Myocardial ischemia reperfusion injury contributes to adverse cardiovascular outcomes after myocardial ischemia, cardiac surgery or circulatory arrest. Primarily, no blood flow to the heart causes an imbalance between oxygen demand and supply, named ischemia (from the greek isch-, restriction and -haema, blood), resulting in damage or dysfunction of the cardiac tissue. Instinctively, early and fast restoration of blood flow has been established to be the treatment of choice to prevent further tissue injury. Indeed, the use of thrombolytic therapy or primary percutaneous coronary intervention is the most effective strategy for reducing the size of a myocardial infarct and improving the clinical outcome. Unfortunately, restoring blood flow to the ischemic myocardium, named reperfusion, can also induce injury. This phenomenon was therefore termed myocardial ischemia reperfusion injury. Subsequent studies in animal models of acute myocardial infarction suggest that myocardial ischemia reperfusion injury accounts for up to 50% of the final size of a myocardial infarct. Consequently many researchers aim to understand the underlying molecular mechanism of myocardial ischemia reperfusion injury to find therapeutic strategies ultimately reducing the final infarct size. Despite of the identification of numerous therapeutic strategies at the bench, many of them are just in the process of being translated to bedside. In the current review, we will discuss the most striking basic science findings made during the last decades that are currently under clinical evaluation, with the ultimate goal to treat patients who are suffering from myocardial ischemia and reperfusion associated tissue injury.

Background: Anesthetic preconditioning is mediated by ␤-adrenergic signaling. This study was designed to elucidate the role of ␤-adrenergic signaling in desflurane-induced postconditioning.Methods: Pentobarbital-anesthetized New Zealand White rabbits were subjected to 30 min of coronary artery occlusion followed by 3 h of reperfusion and were randomly assigned to receive vehicle (control), 1.0 minimum alveolar concentration of desflurane, esmolol (30 mg ⅐ kg ؊1 ⅐ h ؊1 ) for the initial 30 min

Cyclooxygenase (COX)-2 mediates ischemic pre-and postconditioning as well as anesthetic-induced preconditioning. However, the role of COX-1 and -2 in anesthetic-induced postconditioning has not been investigated. We evaluated the role of COX-1 and -2 in sevoflurane-induced postconditioning in vivo. Pentobarbital-anaesthetized male C57BL/6 mice were subjected to 45 minutes of coronary artery occlusion and 3 hours of reperfusion. Animals received either no intervention, the vehicle dimethyl sulfoxide (DMSO, 10 µL/g intraperitoneally), acetylsalicylic acid (ASA, 5 µg/g intraperitoneally), the selective COX-1 inhibitor SC-560 (10 µg/g intraperitoneally), or the selective COX-2 inhibitor NS-398 (5 µg/g intraperitoneally). 1.0 MAC (minimum alveolar concentration) sevoflurane was administered for 18 minutes during early reperfusion either alone or in combination with ASA, SC-560, and NS-398. Infarct size was determined with triphenyltetrazolium chloride. Statistical analysis was performed using 1-way and 2-way analyses of variance with post hoc Duncan testing. The infarct size in the control group was 44% ± 9%. DMSO (42% ± 7%), ASA (36% ± 6%), and NS-398 (44% ± 18%) had no effect on infarct size. Sevoflurane (17% ± 4%; P < .05) and SC-560 (26% ± 10%; P < .05) significantly reduced the infarct size compared with control condition. Sevoflurane-induced postconditioning was not abolished by ASA (16% ± 5%) and SC-560 (22% ± 4%). NS-398 abolished sevoflurane-induced postconditioning (33% ± 14%). It was concluded that sevoflurane induces postconditioning in mice. Inhibition of COX-1 elicits a myocardial infarct size reduction and does not abolish sevoflurane-induced postconditioning. Blockade of COX-2 abolishes sevofluraneinduced postconditioning. These results indicate that sevoflurane-induced postconditioning is mediated by COX-2.

sind direkt an die Schriftleitung zu riditen, sie dürfen nicht gleichzeitig anderen Blättern zum Abdruck angeboten werden. -Mit der Annahme des Manuskriptes erwirbt der Verlag das ausschließliche Redit der Vervielfältigung, Verbreitung und Ubersetzung der in dieser Zeitschrift zum Abdrudc gelangten Beiträge, insbesondere auch das Redit, die Herstellung von fotomedianischen Vervielfältigungen in gewerblichen Unternehmen zum innerbetrieblichen Gebrauch nach Maßgabe des zwischen dein Börsenverein des Deutschen Buchhandels und dem Butidesverban d der Deutschen Industrie abgeschlossenen Rahmenabkominens zu genehmigen. Der Verlag erwirbt weiter das Recht der Verwendung des Manuskriptes für fremdsprachliche Ausgaben. Kein Teil dieser Zeitschrift darf in irgendeiner Form, auch nicht durch Fotokopie, Mikroülm oder irgendein anderes Verfahren ohne schriftliche Genehmigung des Verlages reproduziert werden; jedoch wird gewerblichen Unternehmen die Anfertigung einer fotomechanischen Vervielfältigung (Fotokopie, Mikrokople) für den innerbetrieblichen Gebrauch nach Maßgabe des zwischen dem Börsenverein des Zleutsdien Buchhandels und dem Bundesverband der Deutschen Industrie abgeschlossenen Rahinenabkommens gestattet Werden die Gebühren durch Wertmarken entriditet, so ist für jedes Fotokopierblatt eine Marke im Betrag von DM 0.10 zu verwenden. -Die Aufnahme dieser Zeitschrift in Lesezirkel ist nicht gestattet.