Cardioprotective Effects of Mitochondria-Targeted Peptide SBT-20 in two Different Models of Rat Ischemia/Reperfusion

Purpose Dysfunctional mitochondria are considered to be the major source of intracellular reactive oxygen species and play a central role in the pathophysiology of myocardial ischemia/reperfusion. This study sought to determine effects of mitochondria-targeted cytoprotective peptide SBT-20 on myocardial infarct size in two different models of ischemia/reperfusion. Methods For in vivo studies, anesthetized Sprague Dawley rats were subjected to 30 min of coronary artery occlusion followed by 3 h of reperfusion. Rats received saline (control), low dose SBT-20 (0.3 mg/kg/h) or high dose SBT-20 (3 mg/kg/h) treatment ( n = 15 rats in each group). Saline or SBT-20 were delivered into the jugular vein starting 5 min after coronary artery occlusion and were continued for one hour post coronary artery reperfusion. Body temperature, heart rate and blood pressure were monitored during the procedure. At the end of 3 h reperfusion, the ischemic risk area, no-reflow area, and infarct size were measured. In separate in vitro studies, isolated rat hearts were exposed to 20 min global ischemia, followed by SBT-20 administration (1 μM) or no SBT-20 (control) throughout the 2 h reperfusion. In vitro studies were conducted in cells and heart mitochondria to ascertain the mitochondrial effects of SBT-20 on mitochondrial respiration and reactive oxygen species production. Results In the in vivo study, the ischemic risk areas (as a percentage of the left ventricle) were similar among the saline (49.5 ± 2.3 %), low dose SBT-20 (48.6 ± 2.1 %), and high dose SBT-20 groups (48.7 ± 3.0 %). Treatment with SBT-20 significantly reduced infarct size ( as a percentage of risk area) in low dose (62.1 ± 4.4 %) and high dose (64.0 ± 4.9 %) compared with saline treatment (77.6 ± 2.6 %, p = 0.001 for both doses). There was no difference in infarct size between low and high dose SBT-20 treatment. The no-reflow areas (as a percentage of the risk area) were comparable among the saline (23.9 ± 1.7 %), low dose SBT-20 (23.7 ± 2.8 %), and high dose groups (25.0 ± 2.1 %). Body temperature, heart rate and blood pressure were comparable among the 3 groups at baseline, during ischemia, and at the end of 3 h of reperfusion. In the in vitro study, infarct size was reduced from 43.3 ± 2.6 % in control group ( n = 11) to 17.2 ± 2.8 % in the SBT-20 treatment group ( n = 5, p