Exercise capacity in heart transplant recipients: relation to impaired endothelium-dependent vasodilation of the peripheral microcirculation

Abstract

Objectives: The aim of this study was to examine the responses to endothelium-dependent and -independent vasodilators on the peripheral microcirculation in heart transplant recipients in relation to exercise capacity compared with that in healthy controls.

Background: Impaired endothelium-dependent vasodilation of the microcirculation may play an important role in the limitation of exercise capacity after heart transplantation.

Methods: Microvascular perfusion responses to four graded levels of iontophoretically applied 1% acetylcholine (endothelium-dependent vasodilator) and 1% sodium nitroprusside (SNP) (endothelium-independent) in the forearm skin of 42 transplant recipients and 16 age-matched controls were determined by laser Doppler perfusion measurements. Maximal exercise capacity was assessed by peak oxygen uptake (peak VO2) during progressive, symptom-limited, upright bicycle exercise.

Results: With similar baseline perfusion levels in transplant recipients and controls (4.2 +/- 0.4 vs 4.6 +/- 0.6 arbitrary units [AU]), the increases in perfusion to acetylcholine, but not to SNP, were significantly attenuated in the transplant recipients: 7.0 +/- 1.0 vs 11.0 +/- 2.0, 12.7 +/- 1.5 vs 21.0 +/- 2.8, 21.0 +/- 1.9 vs 32.7 +/- 2.4, and 28.0 +/- 1.6 vs 39.2 +/- 2.4 AU, respectively (all p < 0.01). Peak VO2 was significantly lower in the transplant recipients (22.4 +/- 1.0 vs 38.0 +/- 2.9 ml/kg/min; p < 0.01). Furthermore, acetylcholine responses of the transplant recipients correlated closely to their peak VO2, irrespective of level of application (r = 0.63; p < 0.001, all four acetylcholine responses taken together), whereas no such correlation was found for SNP responses. In the control group, no relation was observed in acetylcholine/SNP responses to peak VO2.

Conclusions: Exercise limitation in transplant recipients appears strongly associated with attenuated endothelium-dependent vasodilation of the peripheral microcirculation.