TY - JOUR
T1 - Autonomic modulation during acute myocardial ischemia by low-dose pirenzepine in conscious dogs with a healed myocardial infarction
T2 - A comparison with β-adrenergic blockade
AU - Pedretti, Roberto F E
AU - Prete, Giovanna
AU - Foreman, Robert D.
AU - Adamson, Philip B.
AU - Vanoli, Emilio
PY - 2003/5/1
Y1 - 2003/5/1
N2 - 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 β-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 antimuscarinic agents side effects. The vagomimetic action of IV lowdose 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.
AB - 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 β-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 antimuscarinic agents side effects. The vagomimetic action of IV lowdose 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.
KW - Autonomic nervous system
KW - Myocardial ischemia
KW - Parasympathetic nervous system
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U2 - 10.1097/00005344-200305000-00002
DO - 10.1097/00005344-200305000-00002
M3 - Article
C2 - 12717096
AN - SCOPUS:0037406301
VL - 41
SP - 671
EP - 677
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
SN - 0160-2446
IS - 5
ER -