Effects of extreme hemodilution with hemoglobin-based O₂ carriers on microvascular pressure

Abstract

-A surface-modified polyethylene glycol-conjugated human hemoglobin (MP4) and ␣␣-cross-linked human hemoglobin (␣␣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 Ϯ 0.2 g/dl blood concentration, significantly lowered mean arterial pressure (MAP) below baseline (99.6 Ϯ 7.6 mmHg) to 82.4 Ϯ 6.9 mmHg (P Ͻ 0.05) and decreased of FCD to 70 Ϯ 9%. ␣␣Hb caused a greater recovery in MAP to 94.4 Ϯ 6.2 mmHg and lowered FCD to 62 Ϯ 8%. However, differences between ␣␣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 ␣␣Hb, with both significantly lower than baseline (P Ͻ 0.05). Pressure in 80-mdiameter arterioles was significantly increased with ␣␣Hb relative to MP4 (P Ͻ 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 ␣␣Hb and MP4 in extreme hemodilution. Microvascular resistance in arterioles with a diameter range of 70 -80 m showed an increase relative to control with ␣␣Hb, whereas MP4 caused a decrease. shear stress; perfusion; plasma expander; blood pressure; blood substitutes

Modulation of Perfusion and Oxygenation by Red Blood Cell Oxygen Affinity during Acute Anemia

“…As in previous studies, hemodilution in combination with a vasoconstrictor effect caused a significant decrease in FCD (13). The lowest FCD coincided with the most pronounced vasoconstriction (Figures 2).…”

“…45%, and arterial O 2 partial pressure (Pa O 2 ) greater than 50 mm Hg; and (2) microscopic examination of the tissue in the chamber observed under a 3650 magnification did not reveal signs of low perfusion, inflammation, edema, or bleeding. Hamsters are a fossorial species with a lower arterial PO 2 ; however, their microvascular PO 2 distribution in the chamber window model is similar to that of other rodents (13).…”

“…O 2 equilibrium curves for RBCs were measured by deoxygenation of O 2 -equilibrated samples in the Hemox buffer at 37.68C, using a Hemox Analyzer (TCS Scientific Corporation, New Hope, PA) (13).…”

Dissociation of local nitric oxide concentration and vasoconstriction in the presence of cell-free hemoglobin oxygen carriers

“…Our previous studies with this experimental model and CFHs introduced in an extreme exchange transfusion protocol found that the pressure drop in the microvascular network was located in different segments of the system. 39 A greater pressure drop and corresponding vasoconstriction prior to the microcirculation was found for PBH and ␣␣Hb, while for MP4 more of the systemic pressure was transmitted to the microcirculation. Maintenance of microvascular perfusion pressure by MP4 should be related to the lack of vasoconstriction observed in the present study.…”

Haemoglobin, oxygen carriers and perioperative organ perfusion

“…The most affected segment appears to be the microcirculation with a reduction of the functional capillary density [60]. It has been observed that haemoglobin solutions with different O 2 affinity caused different degrees of vasoconstrictions [61,62].…”