Alteration of autonomic influence on left ventricular contractility by epicardial superfusion with hexamethonium and procaine.
OBJECTIVE
Since portions of autonomic nerves and receptors are located superficially on the heart, it is possible that neuromodulatory substances in pericardial fluid may modulate cardiac contractile function by altering autonomic neurotransmission. The aim of the study was to examine this hypothesis in anaesthetised dogs instrumented to measure left ventricular pressure and volume (conductance catheter).


METHODS
The effects of electrical stimulation of cardiac sympathetic efferents in the ansa subclavia (n = 6), or parasympathetic efferents in the vagus (n = 6), on left ventricular contractility were evaluated during epicardial superfusion with Tyrode solution, or Tyrode solution containing hexamethonium (1 x 10(-4) M), or procaine (2%). The slope of the end systolic pressure-volume relationship (Ees), a load independent measure of left ventricular contractility, and the position of the relationship (Vmid) were obtained by rapid transient vena caval occlusion.


RESULTS
Ansa subclavia stimulation increased Ees from 4.8(SD 1.8) to 8.3(3.0) mm Hg.ml-1 (p < 0.05), and Vmid shifted to the left, from 9(10) to 0(16) ml (p < 0.05). This response was abolished by epicardial superfusion with procaine, but not with hexamethonium. Vagal stimulation decreased Ees from 13.3(7.4) to 6.3(4.2) mm Hg.ml-1 (p < 0.05) and Vmid 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 methylcholine, indicating that the myocardial contractile response was intact during epicardial superfusion with procaine.


CONCLUSIONS
Neuromodulatory substances in the pericardial space may alter left ventricular contractility by modifying cardiac efferent autonomic neurotransmission on the epicardial surface of the heart.
Department of Internal Medicine (Section of Cardiology), Bowman Gray School of Medicine, Winston-Salem, NC 27157.
R J
RJ
Applegate
W C
WC
Little
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001341:Autonomic Nervous System / Q000187:drug effects*; D004285:Dogs; D004558:Electric Stimulation; D018738:Hexamethonium / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D010477:Perfusion; D010496:Pericardium / Q000187:drug effects*; D011343:Procaine / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects*
D000959:Antihypertensive Agents; D018738:Hexamethonium; D011343:Procaine