TUESDAY MORNING, APRIL 27, 1971

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

Phoenix Ballroom

19. New Developments in the Design of Fabric-Covered Prosthetic Heart Valves

Nina S Braunwald, Constantine Tatooles,* Marko Turina,*

and Don Detmer,* San Diego, California

Further improvement in the design of fabric-covered valves are essential if maximum benefit is to be derived from their use. In clinical and experimental application, a tendency toward stenosis and tissue buildup at the apex of the cage have been noted. This led to the design of a new fabric-covered, ball-valve prosthesis with an open-ended cage, tapered struts, and an ultrathin polypropylene mesh fabric covering on the inflow ring to optimize the benefits anticipated from development of tissue coverings. In vitro hemodynamic assessment of the valve in a pulse duplicator indicated that the average gradient across the mitral model averaged <5 mm Hg at flows up to 15L/min, while that across the aortic valve was <10 mm Hg at flows up to 10 L/min. Examination of valves implanted in the tricuspid and mitral annulus, in a series of 10 calves electively sacrificed up to 6 months postoperatively, demonstrated that there was less tissue buildup than in conventional models of fabric-covered, ball-valve prosthesis and the valves were free of thrombotic deposit. Clinical trial has been initiated in a series of 10 patients followed up to 6 months, and the results are promising.

20. The Flexible Stent: A New Concept in the Fabrication of Tissue Heart Valve Prostheses

Robert L. Reis, Warren D. Hancock,* John W. Yarbrouoh,*

and Andrew G. Morrow, Bethesda, Maryland

Fresh autogenous fascia lata valves and porcine aortic valves fixed in gluteraldehyde were mounted on flexible, dacron covered polypropalene stents. Fascia valves were fabricated by placement of a rectangle of fascia on a fabrication tool. The application of suction orients the fascia producing uniform prostheses rapidly. Cusp design (deep cusps, large coaptive surface) permits closure with minimal motion of the stent (<2 mm at 300 mm Hg). This small amount of stent motion reduced closing stresses on the cusps 90% as measured by a miniature strain gauge attached to the cusp. Valves of this design were evaluated in the pulse duplicator and in 15 calves and sheep, and 17 valves were implanted in patients (aortic, mitral, and tricuspid positions). All patients survived, and no prosthesis malfunction has occurred (6 months). Anticoagulants were not used, and there have been no emboli. Measurements of transvalvular gradient and cardiac output in the basal state and at different flows and heart rates, as well as assessments for valvular regurgitation, were made in each patient. Continued clinical application is planned, and the results including a comparison with the ball valve prosthesis will be presented.

21. Viability of Connective Tissue Cells Following Storage of Aortic Valve Leaflets

Hitoshi Mohri,* Dennis D. Reichenbach.* Murray P. Sands.*

and K. Alvin Merendino, Seattle, Washington

Connective tissue cells within aortic valve leaflets maintain the structural integrity of the leaflet by synthesis and turnover of elastin, collagen and ground substance. Therefore there should be an advantage in homograft aortic valves which contain viable cells capable of maintaining graft leaflet structure. Lack of availability of fresh homograft leaflets necessitates storage of specimens. A study of canine valve leaflets was performed to ascertain the conditions and the length of storage which maintain viable connective tissue cells. Specimens were stored for various periods in saline, Ringer's lactate, Hanks' balanced salt solution, or Waymouth's tissue culture media. Storage conditions included: refrigeration, 37° in closed containers and 37° in Petri dishes in an atmosphere of 95% air, 5% CO₂. Following storage, explants of leaflets were made and outgrowth of the cells was noted. Fibroblast-like cells grew from aortic valve leaflet explants following storage of up to five weeks in warm Waymouth's tissue culture media with viable cells evident following shorter storage periods (3-7 days) in the other media. Tissue culture media is a more suitable storage agent for maintaining viable stromal cells than are simple salt solutions, and cells remain viable for longer periods of storage in a warm environment than in the cold.

