Background-Therapeutic strategies to stabilize advanced arteriosclerotic lesions may prevent plaque rupture and reduce the incidence of acute coronary syndromes. Thiazolidinediones (TZDs), like rosiglitazone, are oral antidiabetic drugs with additional antiinflammatory and potential antiatherogenic properties. In a randomized, placebo-controlled, single-blind trial, we examined the effect of 4 weeks of rosiglitazone therapy on histomorphological characteristics of plaque stability in artery specimen of nondiabetic patients scheduled for elective carotid endarterectomy. Methods and Results-A total of 24 nondiabetic patients with symptomatic carotid artery stenosis were randomly assigned to rosiglitazone (4 mg BID) or placebo in addition to standard therapy. In this population of nondiabetic patients, rosiglitazone treatment did not significantly change fasting blood glucose, fasting insulin, or lipid parameters. In contrast, rosiglitazone significantly reduced CD4-lymphocyte content as well as macrophage HLA-DR expression in the shoulder region, reflecting less inflammatory activation of these cells by lymphocyte interferon-␥. Moreover, rosiglitazone significantly increased plaque collagen content (7.7Ϯ1.6% versus 3.7Ϯ0.7% of plaque area; Pϭ0.036) compared with placebo, suggesting that TZD treatment may stabilize arteriosclerotic lesions. In addition, rosiglitazone reduced serum levels of 2 inflammatory arteriosclerosis markers: C-reactive protein and serum amyloid A.
Conclusions-Four
Left ventricular contractility is increased in vivo by epoprostenol and iloprost but not by adenosine or sodium nitroprusside at equipotent hypotensive dose. A contribution of sympathetic reflex activation of cardiac nerves on the increase in left ventricular contractility cannot be completely ruled out.
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