Objective
This aim of this study was to determine the impact of diabetes on oxidant balance and mitochondrial metabolism of carbohydrate- and lipid-based substrates in myocardium of type 2 diabetic patients.
Background
Heart failure represents a major cause of death among diabetics, and it has been proposed that derangements in cardiac metabolism and oxidative stress may underlie the progression of this co-morbidity, but scarce evidence exists in support of this mechanism in humans.
Methods
Mitochondrial O2 consumption and H2O2 emission were measured in permeabilized myofibers prepared from samples of right atrial appendage obtained from non-diabetic (n=13) and diabetic (n=11) patients undergoing non-emergent coronary artery bypass graft surgery.
Results
Mitochondria in atrial tissue of type 2 diabetic individuals display a sharply decreased capacity for glutamate and fatty acid-supported respiration, in addition to an increased content of myocardial triglycerides, as compared to non-diabetics. Furthermore, diabetics display an increased mitochondrial H2O2 emission during oxidation of carbohydrate- and lipid-based substrates, depleted glutathione, and evidence of persistent oxidative stress in their atrial tissue.
Conclusions
These findings are the first to directly investigate the effects of type 2 diabetes on a panoply of mitochondrial functions in the human myocardium using cellular and molecular approaches, and they demonstrate that mitochondria in diabetic human heart have specific impairments in maximal capacity to oxidize fatty acids and glutamate, yet increased mitochondrial H2O2 emission, providing insight into the role of mitochondrial dysfunction and oxidative stress in the pathogenesis of heart failure in diabetic patients.
TCEP was safe, captured embolic debris in 99% of patients, and did not change neurocognitive function. Reduction in new lesion volume on magnetic resonance scans was not statistically significant. (Cerebral Protection in Transcatheter Aortic Valve Replacement [SENTINEL]; NCT02214277).
INTUITY RDAVR performed effectively in this North American trial. It may lead to a relative reduction in aortic crossclamp time and cardiopulmonary bypass time and has excellent hemodynamic performance. Pacemaker implantation rate observed was somewhat greater than European trials and requires further investigation.
Anderson EJ, Rodriguez E, Anderson CA, Thayne K, Chitwood WR, Kypson AP. Increased propensity for cell death in diabetic human heart is mediated by mitochondrial-dependent pathways.
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