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Updated: Jun 17, 2026
Post-Myocardial Infarction Heart Failure in Closed-chest Coronary Occlusion/Reperfusion Model in Göttingen Minipigs and Landrace Pigs
Published on: April 17, 2021
Preoxygenated hemoglobin-based oxygen carrier HBOC-201 annihilates myocardial ischemia during brief coronary artery
Maaike Te Lintel Hekkert1, Gregory P Dubé, Evelyn Regar
1Dept. of Cardiology, Thoraxcenter, Cardiovascular Research Institute COEUR, Erasmus Univ. Medical Center Rotterdam, The Netherlands.
Insights
Hemoglobin-based oxygen carriers (HBOCs) improved heart function during coronary artery occlusion in swine. The effectiveness of HBOC-201 depended on infusion temperature and rate, showing promise for treating ischemic conditions.
Area of Science:
- Cardiovascular Research
- Biomedical Engineering
Background:
- Hemoglobin-based oxygen carriers (HBOCs) offer potential for treating ischemic conditions by perfusing tissues and delivering oxygen.
- Acute coronary syndromes and high-risk percutaneous interventions are clinical scenarios where HBOCs might be beneficial.
Purpose of the Study:
- To investigate the effects of intracoronary infusion of ex vivo preoxygenated HBOC-201 on myocardial oxygenation and left ventricular (LV) function during coronary artery occlusion (CAO).
- To determine the influence of HBOC-201 temperature and infusion rate on these physiological effects.
Main Methods:
- Utilized a large animal model (open-chest anesthetized swine) with instrumentation for LV function and metabolism monitoring.
- Induced brief total coronary artery occlusions (CAOs) using an intracoronary balloon catheter.
- Administered preoxygenated HBOC-201 (12 g/dL) via intracoronary infusion at varying rates (0-50 ml/min) and temperatures (18°C or 37°C) during CAOs.
Main Results:
- CAO significantly reduced systolic shortening (SS) in the ischemic region, decreased LV pressure rise, and lowered stroke volume.
- HBOC-201 infusion ameliorated CAO-induced reductions in SS and stroke volume, and attenuated reactive hyperemia and adenosine + inosine release.
- Optimal preservation of SS was observed at an HBOC-201 infusion rate of 50 ml/min and 37°C.
Conclusions:
- Intracoronary preoxygenated HBOC-201 effectively preserved myocardial oxygenation and LV function in swine during CAO.
- The therapeutic benefits of HBOC-201 were demonstrated to be dose- and temperature-dependent.
- Preoxygenated HBOC-201 showed potential to substitute for endogenous blood in oxygen delivery to the heart during ischemia.
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.
