Hydroxyethyl Starch Reduces Leukocyte Adherence and Vascular Injury in the Newborn Pig Cerebral Circulation After Asphyxia

Abstract

Background and Purpose-Hydroxyethyl starch (HES) has beneficial effects on ischemic brain injury; however, its mechanism of action remains unclear. The present study was undertaken to test the hypothesis that HES can attenuate increases in leukocyte adherence and vascular permeability in the cerebral vasculature after global cerebral ischemia induced by asphyxia. Methods-Pial venular leukocyte adherence and permeability to sodium fluorescein were quantified in anesthetized newborn piglets by in situ fluorescence videomicroscopy through closed cranial windows during basal conditions and during 2 hours of reperfusion after global ischemia induced by 9 minutes of asphyxia. Experimental animals received HES after the asphyxial insult (10% HES 257/0.47, 600 mg/kg IV bolus 5 minutes after asphyxia, followed by 600 mg/kg per hour IV drip during reperfusion; nϭ9). Results-A progressive and significant (PϽ0.05) increase in adherent leukocytes was observed during the initial 2 hours of reperfusion after asphyxia compared with nonasphyxial controls. In this model, vascular injury, as determined by significant (PϽ0.05) increases in fluorescein permeability at 2 hours of reperfusion, is largely dependent on adherent leukocytes. HES significantly reduced (PϽ0.05) leukocyte adherence at 1 hour and 2 hours of reperfusion and reduced fluorescein permeability at 2 hours. HES did not change hematocrit or alter pial arteriolar diameter. Conclusions-These findings indicate that a vascular anti-inflammatory action may underlie the beneficial effects of HESin global cerebral ischemia secondary to asphyxia. Since this compound is well tolerated by patients, future preclinical and clinical studies may reveal improvements in functional outcome with the early introduction of this or similar agents after perinatal asphyxia or global ischemia. (Stroke. 2000;31:2218-2223.)Key Words: cerebral ischemia, global Ⅲ inflammation Ⅲ leukocytes Ⅲ reperfusion injury H ydroxyethyl starch (HES) is a clinically well-tolerated complex polysaccharide that has recently been used in the therapeutic treatment of stroke and vasospasm after subarachnoid hemorrhage. It is available in multiple preparations, each with different pharmacological characteristics based on concentration, molecular weight, degree of substitution, and C2/C6 hydroxyethylation ratio. While HES has shown a protective effect with reductions in infarct size and/or improvement in outcome in experimental models of ischemic injury in both central nervous system (CNS) 1-6 and peripheral tissues, 7-10 results of its use in clinical stroke trials have been less encouraging. [11][12][13] This may relate to the time window of administration of the compound relative to stroke onset, as well as the pharmacological characteristics of the particular HES preparation; nevertheless, clinical interest still remains, 14 particularly in situations of elevated intracranial pressure. 15 See Editorial Comment, page 2223The mechanistic basis of the beneficial effects of HES remains unclear. Postulated actions inc...

Endothelial Accumulation of Hydroxyethyl Starch and Functional Consequences on Leukocyte-Endothelial Interactions

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Albumin Therapy of Transient Focal Cerebral Ischemia

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