A new oxygen transport agent.
Modern highly purified and chemically modified hemoglobin-based oxygen carriers (HBOC) are free of significant side effects on kidneys and coagulation, and they do not possess ABO antigens, allowing transfusion without knowledge of the respective blood group. Even at room air oxygen concentrations HBOC can compensate for intravascular volume deficits in hemorrhagic shock, including restoration of colloid osmotic pressure and organ perfusion, and deliver oxygen to organs and tissues during nearly complete blood exchange. In animal experiments and clinical trials all HBOC showed a vasoconstrictive side-effect which is mainly caused by nitric oxide scavenging, and to a lesser extent by reactive vasoconstriction because of precapillary oxygen off-loading. The study by Bjorkholm in this issue of the journal (see page 505) investigates the application of a moderate dose of the newly designed HBOC, MP4, in volunteers. MP4 has a high molecular size and a very low p50 resulting in a high oxygen affinity thus avoiding significant (pre)capillary oxygen off-loading. No significant rises in blood pressure or major laboratory abnormalities were seen after MP4 infusion. This new HBOC may be applicable in patients as a red blood substitute where vasoconstriction must be avoided. In addition, poststenotic tissue oxygenation might be a further indication. However, the number of treated volunteers and the infused dose of MP4 were both are very small. Therefore, one cannot draw conclusions on the safety, tolerability and efficacy of MP4 in terms of red cell replacement when large amounts of oxygen carriers are needed.
Standl
Thomas
T
Dept. of Anesthesia and Critical Care Medicine Academic Hospital Solingen, Germany. standl@klinikumsolingen.de.
D000818:Animals; D004796:Clinical Enzyme Tests; D018572:Disease-Free Survival; D006403:Hematologic Tests; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy*; D007262:Infusions, Intravenous; D007668:Kidney / Q000502:physiology; D008301:Maleimides / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015657:Respiratory Transport / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects
D006454:Hemoglobins; D008301:Maleimides; C493836:maleimide-polyethylene glycol-modified hemoglobin, MP4; D011092:Polyethylene Glycols