title: Differential anti-ischaemic effects of muscarinic receptor blockade in patients with obstructive coronary artery disease; impaired vs normal left ventricular function.
abstract: OBJECTIVE
  In patients with coronary artery disease acetylcholine (a muscarinic agonist) causes vasoconstriction. The effect of atropine (a muscarinic antagonist) on coronary vasotone in patients with normal or impaired left ventricular function is unknown.
  
  
  RESULTS
  Twenty-four patients who required atropine infusion (to supplement heart rate response) during atrial pacing (pacing was conducted to assess ischaemia as part of an experimental protocol) were studied; 17 patients had normal and seven impaired left ventricular function (ejection fraction < or =0.40). Two control groups were selected from a large database (from patients in whom atrial pacing was carried out but to whom atropine was not administered) to match the normal (n=20) and dysfunction (n=10) groups. In the normal left ventricular function group atropine increased rate pressure product by 12 +/- 4%, as compared to those without atropine (P < 0.05). Left ventricular end diastolic pressure increased less in the atropine group (+40 +/- 8% vs +78 +/- 6%;P < 0.05). Arterial norepinephrine increased similarly in both groups, but coronary flow (as assessed by using a thermodiluting method in the coronary sinus) increased 23 +/ -4% more in the atropine group (P < 0.05). Further, there were lower levels of myocardial lactate production and ST-segment depression in the atropine group [lactate extraction +13 +/- 6% (atropine) vs -19 +/- 4% (controls), ST-segment depression 1. 3 +/- 0.6 (atropine) vs 1.8 +/- 0.2 mm (control), both P < 0.05 between groups]. In contrast, in the dysfunction group the overall effect of atropine was less pronounced.
  
  
  CONCLUSIONS
  In patients with normal left ventricular function atropine improves coronary flow and reduces myocardial lactate production and ST-segment depression during atrial pacing, suggesting a reduction in myocardial ischaemia.
authors.affiliation: Sticares Research Foundation, Rotterdam, The Netherlands.
authors.forename: A F
authors.initials: AF
authors.lastname: van den Heuvel
authors.forename: D J
authors.initials: DJ
authors.lastname: van Veldhuisen
authors.forename: G L
authors.initials: GL
authors.lastname: Bartels
authors.forename: M
authors.initials: M
authors.lastname: van der Ent
authors.forename: W J
authors.initials: WJ
authors.lastname: Remme
mesh_terms: D001285:Atropine / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity / Q000187:drug effects; D006328:Cardiac Catheterization; D002395:Catecholamines / Q000097:blood; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage*; D009206:Myocardium / Q000378:metabolism; D013318:Stroke Volume / Q000187:drug effects; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D015415:Biomarkers; D002395:Catecholamines; D018727:Muscarinic Antagonists; D019344:Lactic Acid; D001285:Atropine