title: Effect of quinapril or metoprolol on circadian sympathetic and parasympathetic modulation after acute myocardial infarction.
abstract: Abnormal autonomic nervous system impairment in patients with acute myocardial infarction (AMI) has a circadian pattern with the greatest manifestation in the morning hours; it probably plays an important role in the pathogenesis of cardiac arrhythmias and acute ischemic syndromes. Angiotensin-converting enzyme inhibitors improve autonomic function in patients with AMI, but the circadian pattern of this effect has not been studied. Heart rate variability-normalized frequency domain indexes were assessed 5 days (baseline) after the onset of uncomplicated AMI and 30 days after therapy with quinapril (n = 30), metoprolol (n = 30), or placebo (n = 30) with a solid-state digital Holter monitor. Normal subjects (n = 30) were used as controls. Quinapril increased parasympathetic and decreased sympathetic modulation, and improved sympathovagal interactions manifested by an increase in normalized high-frequency power (HFP), and a decrease in normalized low-frequency power (LFP), and their ratio (LFP/HFP) during the entire 24-hour period (p<0.001), with maximal effect on the ratio (p<0.0001) between 02.00 to 04.00 A.M., 08.00 to 11.00 A.M., and 19.00 to 22.00 P.M. (delta% ratio -30%, -32%, and -26%, respectively). Metoprolol increased HFP and decreased LFP and the LFP/HFP ratio mainly between 08.00 A.M. to 12.00 noon, and 19.00 to 22.00 P.M. (delta% ratio -21%, and -12% respectively, p<0.001). Heart rate variability indexes in the placebo group and controls remained unchanged 30 days after the baseline study. In conclusion, quinapril increased parasympathetic, and decreased sympathetic and partially restored sympathovagal interaction in patients with uncomplicated AMI during the entire 24-hour period, with peak effect in the early and late morning and evening hours. Metoprolol had a similar effect during the late morning and evening hours, but at a lower level. These effects may prove beneficial in reducing cardiac arrhythmias and acute ischemic syndromes in past-AMI patients.
authors.affiliation: 2nd Propedeutic Department of Internal Medicine, Aristotelian University, Hippocration Hospital, Thessaloniki, Greece. athyros@med.auth.gr
authors.forename: A G
authors.initials: AG
authors.lastname: Kontopoulos
authors.forename: V G
authors.initials: VG
authors.lastname: Athyros
authors.forename: A A
authors.initials: AA
authors.lastname: Papageorgiou
authors.forename: H
authors.initials: H
authors.lastname: Boudoulas
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000503:physiopathology*; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D011446:Prospective Studies; D000077583:Quinapril; D013564:Sympathetic Nervous System / Q000187:drug effects*; D044005:Tetrahydroisoquinolines
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D008790:Metoprolol; D000077583:Quinapril