Attenuation of microvascular permeability dysfunction in postischemic striated muscle by hydroxyethyl starch.
We examined the effect of hydroxyethyl starch macromolecule (HES-Pz) pretreatment on microvascular transport of macromolecules in ischemia-reperfusion injury. The rat cremaster was splayed, placed in a Lucite intravital chamber, and suffused with bicarbonate buffer. The clearance of fluorescein isothiocyanate dextran 150 (FITC-Dx 150) was measured as an index of microvascular transport. After determination of baseline data, the muscle was made ischemic for 4 hr by clamping the vascular pedicle and subsequently reperfused for 2 hr. In control animals not subjected to ischemia, clearance of FITC-Dx 150 remained constant throughout the experimental 7-hr period. In saline-treated animals, ischemia-reperfusion increased the clearance of FITC-Dx 150 from 1.8 +/- 0.3 to 9.7 +/- 1.0 microliters/15 min/g by the end of the reperfusion period. Pretreatment with HES-Pz, at a concentration of 6% in a volume of saline equivalent to 10% of blood volume, significantly attenuated the microvascular dysfunction produced by ischemia-reperfusion. The mean ratio of postischemic to baseline clearance of FITC-Dx 150 was 1.28 +/- 0.07 (mean +/- SE) for samples taken from the 30th to the 120th min of reperfusion at 15 intervals. Our data support a beneficial effect of HES-Pz on microvascular transport of macromolecules. The role of leukocyte-endothelium adhesion as an underlying mechanism explaining these results was studied by evaluating the effect of HES-Pz on the ability of thrombin-stimulated human umbilical vein endothelial cells (HUVECs) to bind neutrophils. These experiments demonstrated that thrombin-treated HUVECS bound 229% more indium-111-labeled neutrophils than did similarly stimulated HUVECS treated with HES-Pz (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003911:Dextrans / Q000493:pharmacokinetics; D004730:Endothelium, Vascular / Q000166:cytology; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D007511:Ischemia / Q000503:physiopathology; D046911:Macromolecular Substances; D008297:Male; D008657:Metabolic Clearance Rate; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000293:injuries*; D009504:Neutrophils / Q000166:cytology; D051381:Rats; D011920:Rats, Inbred WF; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology
D003911:Dextrans; D006895:Hydroxyethyl Starch Derivatives; D046911:Macromolecular Substances; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate