An in vitro method for the evaluation of antiarrhythmic and antiischemic agents by using programmed electrical stimulation of rabbit heart.
A new model using isolated rabbit hearts perfused at constant flow in the Langendorff mode with the sinus node destroyed and under constant (2 Hz) pacing is described. Ventricular ischemia (24 min) was induced by ligation of the left ventricular branch of the coronary artery (LVB), followed by reperfusion (15 min). The programmed electrical stimulation (PES) technique was used to induce arrhythmias in the ischemic zone (IZ). Three agents with different mechanisms of action were tested to validate this model: dl-sotalol (10(-6) and 10(-5) M), oxfenicine (10(-6) M), and lidocaine (10(-5) M). These compounds were administered 15 min before the ligature and maintained until the end of the experiment. Ventricular effective refractory period (VERP), PES-induced ventricular fibrillation (VF), and coronary perfusion pressure (CPP) were monitored. PES-induced VF was only observed in ischemic tissue. Sotalol slightly reduced VF incidence only during reperfusion. Oxfenicine prevented PES-induced VF during the ischemia, but not during reperfusion, while lidocaine prevented VF during ischemia and throughout the reperfusion period. In conclusion, the rabbit heart model where PES is applied to normal and ischemic myocardium, appears useful to discern different mechanisms involved in ventricular arrhythmias. In addition, this model is considerably cheaper than equivalent dog models.
Bellemin-Baurreau
J
J
Department of Pharmacology, Recherche Syntex France, Leuville-sur-Orge.
Poizot
A
A
Hicks
P E
PE
Armstrong
J M
JM
D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004558:Electric Stimulation; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000517:prevention & control; D011817:Rabbits; D013015:Sotalol / Q000494:pharmacology*; D016276:Ventricular Function
C023010:4-hydroxyphenylglycine; D008012:Lidocaine; D013015:Sotalol; D005998:Glycine