Autonomic modulation during acute myocardial ischemia by low-dose pirenzepine in conscious dogs with a healed myocardial infarction: a comparison with beta-adrenergic blockade.
Experimental and clinical evidence documents the beneficial effects of blocking sympathetic activity and modulating heart rate to reduce risk for lethal events in ischemic heart disease. Beside beta-adrenergic receptor blockade, vagal activation is a meaningful approach but not yet easily attainable. Promising results were shown with low-dose atropine and scopolamine, but no follow-up was done because of significant adverse side effects. Pirenzepine is an atropine analogue approved to treat peptic ulcer disease in Europe that is devoid of central actions, which are mostly responsible for anti-muscarinic agents side effects. The vagomimetic action of IV low-dose pirenzepine was studied at rest under control conditions, at rest during acute coronary artery occlusion, and during exercise in conscious dogs with a healed anterior myocardial infarction (MI). The effects of pirenzepine were then compared, by internal control analysis, with those of atenolol (1 mg/kg). Increasing doses of pirenzepine (from 0.01 to 1 mg/kg) were tested in 11 dogs at rest by measuring time and frequency domain heart rate variability (HRV). The most effective dose (0.1 mg/kg) was used in the study. At the most effective dose, pirenzepine increased all measures of time domain HRV by 40-50%. However, the vagomimetic action of pirenzepine was lost during exercise and brief ischemia and no anti-arrhythmic action was observed. Conversely, pirenzepine effectively modulated the heart rate increase during acute ischemia at rest with an effect comparable to that of atenolol. The vagomimetic action of pirenzepine in the acutely ischemic heart supports the possibility that this intervention may be helpful for chronic autonomic modulation in post-MI patients.
Pedretti
Roberto F E
RF
Fondazione Salvatore Maugeri, Care and Research Institute, Division of Cardiology, Tradate, Italy.
Prete
Giovanna
G
Foreman
Robert D
RD
Adamson
Philip B
PB
Vanoli
Emilio
E
D000208:Acute Disease; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001262:Atenolol / Q000627:therapeutic use*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D009203:Myocardial Infarction / Q000150:complications; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D010277:Parasympathomimetics / Q000627:therapeutic use*; D010805:Physical Conditioning, Animal; D010890:Pirenzepine / Q000627:therapeutic use*; D014630:Vagus Nerve / Q000187:drug effects* / Q000503:physiopathology
D000319:Adrenergic beta-Antagonists; D010277:Parasympathomimetics; D010890:Pirenzepine; D001262:Atenolol