PEG‐Hemoglobin as a Resuscitation Solution in the Treatment of Hypovolemic Shock in the Anesthetized Rat

Abstract

This study was designed to determine the advantages of using the hemoglobin-based oxygen carrier, polyethylene glycol conjugated bovine hemoglobin (PEG-Hb), as an additive to Ringer's lactate solution (RLS) for the treatment of acute hemorrhage in anesthetized female rats. Different compositions of PEG-Hb and RLS were administered intravenously in a paradigm that provided 30 ml/kg of resuscitation fluid following an episode of 15 min of hypotension. Hypotension was achieved by the removal of blood (1 ml/min) from the femoral vein until the mean arterial pressure was lowered to or below 50 mmHg and subsequently maintained until resuscitation. Short-term cardiovascular assessment showed that resuscitation fluids containing PEG-Hb resulted in higher mean arterial pressure, aortic blood flow, renal blood flow, and less dramatic shifts in arterial base excess and respiratory blood gases than plain RLS. The long-term survival experiment showed lower lactate dehydrogenase, alkaline phosphatase, and serum glutamic pyruvic transaminase levels in most groups resuscitated with solutions containing PEG-Hb, but no differences in survival (100%) were observed. The data suggest that the addition of PEG-Hb to RLS improves its resuscitative effects. Specifically, a solution of 50% RLS:50% PEG-Hb appeared to have the most favorable cardiovascular and metabolic effects in this anesthetized rat hypovolemic shock resuscitation model. Presumably, the improved effects seen with the addition of PEG-Hb were due to its innate plasma expansion and oxygen-delivery capabilities.

Effects of isovolemic resuscitation with hemoglobin-based oxygen carrier Hemoglobin glutamer-200 (bovine) on systemic and mesenteric perfusion and oxygenation in a canine model of hemorrhagic shock: a comparison with 6% hetastarch solution and shed blood

“…Consistent with this idea are findings with a second generation HBOC that has recently been developed (Winslow et al. 1998; Conover et al. 1999; Wettstein et al.…”

Hemodynamic response and oxygen transport in pigs resuscitated with maleimide-polyethylene glycol-modified hemoglobin (MP4)

“…Data from clinical studies of polymerized human Hb report efficacy without hypertension in cases of acute trauma (8,17), but published data from preclinical studies are lacking. In contrast, the cumulative evidence with PEG-modified Hb (2,3,36,39) demonstrates the lack of hemodynamic actions in a number of animal models. The primary observation in the present study, i.e., lack of hypertension or rise in systemic vascular resistance, represents the first publication, to our knowledge, of this finding with PEG-modified Hb in a large-animal model of hemorrhage and resuscitation.…”

Modulation of oxidative stability of haemoglobin inside liposome-encapsulated haemoglobin

“…Earliest attempts to use purified Hb from RBCs demonstrated that it is unstable in vivo ; it dissociates into constituent chains and have significant toxic reactions upon administration (Savitsky et al, 1978; White et al, 1986; Chang, 1998; Chan et al, 2000). While the dissociation problems could be partially addressed by approaches such as cross linking (Creteur et al, 2000; Gould et al, 2002; Squires, 2002; Stowell, 2002) and/or its conjugation to poly(ethylene glycol) (Conover et al, 1999), oxidative degradation of Hb at body temperature remains an unsolved problem to date. Oxidation of Hb increases the rate of heme loss resulting in its denaturation.…”