Phentolamine reduces myocardial injury and mortality in a rat model of phenylpropanolamine poisoning.
BACKGROUND
Phenylpropanolamine produces dose-related, life-threatening cardiovascular, and central nervous toxicity from alpha-adrenergic overstimulation. Although some recommend the alpha-adrenergic antagonist, phentolamine, as treatment for such toxicity, its therapeutic efficacy has not been previously studied. We sought to determine if pretreatment with phentolamine could reduce acute myocardial injury and mortality in rats administered an overdose of phenylpropanolamine.


METHODS
In the mortality arm of the study, 28 unanesthetized, male Wistar rats (14 animals per group) were randomized to receive an intraperitoneal injection of phentolamine (3 mg/kg) or an equal volume of normal saline diluent (control group). Twenty-five minutes later, all rats received an intraperitoneal injection of phenylpropanolamine (150 mg/kg). Mortality was compared at 24 hours. In the myocardial injury arm of the study, 20 unanesthetized rats (10 per group) were randomized to receive an intraperitoneal injection of phentolamine (3 mg/kg) or normal saline (control group). Twenty-five minutes later, all rats received an intraperitoneal injection of phenylpropanolamine (75 mg/kg). Seventy-two hours after phenylpropanolamine administration, all surviving animals were sacrificed and 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 lower in the phentolamine-pretreated rats (2/14; 14%) as compared to the control group (10/14; 71%; p = 0.006). The degree of myocardial injury was significantly lower in the phentolamine-pretreated rats (0) as compared to the control group (1.4 +/- 1.6; p = 0.012).


CONCLUSIONS
In this rat model, phentolamine pretreatment prevented acute myocardial injury and significantly reduced lethality from an intraperitoneal phenylpropanolamine overdose.
Burns
M J
MJ
Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. mburns@caregroup.harvard.edu
Dickson
E W
EW
Sivilotti
M L
ML
Cuenoud
H
H
D000316:Adrenergic alpha-Agonists / Q000633:toxicity*; D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000818:Animals; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000187:drug effects* / Q000473:pathology; D007274:Injections, Intraperitoneal; D008136:Longevity / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000139:chemically induced / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D010646:Phentolamine / Q000627:therapeutic use*; D010665:Phenylpropanolamine / Q000633:toxicity*; D011041:Poisoning / Q000401:mortality / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D010665:Phenylpropanolamine; D010646:Phentolamine