Adenoviral βaRKct Cardiac Gene Transfer Ameliorates Postresuscitation Myocardial Injury in a Porcine Model of Cardiac Arrest

摘要

Objective:The aim of the study was to determine whether the inhibition of the G-protein-coupled receptor kinase 2 by adenoviral 睞RKct cardiac gene transfer can ameliorate postresuscitation myocardial injury in pigs with cardiac arrest (CA) and explore the mechanism of myocardial protection.Methods:Male landrace domestic pigs were randomized into the sham group (anesthetized and instrumented, but ventricular fibrillation was not induced) (n=4), control group (ventricular fibrillation 8min, n=8), and 睞RKct group (ventricular fibrillation 8min, n=8). Hemodynamic parameters were monitored continuously. Blood samples were collected at baseline, 30min, 2h, 4h, and 6h after the return of spontaneous circulation (ROSC). Left ventricular ejection fraction was assessed by echocardiography at baseline and 6h after ROSC. These animals were euthanized, and the cardiac tissue was removed for analysis at 6h after ROSC.Results:Compared with those in the sham group, left ventricular +dp/dtmax, -dp/dtmax, cardiac output (CO), and ejection fraction (EF) in the control group and the 睞RKct group were significantly decreased at 6h after the restoration of spontaneous circulation. However, the 睞RKct treatment produced better left ventricular +dp/dtmax, -dp/dtmax, CO, and EF after ROSC. The 睞RKct treatment also produced lower serum cardiac troponin I, CK-MB, and lactate after ROSC. Furthermore, the adenoviral 睞RKct gene transfer significantly increased ? adrenergic receptors, SERCA2a, RyR2 levels, and decreased GRK2 levels compared to control.Conclusions:The inhibition of GRK2 by adenoviral 睞RKct cardiac gene transfer can ameliorate postresuscitation myocardial injury through beneficial effects on restoring the sarcoplasmic reticulum Ca2+-handling proteins expression and upregulating the ?-adrenergic receptor level after cardiac arrest.