Relationships between structure and effects of ACE inhibitors: comparative effects in myocardial ischaemic/reperfusion injury.
1. Coronary artery reperfusion has become the treatment of choice for evolving myocardial infarction. 2. While there is no question that timely restoration of coronary blood flow is essential for the salvage of ischaemic myocardium, coronary reperfusion has also been associated with potentially deleterious consequences. Specifically, the viable tissue salvaged by reperfusion remains 'stunned'--i.e., exhibits prolonged abnormalities in contractile function--for hours to days following reflow. Furthermore, it has been suggested that reperfusion per se may lethally injure some myocytes that were only reversibly injured prior to restoration of blood flow. 3. ACE inhibitors such as captopril and enalapril have been shown to reduce indices of myocardial injury (infarct size, creatine kinase release) and enhance contractile function of stunned myocardium in experimental models of coronary occlusion followed by reperfusion. These effects of ACE inhibitors have largely been attributed to the reduction in myocardial O2-demand and increase in myocardial blood flow associated with blunting of angiotensin II formation. 4. Recent studies suggest that the effects of some ACE inhibitors--particularly captopril--may not solely be explained on the basis of ACE inhibition. In fact, sulphydryl (-SH) containing ACE inhibitors such as captopril appear to act as scavengers of oxygen-derived free radical species thought to be important in the pathogenesis of both postischaemic contractile dysfunction and ischaemia/reperfusion induced myocyte necrosis. 5. Thus, -SH containing ACE inhibitors--which both inhibit ACE and scavenge cytotoxic free radicals--may offer a suitable form of treatment for myocardial ischaemia/reperfusion injury.
Przyklenk
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Heart Institute, Hospital of the Good Samaritan, Los Angeles, CA 90017.
Kloner
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RA
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy; D015427:Reperfusion Injury / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000806:Angiotensin-Converting Enzyme Inhibitors