Late Preconditioning is Blocked by Racemic Ketamine, But Not by S(+)-Ketamine

Abstract

Racemic ketamine blocks KATP channels in isolated cells and abolishes short-term cardioprotection against prolonged ischemia. We investigated the effects of racemic ketamine and S(+)-ketamine on ischemic late preconditioning (LPC) in the rabbit heart in vivo. A coronary occluder was chronically implanted in 36 rabbits. After recovery, the rabbits divided into four groups (each n = 9). LPC was induced in conscious rabbits by a 5-min coronary occlusion. Twenty-four hours later, the animals were instrumented for measurement of left ventricular systolic pressure (LVSP, tip manometer), cardiac output (CO, ultrasonic flowprobe) and myocardial infarct size (triphenyltetrazolium staining). All rabbits were then subjected to 30-min coronary occlusion and 2 h reperfusion. Controls underwent the ischemia-reperfusion program without LPC. To test whether racemic ketamine or S(+)-ketamine blocks the cardioprotection induced by LPC, the drugs (10 mg/kg) were given 10 min before the 30-min ischemia. Hemodynamic values were not significantly different between groups during the experiments (baseline: LVSP, 94 ± 3 mm Hg [mean ± sem] and CO, 243 ± 9 mL/min; coronary occlusion: LVSP, 93% ± 4% of baseline and CO, 84% ± 4%; after 2 h of reperfusion: LVSP, 85% ± 4% and CO, 83% ± 4%). LPC reduced infarct size from 44% ± 3% of the area at risk in controls to 22% ± 3% (P = 0.002). Administration of racemic ketamine abolished the cardioprotective effects of LPC (44 ± 4%, P = 0.002). S(+)-ketamine did not affect the infarct size reduction induced by LPC (26 ± 6%, P = 0.88).