ATTENUATED MICROVASCULAR PERFUSION AND REACTIVITY IN CARDIAC TRANSPLANT RECIPIENTS TREATED WITH CYCLOSPORINE

Orthotopic heart transplant recipients (TX pts) treated with cyclospor ine develop postoperative hypertension and their functional capacity r emains less than normal. Altered responsiveness to adrenegic stimuli a nd impaired release of endothelial-derived relaxing factor are propose d mechanisms of cyclosporine-induced raised peripheral vascular resist ance. We compared responses to vasoconstrictor tests that stimulate sy mpathetic neural outflow (Valasalva maneuver and cold presser test) an d a vasodilator test that is dependent on the presence of a functional ly intact endothelium (postocclusive hyperemia) in 16 TX pts with age- matched healthy controls, applying laser Doppler perfusion measurement s (LDPM). Mean time since transplantation was 4.5 years (1-10 years). All TX pts received the triple regimen of prednisone, azathioprine and cyclosporine. Fourteen were considered hypertensive. Basal LDPM at re st expressed in arbitrary flux units (AU), was significantly lower in the TX pts (15.9 AU) than the controls (21.5 AU; p < 0.01). The maxima l flux changes in the vasoconstrictor and vasodilator responses were c omparable. However, the TX pts recovered faster from these responses a nd flux values at mid-to-late phase were lower following peak hyperemi a and higher at any point following a cold presser test than in the co ntrols. Furthermore, a correlation was found between flux levels 30 s after either stimulus (r = 0.56; p < 0.0009) and time to reach prestim ulus baseline after either test (r = 0.55; p < 0.002). With indirect e vidence of comparable microvascular architecture, our findings suggest endothelial dysfunction in TX pts with intact functional capacity of the sympathetic nervous system.