Effects of short-term and long-term theobromine administration to male dogs

Gans, Joseph H.; Korson, Roy; Cater, Marilyn R.; Ackerly, Cynthia C.

doi:10.1016/0041-008x(80)90360-9

Cited by 66 publications

(32 citation statements)

References 8 publications

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“…Although the coronary arterial lesions in dogs treated with minoxidil were qualitatively similar to those induced by other vasodilators and cardiostimulatory/vasodilator drugs (10,11,21,22,31,38) or even some of the spontaneous cases (17,33), there were some significant quantitative differences. Unlike spontaneous cases (25) and dogs treated with nicorandil (Mesfin, unpublished data) the extramural coronary arteries were not involved in dogs treated with minoxidil.…”

Section: Mechanism Ofright Atrial Lesions In Dogs Treated With Toxic mentioning

confidence: 89%

“…Minoxidillowers blood pressure in experimen- (13), and right ce s, moxi 1 oes no pro uee 0 os a 1C y -, " " t ' , it h littl ffi t atrial hemorrhagic lesions (7,34) , a car lOS imu a ory receptor antagonists, or y antic 0 mergic or antidil t d (J P' tt I . vaso 1a or rug , mco ,persona cornmumcation) and in dogs exposed to x-radiation (36), Coronary arterial injury similar to that seen in dogs treated with minoxidil has also been reported in dogs treated with several other vasodilators including theobromine (10), hydralazine (22), nicorandil (Mesfin, unpublished data), digitalis (38), and other cardiostimulatorylvasodilator drugs [SKF 94120 (11) and CI-920 (31)]. In the dog, atrial hemorrhagic lesions occur on the right side of the heart where coronary vascular injury 'occurs most consistently.…”

Section: Introduction Histaminic Agents; Nor Is It Attenuated By Sympmentioning

confidence: 88%

“…Some ofthe inconsistencies are probably due to dif- (21): coronary arterial medial hemorrhage and necrosis, subendocardial necrosis, and right atrial hemorrhagic lesions. Coronary arterial injury similar to that seen in dogs treated with minoxidil (13,21) has also been associated with several other vasodilators (10,22) and cardiostimulatory drugs (11,31,38). The progressive hemorrhagic right atrial lesions, however, were detected only in association with minoxidil (7,21,34), nicorandil (Mesfin, unpublished data), theobromine (10), and SKF 94120 (J. Pincott, personal communication).…”

Section: Mechanism Ofright Atrial Lesions In Dogs Treated With Toxic mentioning

confidence: 99%

“…However, the relationship, if any, between the vascular lesions and right atrial hemorrhagic lesions has not been defined. There have been several reports dealing with cardiovascular toxicity associated with vasodilators and cardiostimulatory drugs (7,10,11,13,22,31,34,36,38). These reports, however, were limited to either the early or late phase of the lesions, thereby failing to provide the spectrum and progression of these lesions.…”

Section: Introduction Histaminic Agents; Nor Is It Attenuated By Sympmentioning

confidence: 99%

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Pathogenesis of Cardiovascular Alterations in Dogs Treated with Minoxidil

et al. 1989

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Minoxidil and other potent vasodilators cause coronary arterial injury, right atrial hemorrhagic lesions, and subendocardial necrosis in dogs, This paper discusses the pathogenesis of coronary arterial and right atrial lesions associated with minoxidil in the dog, Acute coronary vascular injury characterized by segmental medial hemorrhage and necrosis and perivascular inflammation occurred only during the first few days of treatment, after which tolerance to further acute injury developed, At 30 d or more of treatment, coronary vascular injury was characterized by perivascular fibrosis rarely attended by medial distortion or hyperplasia and subintimal thickening, changes consistent with responses to previous injury, Right atrial hemorrhagic lesions, unlike coronary vascular injury, often became progressively more extensive with continued treatment. At 3 d, atrial hemorrhage and inflammation were confined to the subepicardium ofthe right atrium, evidently around affected subepicardial branches of the right coronary artery, At 30 d, fibrovascular proliferative right atrial lesions (granulation tissue with evidence of continual hemorrhage) extended from the epicardium to the myocardium, with eventual replacement ofthe atrial wall by mature connective tissue at I yr of treatment. Minoxidil-induced cardiovascular lesions were not prevented by treatment with a l3-blocker (propranolol), or an a-blocker (dibenzylene), or by sympathetic neural activity suppression (surgical sympathectomy or constant carotid sinus nerve stimulation), suggesting that the sympathetic response to the pharmacologic activity of minoxidil was not responsible for the induction of the cardiovascular lesions. Minoxidil-related vascular lesions were confined to the most pharmacologically responsive segment of the arterial system, the coronary arteries, suggesting that medial injury may have been associated with tensile changes in the arterial wall.

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Section: Mechanism Ofright Atrial Lesions In Dogs Treated With Toxic mentioning

confidence: 89%

Section: Introduction Histaminic Agents; Nor Is It Attenuated By Sympmentioning

confidence: 88%

Section: Mechanism Ofright Atrial Lesions In Dogs Treated With Toxic mentioning

confidence: 99%

Section: Introduction Histaminic Agents; Nor Is It Attenuated By Sympmentioning

confidence: 99%

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Pathogenesis of Cardiovascular Alterations in Dogs Treated with Minoxidil

et al. 1989

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“…Aminophylline is reported to enhance beta-adrenergic receptor-mediated responses, and is a phosphodiesterase inhibitor (24). Although one way these drugs exert their influence on the myocardium is via the coronary vascular response (17,18,54), there is little evidence that a chronic inflammation of the vessels is responsible.…”

Section: Drug-induced Arteritismentioning

confidence: 99%

Animal Models of Vasculitis

Bishop

1989

Toxicol Pathol

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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.

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Theobromine 83‐67‐0

2004

Sax's Dangerous Properties of Industrial Materials

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Effects of short-term and long-term theobromine administration to male dogs

Cited by 66 publications

References 8 publications

Pathogenesis of Cardiovascular Alterations in Dogs Treated with Minoxidil

Pathogenesis of Cardiovascular Alterations in Dogs Treated with Minoxidil

Animal Models of Vasculitis

Theobromine 83‐67‐0

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