DIPHENYLHYDANTOIN THERAPY IN EXPERIMENTAL MYOCARDIAL INFARCTION

¹ Department of Medicine and the Department of Pathology, Duke University Medical Center, Durham, North Carolina
² Department of Medicine and thex Department of Pathology, Duke University Medical Center, Durham, North Carolina

Experimental myocardial infarction was produced in 40 farm pigs by gradual coronary occlusion with an Ameroid constrictor placed around the left anterior descending coronary artery. Twenty animals were treated with i.v. diphenylhydantoin, 20 mg/kg initially and then 5 mg every 8 hr for a total period of 72 hr. Twenty animals served as controls. Diphenylhydantoin blood concentrations were monitored throughout. Diphenylhydantoin-treated animals showed an increased percentage of survivors over controls (70 vs. 45%), suggesting a beneficial protective effect from drug therapy. Another group of 12 animals was given diphenylhydantoin, 20 mg/kg i.v. Blood concentrations were monitored for 5 hr and myocardial and cerebral tissue concentrations of the drug were measured. Myocardial diphenylhydantoin levels were detected but were considerably lower than cerebral concentrations, suggesting that the myocardium has a lesser ability to concentrate the drug. It is concluded that in the farm pig diphenylhydantoin, in chronic doses sufficient to produce blood concentrations between 10 and 20 µg/ml, prolonged life and improved survival during experimental myocardial ischemia and infarction.