DIFFERENTIAL-EFFECTS OF ARGININE-VASOPRESSIN ON ISOLATED GUINEA-PIG HEART FUNCTION DURING PERFUSION AT CONSTANT FLOW AND CONSTANT-PRESSURE

8-Arginine vasopressin (AVP) is a powerful coronary vasoconstrictor as well as peripheral vasoconstrictor, but AVP also is reported to have negative cardiac inotropic and chronotropic effects in vitro and in vi vo. Our aim was to examine the direct effects of coronary vasoconstric tion by AVP on cardiac function and metabolism in isolated guinea pig hearts perfused either at a constant perfusion pressure (CPP) of 55 mm Hg or at a constant coronary flow (CCF) equal to the initial natural flow at constant pressure. Coronary Vasoconstriction was elicited by p erfusing hearts with increasing concentrations of AVP in random order. Variables assessed were atrial heart rate (HR), atrioventricular (AV) conduction time, left ventricular pressure (LVP), coronary flow, infl ow and outflow O-2 tensions, O-2 delivery (Do(2)), oxygen consumption (MVo(2)), percentage oxygen extraction (%O(2)E) and cardiac efficiency (HR-LVP/MVo(2)). We found that AVP increased coronary vascular resist ance more at CCF than at CPP. The decrease in coronary flow, as a func tion of AVP at CPP, produced concentration-dependent decreases in hear t rate, WP, and MVo(2), a decrease in Do(2)/MVo(2), increases in AV co nduction time and %O(2)E, and no significant change in cardiac efficie ncy. Ln contrast, the increase in perfusion pressure as a function of AVP at CCF caused no change in HR and AV conduction time, much smaller decreases in LVP and Do(2)/MVo(2), a smaller increase in %O(2)E, an i ncrease rather than a decrease in MVo(2), and a decrease in cardiac ef ficiency. Our results indicate that larger decreases in HR, LVP, MVo(2 ), and Do(2)/MVo(2), and the larger increases in AV conduction time an d %O(2)E with the AVP-induced decrease in CF at CPP are consistent wit h myocardial depression resulting from reduced global perfusion. Howev er, cardiac efficiency was maintained at CPP because the decreased HR and LVP product (cardiac work) matched the decrease in MVo(2). At CCF, AVP did not directly produce myocardial depression, but the small tim e-dependent decrease in LVP over time was not matched by the increase in MVo(2), so that cardiac efficiency was not maintained. The demonstr ation of an increase in MVo(2) despite no change or a decrease in card iac work by coronary vasoconstriction with AVP at CCF, but not at CPP, suggests that cardiac O-2 use is dependent more on maintenance of CF, despite increased resistance to perfusion, rather than on maintenance of perfusion pressure. Our data agree that Gregg's phenomenon results from a hydraulic effect to distend coronary vasculature because when flow is not allowed to decrease during vasoconstriction, MVo(2) increa ses even though HR is unchanged and LVP is slightly decreased. This is supported by the finding that AVP does not increase coronary vascular resistance during CCF as much as during CPP, so that O-2 supply is be tter maintained to match MVo(2).