Gene transfection of beta 2–adrenergic receptor into the normal rat heart enhances cardiac response to beta-adrenergic agonist

Abstract

Background: Beta-adrenergic receptor system has a major role in cardiac contraction. If the receptor can be increased by gene transfection by means of intracoronary infusion of beta 2–adrenergic receptor to the hearts in which the receptor is down-regulated, this maneuver may improve the cardiac function and may be applied as one therapeutic approach during cardiopulmonary bypass or percutaneous cardiopulmonary support. Methods and results: The beta 2–adrenergic receptor complementary DNA was transfected in vivo to the normal rat heart by intracoronary infusion by means of a hemagglutinating virus of Japan liposome method, and the transfected heart was transplanted into the abdomen of another rat. Four days after transfection, the sarcolemma of the cardiomyocytes was well labeled by immunohistochemical labeling. Expression of beta-adrenergic receptor in the heart was approximately 4 times greater than that in control hearts (134 ± 42 vs 33 ± 4 fmol/mg protein) according to a ligand binding assay. The cardiac response of the transfected heart to isoproterenol was shown to be enhanced in a Langendorff perfusion system: after isoproterenol, developed pressure and maximal derivative of the left ventricle were greater than in the control heart (200 ± 12 vs 174 ± 6 mm Hg and 4110 ± 130 vs 3491 ± 255 mm Hg/sec), and the minimal derivative of the left ventricle was markedly smaller (–3040 ± 267 vs –2528 ± 131 mm Hg/sec). Conclusions: These results indicate that expression of beta 2–adrenergic receptor was approximately 4 times greater than in normal rat hearts by gene transfection using a hemagglutinating virus of Japan liposome method, and the transfected hearts demonstrated marked enhancements in cardiac response to beta-agonist, suggesting that transfer of this gene by intracoronary infusion has potential as a novel approach to enhance cardiac function. (J Thorac Cardiovasc Surg 1999;118:446-51)