title: Coronary denervation attenuates coronary constriction induced by muscarinic receptor stimulation in pigs.
abstract: 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.
authors.affiliation: Departamento de Medicina, Hospital General Universitari Vall d'Hebron, Barcelona, Spain. jcinca@ar.vhebron.es
authors.forename: J
authors.initials: J
authors.lastname: Cinca
authors.forename: L
authors.initials: L
authors.lastname: Mont
authors.forename: A
authors.initials: A
authors.lastname: Carreño
authors.forename: M
authors.initials: M
authors.lastname: Mourelle
authors.forename: J
authors.initials: J
authors.lastname: Rodés
authors.forename: A
authors.initials: A
authors.lastname: Domingo
authors.forename: J
authors.initials: J
authors.lastname: Soler-Soler
mesh_terms: 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
chemical_list: D016232:Endothelins; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D010636:Phenols; D016210:Methacholine Chloride; D001285:Atropine