Blockade of ATP-sensitive potassium channels increases infarct size but does not prevent preconditioning in rabbit hearts.
Ischemic preconditioning renders the heart resistant to infarction by an unknown mechanism. This study tests whether preconditioning may be working through activation of ATP-sensitive potassium channels. If that were the case, then blockade of the channels should eliminate preconditioning's protection, and activation of these channels should mimic it. Thirty minutes of regional coronary ischemia followed by 3 hours of reperfusion caused 38.0 +/- 3.7% of the risk zone to become infarcted in control rabbits. Preconditioning with 5-minute ischemia followed by a 10-minute reperfusion before the 30-minute insult caused only 8.8 +/- 2.1% infarction, which was a reduction of 29.2% in infarct size by preconditioning (p < 0.01 versus control value). Pretreatment with the potassium channel blocker glibenclamide at three different concentrations significantly elevated infarct size in the nonpreconditioned hearts at all doses. Preconditioning, however, continued to limit infarct size by an amount not different from that seen in the control group at all doses of glibenclamide. Pinacidil, a potassium channel agonist, given before a 30-minute ischemic insult resulted in infarct sizes no different from that seen in nonpreconditioned control rabbits. We conclude that ATP-sensitive potassium channels are not involved in preconditioning in the rabbit heart; however, blocking those channels does exacerbate ischemia.
Thornton
J D
JD
Department of Physiology, University of South Alabama, Mobile.
Thornton
C S
CS
Sterling
D L
DL
Downey
J M
JM
D000818:Animals; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology*; D017202:Myocardial Ischemia / Q000503:physiopathology; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D054328:Proton Pump Inhibitors; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D006146:Guanidines; D015221:Potassium Channels; D054328:Proton Pump Inhibitors; D020110:Pinacidil; D000254:Sodium-Potassium-Exchanging ATPase; D005905:Glyburide