Balancing mitochondrial dynamics via increasing mitochondrial fusion attenuates infarct size and left ventricular dysfunction in rats with cardiac ischemia/reperfusion injury

An uncontrolled balance of mitochondrial dynamics has been shown to contribute to cardiac dysfunction during I/R injury.  Although inhibition of mitochondrial fission could ameliorate cardiac dysfunction, modulation of mitochondrial fusion by giving a fusion promoter at different time-points during cardiac I/R injury has never been investigated.  We hypothesized that giving of a mitochondrial fusion promoter at different time-points exerts cardioprotection with different levels of efficacy in rats with cardiac I/R injury.  Forty Male Wistar rats were subjected to a 30-min ischemia by coronary occlusion, followed by a 120-min reperfusion.  The rats were then randomly divided into 3 groups: pre-ischemia, during-ischemia and onset of reperfusion.  A pharmacological mitochondrial fusion promoter-M1 (2 mg/kg) was used for intervention.  Reduced mitochondrial fusion protein was observed after cardiac I/R injury.  M1 administered prior to ischemia exerted the highest level of cardioprotection by improving both cardiac mitochondrial function and dynamics regulation, attenuating incidence of arrhythmia, reducing infarct size and cardiac apoptosis, which led to the preservation of cardiac function and decreased mortality.  M1 given during ischemia and on the onset of reperfusion, also exerted cardioprotection, but with a lower efficacy than when given at the pre-ischemia time point.  Attenuating a reduction in mitochondrial fusion proteins d...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research