Isoflurane preconditions myocardium against infarction via release of free radicals

Abstract

Background: Isoflurane exerts cardioprotective effects that mimic the ischemic preconditioning phenomenon. Generation of free radicals is implicated in ischemic preconditioning. The authors investigated whether isoflurane-induced preconditioning may involve release of free radicals. Methods: Sixty-one α-chloralose-anesthetized rabbits were instrumented for measurement of left ventricular (LV) pressure (tip-manometer), cardiac output (ultrasonic flowprobe), and myocardial infarct size (triphenyltetrazolium staining). All rabbits were subjected to 30 min of occlusion of a major coronary artery and 2 h of subsequent reperfusion. Rabbits of all six groups underwent a treatment period consisting of either no intervention for 35 min (control group, n = 11) or 15 min of isoflurane inhalation (1 minimum alveolar concentration end-tidal concentration) followed by a 10-min washout period (isoflurane group, n = 12). Four additional groups received the radical scavenger N-(2-mercaptoproprionyl)glycine (MPG; 1 mg · kg -1 · min -1) or Mn(III)tetrakis(4-benzoic acid)porphyrine chloride (MnTBAP; 100 μg · kg -1 · min -1) during the treatment period with (isoflurane + MPG; n = 11; isoflurane + MnTBAP, n = 9) or without isoflurane inhalation (MPG, n = 11; MnTBAP, n = 7). Results: Hemodynamic baseline values were not significantly different between groups (LV pressure, 97 ± 17 mmHg [mean ± SD]; cardiac output, 228 ± 61 ml/min). During coronary artery occlusion, LV pressure was reduced to 91 ± 17% of baseline and cardiac output to 94 ± 21%. After 2 h of reperfusion, recovery of LV pressure and cardiac output was not significantly different between groups (LV pressure, 83 ± 20%; cardiac output, 86 ± 23% of baseline). Infarct size was reduced from 49 ± 17% of the area at risk in controls to 29 ± 19% in the isoflurane group (P = 0.04). MPG and MnTBAP themselves had no effect on infarct size (MPG, 50 ± 14%; MnTBAP, 56 ± 15%), but both abolished the preconditioning effect of isoflurane (isoflurane + MPG, 50 ± 24%, P = 0.02; isoflurane + MnTBAP, 55 ± 10%, P = 0.001). Conclusion: Isoflurane-induced preconditioning depends on the release of free radicals.