Myocardial protection during ventricular fibrillation by reduction of proton-driven sarcolemmal sodium influx
Myocardial protection during ventricular fibrillation by reduction of proton-driven sarcolemmal sodium influx
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DOI：
10.1067/mlc.2001.111693
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发表时间：
2001-01-01
期刊：
影响因子：
--
通讯作者：
Han, Y
中科院分区：
文献类型：
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作者：
Gazmuri, RJ;Hoffner, E;Han, Y
尽管抑制质子驱动的肌膜钠内流可改善静息心肌的缺血性损伤，但当存在室颤时，其影响尚不清楚。我们使用一个分离的大鼠心脏模型来研究在缺血和心室颤动时抑制钠-氢交换异构体-L(与苯甲酰胍的衍生物HOE-694和cariporide)，是否伴随或不伴随着抑制碳酸氢钠共转运体(用N-2-羟乙基哌嗪-N-2-乙烷磺酸(HEPES)的灌流液)可以改善被认为限制心脏复苏力的功能性心肌异常，通常发生在室颤期间的缺血性收缩。使用HEPES缓冲液(14+/-5 mm Hgvs 10+/-3 mm Hgvs10+/-3 mm Hg，P<；0.04)时，改善最大(25+/-14 mm Hgvs 11+/-3 mm Hgvs11+/-3 mm Hg，P<；0.01)，同时伴有除颤后舒张末压力-容量曲线的较小左移，限制钠内流干预可使缺血和室颤时心肌内钠升高76%(P<；0.05)。因此，在缺血和室颤期间限制肌膜钠内流的干预措施可能有助于从室颤中成功复苏。
Although the inhibition of proton-driven sarcolemmal sodium influx ameliorates ischemic injury in the quiescent myocardium, the effects when ventricular fibrillation is present are largely unknown. We used an isolated rat heart model to investigate whether inhibition of the sodium-hydrogen exchanger isoform-l (with the benzoylguanidine derivatives HOE-694 and cariporide) with or without concomitant inhibition of the sodium-bicarbonate co-transporter (with perfusate buffered with N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid (HEPES)) during ischemia and ventricular fibrillation could ameliorate functional myocardial abnormalities presumed to limit cardiac resuscitability Ischemic contracture, which typically develops during ventricular fibrillation, was ameliorated by HOE-694 when either a bicarbonate-buffered (20 +/- 7 mm Hg vs 15 +/- 5 mm Hg, P < .05) or a HEPES-buffered (14 +/- 5 mm Hg vs 10 +/- 3 mm Hg, P < .04) perfusate was used, Maximal amelioration occurred when cariporide and HERES-buffered perfusate were used simultaneously (25 +/- 14 mm Hg vs 11 +/- 3 mm Hg, P < .01), and this was accompanied by lesser leftward shifts of the end-diastolic pressure-volume curves after defibrillation, Intramyocardial sodium increases of 76% during ischemia and ventricular fibrillation (P < .05) were ameliorated by the sodium-influx-limiting interventions. Thus interventions limiting sarcolemmal sodium influx during ischemia and ventricular fibrillation may facilitate successful resuscitation from ventricular fibrillation.