The electrophysiological effects of racemic ketamine and etomidate in an in vitro model of "border zone" between normal and ischemic/reperfused guinea pig myocardium.
BACKGROUND
Etomidate and ketamine are used during induction of anesthesia in high-risk patients. However, their effects on action potential (AP) variables and ischemia/reperfusion-induced arrhythmias and conduction blocks are unknown.


METHODS
Guinea pig right ventricular muscle strips were mounted in a 5-mL double chamber bath with the strips separated into two zones by an impermeable latex membrane. One-half (normal zone) was exposed to normal perfusate while the other half (altered zone) was exposed to hypoxia, hyperkalemia, acidosis, and lack of glucose. AP variables were recorded continuously in the normal and altered zones. Spontaneous arrhythmias and conduction blocks were noted. Etomidate (10(-7), 10(-6), and 10(-5) M) and ketamine (10(-6), 10(-5), and 10(-4) M) were superfused into the bath throughout the experiment and the electrophysiologic effects compared with the control group.


RESULTS
We found that under control conditions, etomidate and ketamine did not modify resting membrane potential, maximal upstroke velocity, AP amplitude, or AP duration at 90% of repolarization (APD90). Ketamine (10(-4) M), but not weaker concentrations and none of the concentration of etomidate, reversed the ischemia-induced shortening of APD90 and APD dispersion. Etomidate and ketamine did not modify the occurrence of conduction block during simulated ischemia. In contrast, ketamine (25% at 10(-6) M, 13% at 10(-5) M, and 13% at 10(-4) M vs 90% in the control group, P < 0.05) but not etomidate (38% at 10(-7) M, 63% at 10(-6) M, and 63% at 10(-5) M vs 90% in the control group, NS) decreased the incidence of reperfusion-induced spontaneous arrhythmias.


CONCLUSIONS
In guinea pig myocardium, our data suggest that ketamine, in clinically relevant concentrations, decreases ischemia-induced AP shortening and spontaneous reperfusion-induced ventricular arrhythmias. Further study is required to precisely determine the effect of etomidate on reperfusion-induced arrhythmias.
Hanouz
Jean-Luc
JL
Département d'Anesthésie réanimation, CHU de Caen, Ave. Côte de Nacre, 14033 Caen Cedex, France. hanouz-jl@chu-caen.fr
Repesse
Yohann
Y
Zhu
Lan
L
Lemoine
Sandrine
S
Rouet
René
R
Sallé
Laurent
L
Plaud
Benoît
B
Gérard
Jean-Louis
JL
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004594:Electrophysiology; D005045:Etomidate / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007649:Ketamine / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium
D007649:Ketamine; D005045:Etomidate