Abstract 15791: Increased Oxygen Content and Decreasing Oxygen Affinity of Hemoglobin Based Oxygen Carrier (HBOC) Reperfusate Can Improve Myocardial Function and Preserve Myocardium Following Global Ischemia
Background: Hemoglobin based oxygen carriers (HBOC) offer a potential adjunct to improve early re-oxygenation of ischemic tissue. However, the optimal oxygen content and oxygen affinity of the HBOC solution to optimize myocardial re-oxygenation is not known. Our objective was to compare myocardial recovery following reperfusion with 3 unique HBOC solutions, each with different oxygen affinity.
Methods: 3 HBOC solutions were prepared to a standard concentration of 2.5g/dL in modified Krebs Henseleit buffer, and oxygenated with either room air (RA) or with 100% oxygen (O2). Hearts isolated from male Sprague-Dawley rats underwent 25 min of global ischemia and then were reperfused for the first 10 min with one of the HBOC's; 1) HBOCR, (polymerized bovine hemoglobin fixed in ‘relaxed’, deoxygenated state) P50 = 2.4 mm Hg, n=8, 2) HBOCT (polymerized bovine hemoglobin fixed in ‘tense’, oxygenated state) P50 = 48 mm Hg, n=8, or 3) HgbB (isolated bovine hemoglobin) P50 = 29 mm Hg, n=8. All hearts were subsequently reperfused for 50 minutes with modified Krebs Henseleit buffer. Continuous LV function was determined. Oxygen content (CO2), oxygen delivery (DO2), and extraction ration were measured at 2, 5, 10, 30, and 60 minutes of reperfusion.
Results: 100% oxygen resulted in greater CO2, compared with room air oxygenation within all groups (p = <0.001 with ANOVA) and was similar between all 3 HBOCs. Recovery of cardiac function (percent of baseline dP/dt) was significantly different between groups. In the 100% oxygenated groups, greater functional improvement was seen with increasing P50 (HBOCRO2 = 34.0 ± 6.3%, HgbBO2 = 48.0 ± 9.0%, HBOCTO2 = 75.3 ± 8.8%, p = <0.01 with ANOVA). In contrast with room air HBOC, cardiac function recovery increased with decreasing P50 (HBOCRRA = 35.5 ± 3.7%, HgbBRA = 22.8 ± 7.2%, HBOCTRA = 20.1 ± 6.3%, p = <0.01 with ANOVA. Myocardial injury (peak creatine kinase activity) was inversely related to dP/dt recovery.
Conclusion: HBOC solutions oxygen content and oxygen affinity (P50) are critical determinants in optimizing ischemic myocardial functional recovery and preservation of myocardial injury.
- © 2011 by American Heart Association, Inc.