title: Preoxygenated hemoglobin-based oxygen carrier HBOC-201 annihilates myocardial ischemia during brief coronary artery occlusion in pigs.
abstract: 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.affiliation: Dept. of Cardiology, Thoraxcenter, Cardiovascular Research Institute COEUR, Erasmus Univ. Medical Center Rotterdam, The Netherlands.
authors.forename: Maaike
authors.initials: M
authors.lastname: Te Lintel Hekkert
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Dubé
authors.forename: Evelyn
authors.initials: E
authors.lastname: Regar
authors.forename: Martine
authors.initials: M
authors.lastname: de Boer
authors.forename: Pascal
authors.initials: P
authors.lastname: Vranckx
authors.forename: Wim J
authors.initials: WJ
authors.lastname: van der Giessen
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Serruys
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Duncker
mesh_terms: D000818:Animals; D001802:Blood Substitutes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D023921:Coronary Stenosis / Q000150:complications*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006454:Hemoglobins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D013552:Swine; D013696:Temperature; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; C096798:HBOC 201; D010100:Oxygen