Paul S Pagel1, John G Krolikowski. 1. Department of Anesthesiology, The Medical Collegeof Wisconsin, Milwaukee, Wisconsin, USA. pspagel@mcw.edu
Abstract
BACKGROUND: Intracellular acidosis during early reperfusion after coronary artery occlusion was recently linked to cardioprotection resulting from myocardial ischemic postconditioning. We tested the hypotheses that transient alkalosis during early reperfusion abolishes helium preconditioning and that the mitochondrial permeability transition pore inhibitor cyclosporin A (CsA) restores the cardioprotective effects of helium during alkalosis in vivo. METHODS: Rabbits (n = 36) instrumented for hemodynamics measurement were subjected to a 30-min left anterior descending coronary artery occlusion and 3-h reperfusion. The rabbits received 0.9% saline (control) or three cycles of 70% helium-30% oxygen administered for 5 min interspersed with 5 min of an air-oxygen mixture before left anterior descending coronary artery occlusion in the absence or presence of transient alkalosis (pH = 7.5) produced by administration of IV sodium bicarbonate (10 mEq) 2 min before reperfusion. Other rabbits preconditioned with helium received CsA (5 mg/kg) in the presence of alkalosis or CsA alone. RESULTS: Helium reduced myocardial infarct size (25% +/- 4% of left ventricular area at risk; P < 0.05) compared with control (44% +/- 6%). Alkalosis during early reperfusion did not alter infarct size alone (46% +/- 2%), but this intervention abolished helium-induced cardioprotection (45% +/- 3%). CsA restored reductions in infarct size produced by helium preconditioning in the presence of alkalosis (28% +/- 6%; P < 0.05 versus control) but did not affect myocardial necrosis alone (43% +/- 6%). CONCLUSIONS: The results demonstrate that transient alkalosis during early reperfusion abolishes helium preconditioning in rabbits. CsA restored helium-induced cardioprotection during alkalosis, suggesting that helium preconditioning inhibits mitochondrial permeability transition pore formation by maintaining intracellular acidosis during early reperfusion.
BACKGROUND: Intracellular acidosis during early reperfusion after coronary artery occlusion was recently linked to cardioprotection resulting from myocardial ischemic postconditioning. We tested the hypotheses that transient alkalosis during early reperfusion abolishes helium preconditioning and that the mitochondrial permeability transition pore inhibitor cyclosporin A (CsA) restores the cardioprotective effects of helium during alkalosis in vivo. METHODS:Rabbits (n = 36) instrumented for hemodynamics measurement were subjected to a 30-min left anterior descending coronary artery occlusion and 3-h reperfusion. The rabbits received 0.9% saline (control) or three cycles of 70% helium-30% oxygen administered for 5 min interspersed with 5 min of an air-oxygen mixture before left anterior descending coronary artery occlusion in the absence or presence of transient alkalosis (pH = 7.5) produced by administration of IV sodium bicarbonate (10 mEq) 2 min before reperfusion. Other rabbits preconditioned with helium received CsA (5 mg/kg) in the presence of alkalosis or CsA alone. RESULTS:Helium reduced myocardial infarct size (25% +/- 4% of left ventricular area at risk; P < 0.05) compared with control (44% +/- 6%). Alkalosis during early reperfusion did not alter infarct size alone (46% +/- 2%), but this intervention abolished helium-induced cardioprotection (45% +/- 3%). CsA restored reductions in infarct size produced by helium preconditioning in the presence of alkalosis (28% +/- 6%; P < 0.05 versus control) but did not affect myocardial necrosis alone (43% +/- 6%). CONCLUSIONS: The results demonstrate that transient alkalosis during early reperfusion abolishes helium preconditioning in rabbits. CsA restored helium-induced cardioprotection during alkalosis, suggesting that helium preconditioning inhibits mitochondrial permeability transition pore formation by maintaining intracellular acidosis during early reperfusion.
Authors: Paul S Pagel; John G Krolikowski; Julien Amour; David C Warltier; Dorothee Weihrauch Journal: J Cardiothorac Vasc Anesth Date: 2009-02-23 Impact factor: 2.628
Authors: Gezina T M L Oei; Michal Heger; Rowan F van Golen; Lindy K Alles; Moritz Flick; Allard C van der Wal; Thomas M van Gulik; Markus W Hollmann; Benedikt Preckel; Nina C Weber Journal: Mol Med Date: 2015-01-20 Impact factor: 6.354