Blood volume and cardiac index in rats after exchange transfusion with hemoglobin-based oxygen carriers

Abstract

We have measured plasma volume and cardiac index in rats after 50% isovolemic exchange transfusion with human hemoglobin cross-linked between the alpha-chains with bis(3,5-dibromosalicyl)fumarate (alpha alpha Hb) and with bovine hemoglobin modified with polyethylene glycol (PEGHb). alpha alpha Hb and PEGHb differ in colloid osmotic pressure (23.4 and 118.0 Torr, respectively), oxygen affinity (oxygen half-saturation pressure of hemoglobin = 30.0 and 10.2 Torr, respectively), viscosity (1.00 and 3.39 cP, respectively), and molecular weight (64,400 and 105,000, respectively). Plasma volume was measured by Evans blue dye dilution modified for interference by plasma hemoglobin. Blood volumes in PEGHb-treated animals were significantly elevated (74.0 +/- 3.5 ml/kg) compared with animals treated with alpha alpha Hb (49.0 +/- 1.2 ml/kg) or Ringer lactate (48.0 +/- 2.0 ml/kg) or with controls (58.2 +/- 1.9 ml/kg). Heart rate reduction after alpha alpha Hb exchange is opposite to that expected with blood volume contraction, suggesting that alpha alpha Hb may have a direct myocardial depressant action. The apparently slow elimination of PEGHb during the 2 h after its injection is a consequence of plasma volume expansion: when absolute hemoglobin (concentration x plasma volume) is compared for PEGHb and alpha alpha Hb, no difference in their elimination rates is found. These studies emphasize the need to understand blood volume regulation when the effects of cell-free hemoglobin on hemodynamic measurements are evaluated.

Paradoxical hypotension following increased hematocrit and blood viscosity

“…where Hct is the Hct right before the blood volume measurement; the trapping factor is 0.96; and F cells, the total body-to-venous Hct ratio, is 0.74 (27). Statistical analysis.…”

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

“…44 Blood volume contracted and expanded in a moderate exchange transfusion study with ␣␣Hb and a bovine Hb modified with PEG, respectively. 45 Mechanistically, the behavior of PEG-Hb must be related to its unique ability of maintaining a significantly higher level of functional capillary density in extreme hemodilution and hemorrhagic shock resuscitation, 46 an effect not attainable with other CFHs. This result was obtained in experiments in the hamster window preparation, and thus there is some uncertainty as to whether it is common to other organs and tissues.…”

Artificial oxygen carriers as a possible alternative to red cells in clinical practice

“…7 Cell-free hemoglobin has oncotic properties and increases the blood volume by an amount greater than the transfused volume. 5,23 This action may be beneficial when plasma expansion is required in cases of shock resuscitation but can also be harmful in the absence of hypovolemia. 5 Because of these oncotic properties, HBOCs may be used as fluid resuscitation in cases of hemorrhagic shock, and for treating surgical blood loss.…”