Document Detail


Hemoglobin vesicles improve wound healing and tissue survival in critically ischemic skin in mice.
MedLine Citation:
PMID:  19574491     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Local hypoxia, as due to trauma, surgery, or arterial occlusive disease, may severely jeopardize the survival of the affected tissue and its wound-healing capacity. Initially developed to replace blood transfusions, artificial oxygen carriers have emerged as oxygen therapeutics in such conditions. The aim of this study was to target primary wound healing and survival in critically ischemic skin by the systemic application of left-shifted liposomal hemoglobin vesicles (HbVs). This was tested in bilateral, cranially based dorsal skin flaps in mice treated with a HbV solution with an oxygen affinity that was increased to a P(50) (partial oxygen tension at which the hemoglobin becomes 50% saturated with oxygen) of 9 mmHg. Twenty percent of the total blood volume of the HbV solution was injected immediately and 24 h after surgery. On the first postoperative day, oxygen saturation in the critically ischemic middle flap portions was increased from 23% (untreated control) to 39% in the HbV-treated animals (P < 0.05). Six days postoperatively, flap tissue survival was increased from 33% (control) to 57% (P < 0.01) and primary healing of the ischemic wound margins from 6.6 to 12.7 mm (P < 0.05) after HbV injection. In addition, higher capillary counts and endothelial nitric oxide synthase expression (both P < 0.01) were found in the immunostained flap tissue. We conclude that left-shifted HbVs may ameliorate the survival and primary wound healing in critically ischemic skin, possibly mediated by endothelial nitric oxide synthase-induced neovascularization.
Authors:
Jan A Plock; Nassim Rafatmehr; Dubravko Sinovcic; Jonas Schnider; Hiromi Sakai; Eishun Tsuchida; Andrej Banic; Dominique Erni
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-07-02
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  297     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-08-26     Completed Date:  2009-09-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H905-10     Citation Subset:  IM    
Affiliation:
Department of Plastic and Hand Surgery, Inselspital, University of Bern, CH-3010 Bern, Switzerland. jan.plock@insel.ch
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Outbred Strains
Anoxia / pathology,  therapy
Blood Substitutes / pharmacology*
Disease Models, Animal
Hemoglobins / pharmacology*
Ischemia / pathology*,  therapy*
Liposomes / pharmacology
Mice
Microcirculation
Necrosis
Nitric Oxide Synthase Type III / metabolism
Oxygen / metabolism
Skin / blood supply,  pathology,  surgery
Surgical Flaps / blood supply,  pathology
Wound Healing / drug effects*
Chemical
Reg. No./Substance:
0/Blood Substitutes; 0/Hemoglobins; 0/Liposomes; 7782-44-7/Oxygen; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos3 protein, mouse

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