22. The Role of Rejection and Mechanical Trauma on Valve Graft Viability

Wally S. Buch,* and William W. Angell,* Palo Alto, California

Sponsored by Norman E. Shumway

Our 4 year clinical results with viable aortic valve homografts have been gratifying. However, the ultimate effects on graft architecture of host rejection, surgical injury and hemodynamic trauma remain controversial. To explore these questions, viable composite valves were constructed consisting of a cusp each from a porcine aortic heterograft, a canine aortic homograft, and a pulmonic autograft. The stented composite was implanted in the mitral position of the dog after repair of the pulmonary outflow tract. The resultant pulmonic insufficiency was well tolerated and immediate prosthetic function was excellent. Twenty implants were performed and all animals were sacrificed at intervals up to one year. A consistent pattern was observed. The autograft was thickened and hypercellular. The homograft, while always cellular and thickened, showed discrete areas of acellularity and necrosis. The heterograft was hypocellular, often thinned and occasionally totally acellular. We conclude that while donor fibro-blasts persist for long periods in all grafts, chronic host rejection plays the dominant role in their fate in heterografts and, to a lesser extent, in homografts. Routine surgical trauma is not detrimental to valve architecture, and hemodynamic trauma may be a stimulus to cellular growth in autografts and homografts.

23. Collagen-Derived Cardiac Valves I: Concept and Experimental Results

Alain Carpentier,* Paris, France

Sponsored by Albert Starr

A new type of valvular substitute made from biopolymers has been developed in our laboratory. The different macroproteins extracted from heart valves and purified or bounded to prosthetic groups were studied with respect to their biochemical properties, their immunological specificity and their thrombogenic activity in contact with blood. Then these biomaterials were used under various combinations and moulded in order to reproduce the shape, the structure and therefore the physiology of a normal aortic valve. The advantages of these bioprostheses seem to be as follows: (1) Excellent hemodynamics with central flow without transvalvular gradient. (2) Absence of thrombo-embolic complication (no anticoagulants are required). (3) No immunological reaction. (4) Availability, standardization and security of use as good as for a mechanical prosthesis. This valvular substitute was tested in mitral and tricuspid position on 24 sheep operated upon under extra-corporeal circulation with results good enough to consider clinical application. (Follow up 2 to 10 months).

24. Cardiac Prosthesis Utilizing Biological Material

Y. Nose,* Y. Imai,* K. Tajima,* H. Ogawa,* M. Klain,*

and K. von Bally,* Cleveland, Ohio

Sponsored by Donald B. Effler

Many cardiac prostheses utilizing plastics have been designed, fabricated and used. However, the clotting tendency of these plastic materials is one of the greatest problems. Aldehyde-treated homologous or heterologous tissue has been used clinically for intravascular implantation. In vitro kinetic clotting studies have indicated that aldehyde-treated aortic wall and pericardium showed 2 times better antithrombogenicity over Silastic. Therefore, aldehyde-treated aortic valve with aorta and pericardium were used to construct a cardiac prosthesis. A purified hydrophilic aldehyde-treated natural rubber developed in our laboratory was used to reinforce the outside surface of the biological materials. Twelve such devices after 10-14 days bypass implantation in calves showed no clot formation inside the heart, while five implanted conventional cardiac prostheses utilizing silicone rubber clotted within 2-5 days. Eight of these cardiac devices have been used to replace the total heart. The longest pumping time was 76 hours, but in all of these experimental animals there was no evidence of thromboembolus formation. Utilization of aldehyde-treated biological material and its combination with biolized (HATAR) natural rubber can be applicable for an antithrombogenic cardiac prosthesis.

