title: Chronotropic dose response of atropine in Nigerians with congestive heart failure: assessment of ethnic variation and reversibility of parasympathetic dysfunction.
abstract: Both ethnicity and disease states may influence cardiac parasympathetic tone. We evaluated the cardiac vagal activity in 9 Nigerians aged 57(11) with congestive heart failure, and 9 age- and sex-matched healthy controls aged 51(11) years, using a cumulative low dose atropine response curve. All subjects demonstrated bradycardia at low doses (100 microg-400 microg) and tachycardia at higher doses (600 microg-1,000 microg). However, both the bradycardic and the tachycardic responses were attenuated in heart failure patients compared to controls: bradycardia -1.1(1.5) beats/min in heart failure patients vs -7.1(2.2) beats/min in controls (P<.01) and tachycardia +4(1.5) beats/min in heart failure patients vs +14.3(3) beats/min in healthy controls (P<.01). EC50 values for brachycardia and tachycardia calculated from the dose response curves were significantly higher in healthy controls compared to heart failure patients, for bradycardia 69(39) microg versus 11(1.6) microg (P<.01) and tachycardia 682(61) microg vs 254(84) microg (P<.01). Treatment of heart failure for 4 weeks with furosemide, digoxin and angiotensin converting enzyme inhibitor (enalapril) caused a significant increase in the magnitude of both the bradycardic responses from -1.1(1.5) beats/min to -4.4(0.9) beats/min after treatment, and tachycardic responses from +4(1.5) beats/min to +10.(2.3) beats/min 4 weeks after treatment (P<.05). After 4 weeks of treatment, EC50 was also increased significantly toward normal values. For tachycardia, the values were 254(88) microg before treatment vs 529(78) microg after treatment (P<.05); and for bradycardia, the values were 2.5(1.6) microg before treatment vs 30(13) microg after treatment (P<.05). These findings demonstrate the early bradycardic effect of atropine in Black Africans (both healthy controls and heart failure patients), contradicting earlier reports of its absence in the negroid race. This confirms the reduction in cardiac parasympathetic responsiveness (both maximal heart rate change and EC50) in hypertensive heart failure using a pharmacological assay. It demonstrates the augmentation and amelioration of cardiac vagal tone with enalapril-dixogin-diuretic therapy in non-ischemic heart failure, and the sequential utility of the low dose atropine-chronotropic response in assessing cardiac parasympathetic activity.
authors.affiliation: Department of Medicine, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria.
authors.forename: A Q
authors.initials: AQ
authors.lastname: Adigun
authors.forename: G G
authors.initials: GG
authors.lastname: Sofowora
authors.forename: A A
authors.initials: AA
authors.lastname: Ajayi
mesh_terms: D000328:Adult; D001285:Atropine / Q000494:pharmacology / Q000627:therapeutic use*; D044383:Black People; D004305:Dose-Response Relationship, Drug; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009549:Nigeria; D010276:Parasympatholytics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D010276:Parasympatholytics; D001285:Atropine