title: Effects of extreme hemodilution with hemoglobin-based O2 carriers on microvascular pressure.
abstract: A surface-modified polyethylene glycol-conjugated human hemoglobin (MP4) and alpha alpha-cross-linked human hemoglobin (alpha alpha Hb) were used to restore oxygen carrying capacity in conditions of extreme hemodilution (hematocrit 11%) in the hamster window model preparation. Changes in microvascular function were analyzed in terms of effects on capillary pressure and functional capillary density (FCD). MP4, at 1.0 +/- 0.2 g/dl blood concentration, significantly lowered mean arterial pressure (MAP) below baseline (99.6 +/- 7.6 mmHg) to 82.4 +/- 6.9 mmHg (P < 0.05) and decreased of FCD to 70 +/- 9%. alpha alpha Hb caused a greater recovery in MAP to 94.4 +/- 6.2 mmHg and lowered FCD to 62 +/- 8%. However, differences between alpha alpha Hb and MP4 in FCD were not statistically significant. Capillary pressures were in the ranges of 17-21 mmHg for MP4 and 15-19 mmHg for alpha alpha Hb, with both significantly lower than baseline (P < 0.05). Pressure in 80-microm-diameter arterioles was significantly increased with alpha alpha Hb relative to MP4 (P < 0.05). These results were compared with previous findings on the relation between capillary pressure and FCD; they supported the concept of a relationship between FCD and capillary pressure. Measurement of changes in arteriolar diameter, microvascular blood flow, and FCD show that there was no statistical difference between using alpha alpha Hb and MP4 in extreme hemodilution. Microvascular resistance in arterioles with a diameter range of 70-80 microm showed an increase relative to control with alpha alpha Hb, whereas MP4 caused a decrease.
authors.affiliation: Department of Bioengineering, University of California-San Diego, La Jolla, CA 92093-0412, USA. pcabrales@ucsd.edu
authors.forename: Pedro
authors.initials: P
authors.lastname: Cabrales
authors.forename: Amy G
authors.initials: AG
authors.lastname: Tsai
authors.forename: Robert M
authors.initials: RM
authors.lastname: Winslow
authors.forename: Marcos
authors.initials: M
authors.lastname: Intaglietta
mesh_terms: D000818:Animals; D001160:Arterioles / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001802:Blood Substitutes / Q000494:pharmacology*; D002196:Capillaries / Q000502:physiology; D006224:Cricetinae; D006438:Hemodilution; D006454:Hemoglobins / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology*; D008647:Mesocricetus; D008833:Microcirculation / Q000502:physiology; D011092:Polyethylene Glycols / Q000494:pharmacology*; D012867:Skin / Q000098:blood supply*; D014661:Vasoconstriction / Q000502:physiology; D014699:Venules / Q000502:physiology
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D008301:Maleimides; C493836:maleimide-polyethylene glycol-modified hemoglobin, MP4; D011092:Polyethylene Glycols