactory position without interference with mitral valve function

15. Experimental Production of Aortic Stenosis.

Anthony J. Munoz (by invitation), and Sam E. Stephenson, Jr

(by invitation), Nashville, Tenn.

The development of lesions simulating acquired valvular heart disease in animals has presented a major problem. In an attempt to evaluate surgical procedures for aortic stenosis lesions of early aortic stenosis have been obtained in mongrel dogs.

Two groups of animals have been studied. One group was rendered euthyroid with I₁₃₁. They were then fed toxic doses of vitamin D and a high cholesterol diet. These animals promptly developed high cholesterol blood levels and in as short a time as thirty days were developing arteriosclerotic-like plaques around the aortic annulus. Dogs sacrificed at 3 to 6 months develop plaques completely encircling the aortic annulus and fusion of the commissures occurs.

The second group of animals demonstrated the same findings. The only variation in the procedure was that propylthiouricil was used instead of I₁₃₁.

Photographs of the specimens obtained along with catheter data and pressure gradients representing early aortic stenosis will be presented. Animals sacrificed after one year will also be discussed.

16. Evaluation of a New Nonwettable Macroporous Membrane with High Permeability Constants for Possible Use in a Membrane Oxygenator.

James S. McCauohan (by invitation), Richard Weeder (by invitation),

John G. Schuder (by invitation), and William S. Blakemore,

Philadelphia, Pa

A recently developed method of producing plastic membranes has made possible the production of membranes with predetermined pores which can be selectively ranged from 3 to 300 micra. These can be prepared either wettable or nonwettable and the per cent of plastic lattice work and pores can be varied by adjusting the relative amounts of filler and plastic in the formulation. A nonwettable polyethylene membrane with pores 10 micra in diameter and representing 80 per cent of the volume was prepared and tested for gas permeability. Since it is nonwettable, liquids will not pass through it and due to its high porosity, gases flow across it rapidly. A simple apparatus and technique were devised for measuring the relative permeability of polyvinyl, polyethylene, Teflon, ethycellulose, and Silastic for comparison with the new macroporous membranes. Under controlled temperature, pressure and flow rate, carbon monoxide (CO) was passed on one side of the membrane which divided a chamber into two parts and oxygen (O₂) was passed on the other side. The amount of CO that diffused into the oxygen stream was then measured with a Stalex CO analyzer which will measure one part of CO per million. From these data and the thickness of the membrane, the permeability constants of the membranes were computed and compared. The membranes that have the highest permeability to CO also have the highest permeability to O₂.

Our results indicate that the new macroporous membranes are over 2000 times as permeable as Teflon, the membrane which is currently in use in membrane oxygenation.

Animal studies using these membranes in an experimental oxygenator are now in progress.

17. Temperature Compensated, Self-Calibrated Oxygen Monitoring Device.

Jesse H. Meredith (by invitation), John H. Artesani (by invitation),

and Joseph Mamlin (by invitation), Winston-Salem, N. C.

Control of the oxygen content in both the venous and arterial blood during cardiopulmonary by-pass has been difficult. This has been from a single obstacle, the inability to monitor the amount of oxygen in the arterial and venous blood. The development of an electrode for the polarographic determination of oxygen by Leland Clarke was a great step in the monitoring of oxygen. This device, however, is sensitive to changes in temperature and must be calibrated with each use and is not auto-clavable.

This paper describes a transistor circuit in which the temperature changes are automatically compensated for and which is self calibrating Autoclavable probes which can be inserted into the venous or arterial lines of the cardiopulmonary by-pass are described. The results of a series of perfusion experiments, during normothermia and severe hypothermia, during which the blood flow was controlled by monitoring the venous oxygen content, will be described.

18. Pulmonary Arterial Hypoxia versus Inspiratory Hypoxia in Relation to Increased Pulmonary Vascular Resistance.

Peter V. Moulder, Joseph Lancaster (by invitation), Robert

W. Harrison (by invitation), Stephen Michel (by invitation),

and Richard G. Thompson (by invitation), Chicago, Ill.

