Biomedical subjects

P W Maffuid

Publications and source records attributed to P W Maffuid.

3 recordsLinked to original sources

PubMed1987

Peritoneal accumulation of infused stroma-free hemoglobin. Potential toxicity of an oxygen-carrying substitute.

The efficacy of stroma-free hemoglobin (SFH) as an oxygen-carrying red blood cell substitute in shock and trauma remains inconclusive. A major problem is the retention of sufficient intravascular persistence. The sites and mechanisms for clearance of SFH or its chemically modified variants are not well characterized. Capillary leakage has been reported. Any significant leak into the peritoneal cavity may be toxic, especially if bacteria are present. The present study quantitates peritoneal accumulation of SFH and chemically modified adenosine triphosphate (ATP)-SFH following a 50% exchange transfusion in rats. m-Dansyl cadaverine, an endocytotic blocking agent, was studied for its ability to alter accumulation of hemoglobin in the peritoneum. Differences in renal clearance corresponded to differences in vascular halflife of SFH (90 minutes) and ATP-SFH (210 minutes). Peritoneal leakage was not related to vascular persistence. We found that MDC significantly decreases the peritoneal accumulation of ATP-SFH but not that of SFH. We also noted that MDC neither inhibits nor alters renal clearance of either hemoglobin variant. Total peritoneal leakage is, at most, 4% of infused SFH at four hours. Molecular size and charge might be factors important in hemoglobin transport from the vasculature to the peritoneum.

Adenosine Triphosphate↗

PubMed1987

Superoxide radicals and hemorrhagic shock: are intravascular radicals associated with mortality?

Superoxide radicals (SORs) are formed during hemorrhagic shock. However, the association between SOR formation and mortality remains undefined. Would neutralization of SORs during shock improve survival? Superoxide dismutase (SOD) was covalently linked to Ficoll to prolong vascular persistence and ensure ongoing neutralization of intravascular SORs. Six groups of Sprague-Dawley rats were studied. Rats were exsanguinated to a mean arterial pressure of 30 Torr, sustained for 60 min. Ficoll linked superoxide dismutase (SOD-F), 5000 Units + catalase, 150 Units, was suspended in 1 ml of saline and injected following the 60-min hypotensive period. Resuscitation followed for appropriate groups. Pretreated SOD-F rats received a 1-ml bolus prior to exsangination. Pretreatment with SOD-F did not improve survival in non-resuscitated groups despite improvement in vascular circulation (P greater than 0.10, NS). In the standard non-resuscitation group, there is also no improvement (P greater than 0.10, NS). Resuscitation with or without SOD-F significantly alters survival rates (P less than 0.025) with respect to non-resuscitated controls. However, application of SOD-F in conjunction with resuscitation does not improve survival with respect to resuscitation controls (P greater than 0.10, NS). Although SOD-F has a vascular half-life advantage over SOD, the improvement in survival is statistically non-significant. Intravascular SORs do not appear to be associated with mortality. SOR release and consequent damage to the vasculature may be preceded by a more significant intracellular damage. Intracellular SOR damage and its association with mortality in hemorrhagic shock remains an open issue.

Animals↗

PubMed1983

Modification of hemoglobin--ring opened dials.

The dialdehyde of ATP (o-ATP) has been synthesized and reacted with SFH. The conditions of reaction have been defined and the yields characterized. Close attention to the oxygenation state of SFH at the time of reaction is necessary; maintenance of the T-state is crucial as is low met-Hb concentrations. The o-ATP modified SFH has a near normal oxy-Hb affinity and a markedly prolonged, compared to SFH alone, intra-vascular retention. The effects of the modification on cooperativity and the specific binding sites are being evaluated. It appears that there is some loss of cooperativity by observation of the oxy-Hb dissociation curve.

Adenosine Triphosphate↗