Telemetric detection of cardiac allograft rejection. Correlation of electrophysiological, histological, and biochemical changes during unmodified rejection.

Intra-abdominal mismatched heterotopic cardiac allograft transplantation without immunosuppression was performed in eight pigs. Postoperatively, daily electrophysiological studies were carried out either with exteriorized temporary epicardial pacing wires (n = 4) or by a telemetrically controlled implanted pacemaker connected to permanent epicardial pacing leads (n = 4). Electrophysiological studies data were correlated with histopathologic and biochemical findings from daily myocardial biopsies. Electrophysiological studies revealed no significant alteration of sinus or atrioventricular node function, refractoriness, or ventricular pacing threshold. However, ventricular voltage amplitude, measured through the electrodes, decreased steadily with time in all donor hearts and was significantly correlated with histopathologic rejection grade (p less than 0.001) and with adenosine 5'-triphosphate (ATP) depletion (p less than 0.001). Ventricular voltage amplitude less than 75% of baseline occurred 4.5 +/- 1.5 days after transplantation, and this decreased voltage amplitude coincided with a moderate to severe (Grade 2 or 3) histological rejection pattern with a sensitivity of 89% (17 of 19) and a specificity of 77% (17 of 22). Similar changes in voltage amplitude were not found in control hearts. Myocardial tissue ATP values fell significantly from control values with early (Grade 1) rejection (p less than 0.05). Evidence for oxygen free radical injury was indicated by a rise in conjugated dienes of free fatty acids; this increase in diene level occurred 4.3 +/- 1.2 days postoperatively and then regressed during the terminal stages.(ABSTRACT TRUNCATED AT 250 WORDS)

Repair of tricuspid atresia: utility of right ventricular incorporation.

During a 10-year period, 62 patients underwent the following modifications of the Fontan operation for repair of tricuspid atresia: direct atriopulmonary connection (N = 15), atriopulmonary connection using a conduit (N = 5), direct atrioventricular (AV) connection (N = 22), and AV connections with a valved conduit (N = 20), including 2 with combined Fontan-arterial switch procedures. The overall hospital mortality was 16.1% (10/62) (70% confidence limits, 11.2 to 22.4%). By multivariate analysis, the risk factors for early and late death included increasing right atrial pressure after repair, use of an atriopulmonary connection, and previous pulmonary artery banding (all variables, p less than 0.05). Postoperative catheterization was performed in 22 patients including 15 with AV valved-conduit connections. Right ventricular (RV) work based on pulmonary artery pressure minus right atrial pressure was correlated with the preoperative RV to left ventricular volume ratio computed from the four-chamber angiographic projection (p = 0.025), and was appreciable only with ratios exceeding about 30%. In 6 of 19 eligible patients, severe conduit obstruction has developed. Considering the survival data, the risk of reoperation, and postoperative hemodynamic findings, analysis of our experience supports the preferential use of nonvalved AV connections in most patients with tricuspid atresia and ventriculoarterial concordance.

A new technique of experimental heterotopic cardiac transplantation.

Heterotopic cardiac transplantation is a useful method for studying allograft rejection. In this study a new technique of cardiac transplantation was carried out, which involved retroperitoneal anastomoses of the donor ascending aorta and main pulmonary artery with the recipient abdominal aorta and inferior vena cava respectively. The procedure was simple and effective and was accomplished with minimal operative mortality and postoperative morbidity. The method allows better access to the allograft for repeated open myocardial biopsies, obviating the limitations of transvenous fluoroscopically directed endomyocardial biopsy. This technique of retroperitoneal heterotopic cardiac transplantation has important advantages compared with similar procedures performed in the neck, abdomen, or thorax.

Loss of the somatosensory evoked response as an indicator of reversible cerebral ischemia during hypothermic, low-flow cardiopulmonary bypass.

