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Cardiovascular alterations in dogs treated with hydralazine
G M Mesfin1, G G Shawaryn, M J Higgins
1Pathology and Toxicology Research, Upjohn Company, Kalamazoo, Michigan 49001.
Toxicologic Pathology
|January 1, 1987
Summary
Hydralazine treatment in dogs caused increased heart rates and cardiac hemorrhages, particularly at higher doses. Some dogs experienced reduced appetite, vomiting, and altered blood chemistry, indicating potential cardiovascular toxicity.
Area of Science:
- Veterinary Pharmacology
- Toxicology
- Cardiovascular Pathology
Background:
- Hydralazine is a vasodilator used in human medicine.
- Understanding its effects in animal models is crucial for safety assessment.
- Beagle dogs are commonly used in preclinical drug studies.
Purpose of the Study:
- To evaluate the clinical and pathological effects of hydralazine in beagle dogs.
- To determine dose-dependent toxicity and target organs.
- To assess cardiovascular responses and hematological/biochemical changes.
Main Methods:
- Male beagle dogs received oral hydralazine (12 or 24 mg/kg) or placebo twice daily for two days.
- Clinical observations, heart rate monitoring, and terminal body weight were recorded.
- Hematology, blood chemistry, and microscopic examination of major organs (heart, liver, kidneys, spleen, thymus) were performed.
Main Results:
- Hydralazine increased heart rates (60-80%) and caused decreased appetite and vomiting at higher doses.
- Cardiac pathology included epicardial and subepicardial hemorrhage in the right atrium.
- Coronary artery medial hemorrhage and necrosis were observed, especially at the 24 mg/kg dose.
Conclusions:
- Hydralazine induces cardiovascular toxicity in beagle dogs, characterized by tachycardia and cardiac hemorrhage.
- Dose-dependent adverse effects on appetite, gastrointestinal function, and blood chemistry were noted.
- The heart, specifically the coronary arteries and right atrium, is a primary target organ for hydralazine toxicity.