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

BACKGROUND:Hydroxyethyl starch (HES) solution is characterized by its mean molecular weight (MW), concentration, and degree of substitution (DS). This character varies worldwide. METHODS: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. RESULTS: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. CONCLUSIONS: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.