PROTECTIVE ROLE OF NERVE GROWTH-FACTOR AGAINST POSTISCHEMIC DYSFUNCTION OF SYMPATHETIC CORONARY INNERVATION

Background Nerve growth factor (NGF) is produced rapidly in myocardium after brief myocardial ischemia. It contributes to the maintenance of neural integrity in several tissues. We examined the effect of exogen ous and endogenous NGF on ischemia-induced dysfunction of cardiac symp athetic nerves. Methods and Results In anesthetized dogs, bilateral st ellate stimulation was performed, measuring changes in coronary vascul ar resistance (%Delta CVR) before and after release of either a 7- or 15-minute occlusion of the left anterior descending coronary artery (L AD). NGF (10 ng . kg(-1). min-L, n=5) or vehicle (n=6) was infused int o the LAD in dogs during a 15-minute LAD occlusion. In separate experi ments, antibody to NGF (anti-NGF, 2 ng . k(-1). min(-1), n=5) or vehic le (n=6) was infused into dogs during a 7-minute LAD occlusion. After release of a 15-minute LAD occlusion, attenuation of the coronary cons triction to stellate stimulation was seen in the vehicle group (30+/-3 % to 15+/-1% increase in CVR, P<.05); however, no such reduction was s een in the group receiving NGF. A 7-minute LAD occlusion with reperfus ion did not alter %Delta CVR in the vehicle group (36+/-6% versus 37+/ -7%, P=NS) but attenuated %Delta CVR in the anti-NGF group (39+/-8% to 17+/-2%, P<.05). Conclusions We conclude that exogenously infused and endogenously released NGF protects against postischemic neural stunni ng of sympathetic cardiac innervation.