Ventricular dysfunction after cardioplegic arrest is improved after myocardial gene transfer of a β-adrenergic receptor kinase inhibitor

48Citations
Citations of this article
14Readers
Mendeley users who have this article in their library.

Abstract

Background - Acute cardiac contractile dysfunction is common after cardiopulmonary bypass (CPB). A potential molecular mechanism is enhanced β-adrenergic receptor kinase (βARK1) activity, because β-adrenergic receptor (βAR) signaling is altered in cardiomyocytes after cardioplegia. Therefore, we examined whether adenovirus-mediated intracoronary delivery of a βARK1 inhibitor (Adv-βARKct) could prevent post-CPB dysfunction. Methods and Results - Rabbits were randomized to receive 5x1011 total viral particles of Adv-βARKct or PBS. After 5 days, hearts were arrested with University of Wisconsin solution, excised, and stored at 4°C for 15 minutes or 4 hours before reperfusion on a Langendorff apparatus. Left ventricular (LV) function measured by end-diastolic pressure response to preload augmentation, contractility (LV dP/dtmax), and relaxation (LV dP/dtmin) was assessed by use of increasing doses of isoproterenol and compared with a control group of nonarrested hearts acutely perfused on the Langendorff apparatus. In the PBS-treated hearts, LV function decreased in a temporal manner and was significantly impaired compared with control hearts after 4 hours of cardioplegic arrest. LV function in Adv-βARKct-treated hearts, however, was significantly enhanced compared with PBS treatment and was similar to control nonarrested hearts even after 4 hours of cardioplegia. Biochemically, several aspects of βAR signaling were dysfunctional in PBS-treated hearts, whereas they were normalized in βARKct-overexpressing hearts. Conclusions - Myocardial gene transfer of Adv-βARKct stabilizes βAR signaling and prevents LV dysfunction induced by prolonged cardioplegic arrest. Thus, βARK1 inhibition may represent a novel target in limiting depressed ventricular function after CPB.

Cite

CITATION STYLE

APA

Tevaearai, H. T., Eckhart, A. D., Shotwell, K. F., Wilson, K., & Koch, W. J. (2001). Ventricular dysfunction after cardioplegic arrest is improved after myocardial gene transfer of a β-adrenergic receptor kinase inhibitor. Circulation, 104(17), 2069–2074. https://doi.org/10.1161/hc4201.097188

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free