Increased peripheral chemoreceptors sensitivity and exercise ventilation in heart transplant recipients

Background - Heart failure is characterized by increased ventilation during exercise, which is positively related to increased peripheral and central chemoreceptor sensitivity. Heart transplantation does not normalize the ventilatory response to exercise, and its effects on the chemoreflex control of ventilation remain unknown. We tested the hypothesis that chemoreceptor sensitivity is increased in heart transplant recipients (HTRs) and linked to exercise hyperpnea. Methods and Results - We determined the ventilatory, muscle sympathetic nerve activity (MSNA), and circulatory responses to isocapnic hypoxia and hyperoxic hypercapnia 7 +/- 1 years after transplantation in 19 HTRs with a normal left ventricular ejection fraction of 60 +/- 2%. Results were compared with those of 11 closely matched referent subjects. Sixteen patients and 10 referent subjects also underwent cycle ergometer exercise tests. HTRs compared with referent subjects presented higher MSNA ( 52 +/- 4 versus 34 +/- 3 bursts/min; P < 0.01) and heart rates ( 83 +/- 3 versus 68 +/- 3 bpm; P < 0.01) during room air breathing. The ventilatory response to hypoxia was higher in HTRs than in referent subjects ( P < 0.01, ANOVA). The increase in MSNA also was more marked during hypoxia in the HTRs than in the referent group ( P < 0.05, ANOVA). Responses to hyperoxic hypercapnia did not differ between the HTRs and the referent group. The ventilatory response to exercise, characterized by the regression slope relating minute ventilation to CO2 output, was steeper in HTRs than in referent subjects ( 38 +/- 2 versus 29 +/- 1 L/mm Hg; P < 0.01). Exercise ventilation in HTRs was related to the ventilatory response to isocapnic hypoxia ( r = 0.57; n = 16; P < 0.05) and to the ventilatory response to hyperoxic hypercapnia ( r = 0.50; n = 16; P < 0.05). Conclusions - Peripheral chemoreceptor sensitivity is increased in HTRs and is related to exercise hyperpnea after heart transplantation.