Document Detail


Preoxygenated hemoglobin-based oxygen carrier HBOC-201 annihilates myocardial ischemia during brief coronary artery occlusion in pigs.
MedLine Citation:
PMID:  20061545     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Because of their ability to perfuse remote regions and deliver oxygen, hemoglobin-based oxygen carriers (HBOCs) may be considered in the treatment of several ischemic conditions such as acute coronary syndromes or high-risk percutaneous intervention. Here we studied the effects of intracoronary infusion of ex vivo preoxygenated HBOC-201 during brief total coronary artery occlusion (CAOs) on myocardial oxygenation and left ventricular (LV) function in a large animal model and investigated the influence of HBOC-201 temperature and infusion rate on these effects. Thirteen open-chest anesthetized swine were instrumented for measurement of global and regional LV function and metabolism. CAOs were induced by inflating an intracoronary balloon catheter; preoxygenated HBOC-201 (12 g/dL) was infused distally through the central lumen of the balloon catheter. Animals underwent consecutive 3-min CAOs interspersed by 30 min of reperfusion, accompanied by different HBOC-201 infusion rates (0, 15, 23, 30, 40, and 50 ml/min) and/or two infusion temperatures (18 degrees C or 37 degrees C) in random order. CAO elicited immediate loss of systolic shortening (SS) in the ischemic region (19 +/- 1% at baseline vs. -3 +/- 2% at end of CAO), resulting in decreases in maximum rate of rise in LV pressure (15 +/- 5%) and stroke volume (12 +/- 4%; all P < 0.05). Balloon deflation resulted in marked coronary reactive hyperemia (to 472 +/- 74% of baseline), increases in coronary venous concentrations of adenosine + inosine (to 218 +/- 26% of baseline; both P < 0.05) and rapid restoration of SS toward baseline. HBOC-201 ameliorated the CAO-induced changes in SS, stroke volume, reactive hyperemia, and coronary venous adenosine + inosine. The effects were temperature and flow dependent with full preservation of SS at 50 ml/min HBOC-201 of 37 degrees C. In conclusion, intracoronary preoxygenated HBOC-201 preserved myocardial oxygenation and LV function in swine during CAO in a dose- and temperature-dependent manner. In our study setting, preoxygenated HBOC-201 can match the oxygen delivery role of endogenous blood in the heart on an almost equivalent-volume basis.
Authors:
Maaike Te Lintel Hekkert; Gregory P Dub?; Evelyn Regar; Martine de Boer; Pascal Vranckx; Wim J van der Giessen; Patrick W Serruys; Dirk J Duncker
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Publication Detail:
Type:  Journal Article     Date:  2010-01-08
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  298     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-25     Completed Date:  2010-04-02     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:  H1103-13     Citation Subset:  IM    
Affiliation:
Dept. of Cardiology, Thoraxcenter, Cardiovascular Research Institute COEUR, Erasmus Univ. Medical Center Rotterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Substitutes / administration & dosage,  pharmacology,  therapeutic use*
Coronary Stenosis / complications*
Disease Models, Animal
Dose-Response Relationship, Drug
Female
Hemodynamics / drug effects,  physiology
Hemoglobins / administration & dosage,  pharmacology,  therapeutic use*
Infusions, Intravenous
Male
Myocardial Reperfusion Injury / etiology*,  physiopathology,  prevention & control*
Myocardium / metabolism
Oxygen / metabolism
Swine
Temperature
Ventricular Function, Left / drug effects,  physiology
Chemical
Reg. No./Substance:
0/Blood Substitutes; 0/HBOC 201; 0/Hemoglobins; 7782-44-7/Oxygen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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