CARDIAC AUGMENTATION CAN BE MAINTAINED BY CONTINUOUS EXPOSURE OF INTRINSIC CARDIAC NEURONS TO A BETA-ADRENERGIC AGONIST OR ANGIOTENSIN-II

The purpose of this work was to determine whether constant increases i n cardiac rate and force can be induced by continuous exposure (20 min ) of intrinsic cardiac neurons to pharmacological agents which activat e such neurons, Intrinsic cardiac neurons within the ventral right atr ial ganglionated plexus were activated by constant infusions of dobuta mine or angiotensin II (100 mu M/min for 10 min followed by 200 mu M/m in for 10 min) via their local arterial blood supply in 12 artificiall y ventilated, open chest anesthetized dogs while monitoring heart rate and indices of regional cardiac contractility. The results were as fo llows: (1) Dobutamine (100 mu M/min for 10 min) enhanced intrinsic car diac neuronal activity by 195% at first, neuronal activity declining t hereafter to +79% of control values in the continued presence of this agonist, When the dose of dobutamine was doubled (200 mu M/min for 10 min) neuronal activity increased +179% above control values and remain ed elevated, as did heart rate as well as right and left ventricular c ontractility, (2) Angiotensin II (100 mu M/min) increased neuronal act ivity at first, with neuronal activity decreasing gradually thereafter such that after 5 min of exposure activity reached control values. Ne uronal activity did not increase further when neurons mere subsequentl y exposed to a higher dose of angiotensin II (200 mu M/min). Heart rat e and ventricular contractility were increased initially more by angio tensin II than by dobutamine. However, cardiac indices fell thereafter concomitant with reductions in neuronal activity as the exposure to a ngiotensin II continued, Thus although cardiac rate and force initiall y were increased more by angiotensin II than by dobutamine, similar au gmentation of cardiac indices was achieved by sustained exposure of a population of intrinsic cardiac neurons to either agent, In conclusion , heart rate and ventricular contractility can be enhanced for relativ ely prolonged periods of time by continuous exposure of a population o f intrinsic cardiac neurons to a beta-adrenoceptor agonist or angioten sin II, with the beta-adrenoceptor agonist inducing more consistent ca rdiac augmentation than angiotensin II. (C) 1996 Academic Press