Coronary denervation attenuates coronary constriction induced by muscarinic receptor stimulation in pigs

Objectives: We tested the hypothesis that coronary denervation attenuates the reactivity of the coronary vessel to cholinergic stimulation. Methods: Heart rate, left ventricular (LV) pressure, LV d P /d t , coronary blood flow at the left anterior descending (LAD) coronary artery, and epicardial ECG mapping were measured before and after topical application of 1% methacholine to the LAD in 10 pigs anesthetized with alpha-chloralose (100 mg/kg, i.V.); these were compared with 10 other pigs submitted 2 weeks previously to a denervation of the LAD with phenol. Coronary denervation was confirmed in all cases by adrenergic histofluorescence and by acetyl-cholinesterase staining. Isolated LAD rings from 10 additional pigs (5 controls and 5 treated with phenol) were stimulated with endothelin-1 to verify whether phenol affected coronary reactivity to noncholinergic stimulation. Results: Methacholine induced a fall in coronary blood flow (10.3 ± 5.3 ml/min vs 4.8 ± 6.2 ml/min, ANOVA: P < 0.001), a drop in systolic LV pressure (113 ± 19 mmHg vs 93 ± 19 mmHg, P < 0.001) and LV d P /d t (1608 ± 363 mmHg/s vs 1203 ± 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 mmHg, 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 to 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 attenuates coronary constriction induced selectively by direct muscarinic receptor stimulation in the in situ pig heart.