Antiarrhythmic agents inhibit the in vitro formation of thromboxane (TX) in platelets from spontaneously hypertensive rats (SHR).
The occurrence of early life threatening arrhythmias in the ischemic myocardium has been associated with local generation of thromboxane (TX). Antiarrhythmic agents are typically classified according to the fundamental mechanism involved in restoring normal rhythm but identifying those agents also capable of suppressing TX formation offers a means of improving the rationale of antiarrhythmic therapy. Accordingly, representative antiarrhythmic agents from classes I-IV were evaluated in the present study for their ability to suppress TX formation from intact rat platelets, in vitro. Agents from class I, II and IV achieved significant reductions in TX levels as compared to a reference TX inhibitor, dazoxiben. The IC-50 value for dazoxiben was 1.5 X 10(-6) M. Nicardipine and flecainide, being the most active of the antiarrhythmic agents tested, had IC-50's of 5 X 10(-6) and 1 X 10(-5) M respectively. Verapamil and propranolol had values of 1 X 10(-5) and 5 X 10(-5) M respectively; labetalol and quinidine were 5 X 10(-5) M, and phenytoin and diltiazem were approximately 1 X 10(-4) M. These data suggest a subsidiary antiarrhythmic property of these particular agents as related to their ability to suppress TX generation in the ischemic myocardium and implies these agents may be preferred in the treatment of early life threatening arrhythmias resulting as an initial response to myocardial ischemia.
Lucas
J
J
Chan
P S
PS
Cervoni
P
P
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000145:classification / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D013929:Thromboxane B2 / Q000097:blood*
D000889:Anti-Arrhythmia Agents; D013929:Thromboxane B2