Negative inotropic and lusitropic effects of intravenous amiodarone in conscious rats.
1. The acute effect of amiodarone on haemodynamics (mean arterial pressure and heart rate) and ventricular function (+dP/dt(max) and -dP/dt(max)) was investigated in conscious rats. In addition, the effects of amiodarone on dobutamine stress were determined. 2. Catheters were inserted in rats into the left ventricle and femoral artery and vein. Three groups of rats received 25 or 50 mg/kg, i.v., amiodarone or vehicle (a 1:1:8 mixture of Tween 80:99.5% ethanol:distilled water), followed by dobutamine (10 microg/kg). 3. The hypotensive effect of 50 mg/kg amiodarone was combined with marked bradycardia and attenuation of +dP/dt(max) and -dP/dt(max). A slight, but significant, hypotension was caused by 25 mg/kg amiodarone, without affecting heart rate, +dP/dt(max) and -dP/dt(max). However, although both doses of amiodarone attenuated the tachycardia caused by dobutamine, neither 25 nor 50 mg/kg amiodarone affected the increase in mean arterial pressure or the enhanced response of +dP/dt(max) and -dP/dt(max). 4. In conclusion, amiodarone caused hypotension, bradycardia, negative inotropic (+dP/dt(max)) and lusitropic (-dP/dt(max)) effects in conscious rats. In addition, amiodarone attenuated the tachycardia without affecting the hypertensive, contractile (+dP/dt(max)) and lusitropic (-dP/dt(max)) responses to dobutamine stress.
Salgado
Helio C
HC
Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. hcsalgad@fmrp.usp.br
Simões
Géssica M
GM
Santana Filho
Valter J
VJ
Dias da Silva
Valdo J
VJ
Salgado
Maria Cristina O
MC
Fazan
Rubens
R
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000638:Amiodarone / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D003243:Consciousness; D004280:Dobutamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D000889:Anti-Arrhythmia Agents; D004280:Dobutamine; D000638:Amiodarone