Shen-fu injection reduces postresuscitation myocardial dysfunction in a porcine model of cardiac arrest by modulating apoptosis

Abstract

Shen-Fu injection (SFI) following cardiac arrest exhibits cardioprotective effects, but its effect on myocardial dysfunction, a critical issue following resuscitation, is unclear. This study sought to examine whether SFI reduces postresuscitation myocardial dysfunction in a porcine model of cardiac arrest by modulating apoptosis. After 8 min of untreated ventricular fibrillation and 2 min of basic life support, 24 pigs were randomized divided into three groups, which received central venous injection of either Shen-Fu (SFI group; 1.0 mL/kg), epinephrine (EP group; 0.02 mg/kg), or saline (SA group). After successful return of spontaneous circulation (ROSC), hemodynamic status and blood samples were obtained at 0, 30, 120, and 360 min after ROSC. Surviving pigs were killed at 24 h after ROSC, and the hearts were removed for analysis by electron microscopy, Western blotting, quantitative real-time polymerase chain reaction, and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay. Compared with the EP and SA groups, animals treated with SFI had improved left ventricular function (P < 0.05), lower troponin T levels (P < 0.01), and increased tissue perfusion and oxygen metabolism (P < 0.05). Shen-Fu injection was associated with a reduction in (i) Bcl-2, Bax, and caspase 3 protein expression (P < 0.05); (ii) caspase 3 mRNA upregulation; and (iii) apoptosis, compared with the EP and SA groups. Caspase 3-mediated apoptosis occurs following myocardial injury after cardiopulmonary resuscitation in pigs. Shen-Fu injection decreased myocardial injury; improved myocardial ultrastructure; inhibited Bcl-2, Bax, and caspase 3 expression; and reduced myocardial apoptosis. Therefore, SFI could significantly attenuate postresuscitation myocardial dysfunction by modulating apoptosis.