Resuscitation with fresh whole blood ameliorates the inflammatory response after hemorrhagic shock

Abstract

Background: Hemorrhagic shock is the leading cause of potentially preventable death after traumatic injury. Hemorrhage and subsequent resuscitation may result in a dysfunctional systemic inflammatory response and multisystem organ failure, leading to delayed mortality. Clinical evidence supports improved survival and reduced morbidity when fresh blood products are used as resuscitation strategies. We hypothesized that the transfusion of fresh whole blood (FWB) attenuates systemic inflammation and reduces organ injury when compared with conventional crystalloid resuscitation after hemorrhagic shock.

Methods: Male mice underwent femoral artery cannulation and hemorrhage to a systolic blood pressure of 25 mm Hg +/- 5 mm Hg. After 60 minutes, the mice were resuscitated with either FWB or lactated Ringer's solution (LR). Mice were decannulated and killed at intervals for tissue histology, serum cytokine analysis, and vascular permeability studies. Separate groups of mice were followed for survival studies.

Results: When compared with FWB, mice resuscitated with LR required increased resuscitation fluid volume to reach goal systolic blood pressure. When compared with sham or FWB-resuscitated mice, LR resuscitation resulted in increased serum cytokine levels of macrophage inflammatory protein-1alpha, interleukin-6, interleukin-10, macrophage-derived chemokine, KC, and granulocyte macrophage colony stimulating factor as well as increased lung injury and pulmonary capillary permeability. No survival differences were seen between animals resuscitated with LR or FWB.

Conclusions: Resuscitation with LR results in increased systemic inflammation, vascular permeability, and lung injury after hemorrhagic shock. Resuscitation with FWB attenuates the inflammation and lung injury seen with crystalloid resuscitation. These findings suggest that resuscitation strategies using fresh blood products potentially reduce systemic inflammation and organ injury after hemorrhagic shock.

Figure 1

SBP of mice undergoing hemorrhagic shock and resuscitation with FWB or lactated Ringer’s solution (LR) versus sham animals or mice hemorrhaged but not resuscitated (unresuscitated). *p < 0.001 versus other groups, n = 20 mice for each group. **p < 0.001 versus other groups, n = 20.

Figure 2

Shed blood volume and resuscitation fluid volume for mice resuscitated with FWB and LR. *p < 0.001 versus FWB, n = 40 for each group.

Figure 3

Cytokine levels of MIP-1α, IL-6, IL-10, MDC, KC, and GMCSF in the serum of sham animals, animals resuscitated with FWB, and animals resuscitated with LR killed at 30 minutes after resuscitation. *p < 0.05 versus other groups, n = 5 for each group.

Figure 4

Concentration of Evans Blue in left lung samples of mice after sham procedure or hemorrhage followed by FWB or LR resuscitation. *p < 0.05 versus FWB, n = 9 for each group.

Figure 5

Representative photomicrographs from lung tissue stained with hematoxylin and eosin and examined with light microscopy. Photomicrograph (A), (B), and (C) represent lung tissue from sham, FWB, and LR mice, respectively. Mice resuscitated with LR exhibited increased alveolar wall thickening and recruitment of inflammatory cells compared with mice resuscitated with FWB or sham animals.