Increased Peripheral Chemoreceptors Sensitivity and Exercise Ventilation in Heart Transplant Recipients

Abstract

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 7Ϯ1 years after transplantation in 19 HTRs with a normal left ventricular ejection fraction of 60Ϯ2%. 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 (52Ϯ4 versus 34Ϯ3 bursts/min; PϽ0.01) and heart rates (83Ϯ3 versus 68Ϯ3 bpm; PϽ0.01) during room air breathing. The ventilatory response to hypoxia was higher in HTRs than in referent subjects (PϽ0.01, ANOVA). The increase in MSNA also was more marked during hypoxia in the HTRs than in the referent group (PϽ0.05, ANOVA

Carotid body function in heart failure

“…Similarly, other clinical studies (Haque et al 1996,van de Borne et al 1996 reported that suppression of peripheral chemoreceptor activity by hyperoxia had no effect on muscle sympathetic nerve activity or arterial pressure. By contrast, other groups ,Ponikowski & Banasiak, 2001,Ciarka et al 2006 have found an enhanced ventilatory response to hypoxia in CHF patients, particularly those in more severe stages of heart failure. In addition, heightened peripheral chemoreflex function correlates significantly with the enhanced ventilatory response to exercise and dyspnea observed in these patients (Chua et al 1997,Ciarka et al 2006).…”

“…By contrast, other groups ,Ponikowski & Banasiak, 2001,Ciarka et al 2006 have found an enhanced ventilatory response to hypoxia in CHF patients, particularly those in more severe stages of heart failure. In addition, heightened peripheral chemoreflex function correlates significantly with the enhanced ventilatory response to exercise and dyspnea observed in these patients (Chua et al 1997,Ciarka et al 2006). …”

Tonic Chemoreflex Activation Contributes to Increased Sympathetic Nerve Activity in Heart Failure–Related Anemia

“…In HF animal models, the augmented sympathetic drive during hypoxia is largely influenced by the tonic excitatory influence of peripheral chemoreflex activity. 20,21 In humans, van de Borne et al 22 showed that tonic chemoreflex activation does not contribute to elevated MSNA in HF patients, whereas Ponikowski et al 23 observed that HF patients with peripheral chemoreceptor hypersensitivity were those with a poor outcome. Our study suggests that anemia, in combination with CHF, could lead to chemoreflex-related sympathetic overactivity.…”

Clinical significance of respiratory compensation during exercise testing in cardiac patients

“…In humans, carotid body chemosensitivity plays a dominant role in constraining variations of arterial pH in response to the acute metabolic acidosis induced by heavy exercise (19). Previous studies on chronic heart failure patients have demonstrated that the exaggerated response from peripheral chemoreceptors leads to a rapid ventilator augmentation, albeit with lower ventilatory efficiency, during exercise (18)(19)(20).…”