Tetsuji Miura and Takayuki Miki Pages 251 - 258 ( 8 )
Different types of ATP-sensitive K+ (KATP) channels have been identified in cardiomyocytes, vascular smooth muscle cells, pancreatic β-cells, neurons and mitochondria. Years before the discovery of the KATP channel in cardiomyocytes, pharmacological openers of this channel had been developed for the treatment of angina pectoris and hypertension. The KATP channel plays an important role not only in coronary blood flow regulation but also in protection of cardiovascular cells from ischemia / reperfusion injury. In animal models of myocardial ischemia / reperfusion, activation of the mitochondrial KATP channels by their pharmacological openers has been shown to attenuate endothelial dysfunction and to reduce myocardial necrosis. Conversely, blockade of the KATP channel aggravates microvascular necrosis and the no-reflow phenomenon after ischemia / reperfusion, resulting in augmentation of post-infarct ventricular dysfunction. Recent clinical studies have shown that a combination of coronary reperfusion therapy and infusion of nicorandil, a hybrid of KATP channel opener and nitrate, improved left ventricular function in patients with acute myocardial infarction. Furthermore, chronic treatment with nicorandil has been shown to significantly improve prognosis of patients with highrisk stable angina pectoris. Both of these clinical benefits cannot be attributed to the nitrate property of nicorandil. However, a recent basic investigation has suggested that the protective function of KATP channel openers is compromised by concurrent hypercholesterolemia and administration of sulfonylureas for diabetes mellitus. These interferences in the beneficial action of KATP channel openers by concurrent illness and pharmacological agents need to be further investigated to allow a more effective use of KATP channel openers in patients with coronary artery diseases.
atp-sensitive, no-reflow phenomenon, coronary blood flow, autoregulation, ischemia, mitochondria, ischemic heart disease
Second Department of Internal Medicine, Sapporo Medical University, School of Medicine, South-1 West-16, Chuo-ku, Sapporo, 060-8543, Japan.