25. Mesothelial Fibrinolysis

John M. Porter,* Frank H. McGregor,.* and Donald Silver,

Durham, North Carolina

Blood clots in pleural, pericardial, and peritoneal spaces usually undergo progressive fragmentation, liquefaction, and absorption without producing significant fibrosis. This study was performed to determine whether mesothelial surfaces can induce fibrinolysis and to localize the site of the fibrinolytic activity. Pleural, pericardial, and peritoneal samples were obtained from 10 patients and incubated on heated and non-heated fibrin plates and fibrin slides to quantitate and localize the fibrinolytic activity. Prior to incubation, portions of these tissues were exposed in vitro to a variety of agents known to produce mesothelial fibrosis, eg., nitrogen mustard, formaldehyde, phenol, and mechanical sponge abrasion. Similar samples were obtained and incubated from 10 mongrel dogs. The chemical and mechanical traumas were induced in vivo in the dogs. Lysis zones of 350 mm² (average) were produced on the non-heated fibrin plates. No lysis occurred on heated plates. Mechanical abrasion reduced the measured fibrinolytic activity by 25%. Nitrogen mustard reduced the activity by 45%. Phenol and formalin eliminated all fibrinolytic activity. The fibrin slides showed zones of fibrinolytic activity at the mesothelial surface and around vessels in the sub-mesothelial tissue. This study indicates that mesothelial surfaces possess fibrinolytic activator(s). Various types of chemical and physical trauma known to produce fibrosis in the mesothelial spaces are associated with a significant reduction in the fibrinolytic activity of mesothelial surfaces.

26. Effective Measures in the Prevention of Intraoperative Aeroembolus

G. Hugh Lawrence, Hunter A. McKay,* and

Robert T. Sherensky,* Seattle, Washington

The danger of coronary and cerebral aeroembolus and its contribution to morbidity and mortality following cardiac surgical procedures has been emphasized. A Doppler ultrasonic sensor has been utilized for the recognition of cerebral arterial aeroembolus during 52 cardiac surgical procedures. This technique has permitted an immediate evaluation of those tactors which contribute to the production of air emboli (oxygenator, cardiotomy suction design, location of cardiotomy and previous operation with adhesion) as well as those techniques which tend to decrease their occurrence (chamber venting, chamber filling, CO₂ insufflation, aortic needle venting, and elective ventricular fibrillation). As a result of these studies, which have had a direct correlation with postoperative electro-encephalographic patterns and neurologic status, certain preventive techniques have been emphasized so as to virtually eliminate aeroembolism from postoperative morbidity of intracardiac procedures during the course of the study.

27. Intracardiac Air Following Cardiotomy: Location, Causative Factors and A Method for Removal

Richard T. Padula,* Theodore E. Eisenstat,*

Merrill H. Bronstein,* and

Rudolph C. Camishion, Philadelphia, Pennsylvania

Embolization of air which enters the heart during cardiotomy remains a significant complication despite the use of vents, induced cardiac asystole, and flooding the operative field with carbon dioxide. To determine the location of air bubbles, the factors which cause their retention, and a method for their removal, intracardiac cinephotography, a technique which has previously been described before this Association, was employed. Isolated dual coronary-systemic perfusion systems were established in anesthetized dogs. With vents in the left ventricle and ascending aorta, the mitral valve was either inspected or replaced through a left atriotomy. As the heart resumed systemic perfusion, high speed color motion pictures of its interior were taken. Careful review of the films indicated air may be retained by gravity and trapping by anatomic structures. This air was readily removed by the vents. However, many fine bubbles remained adherent to the valve leaflets, chordae tendineae, and the endocardium itself. Installation of dilute paraldehyde solution into the left atrium with aspiration via the ventricular vent was found to be effective in removing these bubbles. This appears to be due to the fact that this solution significantly decreases the surface tension of blood and thereby decreases the cohesiveness of bubbles.

