Attenuated microvascular perfusion and reactivity in cardiac transplant recipients treated with cyclosporine.
Orthotopic heart transplant recipients (TX pts) treated with cyclosporine develop postoperative hypertension and their functional capacity remains less than normal. Altered responsiveness to adrenegic stimuli and impaired release of endothelial-derived relaxing factor are proposed mechanisms of cyclosporine-induced raised peripheral vascular resistance. We compared responses to vasoconstrictor tests that stimulate sympathetic neural outflow (Valasalva maneuver and cold pressor test) and a vasodilator test that is dependent on the presence of a functionally intact endothelium (postocclusive hyperemia) in 16 TX pts with age-matched healthy controls, applying laser Doppler perfusion measurements (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 rest 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 maximal flux changes in the vasoconstrictor and vasodilator responses were comparable. However, the TX pts recovered faster from these responses and flux values at mid-to-late phase were lower following peak hyperemia and higher at any point following a cold pressor test than in the controls. Furthermore, a correlation was found between flux levels 30 s after either stimulus (r = 0.56; p < 0.0009) and time to reach prestimulus baseline after either test (r = 0.55; p < 0.002). With indirect evidence of comparable microvascular architecture, our findings suggest endothelial dysfunction in TX pts with intact functional capacity of the sympathetic nervous system.
Andreassen
A K
AK
Department of Medicine, Rikshospitalet, Oslo, Norway.
Simonsen
S
S
Bjørnerheim
R
R
Kvernebo
K
K
D000328:Adult; D001481:Basal Metabolism; D016022:Case-Control Studies; D003326:Coronary Circulation / Q000187:drug effects*; D016572:Cyclosporine / Q000009:adverse effects*; D005069:Evaluation Studies as Topic; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D012867:Skin / Q000098:blood supply*; D014666:Vasomotor System / Q000187:drug effects*
D007166:Immunosuppressive Agents; D016572:Cyclosporine