BackgroundCardiovascular diseases are the leading cause of mortality and morbidity worldwide and coronary heart diseases, particularly myocardial infarction (MI) is the most common heart disease. Cardiac mitochondria play a major role in cell functioning, intracellular Ca2+ regulation, ATP production, and cell death. During MI, the reduction or loss of blood flow induces mitochondrial dysfunction and initiates cell death. Particularly, mitochondria‐mediated cell death during MI is mediated by opening of the mitochondrial permeability transition pores (PTP) in the inner mitochondrial membrane. mPTP opening accompanied by matrix swelling causes ROS production, loss of the membrane potential and ATP depletion leading to cardiac dysfunction. Therefore, PTP inhibition is broadly accepted as a promising therapeutic target for MI. Here we assess the effect of mPTP inhibitor, sanglifehrin A (SfA) on mitochondrial function of the heart during MI with no reperfusion or with subsequent reperfusion.MethodsMI was induced in female rats (BW=200–250g) by coronary artery ligation (CAL) for 30 min without (permanent ligation) or with subsequent reperfusion for 2 and 28 days. Experiments were conducted in the following 6 groups: i) Sham (S, no MI, n=6 and n=11 for 2 and 28 days, respectively); ii) SS (Sham+SfA, n=5 and n=11 for 2 and 28 days, respectively); iii) MI (no reperfusion, n=4 and n=5 for 2 and 28 days, respectively); iv) MI+SfA (n=4 and n=6 for 2 and 28 days, respectively); v) MI+R (MI+reperfusion, n=4 and n=5 for 2 and 28 days, respectively); and vi) MI+RS (MI+reperfusion+SfA, n=6 and n=7 for 2 and 28 days, respectively). SfA (5mg/kg, IV, Novartis) was administered at 25 min after a start of sham surgery or MI. At the end of each experimental protocol, cardiac mitochondria were isolated from left and right ventricles and oxygen consumption was measured using a Clark oxygen electrode. Results were calculated as nmol O2/min per citrate synthase activity.ResultsMitochondria in MI and MI+R groups demonstrated reduced state 3 (49±4 and 56±6, respectively, P<0.01 vs. S) compared to the S group (101±7) at 28 days post‐surgery. Indeed, reperfusion had no additional detrimental effect on mitochondrial dysfunction induced by MI (MI and MI+R). SfA had no effect on respiratory function of mitochondria in MI (MI: 49±4 vs MI+S: 51±5) and MI+R (MI+R: 56±6 vs MI+RS: 51±4) groups. Reperfusion for short (2 days) and long (28 days) affected differently the mitochondrial function in right and left ventricles.ConclusionMI produce considerable damage to mitochondrial function having no difference between reperfused and non‐reperfused hearts.Support or Funding InformationNHLBI NIH (SC1HL118669)