The effects of
perhexiline on survival time and
infarct size were studied in three animal models. Dogs pretreated orally with
perhexiline, 200 mg/day/14 days, and monitored under
anesthesia for 30 hours after
ligation of the left anterior descending coronary artery (LAD) had
infarct weights of 9.1+/-1.9 g as compared to 15.2+/-1.0 g in paired untreated controls (P less than .02). Twelve of 15
perhexiline-pretreated dogs survived the duration of these studies while only 5 of 15 control animals survived for the same period of time (P less than .05). Serum
creatine phosphokinase activity was significantly lower in the treated dogs at 9, 12 and 15 hours after
ligation (P less than .05). Conscious dogs, pretreated orally with
perhexiline 200 mg/day/7 days or 400 mg/day/7 days and monitored without
anesthesia or
analgesia for 72 hours after coronary
ligation had smaller
infarcts (P200=26+/-5; P400=26+/-4;
C=39+/-5 g; P less than .05) lower plasma peak
creatine phosphokinase activity (P less than .05) and reduced heart rate (P400=198+/-8; C=226+/-8 beats/min; P less than .05) and reduced incidence of
ventricular ectopic beats (P less than .05). In
pentobarbital anesthetized open-chest dogs,
perhexiline (3 mg/kg i.v.) reduced the sum of S-T segment elevation after left anterior descending coronary artery occlusion from 32+/-3 to 14+/-1 mV (P less than .001); this effect was associated with and/or preceded by a reduction in arterial pressure (101+/-4 to 78+/-5 mm Hg; P less than .001) and heart rate (151+/-8 to 138+/-7 beats/min P less than .025; Circumflex flow increased from 38+/-4 to 83+/-8 ml/min (P less than .01). In noninfarcted open-chest dogs,
perhexiline administration (3 mg/kg i.v.) resulted in increases in coronary blood flow, narrowing of arterial-coronary sinus O2 difference and a 14% reduction in myocardial O2 consumption. The protective effects of
perhexiline on the ischemic myocardium appear to result from reductions in heart rate and associated decrease in myocardial O2 demand as well as an antiarrhythmic effect.