Human serum albumin incorporating synthetic heme: red blood cell substitute without hypertension by nitric oxide scavenging.
The administration of extracellular, hemoglobin-based oxygen carriers often elicits an acute increase in blood pressure by vasoconstriction. This side effect is now recognized to be due to the depletion of nitric oxide (endothelial-derived relaxing factor) by the extravasuated hemoglobins. We have recently found that the administration of a recombinant human serum albumin (rHSA)-based oxygen carrier involving synthetic tetraphenyporphinatoiron(II) derivative (FeP) (rHSA-FeP) does not induce such hypertensive action, because of its low permeability through the vascular endothelium. The heart rate responses after the rHSA-FeP injection were also negligibly small. Visualization of the intestinal microcirculatory changes clearly revealed the widths of the venule and arteriole to be fairly constant. The entirely synthetic rHSA-FeP becomes a promising material as a new type of red blood cell substitute.
Tsuchida
Eishun
E
Advanced Research Institute for Science and Engineering, Waseda University, Tokyo 169-8555, Japan. eishun@mn.waseda.ac.jp
Komatsu
Teruyuki
T
Matsukawa
Yasuko
Y
Nakagawa
Akito
A
Sakai
Hiromi
H
Kobayashi
Koichi
K
Suematsu
Makoto
M
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001802:Blood Substitutes / Q000737:chemistry / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D004912:Erythrocytes / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006418:Heme / Q000737:chemistry / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced*; D007422:Intestines / Q000098:blood supply / Q000187:drug effects; D008297:Male; D008665:Metalloporphyrins / Q000737:chemistry; D008833:Microcirculation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000737:chemistry; D012039:Regional Blood Flow / Q000187:drug effects; D012709:Serum Albumin / Q000737:chemistry / Q000494:pharmacology*
D001802:Blood Substitutes; D008665:Metalloporphyrins; D011994:Recombinant Proteins; D012709:Serum Albumin; C032547:iron tetraphenylporphyrin; D009569:Nitric Oxide; D006418:Heme