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Background: Reoxygenation of hypoxic myocardium during repair of congenital heart defects results in poor ventricular function and cellular injury. Endothelin-1 (ET-1), a potent vasoconstrictor that increases during hypoxia, may suppress myocardial function and activate leukocytes. The objective was to determine whether administration of an endothelin receptor antagonist could improve ventricular function and decrease cardiac injury after hypoxia and reoxygenation., Methods: Fourteen piglets underwent 90 minutes of ventilator hypoxia, 1 hour of reoxygenation on cardiopulmonary bypass, and 2 hours of recovery (controls). Nine additional animals received an infusion of Bosentan, an ET(A/B) receptor antagonist, (5 mg/kg per hour) during hypoxia and reoxygenation., Results: Right and left ventricular dP/dt in controls decreased to 78% and 52% of baseline, respectively, after recovery (p < 0.05). In contrast, Bosentan-treated animals had complete preservation of RV dP/dt and less depression of LV dP/dt. Bosentan reduced the hypoxia and reoxygenation-induced elevation of ET-1 and iNOS mRNA at the end of recovery (p < 0.05). Bosentan-treated animals had diminished myocardial myeloperoxidase activity and lipid peroxidation compared with controls (p < 0.05). Myocardial apoptotic index, elevated by hypoxia and reoxygenation, was lower in the Bosentan-treated animals (p < 0.05)., Conclusions: Endothelin-1 receptor antagonism improved functional recovery and decreased leukocyte-mediated injury after reoxygenation. The reduction in cardiac cell death might also improve long-term outcome after reoxygenation injury.

Background: Which blood gas strategy to use during deep hypothermic circulatory arrest has not been resolved because of conflicting data regarding the advantage of pH-stat versus alpha-stat. Oxygen pressure field theory suggests that hyperoxia just before deep hypothermic circulatory arrest takes advantage of increased oxygen solubility and reduced oxygen consumption to load tissues with excess oxygen. The objective of this study was to determine whether prevention of tissue hypoxia with this strategy could attenuate ischemic and reperfusion injury., Methods: Infants who had deep hypothermic circulatory arrest (n = 37) were compared retrospectively. Treatments were alpha-stat and normoxia (group I), alpha-stat and hyperoxia (group II), pH-stat and normoxia (group III), and pH-stat and hyperoxia (group IV)., Results: Both hyperoxia groups had less acidosis after deep hypothermic circulatory arrest than normoxia groups. Group IV had less acid generation during circulatory arrest and less base excess after arrest than groups I, II, or III (p < 0.05). Group IV produced only 25% as much acid during deep hypothermic circulatory arrest as the next closest group (group II)., Conclusions: Hyperoxia before deep hypothermic circulatory arrest with alpha-stat or pH-stat strategy demonstrated advantages over normoxia. Furthermore, pH-stat strategy using hyperoxia provided superior venous blood gas values over any of the other groups after circulatory arrest.

Background: Acute hypoxia results in increased pulmonary vascular resistance. Despite reoxygenation, pulmonary vascular resistance remains elevated and pulmonary function is altered. Endothelin-1 might contribute to hypoxia-reoxygenation-induced pulmonary hypertension and to reoxygenation injury by stimulating leukocytes. This study was carried out using an established model of hypoxia and reoxygenation to determine whether endothelin-1 blockade with Bosentan could prevent hypoxia-reoxygenation-induced pulmonary hypertension and reoxygenation injury., Methods: Twenty neonatal piglets underwent 90 minutes of hypoxia, 60 minutes of reoxygenation on cardiopulmonary bypass, and 2 hours of recovery. Control animals (n = 12) received no drug treatment, whereas the treatment group (n = 8) received the endothelin-1 receptor antagonist, Bosentan, throughout hypoxia., Results: In controls, pulmonary vascular resistance increased during hypoxia to 491% of baseline and remained elevated after reoxygenation; however in the Bosentan group, it increased to only 160% of baseline by end-hypoxia, then decreased to 76% at end-recovery. Arterial endothelin-1 levels in controls increased to 591% of baseline after reoxygenation. Arterial nitrite levels decreased during hypoxia in controls but were maintained in the Bosentan group. Consequently, animals in the Bosentan group had better postreoxygenation pulmonary vascular resistance, A-a gradient, and airway resistance along with lower myeloperoxidase levels than controls., Conclusions: Acute hypoxia and postreoxygenation pulmonary hypertension was attenuated by Bosentan, which maintained nitric oxide levels during hypoxia, decreased leukocyte-mediated injury, and improved pulmonary function.

Background: Plasma thromboxane B2 (TXB2), leukotriene B4 (LTB4), and endothelin-1 (ET-1) levels increase on cardiopulmonary bypass (CPB). Elevated levels of TXB2 and ET-1 have been correlated with postoperative pulmonary hypertension in infants undergoing repair of congenital heart defects. LTB4 is a potent chemotactic cytokine whose levels correlate with leukocyte-mediated injury. Modified ultrafiltration (MUF) has been associated with improved hemodynamics and pulmonary function, in addition to its beneficial effects on fluid balance and blood conservation. Recent investigations have suggested that removal of cytokines may be the cause of the improved cardiopulmonary function seen with MUF., Methods: Plasma TXB2, ET-1, and LTB4 levels were measured in 34 infants undergoing CPB: 22 underwent MUF (group 1), and 12 did not (group 2). Samples were obtained at various time points. All patients underwent conventional ultrafiltration during the rewarming phase of cardiopulmonary bypass., Results: In group 1, mean end-CPB TXB2 level was 101.2 pg/mL versus 46.9 pg/mL post-MUF (p < 0.05). The mean TXB2 level 1 hour post-CPB (54.1 pg/mL) was not significantly different from the post-MUF level. In group 2, the mean end-CPB TXB2 level was 123.6 pg/mL versus 53.2 pg/mL 1 hour post-CPB. Hence, TXB2 levels decreased by similar amounts and to similar levels by 1 hour post-CPB in both groups. ET-1 levels increased after CPB and were unaffected by MUF: 1.45, 1.80, 2.55 pg/mL at end-CPB, post-MUF, and 1 hour post-CPB, respectively, in group 1; and 1.51, and 2.73 pg/mL at end-CPB and 1 hour post-CPB in group 2. LTB4 levels post-MUF were 119% of pre-MUF values, and were similar at 1 hour post-CPB in both groups., Conclusions: Despite reduction in TXB2 by MUF, values were similar and approached baseline 1 hour post-CPB in both groups. LTB4 levels increased slightly with MUF. ET-1 levels increased during and post-CPB and were unaffected by MUF. MUF does not appear to have a significant effect on post-CPB levels of TXB2, ET-1, and LTB4. Therefore, the improved hemodynamics observed with MUF do not appear to be related to removal of these cytokines.

Amino acid enrichment of cardioplegic solutions has been shown to improve both the metabolic and functional recovery of ischemic myocardium. However, because of the marked systemic vasodilatation involved, use of amino acid enrichment is limited to the periods of induction and reperfusion. Fumarate is a Krebs' cycle intermediate whose conversion to succinate is responsible for the generation of adenosone triphosphate and the oxidation of the reduced form of nicotinamide-adenine nucleotide which is the pathway by which aspartate exerts its effect. Fumarate may also function as a free-radical scavenger and is involved in calcium transport. To determine if fumarate-enriched blood cardioplegia would improve the functional recovery of the neonatal heart, 14 neonatal piglet hearts were isolated and placed on a blood-perfused working heart circuit. After the baseline functional and metabolic assessment was done, cold ischemic arrest was initiated with either standard blood cardioplegic solution (group I; N = 7) or fumarate-enriched (13 mmol/L) blood cardioplegic solution (group II; N = 7). Cardioplegic solution was given at a pressure of 40 mm Hg every 20 minutes for 2 hours, and topical hypothermia was used. Sixty minutes after warm whole blood reperfusion, the functional recovery at left atrial pressures of 3, 6, 9, and 12 mm Hg was 70%, 66%, 66%, and 65%, respectively, in group I, versus 102%, 106%, 105%, and 109%, respectively, in group II (p < 0.05). The tissue creatinine phosphate levels after reperfusion were significantly higher in group II hearts (15.0 +/- 1.2 mumol/g dry heart tissue) than in group I hearts (9.2 +/- 1.9 mumol/g dry heart tissue), although the adenosine triphosphate levels were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

