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Objectives: Type 2 diabetes causes mitochondrial dysfunction, which increases myocardial susceptibility to ischaemia-reperfusion injury. We investigated the efficacy of transplantation of mitochondria isolated from diabetic or non-diabetic donors in providing cardioprotection from warm global ischaemia and reperfusion in the diabetic rat heart., Methods: Ex vivo perfused hearts from Zucker diabetic fatty (ZDF fa/fa) rats (n = 6 per group) were subjected to 30 min of warm global ischaemia and 120 min reperfusion. Immediately prior to reperfusion, vehicle alone (VEH) or vehicle containing mitochondria isolated from either ZDF (MTZDF) or non-diabetic Zucker lean (ZL +/?) (MTZL) skeletal muscle were delivered to the coronary arteries via the aortic cannula., Results: Following 30-min global ischaemia and 120-min reperfusion, left ventricular developed pressure was significantly increased in MTZDF and MTZL groups compared to VEH group (MTZDF: 92.8 ± 5.2 mmHg vs MTZL: 110.7 ± 2.4 mmHg vs VEH: 44.3 ± 5.9 mmHg; P < 0.01 each); and left ventricular end-diastolic pressure was significantly decreased (MTZDF 12.1 ± 1.3 mmHg vs MTZL 8.6 ± 0.8 mmHg vs VEH: 18.6 ± 1.5 mmHg; P = 0.016 for MTZDF vs VEH and P < 0.01 for MTZL vs VEH). Total tissue ATP content was significantly increased in both MT groups compared to VEH group (MTZDF: 18.9 ± 1.5 mmol/mg protein/mg tissue vs MTZL: 28.1 ± 2.3 mmol/mg protein/mg tissue vs VEH: 13.1 ± 0.5 mmol/mg protein/mg tissue; P = 0.018 for MTZDF vs VEH and P < 0.01 for MTZL vs VEH). Infarct size was significantly decreased in the MT groups (MTZDF: 11.8 ± 0.7% vs MTZL: 9.9 ± 0.5% vs VEH: 52.0 ± 1.4%; P < 0.01 each)., Conclusions: Mitochondrial transplantation significantly enhances post-ischaemic myocardial functional recovery and significantly decreases myocellular injury in the diabetic heart., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: Mitochondrial DNA (mitoDNA) deletions have been shown to increase with aging and ischemia and have been suggested to contribute to myocardial dysfunction. The purpose of this study was to determine the prevalence and specificity of mitoDNA deletions in coronary artery bypass patients., Methods: Right atrial appendix tissue from 51 cardiac surgical patients (30-93 years; mean 64+/-14 years) was obtained during cardiopulmonary bypass cannulation (Control), just prior to the removal of the venous cannula (Ischemia, 169+/-38 min) and following removal of the cannula (Reperfusion) and used for polymerase chain reaction (PCR) and sequence analysis., Results: A novel mitoDNA deletion (approximately 7.3 kb, mitoDNA(7.3)) was found in three unrelated, male patients (53, 67, 75 years old). All mitoDNA(7.3) deletion breakpoints were found downstream of the ATP synthase 8 genes and at the 3' end of the cytochrome b genes. The prevalence of the mitoDNA(7.3) deletion was significantly increased (P<0.05) following ischemia and reperfusion. Clinical data indicated that postoperative left ventricular ejection fraction was lower (38.3 vs. 46.4%), and the incidence of previous myocardial infarction higher (1.7 vs. 0.6) in patients exhibiting mitoDNA deletions., Conclusion: Our results reveal a novel mitochondrial DNA deletion occurring within the genome region coding for the mitochondrial genes of oxidative phosphorylation that is significantly increased during ischemia and reperfusion. The incidence and prevalence of mitoDNA(7.3) deletions in patients with clinical indications of poor recovery suggests that mitoDNA(7.3) deletions may provide an important indicator to surgical outcome in the cardiac surgical patient.

Objective: Mitochondrial ATP-sensitive potassium channels have been proposed to be myoprotective. The relevance and specificity of this mechanism in cardiac surgery was unknown. The purpose of this study was to examine the effects of the mitochondrial potassium ATP-sensitive channel opener diazoxide on regional and global myocardial protection using a model of acute myocardial infarction., Methods: Pigs (n=19) were placed on total cardiopulmonary bypass and then subjected to 30 min normothermic regional ischemia by snaring the left anterior descending coronary artery (LAD). The aorta was then crossclamped and cold blood Deaconess Surgical Associates cardioplegia (DSA; n=6) or DSA containing 50 microM diazoxide (DZX; n=6) was delivered via the aortic root and the hearts subjected to 30 min hypothermic global ischemia. The crossclamp and snare were removed and the hearts reperfused for 120 min., Results: No significant differences in preload recruitable stroke work relationship, Tau, proximal, distal or proximal/distal coronary flow, regional or global segmental shortening, systolic bulging or post-systolic shortening were observed within or between DSA and DZX hearts during reperfusion. Infarct was present only in the region of LAD occlusion in both DSA and DZX hearts. Infarct size (% of area at risk) was 33.6+/-2.9% in DSA and was 16.8+/-2.4% in DZX hearts (P<0.01 versus DSA). Apoptosis as estimated by TUNEL positive nuclei was 120.3+/-48.8 in DSA and was significantly decreased to 21.4+/-5.3 in DZX hearts. Myocardial infarct was located centrally within the area at risk in both DSA and DZX hearts but was significantly increased at borderline zones within the area at risk in DSA hearts., Conclusions: The addition of diazoxide to cardioplegia significantly decreases regional myocardial cell necrosis and apoptosis in a model of acute myocardial infarction and represents an additional modality for achieving myocardial protection.