Quantitative Imaging of Microvascular Permeability in a Rat Model of Lipopolysaccharide-Induced Sepsis

Abstract

The aim of the present study was to evaluate the magnitude of endothelial defects by micro-computed tomography (CT) quantitation of contrast agent diffusion across the vascular endothelium in a rat model of vascular permeability caused by lipopolysaccharide (LPS)-induced sepsis. LPS was administered intraperitoneally (i.p.) at a dose of 10 mg/kg body weight in male Wistar rats (n = 18). Vascular leakage and vascular volume were quantified, by micro-CT and cryostatic micro-CT. The contrast agents used were Fenestra ( approximately 70-nm particle diameter), Microfil (large polymer), and iopamidol (Isovue, MW 777 Dalton). Micro-CT revealed an increase in endothelial permeability as indicated by entry of contrast agent (Fenestra) into the extravascular space after LPS administration (P < 0.01). Endotoxin exposure also induced a decrease of vascular luminal volume in the myocardium, liver, kidney, and colonic wall determined by micro-CT (P < 0.01). Vascular leakage, expressed as the ratio of extravascular to intravascular gray scale intensity (IE/II) after injection of contrast agent, increased significantly in the myocardium, liver, kidney, and colonic wall (P < 0.001). The elimination of iopamidol from the intravascular compartment in LPS-challenged rats was decreased compared with control rats. The endothelial defect size was estimated to be >70 nm and <1 microm. Contrast agents are useful to characterize vascular leakage and vascular volume fraction in an animal model of endotoxin priming.