Targeted O₂ Delivery by Low-p50 Hemoglobin: A New Basis for Hemoglobin-based Oxygen Carriers

Figures & data

Figure 1 A stringent model of efficacy. Rats are exchange-transfused 50% of blood volume, then a controlled, exponential 60% hemorrhage is done over 60 minutes. Animals are observed for an additional hour. The hemoglobin concentrations at the right of the figure are at the start of the 60% hemorrhage. Modified from [[17]].

Figure 2 Hypertensive response in the rat to exchange transfusion with three representative modified hemoglobins. The molecules are drawn to scale at the right and the reaction rate constants for NO binding are shown for each. Data from [[11]].

Figure 3 Coincidence of the blood oxygen saturation and functional capillary density as a function of pO₂. Data from [[8], [18]].[11]].

Figure 4 Schematic drawing of MalPEG-Hemoglobin. MP4 is MalPEG-Hemoglobin formulated for use as a blood substitute (4.2 g/dL in Lactated Ringer's solution). Size exclusion chromatograms comparing elution behavior of MP4 and stroma-free hemoglobin are shown at right. Modified from [[14]].

Table 1 Properties of MP4 compared with blood and hemoglobin [[14]]

	Blood	Hemoglobin	MP4
Viscosity (cPs)	4.0	1.0	2.2
COP (mm Hg)	27	16	49
Hb (g/dL)	14.0	4.2	4.2
p50 (mm Hg)	28.0	15.0	5.4
n (Hill's parameter)	2.6	2.9	1.2
MW (kDa)	–	65	90
Radius (nm)	–	2.7	10

Figure 5 Oxygen equilibrium curves for MP4, hamster blood and PolyBvHb. From [[13]].

Table 2 Hematologic measurements after hemodilution in the hamster [[13]]

	n	Total Hb (g/dL)	Plasma Hb (g/dL)	Hct (%)
MP4	6	4.8 ± 0.1	1.1 ± 0.0	11.2 ± 0.2
PolyBvHb	5	6.7 ± 0.2	3.7 ± 0.3	11.2 ± 0.4
Dextran	7	3.4 ± 0.1	0.0 ± 0.0	11.2 ± 0.5

Figure 6 Microcirculation measurements in the hamster skinfold model. Hemodynamic measurements include flow velocity, vessel diameter and functional capillary density. Oxygen measurements include systemic (arterial) blood gases, and pO₂ measured by the phosphorescence decay technique in arterioles and venules. Modified from [[13]].

Figure 7 Oxygen release in precapillary compared to capillary vessels in the hemodiluted (hematocrit 11%) hamster using the skinfold observation technique. Hemodilution with dextran-70 results in about equal amounts of O₂ released at both levels of the circulation. In PolyBvHb animals O₂ release in precapillary vessels predominates, while the reverse is true in MP4 animals. From [[13]].

Figure 8 Consequences of the location of O₂ release. There is no significant correlation between arterial O₂ content and base excess, while the correlation between capillary release and base excess is highly significant. From [[13]].

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