Submitted on January 18, 2006
Accepted on April 4, 2006
A Polymerized Bovine Hemoglobin Oxygen Carrier Preserves Regional Myocardial Function and Reduces Infarct Size after Acute Myocardial Ischemia
Isaac George1, Geng-Hua Yi2, Allison R Schulman1, Brad T Morrow1, Yanping Cheng2, Anguo Gu2, Geping Zhang2, Mehmet C Oz1, Daniel Burkhoff2, and Jie Wang2*
1 Surgery, Columbia University, New York, New York, United States
2 Medicine, Columbia University, New York, New York, United States
* To whom correspondence should be addressed. E-mail: jw147{at}columbia.edu.
The purpose of this study was to test if HBOC-201, a hemoglobin-based oxygen carrying solution, can decrease infarct size during acute, severe myocardial ischemia and reperfusion. Methods: 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 minutes along with pacing 10% above the spontaneous heart rate, followed by 180 minutes of reperfusion. Animals were randomized to intravenous infusion of HBOC-201 (1 g/kg) (n=6), saline (NS) (n=6), or PHE (n=6, as a control for the increased blood pressure seen with HBOC-201), given 15 minutes after the start of ischemia. Amount of infarct was quantified as the ratio between area at risk (AAR) and infarct size (INF) after Evans Blue and TTC staining. Hearts were divided into five layers from base (A) to apex (E) and photographed for digital image analysis of AAR and INF. Regional myocardial function (RMF) was also measured after 60 minutes of ischemia and 15 minutes of reperfusion. Results: INF/AAR was significantly reduced after HBOC-201 therapy (4.4 ± 2.2%), versus 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 to 11% of baseline after NS (p<0.05) and 49% after PHE (p=NS). Conclusions: HBOC-201 administration after induction of severe myocardial ischemia by acute coronary stenosis reduces infarct size and improves myocardial viability.
