Coronary denervation attenuates coronary constriction induced by muscarinic receptor stimulation in pigs.
OBJECTIVE
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 dP/dt, 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 dP/dt (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.
Cinca
J
J
Departamento de Medicina, Hospital General Universitari Vall d'Hebron, Barcelona, Spain. jcinca@ar.vhebron.es
Mont
L
L
Carreño
A
A
Mourelle
M
M
Rodés
J
J
Domingo
A
A
Soler-Soler
J
J
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D004562:Electrocardiography / Q000187:drug effects; D016232:Endothelins / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology*; D008954:Models, Biological; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D010636:Phenols / Q000494:pharmacology; D013268:Stimulation, Chemical; D013552:Swine; D013563:Sympathectomy, Chemical; D014661:Vasoconstriction / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects
D016232:Endothelins; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010636:Phenols; D016210:Methacholine Chloride; D001285:Atropine