The heart rate response to exercise and circulating catecholamines in heart transplant recipients.
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.
Ferretti
Guido
G
Département de Physiologie, Centre Médical Universitaire, 1 rue Michel Servet, 1211 Genève 4, Switzerland.
Marconi
Claudio
C
Achilli
Guido
G
Caspani
Elisabetta
E
Fiocchi
Roberto
R
Mamprin
Filippo
F
Gamba
Amando
A
Ferrazzi
Paolo
P
Cerretelli
Paolo
P
D000328:Adult; D004837:Epinephrine / Q000097:blood*; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D005260:Female; D006321:Heart / Q000294:innervation / Q000502:physiology; D006339:Heart Rate / Q000502:physiology*; D016027:Heart Transplantation / Q000502:physiology*; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000097:blood*; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology
D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D009638:Norepinephrine; D004837:Epinephrine