The concept of the partial Fontan procedure, first described with the adjustable atrial septal defect (ASD) and more recently with the fenestrated technique, has become an accepted approach for the management of high-risk patients undergoing the Fontan procedure. Experience with both techniques has shown that a patent ASD placed in a prosthetic interatrial baffle may close spontaneously over a period of weeks to months. The mechanism and timing of spontaneous closure, as well as the effect of antiplatelet therapy on this process, are poorly understood. To better define this process, the interatrial septum of 15 mongrel dogs was excised and replaced with a fenestrated Gore-Tex (W.L. Gore, Flagstaff, AZ) patch. Postoperative echocardiography confirmed the patency of the ASD and left-to-right shunting. Animals were sacrificed 4 to 6 weeks postoperatively, or sooner if infection or other postoperative complications developed. Eight animals underwent no antiplatelet or anticoagulation therapy postoperatively, and 7 received antiplatelet therapy with aspirin. Patches were removed at the end of the study period and analyzed. By 6 weeks, all 2.7-mm and 4-mm holes had closed spontaneously in all animals that had not received antiplatelet therapy. The earliest closure occurred at 1 week. With antiplatelet therapy, hole closure was found to be delayed but not prevented, and was complete by 6 weeks in all but 1 animal. Histologic examination of the explanted patches revealed that closure was accomplished primarily through the ingrowth of fibrous tissue, accompanied by an inflammatory cell infiltrate.(ABSTRACT TRUNCATED AT 250 WORDS)

The truncal valve regurgitation that frequently arises in patients with truncus arteriosus accounts for increased operative and late mortality. Five patients underwent truncal valve repair at UCLA Medical Center between August 1990 and September 1991. This group consisted of 2 infants who underwent complete repair and 3 who underwent valve repair together with right ventricle-pulmonary artery conduit replacement. The techniques used for repair were individualized according to the specific valve morphology, and consisted of the suturing of partially developed commissures, suspension of the cusps, resection of redundant portions of the cusps, annuloplasty at the commissures, and resection of excrescences on the surface of valve leaflets. In 1 infant who had a severely dysplastic truncal valve, stenosis and regurgitation recurred and progressed, and he died 4 months after truncal valve replacement. The remaining 4 patients, who were followed for from 8 to 21 months after repair, are in New York Heart Association class I, and have minimal or no aortic regurgitation. Except in patients with severely deformed and dysplastic valves, truncal valve repair can be an attractive and successful alternative to valve replacement.

The precise hemodynamic effects of latissimus dorsi cardiomyoplasty have not been well characterized. We prospectively studied 11 mongrel dogs using a rapid ventricular pacing model of congestive heart failure. Six dogs received a nonstimulated left latissimus dorsi cardiomyoplasty wrap, and 5 control dogs were paced only. Two-dimensional transthoracic echocardiography was performed on all dogs at baseline and then weekly for 4 weeks. Measurements obtained included left ventricular diameters, lengths, volumes, and ejection fractions. Progressive left ventricular enlargement, increase in volumes, and worsening ejection fractions developed in both groups. However, less left ventricular dilatation and higher ejection fractions were seen in dogs that received a cardiomyoplasty wrap. A nonstimulated cardiomyoplasty wrap significantly attenuated the degree of left ventricular enlargement, increase in left ventricular volumes, and decrease in ejection fraction in a rapid pacing model of congestive heart failure. Apart from its effect on systolic augmentation with a stimulated muscle wrap, cardiomyoplasty may have an important "girdling" effect on the left ventricle that prevents dilatation and deterioration of left ventricular function.

In this report, explanted hearts from transplant recipients with the diagnosis of idiopathic cardiomyopathy underwent a blood cardioplegia arrest and extended subatrial resection to preserve their coronary sinus venous system. The coronary sinus and left and right coronary arteries were then cannulated and warm blood cardioplegia retrograde infused at a pressure of 30 to 40 mm Hg. Effluent from the coronary arteries and thebesian veins was then collected. Hearts were subsequently fixed with retrograde glutaraldehyde perfusion and perfused retrograde with NTB-2 (an inert intracapillary marker). Histologic sections were examined from 12 separate sites. There was no significant difference in the percentage of capillaries perfused by retrograde-delivered cardioplegia between corresponding regions of the left and right ventricles. However, effluent analysis indicated that 67.2% +/- 6.4% of retrograde-delivered blood cardioplegia was shunted through thebesian veins, thereby bypassing the microvasculature, whereas 29.3% +/- 6.3% and 3.5% +/- 3.1% traversed the myocardium supplied by the left and right coronary arteries, respectively. The results indicate that all regions of both ventricles are perfused by retrograde blood cardioplegia. However, they also suggest that nutrient flow to the microvasculature of the right ventricle is minimal during retrograde cardioplegia.

