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.
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.
Authors: Rita Campos-Pires; Scott P Armstrong; Anne Sebastiani; Clara Luh; Marco Gruss; Konstantin Radyushkin; Tobias Hirnet; Christian Werner; Kristin Engelhard; Nicholas P Franks; Serge C Thal; Robert Dickinson Journal: Crit Care Med Date: 2015-01 Impact factor: 7.598
Authors: Y Irani; J L Pype; A R Martin; C F Chong; L Daniel; J Gaudart; Z Ibrahim; G Magalon; M Lemaire; J Hardwigsen Journal: Nephron Extra Date: 2012-01-14
Authors: Ruben C Franceschi; Luiz Malbouisson; Eduardo Yoshinaga; Jose Otavio Costa Auler; Luiz Francisco Poli de Figueiredo; Maria Jose C Carmona Journal: Clinics (Sao Paulo) Date: 2013 Impact factor: 2.365
Authors: Christian Stoppe; Achim Rimek; Rolf Rossaint; Steffen Rex; Ana Stevanovic; Gereon Schälte; Astrid Fahlenkamp; Michael Czaplik; Christian S Bruells; Christian Daviet; Mark Coburn Journal: Med Gas Res Date: 2013-06-11