The olprinone-induced cardioprotective effect could be exerted via the activation of PI3K-Akt and the inhibition of mPTP during early reperfusion.

(237 words)Background: Ischemic postconditioning (PostC) protects the liver against ischemia-reperfusion (IR)

Implications statement: A selective COX-2 inhibitor prevents the cardioprotective effect of sevoflurane but not olprinone in rat hearts. (16 words) 2 AbstractPurpose: It is known that selective cyclooxygenase (COX)-2 inhibitors increase mortality in patients with previous myocardial infarction, and it has been suggested that COX-2 plays an important role in cardioprotection against ischemia. The present study was carried out to determine whether COX-2 is involved in the mechanisms of sevoflurane-and olprinone-induced early-phase preconditioning (E-PreC) and postconditioning (PostC) in rat hearts.Methods: Male SD rats were anesthetized with sodium pentobarbital. After opening the chest, all rats underwent 30-min left anterior descending coronary artery occlusion followed by 2-h reperfusion, and the infarct size was measured after the reperfusion. The rats were randomly assigned to groups with pre-and post-ischemic exposure to sevoflurane and administration of olprinone with or without a selective COX-2 inhibitor, NS-398.Results: The infarct size in the control group was 42 ± 6% of the area at risk. Infarct size was significantly reduced by pre-and post-ischemic administration of sevoflurane (16 ± 7% and 17 ± 6%, respectively), as well as by olprinone (14 ± 4% and 15 ± 10%, respectively). NS-398 prevented the protective effects of both pre and post-ischemic exposure to sevoflurane (35 ± 8% and 42 ± 10%, respectively), whereas the protective effect of both pre-and post-ischemic administration of olprinone was not influenced by NS-398 (12 ± 5% and 19 ± 7%, respectively).Conclusions: COX-2 could be a critical mediator of sevoflurane-induced but not olprinone-induced E-PreC or PostC in rat hearts. (236 words) 3

Purpose: Deliberate mild hypothermia (MHT) is applied for cerebroprotection after cardiopulmonary resuscitation and during cardiac surgery. MHT has been shown to alter both contractility and relaxation of blood vessels in the brain. However, the effects of MHT on drug-induced vasodilation are not fully understood. The aim of this study was to clarify the effects of MHT on the coronary vasodilation induced by cromakalim: an ATP-sensitive K channel opener, S-nitroso acetyl-penicillamine (SNAP): a nitric oxide donor, and isoflurane in isolated rat hearts.Methods: Male SD rat hearts were isolated and perfused with Krebs-Henseleit buffer.Coronary flow was measured with the coronary perfusion pressure kept at 60 mmHg, and coronary vascular resistance (CVR) was calculated. After cardiac arrest was induced by tetrodotoxin, the hearts were allocated to one of three temperature groups: 37, 34, and 31˚C (n = 7 for each). All groups received 0.01, 0.1, and 1.0 M of either cromakalim or SNAP or were exposed to isoflurane at 1MAC and 2MAC. Finally, 50 mM of adenosine was administered to obtain maximal coronary vasodilation.Results: CVR significantly increased after cardiac arrest, but did not change after application of each temperature. Cromakalim, SNAP and isoflurane significantly decreased CVR in each temperature group. There were no significant differences in CVR among the three temperature groups with any of the test drugs.