A polymerized bovine hemoglobin oxygen carrier preserves regional myocardial function and reduces infarct size after acute myocardial ischemia

• Published in: American journal of physiology. Heart and circulatory physiology 2006-09, Vol.291 (3), p.H1126-H1137
• Main Authors: George, Isaac, Yi, Geng-Hua, Schulman, Allison R, Morrow, Brad T, Cheng, Yanping, Gu, Anguo, Zhang, Geping, Oz, Mehmet C, Burkhoff, Daniel, Wang, Jie
• Format: Article
• Language: English
• Subjects: Animals; Blood Substitutes - pharmacology; Blood Substitutes - therapeutic use; Cattle; Coronary Stenosis - complications; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Heart - drug effects; Heart - physiopathology; Heart Rate - drug effects; Heart Rate - physiology; Hemodynamics - drug effects; Hemodynamics - physiology; Hemoglobins - pharmacology; Hemoglobins - therapeutic use; Myocardial Infarction - drug therapy; Myocardial Infarction - etiology; Myocardial Infarction - pathology; Myocardial Ischemia - drug therapy; Myocardial Ischemia - etiology; Myocardial Ischemia - pathology; Random Allocation; Reperfusion Injury - drug therapy; Reperfusion Injury - pathology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00076.2006

1 Department of Surgery, Division of Cardiothoracic Surgery and 2 Department of Medicine, Division of Cardiology, Columbia University College of Physicians and Surgeons, New York; and 3 The Jack H. Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation, Orangeburg, New York; and 4 The Medical School of Nanjing University, Nanjing, People's Republic of China Submitted 18 January 2006 ; accepted in final form 4 April 2006 The purpose of this study was to test if HBOC-201, a hemoglobin-based oxygen-carrying solution, can decrease infarct size (or Inf) during acute, severe myocardial ischemia and reperfusion. To test the impact of HBOC-201 on infarct size, ischemia was produced in 18 dogs by coronary stenosis to achieve 80–95% flow reduction for 195 min along with pacing 10% above the spontaneous heart rate, followed by 180 min of reperfusion. Animals were randomized to intravenous infusion of HBOC-201 (1 g/kg) ( n = 6), normal saline (NS) ( n = 6), or phenylephrine (Phe) ( n = 6, as a control for the increased blood pressure seen with HBOC-201), given 15 min after the start of ischemia. Amount of infarct was quantified as the ratio between area at risk (AAR) and Inf after Evans blue and 2,3,5-triphenyltetrazolium chloride staining. Hearts were divided into five layers from base ( layer A ) to apex ( layer E ) and photographed for digital image analysis of AAR and Inf. Regional myocardial function (RMF) was also measured after 60 min of ischemia and 15 min of reperfusion. Inf/AAR was significantly reduced after HBOC-201 therapy (4.4 ± 2.2%) vs. NS (26.0 ± 3.6%) and Phe (25.7 ± 4.1%) (both, P < 0.05). RMF after reperfusion was restored to 92% of baseline with HBOC-201 compared with 11% of baseline after NS ( P < 0.05) and 49% after Phe ( P = not significant). HBOC-201 administration after induction of severe myocardial ischemia by acute coronary stenosis reduces infarct size and improves myocardial viability. coronary; blood; nitric oxide inhibitor Address for reprint requests and other correspondence: J. Wang, The Jack H. Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation, 8 Corporate Dr., Orangeburg, NY 10962 (e-mail: jwang{at}crf.org )