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CARDIOVASCULAR ANESTHESIA

The Influence of Mitochondrial K_ATP-Channels in the Cardioprotection of Preconditioning and Postconditioning by Sevoflurane in the Rat In Vivo

Klinik für Anaesthesiologie, Universitätsklinikum Düsseldorf, Düsseldorf, Germany

Address correspondence and reprint requests to Professor Wolfgang Schlack, DEAA, Klinik für Anaesthesiologie, Universitätsklinikum Düsseldorf, Postfach 10 10 07, D-40001 Düsseldorf, Germany. Address e-mail to schlack{at}med.uni-duesseldorf.de.

Volatile anesthetics induce myocardial preconditioning and can also protect the heart when given at the onset of reperfusion—a practice recently termed "postconditioning." We investigated the role of mitochondrial K_ATP (mK_ATP)-channels in sevoflurane-induced cardioprotection for both preconditioning and postconditioning alone and whether there is a synergistic effect of both. Rats were subjected to 25 min of coronary artery occlusion followed by 120 min of reperfusion. Infarct size was determined by triphenyltetrazolium staining. The following protocols were used: 1) preconditioning (S-Pre, n = 10, achieved by 2 periods of 5 min sevoflurane administration (1 MAC) followed by 10 min of washout); 2) sevoflurane postconditioning (1 MAC of sevoflurane given for 2 min at the beginning of reperfusion; S-Post, n = 10); 3) administration before and after ischemia (S-Pre + S-Post, n = 10). Protocols 1–3 were repeated in the presence of 5-hydroxydecanoate (5HD), a specific mK_ATP-channel-blocker (S-Pre + S-Post + 5HD, S-Pre + 5HD: n = 10; S-Post + 5HD: n = 9). Nine rats served as untreated controls (CON) or received 5HD alone (5HD, n = 10). Both S-Pre (23% ± 13% of the area at risk, mean ± sd) and S-Post (18% ± 5%) reduced infarct size compared with CON (49% ± 11%, both P < 0.05). S-Pre + S-Post resulted in a larger reduction of infarct size (12% ± 5%, P = 0.054 versus S-Pre) compared with administration before or after ischemia alone. 5HD diminished the protection in all three sevoflurane treated groups (S-Pre + 5HD, 35% ± 12%; S-Post + 5HD, 44% ± 12%; S-Pre + S-Post + 5HD, 46% ± 14%;) but given alone had no effect on infarct size (41% ± 13%). Sevoflurane preconditioning and postconditioning protects against myocardial ischemia-reperfusion injury. The combination of preconditioning and postconditioning provides additive cardioprotection and is mediated, at least in part, by mK_ATP-channels.

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