Abstract 101: The Continuous Administration of Sevoflurane Protects the Heart Against Ischemic Injury via Distinct Mitochondrial Mechanisms.

Abstract

Sevoflurane induced cardioprotection against ischemia/reperfusion (I/R) injury represents a well-established phenomenon. Salutary effects of the volatile anesthetic are not only limited to pre- or post-ischemic use, but clinical data also indicate its continuous administration as a beneficial mean. We investigated the hypothesis that the administration of sevoflurane during I/R-injury results in cardioprotection via the recruitment of distinct mitochondrial mechanisms. After IRB approval New Zealand White rabbits (9-12 weeks of age) received sevoflurane (1.0 MAC) or propofol (10 mg/kg/h) during 30 min of coronary artery occlusion followed by 3 h of reperfusion (n=7 per group). Cardiac mitochondria were isolated at the end of reperfusion. TTC-staining was used to determine the myocardial infarct size; in addition, mitochondrial O2 consumption was quantified and expressed as the respiratory control ratio (RCR). Mitochondrial electron transport chain (ETC) complex activities (I-IV) were assayed; including the analysis of an active to dormant (A/D) ratio of complex I. Statistics: ANOVA followed by posthoc Bonferroni, Mean ± SD. Our data indicate a significant infarct size reduction in animals receiving sevoflurane throughout the I/R-injury (p<0,05). The salutary effects were characterized by the maintenance of the RCR (p<0,05), as well as a preserved activity of complex I (p<0,05). Furthermore, the volatile anesthetic stabilized the A/D-ratio of the complex, indicating enhanced stability of the enzyme (p<0,05). Taken together, our findings support the notion that sevoflurane protects the heart against ischemic injury in a setting closely mimicking daily clinical work via the maintenance of mitochondrial respiratory physiology.