The purpose of this study was to identify the effects of a hemoglobin-based oxygen carrier, HBOC-201, on the cardiovascular system. Systemic cardiovascular parameters of mean arterial pressure (MAP), pulse pressure, heart rate, and oxygen saturation, as well as vascular resistance, were examined. A murine model of the cardiovascular system and microvasculature was employed. Sprague-Dawley rats (male; 230-530g; N = 13) were anaesthetised and surgically prepared for intravital microscopy of the spinotrapezius muscle. Increasing doses of HBOC-201 (2 mg/kg, 22 mg/kg, 230 mg/kg, and 780 mg/kg) and an iso-oncotic volume control were administered to assess for a dose-response relationship. MAP displayed a significant increase from baseline for both treatment groups, with no significant difference between the two. Arteriolar diameter displayed no changes from baseline, or between treatment groups or across doses. Based on these results, the noted changes in MAP were due to hypervolemia, and not a property of HBOC-201, itself.

In the US today, blood transfusion is safer than ever. Nevertheless, the century-old quest for a suitable blood substitute persists. The elimination of unwanted side effects, especially transfusion-transmitted diseases, the problems and high cost factor involved in collecting and storing human blood, the pending worldwide shortages, and the need for compatibility testing are the driving forces contributing towards the development of blood substitutes. The leading research is focusing on hemoglobin-based oxygen carriers (HBOCs), which are limited in clinical application due to the pressor effect they induce. In this study, the mechanisms through which HBOCs affect mean arterial pressure (MAP), arteriolar diameter, and nitric oxide levels in the microcirculation were investigated, using Oxyglobin (HBOC-301), a third generation glutaraldehyde-polymerized bovine hemoglobin. The spinotrapezius muscle of female Sprague-Dawley rats was exteriorized for microcirculatory observations. HBOC in doses of 0.1, 1.0, 10.0, and 100.0 μM i.v., LNAME (30 mg/kg, i.v.), and papaverine (100 μM, topically) were given to the rat. Heparinized saline (0.1 ml and 0.5 ml, i.v.) served as control. MAP was monitored continuously through a cannula in the right carotid artery. Images of the feed, arcade and transverse arterioles were captured using a Zeiss Axioplan microscope, equipped with a digital camera, and imaging software. All doses of HBOC produced an overall vasoconstriction of the arterioles leading to an elevated MAP. Following L-NAME pretreatment, HBOC administration alone and with papaverine produced no significant elevation in MAP, indicating that the increase in resistance required basal amounts of nitric oxide (NO). This study concludes that the constriction of the arterioles correlated with the level of hypertension, and that these effects occur in a dose-dependent manner as a consequence of NO scavenging.

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