ALTERATION OF AUTONOMIC INFLUENCE ON LEFT-VENTRICULAR CONTRACTILITY BY EPICARDIAL SUPERFUSION WITH HEXAMETHONIUM AND PROCAINE

Objective: Since portions of autonomic nerves and receptors are locate d superficially on the heart, it is possible that neuromodulatory subs tances in pericardial fluid may modulate cardiac contractile function by altering autonomic neurotransmission. The aim of the study was to e xamine this hypothesis in anaesthetised dogs instrumented to measure l eft ventricular pressure and volume (conductance catheter). Methods: T he effects of electrical stimulation of cardiac sympathetic efferents in the ansa subclavia (n = 6), or parasympathetic efferents in the vag us (n = 6), on left ventricular contractility were evaluated during ep icardial superfusion with Tyrode solution, or Tyrode solution containi ng hexamethonium (1 X 10(-4) M), or procaine (2%). The slope of the en d systolic pressure-volume relationship (E(es)), a load independent me asure of left ventricular contractility, and the position of the relat ionship (V-mid) were obtained by rapid transient vena caval occlusion. Results: Ansa subclavia stimulation increased (E(es)) from 4.8(SD 1.8 ) to 8.3(3.0) mm Hg.ml(-1) (p < 0.05), and V-mid shifted to the left, from 9(10) to 0(16) ml (p < 0.05). This response was abolished by epic ardial superfusion with procaine, but not with hexamethonium. Vagal st imulation decreased E(es) from 13.3(7.4) to 6.3(4.2) mm Hg.ml(-1) (p < 0.05) and V-mid shifted to the right, from 12(10) to 18(8) ml (p < 0. 05). These changes were abolished by both procaine and hexamethonium. Procaine did not affect the positive inotropic response to intravenous noradrenaline nor the cardiac depressor response to intravenous methy lcholine, indicating that the myocardial contractile response was inta ct during epicardial superfusion with procaine. Conclusions: Neuromodu latory substances in the pericardial space may alter left ventricular contractility by modifying cardiac efferent autonomic neurotransmissio n on the epicardial surface of the heart.