Remote ischemic conditioning has been convincingly shown to render the myocardium resistant to a subsequent more severe sustained episode of ischemia. Compared to other organs, little is known regarding the effect of transient liver ischemic conditioning. We proposed the existence cardioprotection induced by remote liver conditioning. Male Sprague Dawley rats were divided into sham-operated, control(CON, no further hepatic intervention) and remote liver ischemic conditioning groups. For liver ischemic conditioning, three cycles of 5min of liver ischemia/reperfusion stimuli were conducted prior to-(liver preconditioning), post-myocardial ischemia (liver postconditioning), or in combination of both (liver preconditioning+liver postconditioning). Rats were exposed to a 45min of left anterior descending coronary artery occlusion followed by 3h of reperfusion thereafter.ECG and hemodynamics were measured throughout the experiment. The coronary artery was re-occluded at the end of reperfusion for infarct size determination. Blood samples were taken for serum lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) test. Heart tissues were taken for apoptosis measurements and western blotting. Our data demonstrate that liver ischemic preconditioning, postconditioning, or a combination of both, offered strong cardioprotection, as evidenced by reduction in infarct size and cardiac tissue damage, recovery of cardiac function, and inhibition of apoptosis after ischemia/reperfusion. Moreover, liver ischemic conditioning increased cardiac (not hepatic)glycogen synthase kinase-3β (GSK-3β) phosphorylation. Accordingly, inhibition of GSK-3β mimicked the cardioprotective action of liver conditioning. These results support that remote liver ischemic conditioning protected the heart against ischemia and reperfusion injury via GSK-3β-dependent cell-survival signaling pathway.
- liver ischemic conditioning
- myocardial ischemia and reperfusion injury
- Copyright © 2016, Journal of Applied Physiology