Reduced capacity of cardiac efferent sympathetic neurons to release noradrenaline and modify cardiac function in tachycardia-induced canine heart failure.
To investigate the capacity of efferent sympathetic neurons to modulate the failing heart, stellate ganglion stimulation was performed in dogs with biventricular heart failure induced by rapid ventricular pacing (240 beats/min) for 4-6 weeks. Less noradrenaline was released from cardiac myoneural junctions into coronary sinus blood in response to left stellate ganglion stimulation in anesthetized failing heart preparations (582 pg/mL, lower and upper 95% confidence intervals of 288 and 1174 pg/mL, n = 19) compared with healthy heart preparations (6391 pg/mL, 95% confidence intervals of 4180 and 9770 pg/mL, n = 14; p < 0.001). There was substantial adrenaline extraction by failing hearts (49 +/- 6%), although it was slightly lower than in healthy heart preparations (65 +/- 9%, p = 0.055). In contrast with healthy heart preparations, no net release of adrenaline occurred during stellate ganglion stimulation in any of the failing heart preparations, and ventricular tissue levels of adrenaline fell below the sensitivity limit of the HPLC technique. In failing heart preparations, maximal electrical stimulation of right or left stellate ganglia resulted in minimal augmentation of left ventricular intramyocardial (17%) and chamber (12%) systolic pressures. These indices were augmented by 145 and 97%, respectively, following exogenous noradrenaline administration. Thus, the cardiac efferent sympathetic neurons' reduced capacity to release noradrenaline and modify cardiac function can contribute to reduction of sympathetic support to the failing heart.
Cardinal
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Départment de pharmacologie, Faculté de médecine, Université de Montréal, QC, Canada.
Nadeau
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Laurent
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C
Boudreau
G
G
Armour
J A
JA
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004525:Efferent Pathways / Q000502:physiology*; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D013610:Tachycardia / Q000503:physiopathology*
D009638:Norepinephrine