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Isoflurane Does Not Produce a Second Window of Preconditioning Against Myocardial Infarction In Vivo
Franz Kehl, M.D.; Paul S. Pagel, M.D., Ph.D.; Wolfgang Toller, M.D.; David C. Warltier, M.D., Ph.D.; Judy R. Kersten, M.D.
Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin
Introduction: Administration of a volatile anesthetic shortly before a prolonged ischemic episode exerts protective effects against myocardial infarction.1 After 2 h the protective effects of IPC dissipates but 24 h later a second window of preconditioning re-emerges.2 Whether delayed exposure to a volatile agent similarly causes myocardial protection is unknown. We tested the hypothesis that administration of isoflurane 24 h before ischemia produces a second window of preconditioning against infarction.

Methods: All experimental procedures conformed to the guidelines of the APS and the NIH and were approved by the Institutional Animal Care and Use Committee. Barbiturate-anesthetized dogs (n=23) were instrumented for measurement of systemic hemodynamics including aortic and left ventricular (LV) pressures and LV +dP/dtmax. Myocardial infarct size was assessed with triphenyltetrazolium chloride staining and myocardial perfusion was measured with radioactive microspheres. All dogs were subjected to a 60 min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Two groups of dogs received 1.0 MAC isoflurane for 30 min or 6 h that was discontinued 30 min (acute) or 24 h (delayed) before ischemia and reperfusion, respectively. A control group of dogs did not receive isoflurane. Statistical analysis of data was performed with ANOVA followed by the Student-Newman-Keuls test. Data were considered statistically significant when P<0.05.

Results: No differences in hemodynamics or transmural myocardial perfusion during or after coronary artery occlusion were observed between groups. The area of the left ventricle at risk for infarction (AAR) and coronary collateral blood flow were similar amongst groups. Myocardial infarct size (IF) expressed as a percentage of the AAR (IF/AAR) was 31±3% (mean±SEM) in CON experiments. Acute but not delayed administration of isoflurane (*P<0.05 vs CON) reduced infarct size (12±1%* and 27±3%, respectively).

Conclusions: The results indicate that isoflurane does not produce a second window of preconditioning against myocardial infarction in vivo.

References: 1) Kersten et al. Isoflurane mimics ischemic preconditioning via activation of KATP channels. Anesthesiology 1997;87:361-370. 2) Kuzuya et al. Delayed effects of sublethal ischemia on the acquisition of tolerance to ischemia. Circulation Research 1993; 72: 1293-9.

Anesthesiology 2002; 96: A602