Effect of E-4031, a class III antiarrhythmic agent, on experimental infarct size in a canine model of myocardial ischemia-reperfusion injury.
Class III antiarrhythmic agents such as E-4031 have demonstrated efficacy in preventing and/or terminating malignant ventricular arrhythmias in experimental models. It has recently been suggested that Class III agents might possess additional antiischemic properties that may translate into a reduction in the frequency or severity of arrhythmia. The potential for the Class III antiarrhythmic agent E-4031 to limit the extent of developing myocardial infarction was assessed in a barbiturate-anesthetized canine model of ischemic-reperfusion injury. Untreated control (n = 13) and E-4031-treated animals (n = 8, 300 micrograms/kg, i.v., immediately preceding myocardial ischemia) were subjected to a 90-min period of left circumflex coronary artery occlusion followed by a 5-h period of reperfusion. The predominant hemodynamic effect displayed by E-4031 was a reduction in heart rate throughout the period of coronary artery occlusion and early reperfusion. Areas at risk of infarction, expressed as percentages of left ventricle, were equivalent in the control and E-4031 treatment groups (38.5 +/- 1.0 and 34.6 +/- 1.9%, respectively). Posterolateral myocardial infarct sizes, expressed either as percentages of risk area or of total left ventricle, were reduced slightly but not significantly in the E-4031 treatment group compared to the control group (35.2 +/- 5.6 and 45.4 +/- 3.0% of risk area, respectively; 12.7 +/- 2.4 and 17.6 +/- 1.4% of left ventricle, respectively). Regional myocardial blood flows in nonischemic and central ischemic zones of myocardium did not differ significantly between the control and E-4031 treatment groups before and during the period of coronary artery occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Holahan
M A
MA
Department of Pharmacology, Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania 19486.
Stranieri
M T
MT
Stabilito
I I
II
Lynch
J J
JJ
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D003326:Coronary Circulation / Q000502:physiology; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D010880:Piperidines / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D014693:Ventricular Fibrillation / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D011725:Pyridines; C063968:E 4031