M Jasova

Mitochondria as a target of cardioprotection in models of preconditioning

Over the recent years the view on mitochondria in the heart as a cellular powerhouse providing ATP supply needed to sustain contractile function, basal metabolic processes, and ionic homeostasis has changed radically. At present it is known that dysfunctions of these organelles are essential in the development of a large number of diseases, including cardiovascular diseases. Moreover, mitochondria are considered to be a very promising target of endogenous strategies that are essential in the protection of the myocardium from acute ischemia/reperfusion injury. These strategies including ischemic preconditioning, remote ischemic preconditioning as well as the acute phase of streptozotocin-induced diabetes mellitus, provide a similar effect of protection. Alterations observed in the functional and structural properties of heart mitochondria caused by short-term pathological impulses are associated with endogenous cardioprotective processes. It seems that the extent of mitochondrial membrane fluidization could be an active response mechanism to injury with a subtle effect on membrane-associated processes which further affect the environment of the whole organelle, thus inducing metabolic changes in the heart. In this review article, we provide an overview of endogenous protective mechanisms induced by hypoxic, pseudohypoxic and ischemic conditions with special consideration of the role of heart mitochondria in these processes.

Changes in mitochondrial properties may contribute to enhanced resistance to ischemia–reperfusion injury in the diabetic rat heart1

Diabetes mellitus, besides having deleterious effects, induces cardiac adaptation that may reduce the hearts susceptibility to ischemia-reperfusion (IR) injury. This study aimed to investigate whether changes in mitochondrial properties are involved in the mechanisms of increased resistance of the diabetic heart to IR. Adult male Wistar rats were made diabetic by a single dose of streptozotocin (65 mg·kg-1, i.p.), and on the day 8, Langendorff-perfused hearts were subjected to 30 min global ischemia and 40 min reperfusion. Baseline preischemic parameters in the diabetic hearts did not differ markedly from those in the nondiabetic controls, except for lower left ventricular developed pressure, higher mitochondrial membrane fluidity, and protein levels of manganese superoxide dismutase. On the other hand, diabetic hearts showed significantly better post-IR functional restoration and reduced arrhythmogenesis associated with lower reactive oxygen species production as compared with healthy controls. IR decreased membrane fluidity in both experimental groups; however, it led to a complete recovery of mitochondrial Mg2+-ATPase activity in diabetics in contrast to its reduction in nondiabetics. These findings indicate that the heart may become adapted to diabetes-induced alterations that might increase its tolerance to an ischemic insult. Preserved mitochondrial function might play a role in the mechanisms of the hearts resistance to IR injury in diabetics.