Hydroxyethyl Starch: The Effect of Molecular Weight and Degree of Substitution on Intravascular Retention In Vivo

Abstract

Hydroxyethyl starch (HES) solution is characterized by its mean molecular weight (MW), concentration, and degree of substitution (DS). This character varies worldwide. After binding fluorescein-isothiocyanate (FITC-HES), we evaluated the retention rate of three types of 6% HES in the A2 and V2 blood vessels of rat cremaster muscles using intravital microscopy in a mild hemorrhage model (10% of total blood volume). After blood withdrawal, we infused three types of FITC-HES: HES-A (MW 150-200 kDa, DS 0.6-0.68), HES-B (MW 175-225 kDa, DS 0.45-0.55), or HES-C (MW 550-850 kDa, DS 0.7-0.8) before determining the FITC-HES retention rate in the intravital microscope. For V2, the FITC-HES retention rates 120 min after the start of the infusion were 27% +/- 7.2% of baseline values (HES-A), 65% +/- 9.1% (HES-B), and 86% +/- 9.6% (HES-C); for A2 they were 27% +/- 6.6%, 73% +/- 10.2%, and 89% +/- 8.7%, respectively. HES-B and HES-C were retained in the vessels longer than HES-A (P = 0.028 for V2, P = 0.038 for A2 between HES-B and HES-A; P = 0.022 for V2, P = 0.037 for A2 between HES-C and HES-A). There was no difference in the rate of disappearance from the vessels between HES-B and HES-C. HES-B and HES-C are equally retained in the blood vessels. Middle-sized HES-B with low DS and middle substitution pattern stayed in the blood vessels as long as the large-sized HES. HES solutions of varying characters should be examined to optimize HES infusion.