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Toxicologic Pathology
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Journal Article

Cardiovascular Alterations in Dogs Treated with Hydralazine

Gabre M. Mesfin

Pathology and Toxicology Research, The Upjohn Company, Kalamazoo, Michigan 49001

Gregory G. Shawaryn

Pathology and Toxicology Research, The Upjohn Company, Kalamazoo, Michigan 49001

Michael J. Higgins

Pathology and Toxicology Research, The Upjohn Company, Kalamazoo, Michigan 49001

Groups of 5 male beagle dogs were treated orally with hydralazine tablets in gelatin capsules at a dose of 12 or 24 mg/kg twice a day (6 hours apart) for 2 consecutive days. Five male dogs treated with empty gelatin capsules served as untreated controls. Clinical findings and heart rate changes during treatment and terminal body weight, hematology, and blood chemistry changes were evaluated. The heart, liver, kidneys, spleen, and thymus of each animal were examined microscopically. Dogs in the 12 mg/kg group ate less than control group. Dogs treated with 24 mg/kg did not eat and vomited. Heart rates in both of the treated groups increased by 60 to 80% within 2 hours of treatment and remained high during the entire treatment period. Significant hematologic change was confined to a slight increase in platelet number of dogs treated with 24 mg/kg. Serum glucose was increased in the hydralazine treated dogs. Conjugated serum bilirubin was increased and serum potassium, chloride and phosphorus were decreased in the 24 mg/kg group. Blood urea nitrogen and serum chloride were slightly increased in dogs treated with 12 mg/kg. Treatment-related pathologic alterations were confined to the heart. Two dogs from each of the hydralazine groups experienced acute localized hemorrhage into the epicardium and subepicardium of the right atrium. The media of the muscular branches of the coronary arteries, especially the left coronary artery, was hemorrhagic in 3 dogs from the 24 mg/kg group. Medial necrosis, when seen, tended to be proportional to the severity of medial hemorrhages. There was no necrosis in the papillary muscles of the heart. These acute cardiovascular alterations in dogs treated with hydralazine for 2 days—believed to be related to exaggerated pharmacologic effects of the drug—were similar to the lesions seen in dogs treated with minoxidil for 2 to 3 days.

Toxicologic Pathology, Vol. 15, No. 4, 409-416 (1987)
DOI: 10.1177/019262338701500404
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