An experimental set-up has been devised with the use of an extra-corporal pump-oxygenator with venous by-pass to control pulmonary arterial oxygen saturation while varying inspired gas oxygen concentrations. Continuous measurement of cardiac output, pulmonary artery and left atrial pressures has been used to calculate pulmonary vascular resistances during the experimental runs. Central aortic pressure and electrocardiogram are monitored to judge normalcy of heart action; right ventricular pressure is monitored to rule out any period of right ventricular failure to be evidenced by elevation of the diastolic pressure. The right atrial pressure is used to monitor inflow pressure in some experiments while in others a constant pressure reservoir has been used to allow the animal to adjust the atrial inflow volume. Pulmonary wedge pressure has been measured in some experiments to rule out any role of pulmonary venospasm. Pulmonary arterial, mixed venous ("well") and aortic oxygen saturations were determined in each run. Inspired gas oxygen concentrations of 40%, 10%, 5% and 3% have been studied.

Spectacular increases m pulmonary arteriolar resistance have been obtained with severe pulmonary arterial hypoxia, inspiratory gas hypoxia and even with pulmonary arterial hyperoxia (with the oxygenator). When severe hypoxia has been produced with low inspiratory gas oxygen concentrations, the increased vascular resistances can be decreased somewhat by rapidly oxygenating the pulmonary arterial blood with the oxygenator but the reversal is not to normal.

19. Treatment of Bank Blood by Resins.

Edward D. McLaughlin (by invitation), Thomas F. Nealon, Jr

and John H. Gibbon, Jr., Philadelphia, Pa

The use of cation exchange resins to reduce abnormally high levels of ammonium and potassium in stored blood has been reported from this laboratory. Blood so treated still has an abnormally low pH chiefly due to the citrate preservative. Using a combination of anion and cation-exchange resins, it has been possible to return the ammonium and potassium to normal levels and also to substitute chiefly bicarbonate for the added citrate and the other increased anions. The harmlessness of large transfusions of old bank blood so treated has been demonstrated by exchange transfusion in dogs.

Pooled canine blood was collected in siliconized glass bottles containing 75 ml. of ACD solution per 500 ml. of blood. Twelve liters were stored at 5°C. for 14 days and a like amount for 21 days. After storage the blood was passed over the resin. The changes were similar in the 24 liters of blood and are averaged in the following table:

	At Collection	After Storage	After passage over Resins
ph	7.35	6.16	7.10
NA mEq/L	141	163	136
K mEq/L	4.1	19.5	0.6
NH4 mcg%	135	412	126
Ca mg%	9.4	1.7	4.6
Cit. mg%	1.5	449.0	2.0
PO4 mg%	3.7	7.3	2.8
Lact. mg%	16.8	157.0	63.0
Pyruv. mg%	1.37	7.26	1.25
Plasma Hb mg%	9.8	49.0	61.3

This blood was then used in exchange transfusions of greater than 200% of the calculated blood volume in eight consecutive dogs without a fatality All blood electrolyte values were normal 24 hours after transfusion. All dogs were sacrificed and autopsied after two weeks observation. No deleterious effect from the transfusions was observed.

The passage of stored ACD blood over combined anion and cation-exchange resins may reduce the danger of massive transfusion of bank blood and facilitate the procurement of blood for use in heart-lung machines.

20. Gas-Exchange Dynamics of Glycerolized Frozen Blood.

Thomas G. O'Brien (by invitation), Chelsea, Mass., and

Elton Watkins, Jr., Boston, Mass

Over one thousand units of glycerolized, frozen, thawed, deglycerohzed red blood cells resuspended in their original or a 5% albumin solution have been administered as blood volume replacement to patients at the Chelsea Naval Hospital. All measured factors would indicate that blood processed in this fashion functions as normal blood in vivo. The units were frozen at minus 80 or minus 120 degrees for periods of from one to 40 months.

Recent work in our laboratory gives every indication that blood, collected in heparin and processed in the above fashion and stored at minus 80 degrees, is very suitable as priming volume in pump-oxygenators. Cell loss following three hours of closed circuit perfusion was negligible in in vitro studies.

The gas exchange characteristics of these frozen red cells have never been determined. It is apparent that they take up oxygen normally Their oxygen releasing capacities are unknown. This problem is being studied by conventional methods of blood gas analysis utilizing tonometric equilibration of reconstituted deglycerolized red cells with oxygen at varying oxygen tensions within the physiologic range. Dissociation curves are to be compared with control curves for fresh blood and ACD preserved blood. Ancillary studies of plasma electrolyte concentrations, pH and carbon dioxide exchange dynamics are to be included.

In view of the fact that the clinical use of frozen blood is an actuality and that frozen blood would seem to tolerate the trauma of perfusion in pump oxygenators at least as well as fresh blood, it is felt that a detailed report of the dynamics of gas-exchange characteristics of frozen blood would be pertinent.

