Quantitative imaging of microvascular permeability in a rat model of lipopolysaccharide-induced sepsis: evaluation using cryostatic micro-computed tomography.
OBJECTIVE
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
Contrast agents are useful to characterize vascular leakage and vascular volume fraction in an animal model of endotoxin priming.
Langheinrich
Alexander C
AC
Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Ritman
Erik L
EL
D000818:Animals; D002199:Capillary Permeability; D003287:Contrast Media / Q000493:pharmacokinetics*; D003331:Coronary Vessels / Q000378:metabolism; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology*; D004926:Escherichia coli; D021621:Imaging, Three-Dimensional; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply; D007668:Kidney / Q000098:blood supply / Q000378:metabolism; D008070:Lipopolysaccharides / Q000009:adverse effects; D008099:Liver / Q000098:blood supply / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000209:etiology / Q000503:physiopathology*; D012826:Silicone Elastomers; D014057:Tomography, X-Ray Computed / Q000379:methods*
D003287:Contrast Media; D008070:Lipopolysaccharides; D012826:Silicone Elastomers