Late preconditioning is blocked by racemic ketamine, but not by S(+)-ketamine

Racemic ketamine blocks K-ATP channels in isolated cells and abolishes shor t-term cardioprotection against prolonged ischemia. We investigated the eff ects of racemic ketamine and S(+)-ketamine on ischemic late preconditioning (LPC) in the rabbit heart in vivo. A coronary occluder was chronically imp lanted 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 occl usion. Twenty-four hours later, the animals were instrumented for measureme nt of left ventricular systolic pressure (LVSP, tip manometer), cardiac out put (CO, ultrasonic flow probe) and myocardial infarct size (triphenyltetra zolium staining). All rabbits were then subjected to 30-min coronary occlus ion and 2 h reperfusion. Controls underwent the ischemia-reperfusion progra m 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 be fore the 30-min ischemia. Hemodynamic values were not significantly differe nt between groups during the experiments (baseline: LVSP, 94 +/- 3 mm Hg [m ean +/- 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%). LFC reduced infarct size from 44% +/- 3% of the area at risk in controls to 22% +/- 3% (P = 0.002). Administration of racemic ke tamine abolished the cardioprotective effects of LPC (44 +/- 4%, P = 0.002) . S(+)-ketamine did not affect the infarct size reduction induced by LPC (2 6 +/- 6%, P = 0.88).