Abstract
Glibenclamide-induced closure of ATP-dependent potassium (KATP) channels decreases coronary blood flow during normoxic and post-ischemic conditions. We have found that post-ischemic cardiac function is improved after glibenclamide treatment. Our theory was that this is a result of higher intracellular calcium concentrations due to reduction in ischemia-mediated hyperpolarization of the myocardial cell membrane. We hypothesized therefore that opening KATP channels would reduce post-ischemic function in our isolated, erythrocyte perfused, working rat heart model. During treatment with 1 or 12 mumol.L-1 pinacidil (protein unbound concentration) both before and after 12 minutes global ischemia coronary blood flow increased 2-3 fold compared with vehicle, while cardiac functional recovery post-ischemically was improved with both concentrations. Because closing and opening cardiac KATP channels both improve post-ischemic function, our calcium theory above can be discounted. The protective effect of glibenclamide may possibly be ascribed to metabolic effects such as preservation of ATP levels during ischemia.
