Adenoviral βARKct Cardiac Gene Transfer Ameliorates Post-resuscitation Myocardial Injury in a Porcine Model of Cardiac Arrest.

Objective: The aim of the study was to determine whether the inhibition of the G-protein-coupled receptor kinase 2 by adenoviral beta ARKct 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 8 min, n = 8), and beta ARKct group (ventricular fibrillation 8 min, n = 8). Hemodynamic parameters were monitored continuously. Blood samples were collected at baseline, 30 min, 2 h, 4 h, and 6 h after the return of spontaneous circulation (ROSC). Left ventricular ejection fraction was assessed by echocardiography at baseline and 6 h after ROSC. These animals were euthanized, and the cardiac tissue was removed for analysis at 6 h after ROSC. Results: Compared with those in the sham group, left ventricular +dp/dt(max), -dp/dt(max), cardiac output (CO), and ejection fraction (EF) in the control group and the beta ARKct group were significantly decreased at 6 h after the restoration of spontaneous circulation. However, the beta ARKct treatment produced better left ventricular +dp/dt(max), -dp/dt(max), CO, and EF after ROSC. The beta ARKct treatment also produced lower serum cardiac troponin I, CK-MB, and lactate after ROSC. Furthermore, the adenoviral bARKct gene transfer significantly increased beta 1 adrenergic receptors, SERCA2a, RyR2 levels, and decreased GRK2 levels compared to control. Conclusions: The inhibition of GRK2 by adenoviral beta ARKct cardiac gene transfer can ameliorate postresuscitation myocardial injury through beneficial effects on restoring the sarcoplasmic reticulum Ca2+-handling proteins expression and upregulating the beta 1-adrenergic receptor level after cardiac arrest.