21. The Relationship of the Sympatho-Adrenal System to Potassium Flux and Cardiac Irritability Induced by Alterations in Blood pH.

Bernard Goott (by invitation), J. Rosenberg (by invitation),

R. C. Lillehei (by invitation), Fletcher A. Miller

(by invitation), and Owen H. Wangensteen,

Minneapolis, Minn.

Previous investigations in our laboratory have demonstrated that following prolonged inhalation of high concentrations of carbon dioxide, ventricular fibrillation frequently occurs in the immediate post-hypercapneic period. During the phase of respiratory acidosis the animal exhibits a significant increase in serum potassium, inorganic phosphorus and blood glucose. These changes are consistent with increased sympatho-adrenal activity, which we have confirmed by demonstrating elevated catecholamine levels during hypercapnia Infusion of epinephrine produces a similar rise in serum potassium levels. This can be prevented by exclusion of the liver from the circulation, thereby suggesting that the liver is a major source of the potassium increase, the stimulus for such increase being the sympatho-adrenal system. Simultaneous sampling of arterial and coronary sinus blood following rapid injection of epinephrine or nor-epinephrine in control animals indicates that this produces an immediate uptake of potassium by the heart. Tissue analysis demonstrates a 15-20% increase in myocardial potassium content during the period of respiratory acidosis. With rapid return of the arterial pH to normal by ventilation with air, the heart loses this excess potassium rapidly, as demonstrated by simultaneous arterial-venous samples. This loss bears a temporal relationship to disturbances in cardiac rhythm and is associated with a precipitous drop in serum catecholamine levels. When epinephrine is infused during the critical post-hypercapneic period, the sudden loss of this excess myocardial potassium has been demonstrated to be inhibited and ventricular fibrillation does not develop. Data will be presented to substantiate these statements.

22. Bronchoscopy and Bacteremia.

Sheldon Oscar Burman (by invitation), Pittsburgh, Pa

A majority of patients subjected to bronchoscopy exhibit mild fever beginning about an hour following the procedure and lasting occasionally for two days The etiology of the fever is obscure, being variously attributed to the stress of the procedure, traumatic inflammation and minute laceration of the bronchial mucosa, the presence of blood within the lumen, or the excitation of pre-existing pulmonary infection. Fever associated with the bacteremias following urethral intubation are commonplace, and, recently, sigmoidoscopic manipulation has been shown to cause transitory bacteremias. The question arose whether the fever of bronchoscopy likewise was attributable to transbronchial dissemination of pyogens into the blood stream

Careful antibiotic records were obtained from each patient studied Just prior to bronchoscopic examination a 10 cc "baseline" blood sample was collected using sterile technique from an antecubital vein. During bronchoscopy a second blood sample was withdrawn and four hours later a third 10 cc sample was obtained Following bronchoscopy, rectal temperatures, pulse, and respiration rates were recorded every four hours for two days and whenever a fever of one degree or more occurred a further 10 cc sample was withdrawn. Aerobes and facultative anaerobes were incubated at 37°C. in trypticase-agar slant bottles also containing 50 cc of trypticaseagar broth. Each blood sample was halved and duplicate innocula planted. Cultures were inspected daily for 21 days and all growth was suitably sub-cultured and characterized. Cultures evidencing any contamination whatever were excluded from the series. To date, unequivocal, pure cultures in moderate to heavy growth have been obtained from four of 24 patients studied or 17 per cent The organisms isolated were streptococcus in two cases, staphylococcus aureus coagulase positive in one case, and staphylococcus citreus in one case. All these patients exhibited one degree or more of fever and all positive cultures were obtained from the aliquot drawn four hours following bronchoscopy The rather striking clinical significance of these findings will be discussed.

23. Altered Hemodynamics in the Pulmonary Circulation Following Reaeration of an Atelectatic Lung.

Edwin Tutt Long (by invitation), Arthur F. Reimann (by invitation),

Takamaru Mikouchi (by invitation), John R. Benfield

(by invitation), and Salvatore L. Nigro (by invitation),

Chicago, Ill.

The physiologic shunting of venous blood through an atelectatic left lung in a dog has been shown to average approximately 15% of cardiac output. Surgical reaeration of the lung eliminates the shunt and returns oxygen saturation to normal. However, the reaerated lung cannot permanently sustain life if the opposite, normal, lung is removed. In our laboratory all such animals have died within 48 hrs. with a boggy, edematous condition in the reaerated lung.

