A novel hemoglobin-based blood substitute protects against myocardial reperfusion injury

Abstract

. A novel hemoglobin-based blood substitute protects against myocardial reperfusion injury. Am J Physiol Heart Circ Physiol 288: H1794 -H1801, 2005 doi:10.1152/ajpheart.00905.2004 Cambridge, MA) is a glutaraldehyde-polymerized bovine hemoglobin (Hb) solution that is stroma free, has lower viscosity than blood, and promotes O 2 unloading. We investigated the effects of HBOC-201 in a canine model of myocardial ischemia-reperfusion injury. Dogs were anesthetized and subjected to 90 min of regional myocardial ischemia and 270 min of reperfusion. HBOC-201 or 0.9% saline vehicle equivalent to 10% total blood volume was infused 30 min before myocardial ischemia. Hemodynamic data and peripheral blood samples were taken at baseline, 1 h of myocardial ischemia, and 1, 2, and 4 h of reperfusion. At 270 min of reperfusion, the area at risk (AAR) per left ventricle and the area of infarction (Inf) per AAR were determined. The myocardial AARs in the two study groups were similar. In addition, myocardial blood flow (as measured by radioactive microspheres) in the ischemic zone was similar between the vehicle and HBOC-201 groups. HBOC-201-infused dogs demonstrated a significant (P Ͻ 0.01) 56% reduction in Inf/AAR. Analysis of blood samples taken at 4 h of reperfusion showed a significant (P Ͻ 0.05) reduction in creatine kinase MB isoform for the HBOC-201 group. Histological analysis of the myocardium demonstrated significant (P Ͻ 0.01) reductions in neutrophil infiltration in the HBOC-201 group. These data indicate that treatment with HBOC-201 before myocardial ischemia-reperfusion reduces the extent of myocardial inflammation and ischemia-reperfusion injury in the canine myocardium.

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

“…Finally, HBOC-201 provides protection against reperfusion injury, consistent with a prior study by Caswell et al (4). Treated animals showed trends to less severe declines in LV dP/dt and LVEDP; despite long reperfusion times, RMF displayed significant improvements after reperfusion, and myo- cardial infarct sizes were reduced with HBOC-201.…”

“…A number of consistent hemodynamic changes were observed with the administration of HBOC-201, similar to previous reports (4,18), as shown in Table 1. A significant increase in MAP was seen immediately after infusion of HBOC-201 at 30% O 2 .…”

“…AAR was defined as the area of the outlined portions of LV unstained by Evans blue (ischemic area), while Inf was defined as infarcted area (appearing white) within the AAR. Total AAR, total LV, and total Inf were expressed as the sum of layers A-E of each area per layer multiplied by the weight per layer, respectively, as previously described (4). This portion of the analysis was performed by an investigator blinded to the treatment group.…”

“…These properties, along with a lower viscosity and smaller mean diameter than a human RBC, suggest that blood substitutes may be an effective therapy in acute myocardial ischemia. Data from a canine model with HBOC-201 given 30 min before myocardial ischemia showed significant protection against reperfusion injury (4). However, pretreatment for myocardial infarction is rare, given the acuity and rapid progression of ischemia with little forewarning.…”

Oxygen Carriers in Cardiac Surgery

“…Free hemoglobin also crosses into the extravascular spaces, where it could interact with nitric oxide and lead to vasoconstriction. As the bovine free hemoglobin does not interact with 2,3-DPG and has a P 50 of ± 30 mm Hg, it could favor oxygen delivery to the tissues, 24 what has not been firmly demonstrated in humans. Bovine hemoglobin is an alternative to the human hemoglobin, especially given its abundant availability and low cost.…”