Isoflurane late preconditioning against myocardial stunning is associated with enhanced antioxidant defenses

Abstract

We tested the hypothesis that an upregulation of antioxidant proteins [Cu-Zn superoxide dismutase (SOD), Mn SOD, catalase, glutathione peroxidase, and glutathione peroxidase] plays a role in the delayed protection against myocardial stunning produced by isoflurane preconditioning (ISOPC). Findings were compared with late ischemic PC (IPC). Fourteen mongrel dogs were chronically instrumented to measure coronary blood flow and myocardial wall thickening (WT) in conscious state. In Group 1, dogs underwent IPC, induced by a 10-min coronary artery occlusion (CAO); after 24 h of reperfusion, they were subjected to a second 10-min ischemia CAO-reperfusion. In Group 2 (ISOPC), dogs inhaled one minimum alveolar concentration (MAC) ISO (1.4% in O(2)) for 60 min, allowed to recover for 24 h, and then subjected to CAO ischemia-reperfusion. Recovery of WT following the initial 10-min CAO in Group 1 served as control response for both ISOPC and IPC. Expression and activity of antioxidant proteins were measured using Western blotting and spectrophotometric techniques, respectively. Two to three hours of reperfusion were required for recovery of WT following either ISOPC or IPC; in contrast, without PC, WT remained markedly reduced (30% below baseline) at this time point and required more than 6 h of reperfusion for recovery. Neither IPC nor ISOPC affected expression of Cu-Zn SOD, Mn SOD, or catalase. However, ISOPC increased activity of Mn SOD (+40%), catalase (+39%), glutathione peroxidase (+37%), and glutathione reductase (+93%) (P < 0.05); IPC had similar effects. ISOPC had powerful, delayed anti-stunning effect that was associated with an enhancement of endogenous antioxidant defenses.