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.

Hyperbaric oxygen limits infarct size in ischemic rabbit myocardium in vivo.

BACKGROUND: We explored the ability of increased oxygen pressure to modify necrosis in an open-chest rabbit model of myocardial ischemia and reperfusion. METHODS AND RESULTS: A branch of the left coronary artery was occluded for 30 minutes followed by 3 hours of reperfusion. Infarction was measured by triphenyl tetrazolium staining and expressed as a percentage of the ischemic zone. Untreated rabbits were ventilated with 100% oxygen at 1 atm absolute. Treatment animals were exposed to hyperbaric oxygen at 2.5 atm absolute. The 1.0-atm control hearts developed 41.5 +/- 4.6% infarction of the ischemic zone. Animals exposed to hyperbaric oxygen during ischemia only, reperfusion only, or ischemia and reperfusion had significantly smaller infarcts with respect to control animals (16.2 +/- 2.9%, 14.5 +/- 3.7%, and 9.8 +/- 2.7%, respectively; P < or = .01), indicating that they had been protected by the procedure. When hyperbaric oxygen was begun 30 minutes after the onset of reperfusion, no protection was seen (35.8 +/- 3.8%). CONCLUSIONS: We conclude that hyperbaric oxygen limits infarct size in the reperfused rabbit heart and that the effect can be achieved when hyperbaric oxygen is begun at reperfusion.