Limiting sarcolemmal Na+ entry during resuscitation from ventricular fibrillation prevents excess mitochondrial Ca2+ accumulation and attenuates myocardial injury
Limiting sarcolemmal Na+ entry during resuscitation from ventricular fibrillation prevents excess mitochondrial Ca2+ accumulation and attenuates myocardial injury
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DOI：
10.1152/japplphysiol.01167.2006
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发表时间：
2007-07-01
影响因子：
3.3
通讯作者：
Gazmuri, Raul J.
中科院分区：
文献类型：
--
作者：
Wang, Sufen;Radhakrishnan, Jeejabai;Gazmuri, Raul J.
Background: intracellular Na+ accumulation during ischemia and reperfusion leads to cytosolic Ca2+ overload through reverse-mode operation of the sarcolemmal Na+: Ca2+ exchanger. Cytosolic Ca2+ accumulation promotes mitochondrial Ca2+ (Ca2+ overload. leading to mitochondrial injury. We investigated whether limiting sarcolemmal Na+ entry during resuscitation from ventricular fibrillation (VF) attenuates Ca-m(2+) overload and lessens myocardial dysfunction in a rat model of VF and closed-best resuscitation. Methods: hearts were harvested from 10 groups of 5 rats each representing baseline, 15 min of untreated VF, 15 min of VF with chest compression given for the last 5 min (VF/CC), and 60 min postresuscitation (PR). VF/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 Na+ channel blocker aidocaine (5.0 mg/kg), their combination, or vehicle control. The left ventricle was processed for intracellular Na+ and Ca2+, measurements. Results: limiting sarcolemmal Na+ entry attenuated cytosolic Na+ increase during VF/CC and the PR phase and prevented Ca-m(2+) overload yielding levels that corresponded to 77% and 71% of control hearts at VF/CC and PR, without differences among specific Na+-limiting interventions. Limiting sarcolemmal Na+ entry attenuated reductions in left ventricular compliance during VF and prompted higher mean aortic pressure (110 +/- 7 vs. 95 11 mmHg, P < 0.001) and higher cardiac work index (159 +/- 34 vs. 126 (-1) +/- 29 g center dot m center dot min(-1)center dot kg(-1), P < 0.05) with lesser increases in circulating,cardiac troponin I at 60 min PR. Conclusions: Na+-limiting interventions prevented excess Ca-m(2+) accumulation induced by ischemia and reperfusion and ameliorated myocardial injury and dysfunction.
