Delayed Protection of the Myocardium: A Novel Therapeutic Window for Cardiac Drug Development

It is known that the administration of drugs can relieve or prevent many of the consequences of myocardial ischemia; this is the basis for the current therapy of angina of effort by, for example, organic nitrites and nitrates and β adrenoceptor-blocking drugs. These are effective in the short term; protection is lost soon after the cessation of the treatment. More recently the emphasis, in experimental situations, of alleviating the consequences of ischaemia in a variety of organs has shifted to the prolonged and delayed protection by adaptation induced by a variety of stimuli, many of which involve some form of cellular stress. It is well known that adaptation to changing conditions is a basic function of living organisms that enables the individual and the species to survive. This phenomenon is effective in different organs and organ systems, and a variety of mechanisms are able to induce it. Delayed cardioprotection induced by adaptation appears to be a universal response. Although some metabolic changes underlie all types of adaptive mechanisms, the metabolic adaptation of an organ to stressful situations is characterized by the predominance of metabolic changes even in the absence of other adaptive alterations.