SIGNALING VIA STIMULATORY α SUBUNIT OF G-PROTEINS UNDERLINES THE PROTECTIVE EFFECTS OF CONCANAVALIN A IN FAILING RAT HEARTS AFTER TRANSPLANTATION

Abstract

1023 We previously reported concanavalin A (Con A) resuscitated transplanted post-ischemic failing hearts. To study the mechanism in vivo, heterotopic cervical heart transplantation was performed in Lewis rats (215±20 g). Three days after transplantation the aortic root of the transplanted hearts was occluded for 30 min. The rats were divided into 3 groups (8 each). Upon reperfusion in the study group, Con A (20 mg in 1.0 ml saline) was injected into transplanted heart via the aortic branch. In the control group, 1.0 ml saline was injected. No aortic occlusion was induced in the normal group. Left ventricular function was studied at 60 min using the balloon method. All hearts were harvested for analyzing cAMP and ATP. Immunoblot was used to measure the stimulatory GTP binding protein α subunit (Gsα). The control group had very low dP/dt max and heart rate, in contrast to the study and the normal groups (p<0.01). Myocardial Gsα level was much higher in the study group than in the control and normal groups (p<0.001). Both cAMP and ATP levels were higher in the study and normal groups than in the control group (cAMP, p<0.001; ATP, p<0.01, Table).TableOur data indicate that Con A resuscitates post-ischemic failing hearts by enhancing the production of Gsα and cAMP. The increase in Gsα could be the key to restoring the compromised myocardium and thus, deserves further study.