Systemic and renal hemodynamics after moderate hemodilution with HbOCs in anesthetized rabbits

Abstract

Hb-based O(2)-carrying solutions (HbOCs) have been developed as red blood cell substitutes for use in patients undergoing hemodilution. Variously modified Hb with diverse solution properties have been shown to produce variable hemodynamic responses. We examined, through pulsed-Doppler velocimetry, the systemic and renal hemodynamic effects of dextran-benzene-tetracarboxylate-conjugated (Hb-Dex-BTC), bis(3,5-dibromosalicyl)fumarate cross-linked (alphaalpha-Hb), and o-raffinose-polymerized (o-raffinose-Hb) Hb perfused in rabbits after moderate hemodilution (30% hematocrit), and we compared the effects of these Hb solutions with the effects elicited by plasma volume expanders. In addition, vascular hindrance (resistance/blood viscosity at 128.5 s(-1)) was calculated to determine whether a moderate decrease in the viscosity of blood mixed with HbOCs may impair vasoconstriction as a result of autoregulation after infusion of cell-free Hb. No changes were observed in renal hemodynamics after hemodilution with reference or Hb solutions. Increase in blood pressure and vascular resistance was found with Hb-Dex-BTC and alphaalpha-Hb (for 180 min) and, to a lesser extent, with o-raffinose-Hb (for 120 min). Furthermore, Hb-Dex-BTC (high viscosity) and o-raffinose-Hb (medium viscosity) induced comparable increases in vascular hindrance (from 0.091 to 0. 159 and from 0.092 to 0.162 cm(-1), respectively) but far less than that produced by alphaalpha-Hb (low viscosity, from 0.092 to 0.200 cm(-1)). These results suggest that maintaining the viscosity of blood by infusing solutions with high viscosity makes it possible to limit vasoconstriction due to autoregulation mechanisms and mainly caused by hemodilution per se.

Measurement of blood volume after haemodilution with haemoglobin‐based oxygen carriers by a radiolabelled‐albumin method

“…Bradycardia is indeed an expected regulatory process mediated by baroreceptors in response to increased blood pressure (Persson, 1996). Strikingly, the rise in MAP was smaller in amplitude and duration compared to that we had previously observed with the same haemoglobin solutions and in the same haemodilution conditions in rabbits anaesthetized with pentobarbital sodium (Caron et al ., 2000). It may therefore be proposed that the pressor action of cell‐free haemoglobin was exacerbated in anaesthetized animals and/or that the potency of blood pressure regulatory elements was inhibited by anaesthesia.…”

“…In addition, haematologic parameters evolved similarly in animals treated by HES or HBOCs, except for metHb which exhibited a transient rise after the administration of HBOCs which was related to the presence of metHb in the infused solution. MetHb, however reduced rapidly since the level decreased approximately twofold within 60 min, confirming the efficacy of metHb reduction processes in rabbits (Faivre et al ., 1998; Caron et al ., 2000). As has already been documented, an infusion of Hb‐Dex‐BTC and αα‐Hb, but not that of HES, produced a rise in blood pressure.…”

“…Haemodilution was performed by exchange transfusion using a previously described method (Caron et al ., 2000). Briefly, a fixed amount of 20% of total blood volume (which was estimated to be 6·5% of the total body weight) was exchanged with one test solution.…”

Pharmacokinetics and mechanisms of plasma removal of hemoglobin-based oxygen carriers

“…As noted in " Considerations and limitations " , the concentration of functional HBOC is reduced by oxidation to the inactive metHb form during storage and circulation (Kramlova et al 1976, DeVenuto 1978, Tam et al 1978, Sehgal et al 1981, Snyder et al 1987, Bush et al 1994, Lee et al 1995, Caron et al 2000, O ' Hara et al 2001, Sprung et al 2002, Wicks et al 2003, Olofsson et al 2006, Vandegriff et al 2006, Buehler et al 2010, Baek et al 2012, Elmer et al 2012. While the predominant oxidant during storage is oxygen, other oxidants are important intravenously, including hydrogen peroxide and nitric oxide (NO) (Brooks 1932).…”

Enhancing oxygen solubility using hemoglobin- and perfluorocarbon-based carriers

“…The dextran molecule, by itself, is a plasma expander that can restore blood volume, but does not have the ability to transport oxygen. Dextran has been conjugated to hemoglobin with the rationale to increase its molecular weight (53,73). Free Hb has the disadvantage of high renal excretion rate when injected as a blood substitute, thereby leading to a rapid clearance from the circulation.…”