Oxidative stress and myocardial injury in the diabetic heart

Abstract

Reactive oxygen or nitrogen species play an integral role in both myocardial injury and repair. This dichotomy is differentiated at the level of species type, amount and duration of free radical generated. Homeostatic mechanisms designed to prevent free radical generation in the first instance, scavenge, or enzymatically convert them to less toxic forms and water, playing crucial roles in the maintenance of cellular structure and function. The outcome between functional recovery and dysfunction is dependent upon the inherent ability of these homeostatic antioxidant defences to withstand acute free radical generation, in the order of seconds to minutes. Alternatively, pre-existent antioxidant capacity (from intracellular and extracellular sources) may regulate the degree of free radical generation. This converts reactive oxygen and nitrogen species to the role of second messenger involved in cell signalling. The adaptive capacity of the cell is altered by the balance between death or survival signal converging at the level of the mitochondria, with distinct pathophysiological consequences that extends the period of injury from hours to days and weeks. Hyperglycaemia, hyperlipidaemia and insulin resistance enhance oxidative stress in the diabetic myocardium that cannot adapt to ischaemia-reperfusion. Altered glucose flux, mitochondrial derangements and nitric oxide synthase uncoupling in the presence of decreased antioxidant defence and impaired prosurvival cell signalling may render the diabetic myocardium more vulnerable to injury, remodelling and heart failure.

Effects of neonatal dexamethasone administration on cardiac recovery ability under ischemia-reperfusion in 24-wk-old rats

“…Metabolic defects such as hyperlipidemia and insulin resistance may impair cardiac functional recovery post-I/R by attenuating mitochondrial biogenesis (29), enhancing oxidative stress, (30) and causing intracellular Ca(2+)-overload (31). Mitochondria may also be affected by early-life factors (32).…”

“…Blood samples were taken from the tip of the tail before (0 min) and after (30,60, and 120 min) the insulin injection and used for blood glucose analyses, which were performed using the ACCU-CHEK Performa glucose meter.…”

Propofol cardioprotection for on-pump aortocoronary bypass surgery in patients with type 2 diabetes mellitus (PRO-TECT II): a phase 2 randomized-controlled trial

“…6). 12,13,21 During ischemia, the mitochondrial electron transport chain (ETC) is damaged. B-cell lymphoma 2, a mitochondrial protein, is depleted.…”

“…[5][6][7][8][9][10][11] As oxidative stress is a major factor in the pathophysiology of IRI, propofol, an anesthetic and phenolic antioxidant, could be a therapeutic alternative. 12,13 Nevertheless, metaanalyses of clinical trials show reduced indices of myocardial injury and dysfunction with inhalational agents compared with propofol anesthesia (2-4 lgÁmL…”

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