Increased susceptibility of ventricular arrhythmias to aconitine in anaesthetized rats is attributed to the inhibition of baroreflex.
1. Aconitine is widely used to produce ventricular arrhythmias in anaesthetized rats. The present work was designed to test the hypothesis that anaesthesia may increase the susceptibility of ventricular arrhythmia to aconitine due to the inhibition of arterial baroreflex. In addition, the susceptibility of ventricular arrhythmia to aconitine at different times during the course of a whole day was also investigated. 2. Male Sprague-Dawley rats were used. Arrhthymias were induced by aconitine infusion at six time points (01.00, 05.00, 09.00, 13.00, 17.00 and 21.00 h) with rats in both anaesthetized and conscious states. In sinoaortic-denervated (SAD) rats, ventricular arrhythmias were induced by aconitine infusion between 09.00 and 13.00 h. 3. There was a significant difference in the lethal dose of aconitine between anaesthetized and conscious rats (99.6 +/- 30.1 vs 58.2 +/- 14.7 micro g/kg; P < 0.001). Anaesthesia did increase the susceptibility of rats to ventricular arrhythmias following aconitine. 4. In SAD rats, the lethal dose of aconitine was less than that for baroreflex-intact rats when determined in the conscious state. The difference in the lethal dose of aconitine between SAD and baroreflex-intact rats disappeared when it was determined in anaesthetized rats. 5. The time of day did not affect the susceptibility of either anaesthetized or conscious rats to ventricular arrhythmias following aconitine, except for a difference in the ventricullar fibrillation threshold dose between 13.00 and 17.00 h in anaesthetized rats. 6. In conclusion, anaesthesia may increase the risk of ventricular arrhythmias following aconitine. Intact arterial baroreflex function is necessary to prevent drug-induced ventricular arrhythmias.
Shu
He
H
Department of Pharmacology, Second Military Medical University, Shanghai, China.
Yi-Ming
Wuliya
W
Xu
Li-Ping
LP
Miao
Chao-Yu
CY
Su
Ding-Feng
DF
D000157:Aconitine / Q000633:toxicity*; D000759:Adjuvants, Anesthesia / Q000633:toxicity*; D000758:Anesthesia / Q000009:adverse effects; D000818:Animals; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007928:Lethal Dose 50; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014693:Ventricular Fibrillation / Q000139:chemically induced* / Q000503:physiopathology
D000759:Adjuvants, Anesthesia; D000157:Aconitine