An experiment, pertinent to this observation, was performed using twenty-six mongrel dogs from 10-15 Kg each. Six animals were normal controls. Twenty animals were subjected to chronic atelectasis of the entire left lung for 1 to 68 weeks. The lungs were then surgically reaerated Eleven animals have been studied 4 to 120 weeks later, using broncho-spirometry. The ventilation and oxygen uptake abilities of the reaerated lungs were found to average 22% to 16% respectively of the total. Since shunting was small or absent in all cases studied it was assumed that the left lung's oxygen uptake of 16% of the total was somewhat indicative of left pulmonary artery flow (% of total), and thus reaeration did not increase left pulmonary artery flow markedly compared to the 15% shunt flow of complete left atelectasis.

To demonstrate the reduced left pulmonary arterial flow (increased resistance) the pulmonary artery circulation to the right lungs was curtailed in various ways forcing up to 100% of cardiac output through the reaerated left lungs. In every instance studied this has resulted in elevated pulmonary artery pressures averaging 31 mm Hg. mean. This average is 50% greater than pressures found after right pneumonectomy in a normal animal and 100% greater than resting pressures in a normal animal The results of these completed studies including a comparison of normal and reaerated lung histology will be presented.

24. Selective Chemotherapy of the Lung During Unilateral Pulmonary Arterial Occlusion with a Balloon Tipped Catheter.

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

Washington, D. C.

The use of pulmonary arterial carcmolytic agents, administered either by trapping in the lung or by selective perfusion of the lung, has been previously reported.

The present technique was devised to permit selective, and possible repeated chemotherapy without thoracotomy

A balloon tipped double or triple lumen cardiac catheter is inserted into a peripheral vein and positioned in the right or left pulmonary artery. The balloon is inflated until the artery is occluded, and the carcinolytic agent injected into the blood stream distal to the occlusion.

Indicator dilution studies with T 1824 (Evans Blue Dye), Cr₅₁ tagged red cells, and Methylene Blue Dye show that a substantial amount of the indicator is retained in the lung and is well distributed during the 10 to 15 minute period of arterial occlusion. A progressive leak of the indicator into the systemic circulation occurs during this period.

Preliminary studies suggest that the tolerance of the lung for the carcinolytic agent will be the limiting factor in dosage rather than the leakage of the agent into the systemic circulation.

Experimental and clinical experience with various carcinolytic agents will be discussed.

25. An Experimental Study of Pulmonary Artery Replacement.

Joseph W. Gilbert, Jr. (by invitation), William P. Cornell

(by invitation), and Theodore Cooper (by invitation),

Bethesda, Md.

The correction of certain congenital cardiovascular malformations such as truncus arteriosus, atresia of the main pulmonary artery and transposition of the great vessels, may be contingent upon effecting communication between the right ventricle and the pulmonary arterial tree. An experimental study of replacement of the pulmonary artery has been undertaken in the dog.

Edwards-Tapp teflon grafts of 5/16" to 3/8" diameter were inserted between the right ventricular outflow tract and the distal end of the divided right or left pulmonary artery. Brief inflow occlusion permitted attachment of the prosthesis to the right ventricle after suture anastomosis to the pulmonary artery had been performed. The proximal end of the graft was adapted to a polyethylene stent, inserted through a stab wound in the outflow tract of the ventricle and secured by a purse-string suture.

The procedure was carried out in 20 dogs. Two died at the time of operation from technical faults and 7 at later periods, from sepsis or secondary hemorrhage. The graft was found to be patent in each of these dogs. The patency of the grafts in the 11 surviving animals has been determined by angiocardiograms and the physiologic effects of the valve-less prostheses studied by means of right heart catheterization.

26. A Simple Device for the Mechanical Anastomosis of Blood Vessels.

Timothy Takaro, Oteen, N. C.

An instrument for the anastomosis of blood vessels has been constructed which is considerably simpler in design than the Soviet vascular stapler. Consisting of but 8 pieces (compared with 26 or more parts in the Russian instrument), the device is essentially a cylindrical vascular clamp, bivalved to permit removal after use. Staple shafts and drivers are carried on one jaw, and clinchers are engraved on the opposing jaw. When a removable circular nut is tightened, the drivers press eight tiny stainless steel staples simultaneously across the interval between the two jaws, in which lie the vessels or grafts to be joined. Two bolts which fit into perforated, slotted wings on the jaws make possible adjustment of the distance between the jaws.

Using this device, dacron grafts were implanted in the thoracic aorta of 15 animals There were 13 long term survivors. Since the average period of occlusion of the thoracic aorta was only 6 minutes, neither shunts nor hypothermia were necessary. Vessels from 13 to 20 mm in diameter were successfully sutured. In some animals, multiple rows, the staples of which were staggered with respect to each other, were placed. Because relatively long cuffs of vessels and grafts remain in apposition by this technique, remarkably few staples as compared with sutures are required to effect a blood-tight anastomosis, and there is therefore minimal foreign material in contact with the blood stream at the anastomotic site This fact, plus the reproducible technical excellence of each anastomosis suggests the usefulness of small-sized models for small vessel anastomoses and organ transplantation work

27. Experimental Left Coronary Artery Perfusion Through an Aortotomy During Cardiopulmonary Bypass.

James B. Littlefield (by invitation), Edward M. Lowicki

(by invitation), and William H. Muller, Jr.,

Charlottesville, Va

A direct surgical approach on the aortic valve often necessitates a prolonged aortotomy and the maintenance of myocardial nutrition is therefore necessary. In this study, perfusion of the left coronary artery alone with oxygenated blood through an aortotomy during Cardiopulmonary bypass is investigated.

Employing total pump dependency with ascending aortic occlusion, a 1.5 cm. vertical aortotomy was made above the aortic valve. A perfusion cannula, connected either to the arterial line of the pump (Group I) or to a suspended bottle (Group II), was inserted into the left coronary ostium. Continuous perfusion rates varied from 50 ml. to 100 ml./min for periods of 15 to 60 minutes at 32° to 35° C. Aortic pressures, continuous electrocardiographic tracings (before, during and after operation), coronary venous flows and coronary arterial-venous oxygen saturations were recorded.

RESULTS: Control dogs tolerated an open aortotomy without coronary perfusion for 8 5 minutes (mean) before ventricular fibrillation occurred.

Continuous perfusion of the left coronary artery alone was performed for periods from 15 to 60 minutes without evidence of ventricular fibrillation A coronary flow of 50 ml./min. proved adequate. The coronary venous oxygen saturation averaged 64% (Control: 44%) during perfusion The factor limiting adequate perfusion in the dog is the anatomical variation of the left coronary artery characterized by its early bifurcation or trifurcation. This limitation necessitated the use of specially designed cannula tips Long-term survivors include animals from both Group I and II Postoperative aortotomy bleeding was a serious problem early in this study.

SUMMARY: The left coronary artery alone may be continuously perfused in the dog for as long as 60 minutes without the development of ventricular fibrillation. Left coronary artery perfusion in patients has proven satisfactory.

28. Growth of Cardiovascular Chambers Following Cardiac and Aortic Surgery.

Sigmund A Wesolowski (by invitation), Lester R. Sauvage

(by invitation), Philip N. Sawyer (by invitation), and

Karl E. Karlson, Brooklyn, N. Y.

The development of intracardiac surgery for the correction of human congenital cardiac defects has been so rapid as to outstrip the available knowledge from the experimental laboratory concerning the long-term fate of the intracardiac procedures themselves. This has been disturbing to certain surgeons and represents the basis of criticism, with some justification, from our medical colleagues.

In our studies of over 500 growing pigs over the past five years, we have come to rely upon the changes of cavity mensuration and the ventricular myocardial weights as sensitive indices of hemodynamic changes with growth in the cardiac outflow tracts, and of the attraction and deposition of calcium salts as an index of degenerative change at the operative site. The present communication presents the results of the changes of these indices in 300 experimental animals bearing various degrees of stenotic thoracic aortic grafts, and various mild abnormalities of the outflow tract of the right ventricle.

We have found that lesions considered clinically insignificant produce statistically significant changes in the above-mentioned indices as follows-mild degrees of stenosis (between 0 and 50% diameter loss) of grafts in the descending thoracic aorta produce absolute increase in the left ventricular weight; mild degrees of right infundibular stenosis, pulmonary valve regurgitation, and insertion of patches of Ivalon and of pericardium in the outflow tract lead to moderate to marked increase in right ventricular weight.

The presentation will include the detailed results and will relate them to (1) the problem of arterial graft selection in the growing human, (2) the selection of materials for outflow tract widening, and (3) the application of the preparation for screening of new intracardiac procedures