Microvascular responses to hemodilution with Hb vesicles as red blood cell substitutes: influence of O2 affinity

Phospholipid vesicles encapsulating purified hemoglobin (HbV) were developed to provide O2-carrying capacity to plasma expanders. Microvascular perfusion was determined for HbV with different O2 affinity (P50 = 9, 16, and 30 mmHg) prepared by coencapsulating pyridoxal 5'-phosphate (PLP) at the molar ratios of [PLP]/[Hb] = 0, 0.5, and 3, respectively (cf. hamster blood, P50: 28 mmHg), and suspended in 8 g/dl human serum albumin (HSA). Eighty percent of the red blood cell (RBC) mass of conscious Syrian golden hamsters fitted with dorsal skinfold windows was substituted with either of the HbV-HSA suspensions, washed hamster RBC suspended in HSA (RBC-HSA), and HSA alone. All three HbV-HSA groups and RBC-HSA groups showed stable blood pressure and heart rate, which could not be sustained with HSA alone. Only the HbV (P50 = 9)-HSA group showed an increase in arterial O2 tension (89.8 +/- 14.7 mmHg, baseline 58.4 +/- 4.0 mmHg) because of hyperventilation, and microvascular perfusion was decreased, indicating that facilitated O2 unloading of HbV by decreasing the O2 affinity (increasing P50) with PLP as an allosteric effector is important. Microvascular perfusion and microvascular and interstitial O2 tensions in the HbV (P50 = 16 and 30)-HSA groups were significantly higher than those in the HSA group. The O2 release rate from the HbV was 18-32 s-1 vs. 4.4 s-1 for RBC. Functional capillary density was improved from 17 to 41% on average by decreasing P50 from 30 to 16 mmHg, which appears to be an optimal value for the P50 in this system.