Between October 1983 and August 1991, 29 consecutive Damus-Stansel-Kaye procedures were performed. Indications for operation included restrictive bulboventricular foramen or subaortic stenosis associated with complex univentricular congenital heart disease (25) and Taussig-Bing heart, subaortic stenosis, or both associated with complex biventricular congenital heart disease (4). Twelve patients underwent concurrent Fontan procedures. Average age at operation was 39.8 months (range, 1 to 132 months). Average outflow tract gradient was 28 mm Hg (range, dynamic to 80 mm Hg). Of the 29 patients, 23 were male and 6 were female. There were three early deaths (10%), two in patients who had a concurrent Fontan procedure. Although there was a trend toward lower age and higher outflow tract gradients in nonsurvivors, these and other factors were not statistically significant predictors of death. Actuarial freedom from cardiac-related death was 88% at 5 years (n = 7). In a mean follow-up of 3.5 years (range, 0.1 to 7.7 years), 3 patients have required reoperation (10%), 2 for aortic valve insufficiency (5 days and 2.75 years) and 1 for a gradient across the anastomosis (5.75 years). Actuarial freedom from reoperation related to a failed Damus-Stansel-Kaye procedure was 90% at 4 years and 75% at 6 years (n = 7).

Reperfusion injury remains a limiting factor in extending ischemic storage time for human heart transplantation. In this study, initial myocardial reperfusion with an oxygenated perfluorochemical (Fluosol) was investigated as a means of limiting such injury. Neonatal piglet hearts were arrested with crystalloid cardioplegia, excised, and stored for 12 hours in saline solution at 0 degrees C. Initial reperfusion (10 minutes) was either with whole blood (n = 6), unmodified perfluorochemical (n = 8), or aspartate/glutamate-enriched perfluorochemical cardioplegia (n = 6), and was followed by an additional 40 minutes of whole blood perfusion. Functional evaluation was then completed, and left ventricular biopsy specimens were taken. A control group (n = 7) was evaluated without an intervening period of ischemia. At a left ventricular end-diastolic pressure of 9 mm Hg, hearts stored in whole blood cardioplegia developed a left-ventricular stroke work index of 3.8 +/- 2.3 x 10(3) erg/g (mean +/- standard error of the mean). Under the same conditions, perfluorochemical-reperfused hearts achieved a stroke work index of 14.6 +/- 1.3 x 10(3) erg/g, significantly greater than that of the whole blood group (p < 0.001). Stroke work index for hearts reperfused with aspartate/glutamate-enriched perfluorochemical cardioplegia was 19.8 +/- 1.6 x 10(3) erg/g, significantly increased over that of the nonenriched perfluorochemical group (p < 0.01) and not different from values obtained in controls (19.2 +/- 0.8 x 10(3) erg/g).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood cardioplegia is considered by many to be the preferred solution for myocardial protection. Proposed benefits include the ability to deliver oxygen and the ability to maintain metabolic substrate stores. However, the decreased capacity of blood to release oxygen at hypothermic conditions as well as the presence of deleterious leukocytes, platelets, and complement may limit complete functional recovery. Fluosol is an asanguineous solution with the ability to bind and release oxygen linearly at low temperatures. Neonatal piglet hearts (24 to 48 hours old) were excised and supported on an isolated, blood-perfused working heart model. After baseline stroke-work index was determined, hearts were arrested with either normocalcemic blood cardioplegia (group 1, n = 8) or normocalcemic Fluosol cardioplegia (group 2, n = 8). Cold cardioplegia was administered at 45 mm Hg every 20 minutes for 2 hours. Hearts were then reperfused with whole blood. Functional recovery, expressed as percent of control stroke-work index, was determined 60 minutes after reperfusion at left atrial pressures of 3, 6, 9, and 12 mm Hg. Functional recovery at 60 minutes was similar between group 1 (95%, 93%, 93%, 88%) and group 2 (100%, 94%, 94%, 95%) at left atrial pressures of 3, 6, 9, and 12 mm Hg, respectively. Mean lactate consumption 5 minutes after reperfusion was significantly greater (p = 0.0001) in group 1 (31.8 +/- 6.3 micrograms.min-1 x g-1) than in group 2 (-0.59 +/- 0.1 microgram.min-1 x g-1), indicating superior metabolic recovery in the blood cardioplegia hearts. Edema formation, as determined both by water content (group 1, 81.10%; group 2, 81.63%) and by electron microscopy, was not significantly different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Standard methods of myocardial preservation for heart transplantation have generally provided good results. Preservation times beyond 3 hours, however, have been associated with decreased survival. Leukocyte-mediated reperfusion injury is partly responsible for decreased graft function after prolonged graft ischemia. Leukocyte-depleted reperfusion has been shown experimentally to improve cardiac function after cold ischemic arrest. To determine the efficacy and safety of leukocyte-depleted reperfusion, 20 patients were enrolled in a randomized, double-blind clinical trial to be treated with either warm whole blood reperfusion (group I; n = 9) or warm leukocyte-depleted blood reperfusion (group II; n = 11). Reperfusion with leukocyte-depleted blood or whole blood was carried out for 10 minutes, with enriched cardioplegic solution added for the first 3 minutes of reperfusion. The mean donor and recipient age and the ischemic time (142 versus 153 minutes) were not significantly different between the two groups. Coronary sinus release of creatinine phosphokinase-MB 5 minutes after reperfusion was significantly less in group II (1.65 EU/min) than in group I (3.83 units/min; p = 0.05). Thromboxane B2 release was also significantly less (p = 0.05) in group II (33.6 pg/min) than in group I (67.0 pg/min). All hearts functioned adequately in both groups. The duration of inotropic support was shorter in group II than in group I, but the difference was not statistically significant. Postoperative hemodynamics, rejection episodes, and infectious complications were also not significantly different between groups in a mean follow-up of 9 months. Mean ejection fraction 1 month after operation was 65% in both groups. One early death occurred at 66 days secondary to infection; two late deaths occurred in group II, both from rejection. Leukocyte-depleted reperfusion is safe and easily applied in the operating room. Furthermore, leukocyte-depleted reperfusion decreases biochemical evidence of reperfusion injury. Although not influencing postoperative cardiac function when the ischemic time is short, less than 3 hours, leukocyte-depleted reperfusion may prevent significant reperfusion injury and improve posttransplantation graft function when ischemic times are long. Safe extension of the ischemic time would expand the donor pool and allow for better crossmatching.

