Pinacidil-induced opening, like glibenclamide-induced closure of cardiac K_ATP channels, protects cardiac function against ischemia in isolated, working, erythrocyte perfused rat hearts
Roger J. Legtenberg, Ralph J.F. Houston, Paul Smits, Berend Oeseburg

Glibenclamide-induced closure of ATP-dependent potassium (K_ATP) 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 K_ATP­ channels would reduce post-ischemic function in our isolated, erythrocyte perfused, working rat heart model. During treatment with 1 or 12 µmol.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 K_ATP 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.

Keywords: Coronary blood flow, diabetes mellitus, glibenclamide, isolated rat heart, K_ATP channels, pinacidil

Applied Cardiopulmonary Pathophysiology 9: 354-358, 2000

Roger J. Legtenberg, M.D.
Department of Physiology 237
Faculty of Medical Sciences
University of Nijmegen
Post Box 9101
NL-6500 HB Nijmegen
The Netherlands
E-mail: r.legtenberg@fysio.kun.nl