Effects of propafenone on pacing-induced ventricular fibrillation and intracellular calcium in rat hearts.
Propafenone is an antiarrhythmic agent with fast sodium channel, calcium channel, and beta-adrenergic receptor blocking properties. The effects of propafenone on arrhythmias, free intracellular calcium and left ventricular performance were studied using perfused rat hearts during (i) pacing-induced ventricular fibrillation and (ii) infusion with 2.65 x 10(-6) M, 5.3 x 10(-6) M and 7.9 x 10(-6) M propafenone hydrochloride (corresponding to approximately 1, 2 and 3 mg kg-1 body weight). A bolus of 1 mg kg-1 propafenone during ventricular fibrillation resulted in a decrease in intracellular calcium, with subsequent conversion to sinus rhythm. In perfused hearts with sinus rhythm propafenone produced a dose-dependent decrease in heart rate and myocardial oxygen consumption together with a rise in left ventricular diastolic pressure, and diastolic [Ca2+]i, indicative of depression of left ventricular function. We conclude that a bolus of propafenone during ventricular fibrillation leads to a decrease in [Ca2+]i preceding conversion to sinus rhythm. In rat hearts with sinus rhythm the depressive effects of propafenone on [Ca2+]i are dose dependent.
Stefenelli
T
T
Department of Medicine, University of California, San Francisco 94143.
Wu
S T
ST
Parmley
W W
WW
Wikman-Coffelt
J
J
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial; D004305:Dose-Response Relationship, Drug; D005470:Fluorometry; D006321:Heart / Q000187:drug effects; D010477:Perfusion; D011405:Propafenone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000187:drug effects; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects*
D002121:Calcium Channel Blockers; D015222:Sodium Channels; D011405:Propafenone; D002118:Calcium