Shen-Fu injection reduces impaired myocardial β-adrenergic receptor signaling after cardiopulmonary resuscitation

Background Post-resuscitation myocardial dysfunction has been implicated as a major cause of fatal outcome in patients who survive initially successful cardiopulmonary resuscitation （CPR）. In our previous study, we found that impaired myocardial β-adrenergic receptor （AR） signaling is a key mechanism in post-resuscitation myocardial dysfunction and Shen-Fu injection （SFI） can attenuate post-resuscitation myocardial dysfunction. However, whether SFI can prevent impaired post-resuscitation myocardial β-AR signaling is not yet known. In this study, we investigated the effect of SFI on impaired myocardial β-AR signaling occurring post-resuscitation in a porcine model of cardiac arrest. Methods Ventricular fibrillation was induced electrically in anesthetized male landrace domestic pigs. After 4 minutes of untreated ventricular fibrillation, cardiopulmonary resuscitation was initiated. Sixteen successfully resuscitated pigs were randomized to receive a continuous infusion of either SFI （0.5 ml/min; n=8） or saline （placebo; n=8） for 6 hours, beginning 15 minutes after the return of spontaneous circulation （ROSC）. Hemodynamic and echocardiographic data were recorded. β-AR signaling was assessed at 6 hours after the intervention by measuring myocardial adenylate cyclase activity, β-AR density and β-AR kinase expression. Results Treatment with SFI produced better maximum rate of left ventricular pressure increase （dp/dtmax） and maximum rate of left ventricular pressure decline （-dp/dtmax）, cardiac output, and ejection fraction after ROSC. SFI treatment was also associated with lower myocardial β-adrenergic receptor kinase expression, whereas basal and isoproterenol- stimulated adenylate cyclase activity and the total β-AR density were significantly increased in the SFI group when compared with the placebo group. Conclusion SFI attenuated post-resuscitation myocardial dysfunction by preventing impaired myocardial β-AR signaling after CPR.