The Damus-Stansel-Kaye procedure has been applied for the relief of outflow tract obstruction caused by a restrictive bulboventricular foramen or subaortic stenosis in patients with complex univentricular heart disease. The procedure may also be part of a biventricular repair of a Taussig-Bing transposition of the great arteries. This report details technical modifications of the procedure to ensure unobstructed blood flow from the pulmonary artery to the aorta and to maintain the integrity of the pulmonary and aortic valves.

Systemic venous hypertension after the Fontan procedure is a major cause of mortality and morbidity, accounting for 11 of 16 deaths in our series of 228 Fontan procedures. A partial Fontan with a residual atrial septal defect (ASD) would allow controlled right-to-left shunting to reduce venous pressure and improve cardiac output while maintaining a reduced but acceptable arterial oxygen saturation. This allows complete or graded closure of the ASD after the discontinuation of cardiopulmonary bypass in the operating room or at any time in the postoperative period by exposing the snare under local anesthesia. From 1987 to 1990, 36 patients undergoing the modified Fontan procedure had placement of an adjustable interatrial communication. Indications for placement of an adjustable ASD included increased pulmonary artery pressures, increased pulmonary vascular resistance, reactive airway disease, previously increased or unknown pulmonary vascular resistance, small pulmonary arteries, and borderline ventricular function. Fourteen patients had the adjustable ASD closed at the time of operation, 8 patients underwent narrowing, and 12 underwent closure of the ASD in the postoperative period. Eight patients were discharged with the ASD partially open, and 2 patients underwent delayed closure. The partial Fontan with an adjustable ASD may increase the safety of the Fontan procedure for high-risk groups such as those with increased pulmonary vascular resistance, pulmonary hypertension, and impaired left ventricular function and for infants, who tolerate venous hypertension poorly. The ability to adjust the ASD in stages depending on the hemodynamic response increases flexibility and safety.

