Limiting sarcolemmal Na+ entry during resuscitation from ventricular fibrillation prevents excess mitochondrial Ca^sup 2+^ accumulation and attenuates myocardial injury

• Published in: Journal of applied physiology (1985) Vol. 103; no. 1; p. 55
• Main Authors: Wang, Sufen, Radhakrishnan, Jeejabai, Ayoub, Iyad M, Kolarova, Julieta D
• Format: Journal Article
• Language: English
• Published: Bethesda American Physiological Society 01.07.2007
• Subjects: Calcium; Cardiac arrhythmia; Cardiopulmonary resuscitation; CPR; Heart; Sodium
• ISSN: 8750-7587; 1522-1601

Intracellular ... accumulation during ischemia and reperfusion leads to cytosolic ... overload through reverse-mode operation of the sarcolemmal ... exchanger. Cytosolic ... accumulation promotes mitochondrial ... overload, leading to mitochondrial injury. We investigated whether limiting sarcolemmal ... entry during resuscitation from ventricular fibrillation (VP) attenuates ... overload and lessens myocardial dysfunction in a rat model of VP and closed-chest resuscitation. Hearts were harvested from 10 groups of 6 rats each representing baseline, 15 min of untreated Vp, 15 min of VP with chest compression given for the last 5 min (VP/CC), and 60 min postresuscitation (PR). VP/CC and PR included four groups each randomized to receive before starting chest compression the new NHE-1 inhibitor AVE4454B (1.0 mg/kg), the ... channel blocker lidocaine (5.0 mg/kg), their combination, or vehicle control. The left ventricle was processed for intracellular ... and ... measurements. Limiting sarcolemmal ... entry attenuated cytosolic ... increase during VP/CC and the PR phase and prevented ... overload yielding levels that corresponded to 77% and 71% of control hearts at VP/CC and PR, without differences among specific ...-limiting interventions. Limiting sarcolemmal ... entry attenuated reductions in left ventricular compliance during VP and prompted higher mean aortic pressure (110 ± 7 vs. 95 ± 11 mmHg, P < 0.001) and higher cardiac work index (159 ± 34 vs. 126 ± 29 ..., P < 0.05) with lesser increases in circulating cardiac troponin I at 60 min PR. ...-limiting interventions prevented excess ... accumulation induced by ischemia and reperfusion and ameliorated myocardial injury and dysfunction. (ProQuest-CSA LLC: ... denotes formulae/symbols omitted.)