Attenuation of Microvascular Permeability Dysfunction in Postischemic Striated Muscle by Hydroxyethyl Starch

• Published in: Microvascular research 1995-07, Vol.50 (1), p.71-79
• Main Authors: Oz, Mehmet C., FitzPatrick, Michael F., Zikria, Bashir A., Pinsky, David J., Durán, Walter N.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Capillary Permeability - drug effects; Cell Adhesion - drug effects; Cells, Cultured; Dextrans - pharmacokinetics; Endothelium, Vascular - cytology; Fluorescein-5-isothiocyanate - analogs & derivatives; Fluorescein-5-isothiocyanate - pharmacokinetics; Humans; Hydroxyethyl Starch Derivatives - pharmacology; In Vitro Techniques; Ischemia - physiopathology; Macromolecular Substances; Male; Medical sciences; Metabolic Clearance Rate; Muscle; Muscle, Skeletal - blood supply; Muscle, Skeletal - drug effects; Muscle, Skeletal - injuries; Neutrophils - cytology; Pharmacology. Drug treatments; Rats; Rats, Inbred WF; Reperfusion Injury - drug therapy; Reperfusion Injury - physiopathology
• ISSN: 0026-2862; 1095-9319
• DOI: 10.1006/mvre.1995.1039

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 μl/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 ischemiareperfusion. 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). We propose that HES-Pz may act by sealing and restoring microvascular integrity and by blunting the increased adhesiveness of stimulated endothelial cells for neutrophils.