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From the *Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Academic Medical Center (A.M.C.), University of Amsterdam, Amsterdam, The Netherlands; and Department of Anesthesiology, University Hospital, Düsseldorf, Germany.
Address correspondence to Benedikt Preckel, MD, MA, DEAA, Department of Anesthesiology, Academic Medical Center (AMC), University of Amsterdam, Meibergdreef 9, Amsterdam 1100 DD, The Netherlands. Address e-mail to B.Preckel{at}amc.uva.nl.
Abstract
BACKGROUND: Xenon induces early myocardial preconditioning of the rat heart in vivo, but whether xenon induces late cardioprotection is not known. Cyclooxygenase-2 (COX-2) has been shown to be an important mediator in the signal transduction of myocardial ischemic late preconditioning (i-LPC). We investigated whether xenon induces late preconditioning (Xe-LPC) and whether COX-2 activity and/or expression are involved in mediating this effect.
METHODS: Anesthetized male Wistar rats were instrumented with a coronary artery occluder. After 7 d of recovery, animals were randomized to 1 of 5 groups each containing 8 animals. The i-LPC group underwent 5 min of coronary occlusion to induce i-LPC. Xe-LPC was achieved by administration of xenon (70 volume%) for 15 min. Additional rats were pretreated with the COX-2 inhibitor NS-398 (5 mg kg–1 body weight i.p.) with and without Xe-LPC. A group of sham operated animals not undergoing i-LPC or Xe-LPC served as controls (Con). After 24 h, all animals were anesthetized and underwent 25 min of myocardial ischemia induced by tightening of the coronary artery occluder followed by 2 h of reperfusion. Myocardial infarct size was assessed by triphenyltetrazolium chloride staining. In additional experiments, hearts were excised at different time points after preconditioning to investigate COX-2 mRNA and protein expression by polymerase chain reaction and infrared Western blot, respectively.
RESULTS: Both i-LPC and Xe-LPC reduced myocardial infarct size (% of the area at risk) compared with Con (i-LPC: 29 ± 7%; Xe-LPC 31 ± 8%, both P < 0.05 vs Con 64 ± 6%). NS-398 abolished the cardioprotective effect of Xe-LPC (61 ± 6%, P < 0.05 vs Xe-LPC). COX-2 mRNA and protein expression was only increased in the i-LPC group, but not in the Xe-LPC group.
CONCLUSION: Xenon induces late myocardial preconditioning that is abolished by functional blockade of COX-2 activity. In contrast to i-LPC, Xe-LPC did not lead to an increased expression of COX-2 mRNA and protein. These data suggest differences in COX-2 regulation in i-LPC and Xe-LPC.
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