Circadian changes in autonomic function in conscious rats with heart failure: effects of amiodarone on sympathetic surge.
Cardiovascular events are characterized by circadian periodicity with a peak prevalence during the awakening period, which suggests a morning surge in sympathetic activity. We developed an experimental system to determine circadian changes in heart rate (HR), blood pressure (BP), locomotor activity (Loc), respiratory rate and autonomic function in conscious, unrestrained rats. The effects of amiodarone on circadian variation of these variables were determined in rats with myocardial infarction and subsequent congestive heart failure (CHF). We continuously recorded BP, HR and Loc for 24h in rats with CHF (n=16) or after a sham operation (Sham; n=7). To determine circadian changes in sympathovagal balance, digitized BP and HR data throughout 24h were analyzed based on maximum entropy. The study was repeated after 3 weeks of oral amiodarone (50mg/kg/day) or saline administration. Baseline HR, mean BP, and Loc were higher in the dark period than in the light period (all p<0.05) in both CHF and Sham rats, which is consistent with the circadian periodicity of nocturnal animals. Low-frequency components of diastolic BP variability (LFdp), an index of sympathetic tone, were significantly higher during the awakening period (16:00-20:00) than during the sleeping period (08:00-14:00), a finding analogous to the sympathetic morning surge in men. Amiodarone suppressed this transient increase in LFdp power during the awakening period. Our experimental system could detect sympathetic surge in conscious rats. Amiodarone suppressed the sympathetic surge, which could explain, at least in part, beneficial effects of amiodarone in patients with CHF.
Ohori
Takashi
T
The Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. horio@fsinet.or.jp
Hirai
Tadakazu
T
Joho
Shuji
S
Kameyama
Tomoki
T
Nozawa
Takashi
T
Asanoi
Hidetsugu
H
Inoue
Hiroshi
H
D000638:Amiodarone / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001342:Autonomic Nervous System Diseases / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D021081:Chronobiology Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D002940:Circadian Rhythm / Q000502:physiology*; D004195:Disease Models, Animal; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D000638:Amiodarone