Transfusion restores blood viscosity and reinstates microvascular conditions from hemorrhagic shock independent of oxygen carrying capacity

Abstract

Systemic and microvascular hemodynamic responses to transfusion of oxygen using functional and non-functional packed fresh red blood cells (RBCs) from hemorrhagic shock were studied in the hamster window chamber model to determine the significance of RBCs on rheological and oxygen transport properties. Moderate hemorrhagic shock was induced by arterial controlled bleeding of 50% of the blood volume, and a hypovolemic state was maintained for 1h. Volume restitution was performed by infusion of the equivalent of 2.5 units of packed cells, and the animals were followed for 90 min. Resuscitation study groups were non-oxygen functional fresh RBCs where the hemoglobin (Hb) was converted to methemoglobin (MetHb) [MetRBC], fully oxygen functional fresh RBCs [OxyRBC] and 10% hydroxyethyl starch [HES] as a volume control solution. Measurement of systemic variables, microvascular hemodynamics and capillary perfusion were performed during the hemorrhage, hypovolemic shock and resuscitation. Final blood viscosities after the entire protocol were 3.8 cP for transfusion of RBCs and 2.9 cP for resuscitation with HES (baseline: 4.2 cP). Volume restitution with RBCs with or without oxygen carrying capacity recovered higher mean arterial pressure (MAP) than HES. Functional capillary density (FCD) was substantially higher for transfusion versus HES, and the presence of MetHb in the fresh RBC did not change FCD or microvascular hemodynamics. Oxygen delivery and extraction were significantly lower for resuscitation with HES and MetRBC compared to OxyRBC. Incomplete re-establishment of perfusion after resuscitation with HES could also be a consequence of the inappropriate restoration of blood rheological properties which unbalance compensatory mechanisms, and appear to be independent of the reduction in oxygen carrying capacity.

Figure 1

Relative changes to baseline in arteriolar and venular hemodynamics for HES, MetRBC and OxyRBC. Broken line represents baseline level. †, P < 0.05 relative to baseline; ★, P<0.05. Diameters (µm, mean ± SD) in Figures 1A (arteriolar) and 1B (venular) for each animal group were as follows: Baseline: HES (arterioles (A): 59.1 ± 9.4, n = 42; venules (V): 59.9 ± 8.0, n = 44); MetRBC (A: 58.1 ± 9.4, n = 44; V: 56.8 ± 9.6, n = 47); OxyRBC (A: 57.9 ± 8.6, n = 43, V: 58.6 ± 8.9, n = 44). n = number of vessels studied. RBC velocities (mm/s, mean ± SD) in Figures 2C (arteriolar) and 2D (venular) for each animal group were as follows: Baseline: HES (A: 4.4 ± 1.1, V: 2.4 ± 0.8); MetRBC (A: 4.4 ± 0.9; V: 2.4 ± 0.8); OxyRBC (A: 4.5 ± 0.8; V: 2.6 ± 0.6). Calculated flows (nl/s, mean ± SD) in Figures 2E (arteriolar) and 2F (venular) for each animal group were as follows: Baseline: HES (A: 11.5 ± 3.6; V: 6.7 ± 2.3); MetRBC (A: 11.5 ± 3.1; V: 6.6 ± 2.0); OxyRBC (A: 11.0 ± 2.5; V: 6.5 ± 2.1).

Figure 2

Effects of resuscitation on capillary perfusion during hemodilution. Functional capillary density (FCD) was drastically reduced after hemorrhage. FCD was lower after resuscitation with HES compared to volume restitution with RBCs. FCD (cm⁻¹) at baseline was as follows: HES (107 ± 10); MetRBC (112 ± 12); and OxyRBC (105 ± 12). ★, P < 0.05 and ★★, P<0.01 among groups.

Figure 3

Microvascular oxygen partial pressure (arterioles, venules and tissue) 90 min after resuscitation from hemorrhagic shock. ★, P < 0.05.

Figure 4

Microvascular oxygen delivery and extraction 90 min after resuscitation. ★, P<005. Calculations of global oxygen transport are not directly measurable in our model. However, the changes relative to baseline can be calculated using the measured variables. The extraction was calculated as the difference of averaged arterioles and venules for each animal. The difference in oxygen delivery and extraction between HES and MetRBC are not statistically significant.