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Testing the Efficacy of Pharmacological Agents in a Pericardial Target Delivery Model in the Swine
Published on: July 7, 2016
Dexamethasone could improve myocardial infarction outcomes and provide new therapeutic options for non-interventional
1Marshfield Clinic Research Foundation, 1000 Oak Avenue, Marshfield, WI 54449, USA. Alisky.Joseph@Marshfieldclinic.org
Background:
Statins reduce death and morbidity of acute myocardial infarction in part through immunosuppressive mechanisms, suggesting glucocorticoids could produce similar benefits. Glucocorticoids inhibit proliferation of smooth muscle cells and activation of macrophages within atherosclerotic plaques and protect ischemic myocardium through inhibition of a heat shock protein. Dexamethasone-eluting coronary stents have a decreased rate of restenosis, and oral prednisone reduces restenosis of conventional stents. Some studies from the 1970's and 1980's showed that steroids improve survival in myocardial infarction, but no conclusive large-scale randomized well-powered trials have been conducted.
Presentation Of The Hypothesis:
Dexamethasone administered alongside statins in the setting of acute myocardial infarction could attenuate myocardial damage in patients with diffuse disease.
Testing The Hypothesis:
Patients with acute myocardial infarction who cannot undergo angioplasty or coronary artery bypass grafting could be given a statin and intravenous and oral dexamethasone. Dexamethasone minimizes fluid retention and avoids mineralocorticoid-induced cell proliferation in plaques. Blood glucose monitoring should be ordered for all patients, but diabetic patients need not be excluded. There should be measures to prevent steroid-induced homocystinuria or more common complications such as ulcers, osteoporosis, infections and psychosis.
Implications Of The Hypothesis:
Showing that acute coronary syndrome is a steroid-responsive disorder would have immediate relevance for patients limited to medical management because of anatomy and comorbidities, and results would similarly have application for acute ischemic stroke.
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