Protective Role of Nerve Growth Factor Against Postischemic Dysfunction of Sympathetic Coronary Innervation

Abstract

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 exogenous and endogenous NGF on ischemia-induced dysfunction of cardiac sympathetic nerves. Methods and Results In anesthetized dogs, bilateral stellate stimulation was performed, measuring changes in coronary vascular resistance (%ΔCVR) before and after release of either a 7- or 15-minute occlusion of the left anterior descending coronary artery (LAD). NGF (10 ng·kg −1 ·min −1 , n=5) or vehicle (n=6) was infused into the LAD in dogs during a 15-minute LAD occlusion. In separate experiments, antibody to NGF (anti-NGF, 2 ng·kg −1 ·min −1 , n=5) or vehicle (n=6) was infused into dogs during a 7-minute LAD occlusion. After release of a 15-minute LAD occlusion, attenuation of the coronary constriction to stellate stimulation was seen in the vehicle group (30±3% to 15±1% increase in CVR, P <.05); however, no such reduction was seen in the group receiving NGF. A 7-minute LAD occlusion with reperfusion did not alter %ΔCVR in the vehicle group (36±6% versus 37±7%, P =NS) but attenuated %ΔCVR 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 stunning of sympathetic cardiac innervation.