Differential effects of propofol and sevoflurane on ischemia-induced ventricular arrhythmias and phosphorylated connexin 43 protein in rats.
BACKGROUND
The effects of anesthetics on ischemia-induced ventricular arrhythmias remain poorly studied. This study investigated the effects of propofol and sevoflurane on the survival rate and morbidity as a result of ventricular arrhythmias, and defined a possible mechanism for the arrhythmogenic properties of anesthetics during acute myocardial ischemia.


METHODS
Under anesthesia with intraperitoneal sodium pentobarbital, Sprague-Dawley rats underwent 30 min of left anterior descending coronary artery ligation. The rats were divided into a low-dose propofol (Prop-LD) group (39 mg X kg(-1) X hr(-1), n = 18), a high-dose propofol group (78 mg x kg(-1) x hr(-1), n = 18), a sevoflurane group (2.5%, n = 18) and a control group (n = 18). The survival rate and morbidity as a result of ventricular arrhythmias were determined, and the amount of phosphorylated connexin 43 protein was measured 30 min after coronary artery ligation.


RESULTS
The survival rate was 83% (15 of 18), 94% (17 of 18), 89% (16 of 18), and 67% (12 of 18, P = 0.038 vs. Prop-LD) in the control, Prop-LD, high-dose propofol, and sevoflurane groups, respectively. Sustained ventricular tachycardia was observed in 83% (15 of 18), 39% (7 of 18, P = 0.011 vs. control), 50% (9 of 18, P = 0.039 vs. control) and 94% (17 of 18, P < 0.01 vs. Prop-LD) in the control, Prop-LD, high-dose propofol, and sevoflurane groups, respectively. Immunoblotting showed a marked reduction in the amount of phosphorylated connexin 43 in the control and sevoflurane groups, as compared with the Prop-LD and high-dose propofol groups (P < 0.05).


CONCLUSIONS
The authors' results suggest that propofol preserves connexin 43 phosphorylation during acute myocardial ischemia, as compared with sevoflurane, and this might protect the heart from serious ventricular arrhythmias during acute coronary occlusion.
Hirata
Naoyuki
N
Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Japan. nhirata@sapmed.ac.jp
Kanaya
Noriaki
N
Kamada
Noriko
N
Kimura
Saori
S
Namiki
Akiyoshi
A
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000378:metabolism; D018031:Connexin 43 / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology / Q000627:therapeutic use*; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D015742:Propofol / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000378:metabolism
D018031:Connexin 43; D008738:Methyl Ethers; D000077149:Sevoflurane; D015742:Propofol