Protective Effect Of Remote Preconditioning Research Articles

Liver ischemia preconditions the heart against ischemia-reperfusion arrhythmias.

This study aimed to examine the hypothesis that an antiarrhythmic effect might be obtained by ischemic preconditioning of the liver, and also to characterize the potential underlying mechanisms. Male Wistar rats were anesthetized by thiopental sodium (50 mg/kg, IP) followed by IV injection of heparin (250 IU). Remote ischemic preconditioning (RIPC) was induced by 3 cycles of 5 min liver ischemia followed by 5 min of reperfusion. The hearts were excised within 5 min after the final cycle of preconditioning and perfused using Langendorff's system. The isolated perfused hearts were subjected to 30 min global ischemia followed by 90 min reperfusion. The myocardial arrhythmias induced by ischemia- reperfusion (I/R) were determined in accordance with the guidelines of Lambeth Conventions. The potential role of KATP channels on RIPC was assessed by injection of glibenclamide (nonselective KATP blocker) or 5-hydroxydecanoate (mitochondrial KATP blocker) on rats 30 and 15 min before induction of RIPC in the liver, respectively. Hepatic remote preconditioning of the heart significantly (P<0.0001) prevented the incidence of myocardial arrhythmias induced by I/R in the perfused hearts (5.33±1.54 vs. 32.33±6.44,). However, the protective effects of remote preconditioning was significantly (P<0.01) abolished by the KATP blocker, glibenclamide (25.5±4.9 vs. 5.33±1.54,). Hepatic RIPC may prevent the arrhythmias induced by I/R in the isolated perfused hearts via KATP channels.

Cannabinoid 1 receptor mediation of spinal cord ischemic tolerance induced by limb remote ischemia preconditioning in rats

The aim of this study was to examine the influence of endogenous cannabinoids on neuroprotection of the spinal cord afforded by limb remote ischemic preconditioning. In experiment 1 (RIPC group), 3 cycles of limb remote ischemic preconditioning within different episodes (2, 3, or 5 minutes) were induced before spinal cord ischemia in rats (N = 5, n = 8). In experiment 2, animals were pretreated intravenously by the vehicles, cannabinoid 1 (AM251, 1 mg/kg) or cannabinoid 2 (AM630, 1 mg/kg) receptor antagonist 15 minutes before remote ischemic preconditioning, or else they were subjected to a sham operation. Thirty minutes after the pretreatment, spinal cord ischemia was induced (N = 8, n = 8). In experiment 3, the arachidonylethanolamide and 2-arachidonoylglycerol contents in the spinal cord after remote ischemic preconditioning and spinal cord ischemia were detected in rats (N = 2, n = 12). Spinal cord ischemia was induced by 12 minutes of thoracic aorta occlusion in rats. Neurologic function was assessed 24 and 48 hours after reperfusion. Histopathologic examination was performed and the number of normal neurons in anterior spinal cord were counted. In experiment 1, 3 cycles of limb remote ischemic preconditioning (3 minutes of ischemia/3 minutes of reperfusion) induced ischemic tolerance on the spinal cords of the rats. The RIPC group showed a significant reduction in motor deficit index (P < .01) as well as an increase in the number of normal neurons (P < .01). In experiment 2, the cannabinoid 1 receptor antagonist AM251 pretreatment abolished the protective effects of remote preconditioning. In experiment 3, arachidonylethanolamide content in spinal cord was elevated by remote ischemic preconditioning in rats. These results indicated that endogenous cannabinoids, through acting on cannabinoid 1 receptors, were involved in the neuroprotective phenomenon on spinal cords of limb remote ischemic preconditioning.

