Transfusion-Related Acute Lung Injury in a Rat Model of Trauma-Hemorrhage

Abstract

Major trauma often causes hemorrhage and predisposes to transfusion-related acute lung injury (TRALI). TRALI is a leading cause of transfusion-related deaths; however, its pathophysiology is uncertain. In the existing two-event models of TRALI, infection (lipopolysaccharide injection) is followed by the infusion of aged blood products. Our objective was to develop a trauma-relevant two-event model of TRALI by examining the effect of aged packed red blood cells (PRBC) on lung injury in rats with trauma-hemorrhage. Male Lewis rats were used. Rat PRBC were prepared similar to human PRBC. Recipients were implanted with femoral arterial and venous catheters (isoflurane anesthesia) and then subjected to 30% controlled arterial hemorrhage after 16-hour recovery. After a 60-minute shock period, rats were resuscitated with crystalloid and PRBC (0-35 days old; 3:1 ratio) and followed for up to 6 hours. Lung edema was evaluated by Evans blue dye (EBD), protein, and cytokine-induced neutrophil chemoattractant-1 (CINC-1) accumulation in bronchoalveolar lavage fluid, and arterial blood gases were measured (iSTAT). CINC-1 levels increased over time in our PRBC stored for over 21 days. Transfusion survival was reduced, and Evans blue dye, protein, and CINC-1 accumulation in bronchoalveolar lavage fluid were increased in rats transfused with 28-day-old and 35-day-old PRBC compared with the 0-day group. Arterial PO2 and O2 saturation were decreased in rats transfused with 28-day-old and 35-day-old PRBC. However, pH and PCO2 were not different between groups. These results suggest that transfusion of 28-day-old and 35-day-old PRBC reliably promotes lung edema in a rat model of catheter surgery and hemorrhage. We propose that this model can be used as a trauma-relevant two-event model of TRALI.