Short-term effects of stored homologous red blood cell transfusion on cardiorespiratory function and inflammation: an experimental study in a hypovolemia model

Abstract

The pathophysiological mechanisms associated with the effects of red blood cell (RBC) transfusion on cardiopulmonary function and inflammation are unclear. We developed an experimental model of homologous 14-days stored RBC transfusion in hypovolemic swine to evaluate the short-term effects of transfusion on cardiopulmonary system and inflammation. Sixteen healthy male anesthetized swine (68±3.3 kg) were submitted to controlled hemorrhage (25% of blood volume). Two units of non-filtered RBC from each animal were stored under blood bank conditions for 14 days. After 30 min of hypovolemia, the control group (n=8) received an infusion of lactated Ringer's solution (three times the removed volume). The transfusion group (n=8) received two units of homologous 14-days stored RBC and lactated Ringer's solution in a volume that was three times the difference between blood removed and blood transfusion infused. Both groups were followed up for 6 h after resuscitation with collection of hemodynamic and respiratory data. Cytokines and RNA expression were measured in plasma and lung tissue. Stored RBC transfusion significantly increased mixed oxygen venous saturation and arterial oxygen content. Transfusion was not associated with alterations on pulmonary function. Pulmonary concentrations of cytokines were not different between groups. Gene expression for lung cytokines demonstrated a 2-fold increase in mRNA level for inducible nitric oxide synthase and a 0.5-fold decrease in mRNA content for IL-21 in the transfused group. Thus, stored homologous RBC transfusion in a hypovolemia model improved cardiovascular parameters but did not induce significant effects on microcirculation, pulmonary inflammation and respiratory function up to 6 h after transfusion.

Figure 1.. Sequential hemodynamic parameters of the groups during the study. Panel A, Mean systemic arterial blood pressure (ANOVA between factor P=0.156, within factor P<0.001 and factor-time interaction P=0.054). Panel B, Cardiac output (ANOVA between factor P=0.013, within factor P<0.001 and factor-time interaction P=0.773). Panel C, Mixed venous oxygen saturation (SvO₂) (ANOVA between factor P<0.001, within factor P<0.001 and factor-time interaction P=0.019). Panel D, Stroke volume variation (ANOVA between factor P=0.037, within factor P<0.001 and factor-time interaction P=0.207). Gray lines and markers denote all data recorded for 8 animals per group. Black markers denote the data that were chosen a priori to be analyzed. *P<0.05 vs baseline, ^#P<0.05 vs control group, ^§P<0.05 vs hemorrhage (post-hoc Bonferroni correction).

Figure 2.. Sequential oxygenation and perfusion parameters of the groups during the study. Panel A, Arterial oxygen content (ANOVA between factor P<0.001, within factor P=0.039 and factor-time interaction P=0.015). Panel B, Arbitrary microcirculatory perfusion units (ANOVA between factor P=0.026, within factor P=0.146 and factor-time interaction P=0.841). Gray lines and markers denote all data recorded for 8 animals per group. Black markers denote the data that were chosen a priori to be analyzed. *P<0.05 vs baseline, ^§P<0.05 vs hemorrhage (post-hoc Bonferroni correction).

Figure 3.. Inflammatory parameters of the groups during the study. Panel A, pulmonary IL-6 concentrations (P=0.401, t-test). Panel B, pulmonary IL-10 concentrations (P=0.817, t-test). Panel C, pulmonary IL-21 concentrations (P=0.567, t-test). Panel D, pulmonary IL-1 concentrations (P=0.844, t-test). Panel E, Relative mRNA quantification (RQ) for cytokines and NOS2 in lung tissue. Data are reported as means±SD for 8 animals per group. Animals were sacrificed 6 h after the end of transfusion. *P<0.05 vs Control (t-test).

Figure 4.. Nitrate concentrations of the groups during the study. Panel A, plasma nitrate concentrations of both groups (P=0.021, Friedman test). *P<0.05 vs baseline (Tukey post-hoc analysis). Panel B, pulmonary nitrate concentrations of both groups (P=0.505, Mann-Whitney rank sum test). Data are reported as medians and interquartile range for 8 animals per group. Animals were sacrificed 6 h after the end of transfusion.