Sodium-hydrogen exchange inhibition during ventricular fibrillation - Beneficial effects on ischemic contracture, action potential duration, reperfusion arrhythmias, myocardial function, and resuscitability

Article

关键词: NA+-H+ EXCHANGE;    CARDIAC-ARREST;    CARDIOPULMONARY-RESUSCITATION;    CORONARY ISCHEMIA;    HEART;    CARIPORIDE;    DYSFUNCTION;    INJURY;    PIGS;   

DOI  :  10.1161/01.CIR.0000058704.45646.0D

来源: SCIE

【 摘 要 】

Background-Inhibition of the sarcolemmal sodium-hydrogen exchanger isoform-1 (NHE-1) is emerging as a promising novel strategy for ameliorating myocardial injury associated with ischemia and reperfusion. We investigated whether NHE-1 inhibition (with cariporide) could minimize mechanical and electrical myocardial abnormalities that develop during ventricular fibrillation (VF) and improve outcome using a porcine model of closed-chest resuscitation. Methods and Results-Two groups of 8 pigs each were subjected to 8 minutes of untreated VF and randomized to receive either a 3-mg/kg bolus of cariporide or 0.9% NaCl immediately before an 8-minute interval of conventional closed-chest resuscitation. Cariporide prevented progressive increases in left ventricular free-wall thickness (from 1.0+/-0.2 to 1.5+/-0.3 cm with NaCl, P<0.001 versus 0.9+/-0.1 to 1.1+/-0.3 cm with cariporide, P=NS), maintained the coronary perfusion pressure above resuscitability thresholds (10+/-8 versus 19+/-3 mm Hg before attempting defibrillation, P<0.05), and increased resuscitability (2 of 8 versus 8 of 8, P<0.005). In 2 additional groups of 4 pigs each subjected to a briefer interval of untreated VF, cariporide ameliorated postresuscitation shortening of the action potential duration (APD) at 30%, 60%, and 90% repolarization (ie, APD(60) at 2 minutes after resuscitation; 75+/-29 versus 226+/-16 ms, P<0.05), minimized postresuscitation ventricular ectopic activity preventing recurrent VF, and lessened postresuscitation myocardial dysfunction. Conclusions-NHE-1 inhibition may represent a highly potent novel strategy for resuscitation from VF that can ameliorate myocardial manifestations of ischemic injury and improve the effectiveness and outcome of closed-chest resuscitation.

【 授权许可】

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