CORONARY DENERVATION ATTENUATES CORONARY CONSTRICTION INDUCED BY MUSCARINIC RECEPTOR STIMULATION IN PIGS

Objectives: We tested the hypothesis that coronary denervation attenua tes the reactivity of the coronary vessel to cholinergic stimulation. Methods: Heart rate, left ventricular (LV) pressure, LV dP/dt, coronar y blood flow at the left anterior descending (LAD) coronary artery, an d epicardial ECG mapping were measured before and after topical applic ation of 1% methacholine to the LAD in 10 pigs anesthetized with alpha -chloralose (100 mg/kg, i.v.); these were compared with 10 other pies submitted 2 weeks previously to a denervation of the LAD with phenol. Coronary denervation was confirmed in all cases by adrenergic histoflu orescence and by acetyl-cholinesterase staining. Isolated LAD rings fr om 10 additional pigs (5 controls and 5 treated with phenol) were stim ulated with endothelin-1 to verify whether phenol affected coronary re activity to noncholinergic stimulation. Results: Methacholine induced a fall in coronary blood flow (10.3 +/- 5.3 ml/min vs 4.8 +/- 6.2 ml/m in, ANOVA: P < 0.001), a drop in systolic LV pressure (113 +/- 19 mmHg vs 93 +/- 19 mmHg, P < 0.001) and LV dP/dt (1608 +/- 363 mmHg/s vs 12 03 +/- 302 mmHg/s, P = 0.02) and elevation of the ST segment (1.4 +/- 0.9 vs 11.1 +/- 4.7 mV, P < 0.001) in controls. These changes were not preceded by heart rate variations and were inhibited by atropine. As compared to controls, phenol-treated pigs showed a smaller decline in coronary blood flow (13.1 +/- 4.5 ml/min to 10.4 +/- 5.4 ml/min, P < 0 .001), a lower drop in LV pressure (107 +/- 20 mmHg to 100 +/- 19.7 mm Hg, P < 0.001) and lesser ST segment elevation (2.2 +/- 1.7 mV to 5.6 +/- 4.2 mV, P < 0.001). Isolated LAD rings contracted after exposure t o endothelin-1 in both controls and phenol-treated pigs (3.5 +/- 0.7 g vs 2.4 +/- 1.0 g, P = 0.06). Conclusions: Coronary denervation attenu ates coronary constriction induced selectively by direct muscarinic re ceptor stimulation in the in situ pig heart.