| pubmed-article:11755163 | pubmed:abstractText | Previous research has shown that the sulfonylurea derivative glibenclamide may improve post-ischemic cardiac functional recovery. Although K(ATP) channel blockade is a possible explanation for this observation, alternative mechanisms exist. Therefore, we simultaneously recorded cardiac function and the intracellular concentration of ATP, phosphocreatine, Pi and pH before and after ischemia in the presence of glibenclamide or vehicle. (31)Phosphorus magnetic resonance (MS) spectroscopy on erythrocyte-perfused, isolated working rat hearts was performed. Glibenclamide 4 micromol l(-1) or vehicle alone was tested (both n=5). The following protocol was used: 8 min performance assessment, 10 min drug treatment, 12 min global ischemia, 20 min reperfusion with drug treatment and 8 min functional recovery assessment. Compared with vehicle, glibenclamide significantly decreased coronary blood flow (59.5+/-7.0% vs. 94.3+/-1.3%, P=0.008), ischemia-induced cardiac functional loss (7.4+/-1.3% vs. 18.8+/-3.3%; P=0.019) as well as the ischemia-induced intracellular acidosis (6.75+/-0.01 vs. 6.43+/-0.03 for vehicle, P=0.03). In conclusion, glibenclamide is able to reduce the myocardial functional loss after ischemia while preserving pH but not ATP levels during ischemia. This suggests that the beneficial response to glibenclamide is probably not the result of myocardial K(ATP) channel blockade, but may be explained by inhibition of glycolysis. | lld:pubmed |
