Preoxygenated hemoglobin-based oxygen carrier HBOC-201 annihilates myocardial ischemia during brief coronary artery occlusion in pigs

MTL Hekkert, GP Dube, Evelyn Regar, Martine Boer, Pascal Vranckx, Wim Giessen, PWJC (Patrick) Serruys, Dirk-jan Duncker

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Abstract

te Lintel Hekkert M, Dube GP, Regar E, de Boer M, Vranckx P, van der Giessen WJ, Serruys PW, Duncker DJ. Preoxygenated hemoglobin-based oxygen carrier HBOC-201 annihilates myocardial ischemia during brief coronary artery occlusion in pigs. Am J Physiol Heart Circ Physiol 298: H1103-H1113, 2010. First published January 8, 2010; doi:10.1152/ajpheart.00667.2009.-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.
Original languageUndefined/Unknown
Pages (from-to)H1103-H1113
JournalAmerican Journal of Physiology-Heart and Circulatory Physiology
Volume298
Issue number3
DOIs
Publication statusPublished - 2010

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  • EMC COEUR-09

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