Acute cardiomyopathy induced by the vasodilating antihypertensive agent minoxidil

Herman, Eugene H.; Balázs, T.; Young, Robert S.; Earl, Francis L.; Krop, Stephen; Ferrans, Víctor J.

doi:10.1016/0041-008x(79)90520-9

Cited by 51 publications

(30 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Right atrial epicardial hemorrhage, necrosis and granulation tissue formation was seen with all 4 compounds at the higher dose levels with early changes probably occurring in the first few days of treatment. These findings are consistent with those previously described for the vasodilating agent minoxidil (6,11).…”

Section: Long-term Changes (6 Months)supporting

confidence: 83%

See 1 more Smart Citation

Coronary Vascular Lesions in Dogs Treated with Phosphodiesterase III Inhibitors

Isaacs¹,

Joseph²,

Betton³

1989

Toxicol Pathol

View full text Add to dashboard Cite

ABSTRACfA treatment-related coronary arteriopathy has been observed in the dog following the oral or intravenous administration of 4 potent phosphodiesterase type III inhibiting inodilators at high multiples of their ED so for periods from 1 day to 6 months. A fifth compoundofa similarpharmacological class exhibitedlimiting toxicity at lowmultiples ofits ED so and thiscompoundfailed to inducecoronary arteriallesions. The earliest treatment-related findings observed were medial hemorrhage and necrosis with focal breaks in the internal elastic lamina. Laterchanges, observed fromday 9 onwards, included intimalthickening consisting ofsmooth muscle proliferation with a mucoid ground substance, variable and inconsistent inflammatory changes involving one or morearterialtunicsand adventitial hemorrhage, fibrosis and neovascularization. The changes were restricted to the coronary arteries including the extramural and intramural branches. The distribution oflesions variedfrom widespread, multifocal involvement of both coronary arterialsystems to focal lesions with no obvious site of predilection. Induction of this lesion may involve changes in coronary flow and pressure as a result of an exaggerated pharmacological response to this class of compound. The susceptibility of other species (rat, cynomolgus monkey, or pig) to this effect has been investigated with no treatmentrelated arteriopathy being observed.

show abstract

Section: Long-term Changes (6 Months)supporting

confidence: 83%

“…Drug-induced changes in the coronary arteries have been reported infrequently in the dog and are often associated with compounds possessing inotropic and/or vasodilating activity (3,4,6,13,15,16). The majority oflesions are reported as arteritis/ peri-arteritis affecting both intramural and extramural vessels.…”

Section: Introductionmentioning

confidence: 99%

Coronary Vascular Lesions in Dogs Treated with Phosphodiesterase III Inhibitors

Isaacs¹,

Joseph²,

Betton³

1989

Toxicol Pathol

View full text Add to dashboard Cite

show abstract

“…In addition to the hypersensitivity type reactions to various drugs, several agents have been described which have specific effects on coronary vasculature. Minoxidil is one of the best known (22,23,53), affects the small arteries and arterioles especially in the atria, causes epicardial hemorrhagic lesions, and eventually results in fibrotic lesions. This compound has been adequately described by others at this symposium.…”

Section: Drug-induced Arteritismentioning

confidence: 99%

Animal Models of Vasculitis

Bishop

1989

Toxicol Pathol

View full text Add to dashboard Cite

There are .several naturally occurring and iatrogenic models of vasculitis available in animals, although few have primary coronary vessel lesions. Aleutian disease of mink and equine viral arteritis are 2 well studiednaturaldiseases whichmaybe produced experimentally and, thus, makegoodanimalmodels. Several drugs have beenidentified which produce myocardial lesions, including vasculitis, in susceptible individuals o~whe? given in highenough doses. Immune mediatedmechanisms are probably amongthe most important etiologic factors for the development of vasculitis and must be given high priority when exploring the pathogenesis of any vasculitis.

show abstract

“…Coronary vascular injury and persistent hemorrhage into the right atrium, discovered in dogs treated with minoxidil (5, 12,22), have recently been noted in dogs treated with other vasodilators such as theobromine (8) and nicorandil (Mesfin, unpublished). Coronary vascular injury with these and other vasodilator/cardioactive drugs including.SK&F 94 120 (10) and CI-930 (Gough, personal communication), like papillary necrosis (2,3), apparently occurs only during the initial few days of treatment.…”

Section: Introductionmentioning

confidence: 99%

“…Coronary vascular injury with these and other vasodilator/cardioactive drugs including.SK&F 94 120 (10) and CI-930 (Gough, personal communication), like papillary necrosis (2,3), apparently occurs only during the initial few days of treatment. Vascular injury in dogs treated with vasodilators for 2 to 3 days was characterized by medial hemorrhage and necrosis of the muscular branches of the coronary arteries (12,16). Lesions seen in dogs treated with vasodilators for 30 days or longer were characterized by medial fibrosis or hypertrophy and/or subintimal fibrosis (10, 16)-alterations consistent with response to a previous vascular injury.…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular Alterations in Dogs Treated with Hydralazine

1987

View full text Add to dashboard Cite

Groups of 5 male beagle dogs were treated orally with hydralazine tablets in gelatin capsules at a dose of 12 or 24 mdkg 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 mdkg group ate less than control group. Dogs treated with 24 mdkg did not eat and vomited. Heart rates in both ofthe 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 mglkg. 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.

show abstract

Acute cardiomyopathy induced by the vasodilating antihypertensive agent minoxidil

Cited by 51 publications

References 14 publications

Coronary Vascular Lesions in Dogs Treated with Phosphodiesterase III Inhibitors

Coronary Vascular Lesions in Dogs Treated with Phosphodiesterase III Inhibitors

Animal Models of Vasculitis

Cardiovascular Alterations in Dogs Treated with Hydralazine

Contact Info

Product

Resources

About