The Mechanism of Hepatic Heme Oxygenase-1 Expression by Limb Remote Ischemic Preconditioning

In vitro studies (1–3) have found the molecular signaling pathways of heme oxygenase (HO)-1 induction included MAPKs, Nrf2, and Bach1. However, the cellular mechanism of HO-1 induction in the target tissue (liver) by remote ischemic preconditioning (limb) is still under investigation. It has been proposed that either neurogenic and/or humoral factors were responsible for the induction of HO-1. The blocking assays were the commonly used methods to prove these theories. For example, ganglion blockers (4, 5) or mitochondria KATP channel blocker (6) have been shown to inhibit the protective effect of remote preconditioning. In our study, though we demonstrated the HO-1 was not induced in the peripheral lymphocytes but in the liver, we did not find the exact mechanism of remote HO-1 induction. Kanoria et al. (7) has indicated nitric oxide (NO) as an important mediator of the protective effect of limb remote ischemic preconditioning (RIPC). Is it possible that NO also is an important inducer of HO-1 expression? Choi et al. had shown that NO donor upregulated HO-1 expression in hepatocyte cultures (8, 9). The endothelium of limb vessels might produce NO derivatives in the process of limb ischemia-reperfusion. The study of Kanoria et al. (7) showed increased nitrate/nitrite levels in hepatic vein and systemic arterial plasma after RIPC. However, there existed another puzzle that how the short-lived NO derivatives transfer signals to induce HO-1 in remote liver. Of course, remote hepatic HO-1 induction might simply reflect secondary liver ischemic stress originating from limb ischemia-reperfusion. To solve this problem, we have to investigate the perfusion dynamics of liver during limb ischemia-reperfusion. I-Rue Lai King-Jen Chang Department of Surgery National Taiwan University Hospital National Taiwan University College of Medicine Taipei, Taiwan Chau-Fong Chen Department of Physiology National Taiwan University College of Medicine Taipei, Taiwan

Remote preconditioning reduces ischemic injury in the explanted heart by a KATP channel-dependent mechanism

Local and remote ischemic preconditioning (IPC) reduce ischemia-reperfusion (I/R) injury and preserve cardiac function. In this study, we tested the hypothesis that remote preconditioning is memorized by the explanted heart and yields protection from subsequent I/R injury and that the underlying mechanism involves sarcolemmal and mitochondrial ATP-sensitive K(+) (K(ATP)) channels. Male Wistar rats (300-350 g) were randomized to a control (n = 10), a remote IPC (n = 10), and a local IPC group (n = 10). Remote IPC was induced by four cycles of 5 min of limb ischemia, followed by 5 min of reperfusion. Local IPC was induced by four cycles of 2 min of regional myocardial ischemia, followed by 3 min of reperfusion. The heart was excised within 5 min after the final cycle of preconditioning, mounted in a perfused Langendorff preparation for 40 min of stabilization, and subjected to 45 min of sustained ischemia by occluding the left coronary artery and 120 min of reperfusion. I/R injury was assessed as infarct size by triphenyltetrazolium staining. The influence of sarcolemmal and mitochondrial K(ATP) channels on remote preconditioning was assessed by the addition of glibenclamide (10 microM, a nonselective K(ATP) blocker), 5-hydroxydecanoic acid (5-HD; 100 microM, a mitochondrial K(ATP) blocker), and HMR-1098 (30 microM, a sarcolemmal K(ATP) blocker) to the Langendorff preparation before I/R. The role of mitochondrial K(ATP) channels as an effector mechanism for memorizing remote preconditioning was further studied by the effect of the specific mitochondrial K(ATP) activator diaxozide (10 mg/kg) on myocardial infarct size. Remote preconditioning reduced I/R injury in the explanted heart (0.17 +/- 0.03 vs. 0.39 +/- 0.05, P < 0.05) and improved left ventricular function during reperfusion compared with control (P < 0.05). Similar effects were obtained with diazoxide. Remote preconditioning was abolished by the addition of 5-HD and glibenclamide but not by HMR-1098. In conclusion, the protective effect of remote preconditioning is memorized in the explanted heart by a mechanism that involves mitochondrial K(ATP) channels.