Myocardial infarct-sparing effect of ischemic preconditioning abrogated in cirrhotic rat through involvement of mitochondrial permeability transition pore
Despite all studies undertaken mechanism of cirrhotic cardiomyopathy the role of cirrhosis on ischemia-reperfusion (I/R) injury and ischemic preconditioning (IPC) phenomenon hasn't been explored yet. The aim of present study is to assess the relation between cirrhosis and IPC and the mitochondrial permeability transition pore (mPTP) role in IPC cardioprotective effects in cirrhotic rats.
Material and method: Rat's heart were isolated and perfused with Krebs buffer by Langendorff method. Animals were equally divided into six groups (n=6): (I) I/R; hearts were subjected to 30 min ischemia and 45 min reperfusion, (II) IPC; IPC was induced via four cycle of 5 min regional ischemia followed by 5 min of reperfusion (III) common bile duct ligated (CBDL); hearts were subjected ischemia and reperfusion in cirrhotic rats, (IV) IPC-CBDL; four cycle of 5 min regional ischemia followed by 5 min of reperfusion in cirrhotic rats (V) CSA; Cyclosporine A was added 40 min prior to main ischemia (VI) CBDL+CSA.
Results: Infarct size was increased significantly in IPC-CBDL group in comparison with IPC group (p< 0.05). Addition of CSA in CBDL+CSA group significantly decreased infarct size in comparison with IPC-CBDL group (p< 0.05). Ventricular arrhythmia severity was decreased significantly in IPC group compared to IR group, whereas it was increased significantly in IPC-CBDL group compared to IPC group (p< 0.05). CSA did not decrease arrhythmia score in CBDL group.
Conclusion: The results showed that the cardioprotective effects of IPC are eliminated in cirrhosis. MPTP signaling in partly involve in cirrhotic cardiomyopathy
