Related Experiment Videos
The heart rate response to exercise and circulating catecholamines in heart transplant recipients
Guido Ferretti1, Claudio Marconi, Guido Achilli
1Département de Physiologie, Centre Médical Universitaire, 1 rue Michel Servet, 1211 Genève 4, Switzerland.
Insights
Heart transplant recipients (HTR) show a heart rate response to plasma catecholamines similar to healthy subjects, suggesting potential sympathetic reinnervation and beta-receptor modulation over time.
Area of Science:
- Cardiovascular Physiology
- Transplantation Medicine
- Autonomic Nervous System
Background:
- Plasma concentrations of noradrenaline ([NA]) and adrenaline ([A]) are higher in normal subjects and heart transplant recipients (HTR).
- The denervated heart's chronotropic response to plasma [NA] and [A] is hypothesized to mimic beta1-adrenergic receptor stimulation due to higher myocardial beta1 than beta2 receptor density.
Purpose of the Study:
- To investigate the chronotropic response of HTRs' hearts to changes in plasma [NA] and [A] during exercise.
- To test the hypothesis that the denervated heart's response mimics beta1-adrenergic receptor stimulation.
Main Methods:
- 17 HTRs and 9 healthy controls (CTL) underwent incremental exercise on a cycle ergometer.
- Heart rate (HR) was monitored via electrocardiography.
- Plasma [NA] and [A] were measured using high-pressure liquid chromatography at rest and varying workloads.
Main Results:
- In both groups, HR and plasma catecholamine levels ([NA+A]) increased with workload.
- Normalized HR values correlated significantly with the logarithm of [NA+A] in both HTRs and CTLs.
- Affinity constants for catecholamine response differed between HTRs (2599+/-350 ng.l(-1)) and CTLs (487+/-37 ng.l(-1)).
Conclusions:
- The chronotropic effect of plasma catecholamines in HTRs resembles combined beta1 and beta2 adrenergic activation.
- Findings suggest potential sympathetic reinnervation and beta-receptor modulation in HTRs over time.
- The hypothesis of persistent heart denervation in HTRs is challenged.
Abstract:
The plasma concentration of noradrenaline ([NA]) is higher than that of adrenaline ([A]) both in normal subjects and in heart transplant recipients (HTR). Since in both groups the myocardial density of beta1-adrenergenic receptors is much greater than that of beta2-adrenergenic receptors, the chronotropic response of a denervated heart to changes in plasma [NA] and [A] in the absence of reinnervation should be similar to that of agonist stimulation of beta1-receptors. To test this hypothesis, 17 HTR and 9 healthy subjects (CTL) performed incremental exercise on a cycle ergometer to voluntary exhaustion. Heart rate (HR) was recorded by electrocardiography. [NA] and [A] were measured by high-pressure liquid chromatography at rest and at increasing workloads (w). In both groups, HR and [NA+A] increased with w, and HR with [NA+A]. Normalized HR values, plotted against the logarithm of [NA+A], fitted significantly logistic curves. The affinity constants were different, i.e. 2599+/-350 and 487+/-37 ng.l(-1), for HTR and CTL, respectively. The chronotropic effect of changes in [NA+A] in HTR was similar to that of combined beta1- and beta2-adrenergic activation evoked by applying isoprenaline to isolated heart myocytes (Brodde OE, Pharmacol Ther 60:405-430, 1993). These findings suggest that over time sympathetic reinnervation and the modulation of beta-receptors may take place in HTR, ruling out the hypothesis of persistent heart denervation.