Hemodynamic Correlates of Drug-induced Vascular Injury in the Rat Using High-frequency Ultrasound Imaging
| Autor: | E. Clive Joseph, Teri Conte, Ben Deeley, Susan Portugal, Bradley E. Enerson, Sharon A. Sokolowski, Todd Wisialowski, John M. Kreeger, Catherine Rief, Michael P. Lawton, Paul Nugent, Terri A. Swanson, Leslie A. Obert |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Niacinamide Tunica media Pathology medicine.medical_specialty Drug-Related Side Effects and Adverse Reactions Fenoldopam Pyridines Hemodynamics Vasodilation Toxicology Peripheral blood mononuclear cell Pathology and Forensic Medicine Rats Sprague-Dawley medicine Animals Molecular Biology Mesenteric arteries Ultrasonography business.industry Tunica Adventitia Azepines Cell Biology Blood flow Vascular System Injuries Mesenteric Arteries Rats Pyridazines medicine.anatomical_structure business medicine.drug |
| Zdroj: | Toxicologic Pathology. 42:784-791 |
| ISSN: | 1533-1601 0192-6233 |
| DOI: | 10.1177/0192623314525687 |
| Popis: | Several classes of drugs have been shown to cause drug-induced vascular injury (DIVI) in preclinical toxicity studies. Measurement of blood flow and vessel diameter in numerous vessels and across various tissues by ultrasound imaging has the potential to be a noninvasive translatable biomarker of DIVI. Our objective was to demonstrate the utility of high-frequency ultrasound imaging for measuring changes in vascular function by evaluating blood flow and vessel diameter in the superior mesenteric arteries (SMA) of rats treated with compounds that are known to cause DIVI and are known vasodilators in rat: fenoldopam, CI-1044, and SK&F 95654. Blood flow, vessel diameter, and other parameters were measured in the SMA at 4, 8, and 24 hr after dosing. Mild to moderate perivascular accumulations of mononuclear cells, neutrophils in tunica adventitia, and superficial tunica media as well as multifocal hemorrhage and necrosis in the tunica media were found in animals 24 hr after treatment with fenoldopam and SK&F 95654. Each compound caused marked increases in blood flow and shear stress as early as 4 hr after dosing. These results suggest that ultrasound imaging may constitute a functional correlate for the microscopic finding of DIVI in the rat. |
| Databáze: | OpenAIRE |
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