Design and rationale of CONTRAST--a prospective, randomized, placebo-controlled trial of fenoldopam mesylate for the prevention of radiocontrast nephropathy.

Radiocontrast-induced nephropathy develops in approximately 10% to 20% of patients following administration of iodine-based dye and is one of the most prognostically detrimental complications that invasive cardiologists and radiologists encounter. Preexisting renal dysfunction and diabetes mellitus are two of the most powerful predictors of the likelihood of developing acute renal insufficiency after contrast delivery. To date, only adequate preprocedural hydration and postprocedural hydration to offset dehydration from contrast-induced diuresis have been shown to be effective in preventing this condition. Fenoldopam mesylate, a systemic vasodilator currently FDA-approved for short-term, in-hospital management of severe hypertension, has been shown to increase renal plasma flow in patients with and without chronic renal insufficiency. As a selective agonist of the dopamine-1 receptor, fenoldopam may preserve outer medullary renal blood flow and thereby attenuate radiocontrast-induced nephropathy. Small studies with fenoldopam prior to iodine-based dye administration have demonstrated low rates of radiocontrast nephropathy, and a larger, randomized trial has found that renal blood flow 1 hour after angiography rose in the fenoldopam group compared to a decline in the placebo group. The CONTRAST study has been designed to determine whether fenoldopam is indeed effective in diminishing the occurrence of radiocontrast-induced nephropathy.

Anorexigen-related cardiopulmonary toxicity.

Three years after the withdrawal of fenfluramine and dexfenfluramine from the market, the magnitude and prevalence of their deleterious cardiopulmonary effects remain undetermined. The links between these anorexigens and valvular heart disease and primary pulmonary hypertension, however, are clearly established. Because some evidence indicates that the valvular lesions may regress with cessation of the drug, management guidelines are still in flux. Patient reassurance and close surveillance, including serial echocardiography in selected cases, are warranted.

Radiocontrast nephropathy: the dye is not cast.

A significant source of morbidity and inhospital mortality following percutaneous coronary intervention is radiocontrast-induced nephropathy. Newer strategies, such as using low-osmolar nonionic contrast agents and selective dopamine agonists, are making it possible to greatly reduce the incidence of postcatheterization nephropathy.

Intravascular ultrasound imaging of ruptured atherosclerotic plaques in coronary arteries.

Intravascular ultrasound demonstrated plaque ruptures that occurred in regions involved with large complicated atherosclerotic plaques in the coronary artery. Because intravascular ultrasound evaluates both plaque and luminal dimensions, it contributes to our understanding of the pathophysiology of coronary artery disease.

Does nitroglycerin induce heparin resistance?

We studied the possibility that intravenous nitroglycerin may produce heparin resistance both in vitro and prospectively in a group of 10 patients following coronary angioplasty. Nitroglycerin in physiologic to pharmacologic concentrations (41-250 micrograms/ml) did not produce heparin resistance in vitro as measured by activated partial thromboplastin time and thrombin time. The maximum reduction in activated partial thromboplastin time was 7%. In patient studies, the activated partial thromboplastin time at baseline on heparin alone (93 + 22 s) was not significantly different (p = 0.61) from activated partial thromboplastin measured upon addition of nitroglycerin (94 +/- 27 s) or 30 min following cessation of the nitroglycerin infusion while continuing the same dose of heparin (91 +/- 24 s). We conclude that intravenous nitroglycerin does not induce heparin resistance in vitro or in patients during short-term administration.