The effects of ropivacaine at clinically relevant doses on myocardial ischemia in pigs.
A major risk associated with bupivacaine during myocardial ischemia is ventricular fibrillation. We investigated the influence of ropivacaine on cardiac contractility and the propensity to ventricular fibrillation before and after myocardial ischemia in a placebo-controlled pig study. Anesthetized domestic pigs were administered 1 mg.kg(-1) of ropivacaine intravenously over 1 min and then 0.03 mg.kg(-1).min(-1) as a 30-min infusion, or saline. The following endpoints were measured before and after ropivacaine administration: (1) the ventricular fibrillation threshold (VFT) before and during myocardial ischemia induced by total transient ligation of the anterior interventricular artery and (2) electrophysiological (sinus heart rate, duration of QRS and QT intervals) and hemodynamic (blood pressure, the time derivative of left ventricular pressure [peak LV dP/dt]) parameters. Ropivacaine induced no changes in sinus heart rate, QRS, and or QT before or during ischemia. In contrast, there was a mild increase in the VFT before ischemia, which was drastically and significantly reduced during ischemia. The reduction of peak LV dP/dt during ischemia was further increased by ropivacaine. We also found that the effect of ropivacaine on the VFT was coronary blood flow-dependent, with a markedly decreased threshold in the presence of ischemia. Similar effects have been observed in humans with several other local anesthetics, as well as with class I antiarrhythmic drugs. The results of this study should be taken into account by anesthesiologists when administering ropivacaine to coronary patients.
Tsibiribi
Panayota
P
Laboratoire de Pharmacologie Médicale (EA 1896), Faculté de Médecine Lyon Grange-Blanche, 8 avenue Rockefeller, 69373, Lyon, cedex 08, France.
Bui-Xuan
Cécile
C
Bui-Xuan
Bernard
B
Tabib
Alain
A
Descotes
Jacques
J
Chevalier
Philippe
P
Gagnieu
Marie-Claude
MC
Belkhiria
Majda
M
Timour
Quadiri
Q
D000577:Amides / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D005260:Female; D008297:Male; D008991:Monitoring, Physiologic; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D000077212:Ropivacaine; D013552:Swine; D014693:Ventricular Fibrillation / Q000139:chemically induced* / Q000503:physiopathology
D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine