HALOTHANE REDUCES RELEASE OF ADENOSINE, INOSINE, AND LACTATE WITH ISCHEMIA AND REPERFUSION IN ISOLATED HEARTS

We investigated the protective effects of halothane on cardiac functio n of isolated hearts during global hypoperfusion and reperfusion by ex amining halothane's effects on altering coronary flow, myocardial oxyg en utilization (MVO2), and release of adenosine (ADE), inosine (INO), and lactate (LAC). Isolated perfused guinea pig hearts were divided in to three groups of perfusion at 25% (14 mm Hg), 10% (5.5 mm Hg), and 0 % (no perfusion) from control perfusion pressure (PP, 55 mm Hg). Each of these PP groups was subdivided into three subgroups and perfused wi thout halothane (control), with 0.23 +/- 0.01 mM (0.74%) halothane, or with 0.51 +/- 0.01 mM (1.65%) halothane. Halothane was present 10 min before reducing PP, during reduced PP (30 min), and for 10 min after reducing PP. Hypoperfusion was followed by 40 min of reperfusion at th e control (100%, 55 mm Hg) PP. An additional group of control hearts w as followed for the same period without reducing PP or perfusing with halothane. Exposure to 0.74% and 1.65% halothane, before reducing PP, decreased MVO2 and percent oxygen extraction (% O2E), but produced no significant change in coronary flow or release of ADE, ISO, or LAC. Du ring early hypoperfusion (10 min) at 25% PP, 1.65% halothane significa ntly reduced release of ADE, INO, and LAC. During late hypoperfusion ( 40 min) the differences in LAC release diminished, but release of ADE and INO remained lower in the 1.65% halothane group. With early reperf usion there was a large increase in release of these metabolites, that was dependent on the decrease in perfusion pressure. The release of I NO during reperfusion was reduced by halothane; however, ADE release i ncreased with halothane suggesting less conversion of ADE to INO. The release of LAC was not affected by halothane. The reduction of cardiac work effected by halothane either before, during, or after graded red uctions in PP may decrease the loss of purine substrate so that synthe sis of high energy phosphates is less impaired. This study suggests th at our earlier finding that halothane improved contractile function an d reduced the severity of dysrhythmias in isolated hearts following gr aded reductions in PP is due, at least in part, to a decrease in oxyge n demand relative to oxygen supply, resulting in a decrease in purine release.