We assessed somatosensory evoked response (SSER) as a monitor of cerebral protection during nonpulsatile, hypothermic cardiopulmonary bypass (CPB). In 13 dogs under CPB, extracorporeal flow rate (EFR) thresholds for loss of SSER were determined by stepwise reduction of the EFR from 2.0 to 0.25 L/min/m2 at perfusion temperatures of 35 degrees C, 30 degrees C, 25 degrees C, and 20 degrees C. Testing began at 35 degrees C in Group 1 (N = 6) and at 20 degrees C in Group 2 (N = 7). Immediately on loss of SSER (denoted as a decrease of 80% or more in the amplitude of the somatosensory evoked potentials), EFR was restored to 2.0 L/min/m. Thresholds for loss of SSER ranged between 0.75 and 0.25 L/min/m2. SSER was always restored on return of EFR to 2.0 L/min/m2; thus loss of SSER was a reversible ischemic change. Both groups had similar threshold values at 35 degrees C, but at lower temperatures, Group 1 thresholds were significantly higher than those in Group 2. Since 35 degrees C was the first test temperature for Group 1 but the last for Group 2, EFR reduction at 35 degrees C apparently caused neurophysiological changes (depletion of cortical energy reserves), which diminished subsequent tolerance to ischemia, but EFR reduction at 20 degrees C did not. Our findings show that loss of SSER warns of reversible cerebral ischemia, and support SSER monitoring as a useful measure of cerebral function during low-flow, hypothermic CPB.

Impaired left ventricular postischemic function and metabolism in chronic right ventricular hypertrophy.

Chronic right ventricular hypertrophy (RVH) has been shown to produce changes in left ventricular diastolic properties but minimal effects on left ventricular systolic function. We studied the effects of chronic pressure overload RVH on left ventricular systolic function before and after reversible hypothermic global ischemia. RVH was induced by pulmonary artery banding (PAB) in newborn piglets (5 to 7 days). At 2 months of age the PAB group (n = 6) and a control group (n = 8) were subjected to cardiac arrest on cardiopulmonary bypass with cold crystalloid cardioplegia (10 degrees C) for 2 hr and were reperfused for 1 hr. Left ventricular function was assessed by a conductance catheter in the left ventricle measuring the end-systolic pressure-volume relationship (Emax). Preischemic and postischemic Emax were the same in the control group (4.1 +/- 0.4 mm Hg/ml before vs 4.1 +/- 0.4 mm Hg/ml after ischemia), but significantly different in the PAB group (4.7 +/- 0.5 mm Hg/ml before vs 2.97 +/- 0.7 mm Hg/ml after ischemia, p less than .05). There also was a marked drop in ATP and phosphocreatine (CP) content in the PAB group during ischemia (ATP, 20 +/- 2 mmol/kg dry wt before vs 10 +/- 2 mmol/kg dry wt after ischemia, p less than .05; PC, 26 +/- 3 mmol/kg dry wt before vs 11 +/- 1 mmol/kg dry wt after ischemia, p less than .05). In the control group there was no change in ATP content and, although CP did drop by end-ischemia, there was complete recovery by 1 hr of reperfusion but minimal CP recovery in the PAB group.(ABSTRACT TRUNCATED AT 250 WORDS)

Surgical experience with the modified Fontan procedure.

During a 10 year period 109 patients (3 months to 47 years old) underwent modifications of the Fontan procedure for repair of classic tricuspid atresia (TA) (n = 58), univentricular atrioventricular connection (UVH) (n = 38), or other complex malformations (CM) (n = 13). Among patients with TA, an atriopulmonary connection was used in 19 (33%) and incorporation of the right ventricle with the Björk modification and with a right atrial-to-right ventricular valved conduit was used in 20 (34%) and in 19 (33%), respectively. Three of the latter 19 also underwent a combined Fontan-switch procedure. The hospital mortality rate was 13.8% (70% confidence limits, 9.3% to 18.3%) for patients with TA, 28.9% (70% confidence limits, 21.3% to 37.0%) for patients with UVH, and 7.7% (70% confidence limits, 0% to 15.4%) for patients with CM. Multivariate analysis identified with the following variables as risk factors for both early and late deaths: diagnosis of UVH, previous pulmonary artery banding (PAB), and postrepair right atrial pressure, and, in patients with TA, the use of a direct atriopulmonary connection (all variables, p less than .05). Morphometric lung biopsy scores were not different in patients with PAB, implicating the role of ventricular hypertrophy rather than pulmonary vascular disease as the mechanism for the adverse effect of PAB. Right atrial pressure was a predictor of serious late cardiac symptoms, which were present in 10% of eligible patients (p = .032). This review demonstrates a survival advantage with modifications of the Fontan procedure that incorporate the hypoplastic right ventricle in patients with TA.(ABSTRACT TRUNCATED AT 250 WORDS)