LACK OF CIRCADIAN-RHYTHM OF PLASMA-CONCENTRATIONS OF VASOACTIVE-INTESTINAL-PEPTIDE IN PATIENTS WITH ORTHOTOPIC HEART-TRANSPLANTS

Objective-To study the circadian pattern of plasma concentrations of v asoactive intestinal peptide (VIP) in patients with orthotopic heart t ransplants. Circulating VIP is known to have neural and immunological sources. Patients and methods-13 patients with orthotopic heart transp lants were studied 12-53 months (mean 31.8 months) after operation. Al l were haemodynamically compensated and had no histological evidence o f rejection. They were being treated with cyclosporin, azathioprine, a nd prednisone. Ten healthy individuals were studied as controls. Circu lating VIP was assayed six times within a 24h period. Time qualified d ata were analysed by ANOVA and the cosinor method. Student's t test fo r unpaired data and Bingham's test for cosinor-derived parameters were used for statistical comparisons. Results-Plasma concentrations of VI P were lower in the patients with orthotopic heart transplants than in the controls (p < 0.001). ANOVA and the cosinor method respectively s howed a statistically significant within-day variability and circadian rhythm in the controls but not in the patients with heart transplants . Discussion-The low plasma concentrations of VIP in the patients with heart transplants could be the result of the lack of contribution by the cardiac VIPergic fibres, a reduction of VIP release by the pharmac ologically suppressed immune system, the inhibitory effects of cyclosp orin on neural function and humoral secretions, and the effects of neg ative feedback on VIP release of high concentrations of atrial natriur etic peptide. The lack of the circadian rhythm suggests a structural d isorder, which should be further investigated.