Phentolamine reduces myocardial injury and mortality in a rat model of phenylpropanolamine poisoning

Background: Phenylpropanolamine produces dose-related, life-threatening car diovascular, and central nervous toxicity from alpha-adrenergic overstimula tion. Although some recommend the alpha-adrenergic antagonist, phentolamine , as treatment for such toxicity, its therapeutic efficacy has not been per viously studied. We sought to determine if pretreatment with phentolamine c ould reduce acute myocardial injury and mortality in rats administered an o verdose of phenylpropanolamine. Methods: In the mortality arm of the study, 28 unanestetized, male Wistar rats (14 animals per group) were randomized to receive an intraperitoneal injection of phentolamine (3 mg/kg) or an equ al volume of normal saline diluent (control group). Twenty-five minutes lat er, all rats received an intraperitoneal injection of phenylpropanolamine ( 150 mg/kg). Mortality was compared at 24 hours. In the myocardial injury ar m of the study, 20 unanesthetized rats (10 per group) were randomized to re ceive an intraperitoneal injection of phentolamine (3 mg/kg) or normal sali ne (control group). Twenty-five minutes later, all rats received an intrape ritoneal injection of phenylpropanolamine (75 mg/kg). Seventy-two hours aft er phenylpropanolamine administration, all surviving animals were sacrifice d and a transverse sections of their hearts were graded histologically for injury by a blinded cardiac pathologist. Results: Twelve rats died within 6 hours of phenylpropanolamine administration. Mortality was significantly l ower in the phentolamine-pretreated rats (2/14; 14%) as compared to the con trol group (10/14; 71%; p = 0.006). The degree of myocardial injury was sig nificantly lower in the phentolamine-pretreated rats (0) as compared to the control group (1.4 +/- 1.6; p = 0.012). Conclusion: In this rat model, phe ntolamine pretreatment prevented acute myocardial injury and significantly reduced lethality from an intraperitoneal phenylpropanolamine overdose.