Immunosuppression may have an important impact on early graft coronary endothelial injury. We investigated functional and morphologic coronary alterations, myocardial expression, and cardiac release of possible mediators of allograft vasculopathy within 6 months after cardiac transplantation with respect to different immunosuppressive regimens. Epicardial and microvascular endothelium-dependent and endothelium-independent vasomotor function and epicardial intimal thickening were measured in 8 transplant recipients treated with cyclosporin A (CyA), azathioprine, and prednisone (group 1), 9 transplant recipients treated with tacrolimus (TKL), azathioprine, and prednisone (group 2), and 14 patients treated with TKL, mycophenolate mofetil (MMF), and prednisone (group 3). The gene expressions of inducible and endothelial nitric oxide synthase (iNOS and eNOS), endothelin-1, prostacyclinsynthase, and thromboxansynthase were analyzed in endomyocardial biopsy specimens using semiquantitative reverse transcription polymerase chain reaction. Transcardiac cytokine release, endothelin-1, and nitrate-release were determined from plasma samples. Epicardial endothelial dysfunction (vasoconstriction to acetylcholine > 10%) and microvascular smooth muscle cell dysfunction (flow velocity increase to adenosine and nifedipine < 2.0) were enhanced in heart transplant recipients immunosuppressed with TKL, azathioprine, and prednisone. The prevalence of epicardial dysfunction was 78% in group 2 versus 44% and 46% in group 1 and 3 (p < 0.05), respectively. The prevalence of microvascular dysfunction was 56% in group 2 versus 13% and 7% in group 1 and 3 (p < 0.02), respectively. Coronary vasomotor dysfunction was associated with increased myocardial iNOS expression (p < 0.05), decreased eNOS expression (p < 0.05), and enhanced cardiac immunoreactive interleukin-6 (p < 0.01). Coronary intimal thickening was not different between the groups. The combination of TKL and MMF appears to be superior to TKL and azathioprine (and comparable to CyA and azathioprine) concerning preservation of early coronary vasomotor function, eNOS expression, iNOS suppression as well as cardiac interleukin-6 release. This may have an important impact on subsequent development of transplant coronary atherosclerosis.

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The response of various thyroid hormone parameters to maximal physical exercise (MPE) was investigated in 14 medium and long distance runners and 13 divers. The effects of submaximal long time physical exercise (SMPE) was examined in seven divers. The TSH-level decreases significantly during MPE and slightly rises again after the end of the exercise. In SMPE, however, TSH continuously rises until 15 min after the end of the exercise. The T3 level rises significantly in MPE and falls below the initial value 15 min after the exercise finishes, during SMPE it remains practically unchanged and slightly decreases after the finish. In MPE, the rT3 level does not change and slightly decreases after termination, while the fT4 level continuously decreases from the beginning till 15 min after the exercise period. The latter two parameters do not show any change in SMPE. As possible reasons for the changes of TSH levels a decrease (MPE) or an increase (SMPE) of pituitary secretion might play a role. Furthermore, in MPE the rise in T3 level might be related to hemoconcentration, and the decrease in fT4 level to an elevated cellular utilization.

The serum levels of FSH, LH, and testosterone were determined by radioimmunoassay in 63 men before, during, and after maximal and submaximal physical short- and long-term exercise (800-n running, climbing, 36-k cross-country skiing). In the 800-meter run, significant elevations of FSH, LH, and testosterone were observed, while in all other field and laboratory test (climbing, 36-km cross-country skiing, maximal stepwise bicycle and treadmill ergometry, 90-min submaximal bicycle ergometry) the hormone levels remained unchanged or were decreased. In contrast to FSH and LH, which did not show any clear modification with duration or intensity of exercise or with the state of training, changes of testosterone in the endurance field test (36-km cross-country skiing) seemed to be training dependent. In highly endurance-trained subjects, there was an increase and in less well-trained subjects a decrease of testosterone for equal distances and intensities of exercise.

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