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 O-2-carrying capacity to plasma expanders. Microvascular perfusion was determined for HbV with different O-2 affinity (P-50 = 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, P-50: 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 (P-50 = 9)-HSA group showed an increase in arterial O-2 tension (89.8 +/- 14.7 mmHg, baseline 58.4 +/- 4.0 mmHg) because of hyperventilation, and microvascular perfusion was decreased, indicating that facilitated O-2 unloading of HbV by decreasing the O-2 affinity (increasing P-50) with PLP as an allosteric effector is important. Microvascular perfusion and microvascular and interstitial O-2 tensions in the HbV (P-50 = 16 and 30)-HSA groups were significantly higher than those in the HSA group. The O-2 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 P-50 from 30 to 16 mmHg, which appears to be an optimal value for the P-50 in this system.