Biomedical subjects
Publications and source records attributed to T DeMarco.
Recent interest in transperitoneal live donor nephrectomy prompted us to review our experience with 104 live donor nephrectomies performed through a standard flank extraperitoneal approach. There were no deaths and 14.4 per cent of the patients had minor complications that were managed easily. Factors influencing morbidity in the voluntary donor are analyzed.
Dogs were subjected to hemorrhagic shock and then resuscitated according to physiological parameters. Randomly selected dogs received a sublethal dose of intratracheal microorganisms. In comparing the results with those previously reported from our laboratory, in which animals received an 85% greater resuscitation of Ringer's lactate, it appears that pulmonary edema in the post-shock contaminated state can be limited. Furthermore, through minimization of pulmonary edema, pulmonary defenses appear to be improved and mortality from infection reduced.
Neurotoxicity is a recognized complication of cyclosporin A (CsA) therapy in patients undergoing organ transplantation. It is most commonly manifested by fever, seizures, and altered mental status. Cortical blindness and speech and motor disturbances can also occur. Changes seen in cerebral white matter on imaging studies are nonenhancing areas of hypoattenuation on CT and T2 prolongation on MR. We report three cases of CsA-induced neurotoxicity in which reversible changes were observed in the cerebral white matter. In the first patient, CsA neurotoxicity occurred 1 week following orthotopic liver transplantation. In the second patient, CsA neurotoxicity coincided with an episode of severe systemic hypertension 4 weeks after cardiac transplantation. The third patient experienced seizures 1 month after heart/lung transplantation for cystic fibrosis. A current theory postulates a relationship between diminished serum cholesterol and CsA neurotoxicity. This theory, however, does not satisfactorily address all cases of CsA neurotoxicity. In particular, serum cholesterol measurements were normal in cases 2 and 3 and probably were normal in case 1, despite diminished cholesterol levels preoperatively. Although the matter of CsA-induced neurotoxicity remains unresolved, we suggest that endothelin, a newly described neuropeptide that causes intense vasoconstriction and that has been implicated in cerebral vasospasm, may potentiate CsA-induced damage to endothelium and promote CsA neurotoxicity.
BACKGROUND: Endothelin-1, a potent endothelium-derived vasoconstrictor peptide, has recently been shown to be elevated in heart transplant recipients and may be a participant in posttransplantation vasculopathy. METHODS: We measured peripheral venous endothelin-1 concentrations in eight heart transplant recipients and eight age- and gender-matched healthy controls. Subsequently, in 21 transplant recipients, right atrial, aortic, and coronary sinus plasma was obtained and endothelin-1 levels were measured. Potential correlations to donor and recipient age, cyclosporine levels, hemodynamic parameters, donor heart ischemic time, time from transplantation, and serum creatinine were examined. In eight more patients, right atrial levels of endothelin-1 were measured before and after endomyocardial biopsy to examine the effect of this procedure on endothelin-1 concentrations. RESULTS: Peripheral endothelin-1 concentrations were significantly higher in heart transplant recipients (45.6 +/- 1.8 versus 25.8 +/- 2.3, p < 0.001). Multiple regression analysis showed a significant correlation between right atrial endothelin-1 and pulmonary artery systolic pressure (r = 0.48), as well as serum creatinine (r = 0.52). No relation to blood pressure, right atrial pressure, pulmonary vascular resistance, recipient age, cyclosporine levels, or donor heart ischemic time was observed. In 11 patients, a 38% +/- 7% fall in endothelin-1 levels across the pulmonary bed was observed, suggesting extraction across the lung in these subjects. Nine patients had net release of endothelin-1 (95% +/- 26% rise) across the coronary vascular bed, whereas 12 patients showed net extraction (24% +/- 4% fall). Endomyocardial biopsy had no influence on endothelin-1 levels (prebiopsy: 48.3 +/- 1.7; postbiopsy: 42.3 +/- 2.34; p = Not significant). CONCLUSION: These findings suggest that endothelin-1 levels in transplant recipients may be influenced by renal function and may contribute to pulmonary hypertension. The significance of transcardiac release of endothelin in some patients is unclear: further studies are needed to determine the pathophysiologic significance of endothelin-1 in heart transplant recipients.
We report a case of hemolytic uremic syndrome associated with the use of cyclosporine in a heart transplant recipient. The patient manifested many classic signs and symptoms of hemolytic uremic syndrome, and a diagnosis was confirmed by kidney biopsy. Treatment with plasma exchange was effective in halting the hemolysis, but renal function failed to improve. Rechallenge with cyclosporine caused recurrence of microangiopathic hemolysis. Because of concerns regarding allograft rejection, an experimental immunosuppressive agent, RS-61443, was used that was effective in controlling rejection and was not associated with recurrence of hemolytic uremic syndrome.
The pulmonary artery pressure response to exercise has been used as an index of cardiac reserve and frequently mirrors diastolic conditions. To define this response after orthotopic heart transplantation, we exercised 27 subjects on supine bicycle ergonometers. Stroke volume and pulmonary artery pressure were monitored with contrast-enhanced Doppler imaging. Study patients had undergone orthotopic heart transplantation. Seventeen patients were screened, and eight were subsequently determined by endomyocardial biopsy to be histologically free of acute cardiac allograft rejection. A control population of nonconditioned normal volunteers was also evaluated (heart transplant patients: n = 8, age = 45.7 +/- 7.3 years, seven men; normals volunteers: n = 10, age = 49.4 +/- 12.8 years, nine men; P = NS). Total exercise time and peak heart rate were reduced in heart transplant patients: 7.6 +/- 2.5 minutes, 123 +/- 4 beats/min versus normal volunteers: 16.2 +/- 4.5 minutes, 134 +/- 4 beats/min (P < 0.05). Change in stroke volume from baseline to peak exercise was greater in heart transplant patients: 29.9 +/- 4.6 ml versus normal volunteers: 3.9 +/- 5.7 ml (P < 0.01). No difference was observed in the pulmonary artery pressure response to exercise. In patients with uncomplicated heart transplantation a reduction in exercise capacity is shown; however, the pulmonary artery pressure response to exercise is comparable to normal subjects. A blunted heart rate response is observed, which is partially compensated by increases in stroke volume. These findings suggest that cardiac diastolic function is preserved and that denervation of the heart accounts for impaired exercise tolerance.