NEURALLY-MEDIATED NEGATIVE INOTROPIC EFFECT IMPAIRS MYOCARDIAL-FUNCTION DURING CHOLINERGIC CORONARY VASOCONSTRICTION IN PIGS

Background Myocardial dysfunction elicited during cholinergic coronary vasospasm is generally ascribed to myocardial ischemia. However, when pericoronary nerves extend to the ventricles, efferent vagal discharg es that elicit coronary vasoconstriction may, at the same time, depres s myocardial contractility by releasing acetylcholine into the myocard ium. We analyzed whether a neurally mediated effect contributes to imp airment of ventricular function during cholinergic coronary vasoconstr iction. Methods and Results Left Ventricular (LV) function, ECG mappin g, and coronary angiography were analyzed during pericoronary applicat ion of methacholine (MCh) to the left anterior descending coronary art ery in 53 chloralose-anesthetized open-chest pigs. MCh induced local c oronary vasoconstriction and depressed coronary blood flow (13.3+/-3.7 to 6.0+/-4.6 mL/min [54%]; ANOVA, P<.001), systolic LV pressure (105/-10 to 91+/-10 mm Hg [13%], P<.001), peak LV (+)dP/dt (2890+/-524 to 2270+/-447 mm Hg/s [21%], P<.001), peak LV (-)dP/dt (1446+/-484 to 104 8+/-276 mm Hg/s [27%], P<.001), and regional systolic segment shorteni ng (0.32+/-0.09% to 0.18+/-0.14% [43%], P=.02) and caused local ST-seg ment elevation (0.9+/-0.8 to 8.4+/-3.9 mV, P<.001). These changes were not preceded by heart rate variations, were reproducible, and were in hibited by atropine. MCh during perfusion of nitroglycerin (2 mu g . k g(-1). min(-1) IV) continued to depress LV pressure (9%, P=.002), LV ( +)dP/dt (16%, P<.01), LV (-)dP/dt (20%, P<.01), and segment shortening (18%, P=.03) even though coronary blood flow drop was markedly attenu ated (7% versus 54%; ANOVA, P<.01). Disruption of pericoronary nerves with phenol attenuated MCh-induced LV pressure fall (P<.05). Histologi cal data show that cholinergic and adrenergic pericoronary nerves exte nd into the ventricular myocardium. Conclusions A neurally mediated ef fect, in addition to ischemia, impairs LV function during cholinergic coronary constriction in a model with pericoronary nerves extending in to the ventricles.