Mj. Burns et al., Phentolamine reduces myocardial injury and mortality in a rat model of phenylpropanolamine poisoning, J TOX-CLIN, 39(2), 2001, pp. 129-134
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.