28. Transvenous Stimulation of the Phrenic Nerves

Seymour Furman,* Spencer K. Koerner,* Doris J. W. Esoher,*

A. Joel Papowitz,* James Benjamin,* and

Peter Tarjan,* Bronx, New York

Sponsored by George Robinson

Transvenous stimulation of the right phrenic nerve was accomplished in dogs with a soft, distensible loop catheter inserted via a larger straight lumen catheter, to assume a fully curved position in the low superior vena cava. The catheter electrodes pressed lightly against the vena cava wall and the catheter was axially rotated until the most sensitive and stable stimulating position was found. The pulse generator was uniquely versatile, capable of altering the impulse trains, their modulation, timing, amplitude, wave form, duration, polarity and respiratory rate. After rendering the.animals apneic with morphine, their tidal volume (Vj) and minute ventilation (V) could be regulated with ease to almost any level. Trie figures for V-p and V represent the average maximum volumes that could be obtained.

	VT	V	PCO2
Before Morphine	250ml	6.0 L/min.	42
After Morphine	apneic	apneic	-
During Phrenic Stimulation	800ml	16.9 L/min.	38

Minimal energy output and smoothest inspiration and expiration were obtained by increasing the modulation of the stimuli from 30 to 100 pulses/sec at a pulse duration of 0.5 msec with a respiratory rate of 16/minute. Permanently implant-able respiratory stimulators are being developed and, because of the relatively large energies required, conventional battery sources are being replaced by a 1 milliwatt nuclear source.

29. Influence of Ischemia and Hypothermia on the Ability of the Transplanted Primate Lung to Provide Immediate and Total Respiratory Support

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

Sponsored by Paul C. Adkins

Cadavers appear to be the only practical source for clinical lung allotransplantation. As a result, a period of ischemia of the donor lung will be unavoidable necessitating adequate organ preservation for maintaining pulmonary viability. Most studies of lung preservation in the dog and baboon have been performed with the contralateral lung intact. However, the ultimate test of a preservation technique is immediate and total respiratory function following transplantation. Thirty-six baboons underwent left lung autotransplantation and immediate contralateral PA hgation. Eleven out of 12 with varying periods of normothermic ischemia up to four hours survived with adequate gas exchange (mean pO₂: 88.6 mm. Hg) postoperatively, while six others failed to survive five or six hour ischemia. External cooling (at 10-15° C) or continuous ventilation (at 36° C) provided an additional hour of ischemia time in five out of six additional animals. Intermittent cold internal perfusion allowed only three hours of ischemia with consistent survival Those primates who died showed progressive infra-alveolar congestion and proteinogenous exudate in the transplanted lung with a decreased arterial pO₂, (mean < 50 mm. Hg) and elevated PA pressure (mean > 35 mm. Hg) postoperatively. The primate lung tolerates up to five hours of ischemia and still provides immediate and total gas exchange to insure survival.

30. Preclinical Testing of a Redundant Rechargeable Cardiac Pacemaker

G. Frank O. Tyers,* R. A. Foresman, Jr.,* E.H. Lerner,*

and J. A. Waldhausen, Hershey, Pennsylvania

Implantable pacemakers provide the best treatment for patients with complete heart-block. Unfortunately, two failure modes necessitate frequent reoperation: 1. premature component failure - 20% in the first 18 months, 2. battery failure - inherent in the design of all internal pacemakers used clinically. A small redundant rechargeable pacemaker has been developed to eliminate frequent reoperation on pacemaker patients. Six units with high drains to maximize discharge-recharge stress have paced dogs with complete heart-block for 4-18 months (mean 11 months). Premature component failure was eliminated by high reliability stress tested components, bench testing, and redundancy - i.e. each implantable unit includes a complete reserve stimulator including power source and three cathodal cardiac leads. Battery failure was avoided by modifying to a rechargeable configuration the mercury silver cell (not Ni-Cd) used in all clinical units. Continuing battery bench tests at body temperature have simulated 12 years of pacing. Recharging and repair in case of failure are accomplished magnetically through the intact skin. Clinical units require five minutes charging daily to prevent battery rundown. Each circuit provides 18 months pacing without recharging. A biological life in excess of 10 years is projected for each circuit for a total pacemaker life (primary plus reserve circuit) approaching 20 years.

*By Invitation