Improvements in myocardial protection, surgical technique, and postoperative care have decreased operative mortality for neonatal repair of truncus arteriosus. Primary repair of truncus arteriosus in infancy without prior pulmonary artery banding is currently the preferred approach. During the period from 1982 to December 1990, 32 patients under the age of 12 months underwent surgical correction of truncus arteriosus at UCLA. The average age was 3.5 months (range, 12 days to 12 months). Three patients had interrupted aortic arch. Early mortality for the entire group was 15.6% (5/32); for those older than 1 month early mortality was 7% (2/28). In the past 4 years, early mortality has decreased to 8.3% (2/24); both of these patients had interrupted aortic arch. Excluding patients with interrupted aortic arch, there were no early deaths in the last 22 patients (1986 to 1990). Late mortality overall was 7.4% (2/27). In a mean follow-up of 73 months (range, 40 to 110 months), 71% (5/7) of the survivors with Dacron porcine-valved conduits required conduit replacement secondary to obstruction. In a mean follow-up of 36 months (range, 1 to 89 months), only 14% (3/21) of the patients with homografts required replacement secondary to obstruction.

The total cavopulmonary anastomosis, lateral tunnel Fontan, has been advocated as a preferred method for Fontan type repair. From 1987 to July 1990, 39 patients underwent total cavopulmonary anastomoses (group 1) and 39 patients underwent modified Fontan procedures (group 2); patients receiving adjustable atrial septal defects were excluded. Diagnoses in group 1 included tricuspid atresia in 5 patients, single ventricle in 32, and pulmonary atresia and intact ventricular septum in 2. Diagnoses in group 2 included tricuspid atresia in 20, single ventricle in 17, hypoplastic left heart syndrome in 1, and pulmonary atresia and intact ventricular septum in 1. There were no significant differences in age, weight, cross-clamp time, duration of inotropic support, postoperative effusions, or hospital stay between the two groups. Early mortality in group 1 was 7.7% (3/39) and in group 2, 2.6% (1/39). There was no difference in the incidence of early dysrhythmias or early pacemaker placement. Late mortality was 2.8% in group 1 and 8% in group 2 with a mean follow-up of 18 and 25 months, respectively. Follow-up in group 1 revealed 33 patients in normal sinus rhythm and 1 patient with episodes of supraventricular tachycardia; no additional patients have required pacemakers. Follow-up in group 2 revealed 27 patients in normal sinus rhythm and supraventricular tachycardia in 4 patients; 5 additional patients have required pacemaker placement. There is no apparent difference in early outcome between the total cavopulmonary anastomosis and the conventional modified Fontan. However, there appears to be an increased incidence of late dysrhythmias and the need for pacemaker placement in the conventional modified Fontan group compared with the lateral tunnel group.

Heart and heart-lung xenografts are a potential solution to the shortage of donors. Concern over the adequacy of conventional immunosuppression in prevention of xenograft rejection, however, has hindered their use. Cyclosporine has not been successful in suppressing the rejection process in cardiac xenotransplantation, and other methods of immunosuppression need to be investigated. Therefore we studied the effect of preoperative total lymphoid irradiation (TLI) in combination with cyclosporine in a primate heart-lung xenograft model using cynomolgus monkey donors and baboon recipients. Heart-lung grafts were harvested from donors and transplanted orthotopically in baboons with use of cardiopulmonary bypass. Recipients were treated in one of three groups: (1) cyclosporine and steroids (controls), (2) cyclosporine and steroids plus TLI 20 Gy, or (3) cyclosporine, steroids, antithymocyte globulin, and TLI 6 Gy. Mean survival time of the baboons treated with cyclosporine and steroids was 8 +/- 0.6 days. The group receiving 20 Gy TLI had prohibitive perioperative mortality; however, one baboon lived an additional 90 days, and at autopsy the heart showed minimal rejection. Treatment with TLI at 6 Gy in combination with cyclosporine, antithymocyte globulin, and steroids comparatively prolonged survival (16 +/- 7.8 vs 8 +/- 0.6 days; p less than 0.001), and all animals in this group died of infection, with only minimal evidence of heart rejection noted in animals surviving 30 days. We conclude that the addition of TLI and antithymocyte globulin to cyclosporine-based standard immunosuppression is a potent immunosuppressant in heart-lung xenotransplantation; nevertheless, infection remains a common complication.