PREVENTION OF ISCHEMIA-INDUCED CORONARY VASCULAR DYSFUNCTION

Myocardial ischaemia and reperfusion cause dysfunction of the coronary vasculature leading to a sustained reduction in coronary blood flow a nd an impairment of responses to both endothelium-dependent and endoth elium-independent vasodilators. In contrast, when previously ischaemic arteries are removed from the myocardium and vascular function is exa mined in vitro, it is evident that while endothelial function is impai red, smooth muscle reactivity remains intact. Therefore, other changes must be responsible for the general reduction in vasodilator reserve. Examination of the vasculature in the ischaemic myocardium by electro n microscopy reveals adhesion of leukocytes and plugging of capillarie s. There also is evidence that polymorphonuclear leukocytes (PMNs) rel ease a factor that constricts coronary arterioles, and that release of this factor is increased by atherosclerosis. The identity of this fac tor remains uncertain, but the calcium antagonist amlodipine prevents the coronary vasoconstriction. Amlodipine is also able to prevent the impaired perfusion and the reduction in vasodilator reserve that occur s after myocardial ischaemia and reperfusion in the dog. In addition, amlodipine prevents the endothelial dysfunction observed in isolated a rteries after ischaemia and reperfusion. The interaction between the e ndothelium and activated PMNs may be a suitable target for pharmacolog ical intervention to improve postischaemic vascular function. (C) 1997 Elsevier Science Ireland Ltd.