The effect of antiarrhythmic drugs on life-threatening arrhythmias induced by the interaction between acute myocardial ischemia and sympathetic hyperactivity.
Transient myocardial ischemia, with attendant sympathetic hyperactivity, seems to play a major role in sudden cardiac death among patients with ischemic heart disease. Ventricular tachycardia (VT) and fibrillation (VF) are consistently and repeatedly elicited in cats by the interaction between a 2-minute occlusion of the left descending coronary artery and a 30-second stimulation of the left stellate ganglion. When three consecutive trials yield almost identical results, time alone will not modify the response and a given drug can be injected to test its efficacy with an internal control analysis. In 90 cats the efficacy of the following drugs was assessed: lidocaine (n = 11), mexiletine (n = 12), propafenone (n = 12), propranolol (n = 19), prazosin (n = 10), amiodarone (n = 14), and verapamil (n = 12). Class I antiarrhythmic drugs completely failed to afford protection and worsening of arrhythmia was observed in several instances. Propranolol and prazosin showed efficacy in approximately 80% and 60% of the animals, respectively. Amiodarone and verapamil completely prevented the onset of VT and VF. Protection from arrhythmias seems to be related to the combined presence of a noncompetitive adrenergic blockade associated with salutary effects on coronary circulation. These findings correlate with and help to explain the results of clinical trials in postmyocardial infarction patients. This model may help to provide a rational choice of antiarrhythmic drugs to be tested in clinical trials.
D000638:Amiodarone / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000209:etiology*; D002415:Cats; D003327:Coronary Disease / Q000150:complications* / Q000188:drug therapy; D004195:Disease Models, Animal; D004562:Electrocardiography; D006439:Hemodynamics / Q000187:drug effects; D008012:Lidocaine / Q000494:pharmacology; D008801:Mexiletine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D013233:Stellate Ganglion / Q000503:physiopathology*
D000889:Anti-Arrhythmia Agents; D008801:Mexiletine; D008012:Lidocaine; D011433:Propranolol; D000638:Amiodarone; D011224:Prazosin