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Publisher Summary This chapter focuses on the pharmacological effects of the adenosine triphosphate (ATP)-sensitive class of potassium channel blockers and openers on the function of the ischemic-reperfused myocardium. The importance of ATP-sensitive potassium channel (K+ATP) blockers and openers is recognized in the regulation of stress-induced, functional changes in the myocardium (example, by ischemia, reperfusion, and preconditioning) and this recognition is having a major impact on the regulation of cardiac function in ischemic-reperfused hearts. The use of (K+ATP) blockers or openers is not always beneficial and may have some detrimental effects, especially in the ischemic-reperfused myocardium. The chapter also discusses (K+ATP) channel openers. The properties of KATPchannels vary according to the type of tissue, and at least three major classes are currently recognized: (1) the type I channels, blocked by micromolar concentrations of intracellular ATP, are present in cardiac, skeletal, smooth muscle, and pancreatic β cells. The pancreatic β cell is the more sensitive to ATP, and these cells are sensitive to voltage and calcium ions. (2) The type II channel, originally described in neurons is inhibited by millimolar concentrations of ATP. (3) The type III channel, found in tracheal smooth muscle and some epithelial cells, is similar to the type II in its sensitivity to ATP, but differs in being activated by micromolar concentrations of calcium.

The effect of adrenalectomy has been investigated in a model of global cerebral ischemia. After bilateral carotid ligation the mortality rate was increased in adrenalectomized rats, and this effect was prevented by glucocorticoid pre-treatment. Adrenalectomy accelerated the appearance of the symptoms of cerebral ischemia, resulting in a moderate aggravation of brain edema and in a significant decrease in the concentration of high-energy phosphate esters. Our findings support the view that endogenous glucocorticoids may play a role in the amelioration of ischemic brain injuries in rats.

Our previous experiments have showed that dexamethasone exerts a beneficial effect on myocardial and cerebral ischaemia induced by ligation of the main coronary artery, and of both common carotid arteries in awake rats. The protective effect was abolished by actinomycin D, indicating that the steroid action is generated at the level of genetic expression. The effect of lipocortin, a phospholipase A2 /PLA2/ inhibitory polypeptide, considered as a second messenger of glucocorticoid action, on the ischaemic disorders in the heart and brain was studied. The 15k fraction obtained by molecular sieving from the supernatant of rat peritoneal leukocytes incubated in the presence of dexamethasone, inhibited PLA2 in vitro, and, when it was given intravenously or intracisternally, a marked protection against fatal postocclusion arrhythmias or stroke was detected. Lipocortin injected subcutaneously into carotid artery ligated rats exerted no cerebroprotective effect, showing that it does not pass the blood brain barrier. These results suggest that the cardioprotective and cerebroprotective effect of glucocorticoids may be mediated via the formation and release of lipocortin-like substances.