Cardioprotective action of fentanyl in a model of central sympathetic overactivity in rabbits: antiarrhythmic and anti-ischemic effects.
BACKGROUND
Sympathetic overactivity resulting from perioperative noxious stimuli elicits hyperdynamic cardiovascular responses that may lead to myocardial ischemia and/or ventricular arrhythmia, especially in patients presenting with coronary artery disease. In the present study we investigated the cardioprotective effects of clinically relevant doses of fentanyl in an experimental model of sympathetic overactivity associated with myocardial ischemia in anesthetized rabbits.


METHODS
Central sympathetic stimulation was achieved through intracerebroventricular (i.c.v.) injection of L-glutamate (10 micro mol), with simultaneous inhibition of nitric oxide (NO) synthesis through i.v. administration of N(omega)-nitro-l-arginine methyl ester (L-NAME; 40 mg kg(-1)).


RESULTS
L-glutamate triggered ventricular arrhythmia and electrocardiographic alterations indicative of myocardial ischemia. The intravenous administration of fentanyl (5, 10 or 50 micro g kg(-1)) reduced the incidence of ST-segment shift (70, 20 and 10%, respectively, vs. 66.7% in controls) as well as of T-wave inversion from 58.3% to 30, 20 and 10%, respectively. The total number of ventricular premature complexes per minute fell from 65.2 +/- 16 in the control group to 6.8 +/- 3, 3.5 +/- 2 and 2.6 +/- 1.5, respectively. The occurrence of ventricular tachycardia and bigeminy was completely abolished by fentanyl. Finally, the i.v. administration of fentanyl did not induce significant hemodynamic effects (except for dP/dt(max) in the 50 micro g kg(-1)-dose).


CONCLUSIONS
Fentanyl elicits significant cardioprotective effects in a model of arrhythmia resulting from the association of central sympathetic overactivity with myocardial ischemia in rabbits, independently from its systemic hemodynamic actions.
Lessa
M A
MA
Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro, Brazil.
Rodrigues
E
E
Tibiricá
E
E
D000758:Anesthesia; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000889:Anti-Arrhythmia Agents; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control; D001342:Autonomic Nervous System Diseases / Q000150:complications / Q000188:drug therapy*; D003326:Coronary Circulation / Q000187:drug effects; D004562:Electrocardiography / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000627:therapeutic use*; D018698:Glutamic Acid; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D017202:Myocardial Ischemia / Q000209:etiology / Q000517:prevention & control*; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011817:Rabbits
D018686:Anesthetics, Intravenous; D000889:Anti-Arrhythmia Agents; D004791:Enzyme Inhibitors; D018698:Glutamic Acid; D019001:Nitric Oxide Synthase; D005283:Fentanyl; D019331:NG-Nitroarginine Methyl Ester