K+ channel blockade in the prevention of ventricular fibrillation in dogs with acute ischemia and enhanced sympathetic activity.
The value of K+ channel blockade in preventing lethal arrhythmias, and specifically those triggered by acute myocardial ischemia and sympathetic hyperactivity, remains unproven. To address this issue, we tested the antifibrillatory effect of d-sotalol, and Ikr blocker, d,l-sotalol, its racemic compound which blocks Ikr, and beta-adrenoreceptors, and propranolol. Ten dogs with a healed anterior myocardial infarction (MI) had ventricular fibrillation (VF) during a 2-min occlusion of the circumflex coronary artery performed toward the end of a submaximal exercise stress test. In successive trials in the same animals, d-sotalol (three injections of 8 mg/kg, one every 12 h), d,l-sotalol (8 mg/kg), and propranolol (1 mg/kg) were tested. All three interventions significantly reduced heart rate (HR) response to exercise, but only d,l-sotalol and propranolol also blunted the reflex HR increase during acute myocardial ischemia. With d-sotalol, HR at 30 s of coronary occlusion was similar (253 +/- 28 beats/min) to that observed in the control tests (259 +/- 35 beats/min). d-Sotalol prevented recurrence of VF in only 1 of 10 dogs tested. One dog was lost to the continuation of the study after occurrence of VF with d-sotalol. Six of 9 dogs (67%) tested with d,l-sotalol and 5 (56%) of the same 9 dogs tested with propranolol were protected from VF. d-Sotalol does not reduce risk of VF during acute myocardial ischemia associated with sympathetic hyperactivity, and lethal events can be prevented by antiadrenergic interventions.
Vanoli
E
E
Istituto di Clinica Medica Generale e Terapia Medica, Università di Milano, Italy.
Hull
S S
SS
Adamson
P B
PB
Foreman
R D
RD
Schwartz
P J
PJ
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D017202:Myocardial Ischemia / Q000150:complications* / Q000503:physiopathology; D026902:Potassium Channel Blockers; D011433:Propranolol / Q000494:pharmacology; D013015:Sotalol / Q000494:pharmacology*; D013237:Stereoisomerism; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000517:prevention & control*
D000889:Anti-Arrhythmia Agents; D026902:Potassium Channel Blockers; D011433:Propranolol; D013015:Sotalol