Effects of Hemorrhagic Shock and Rhabdomyolysis on Renal Microcirculation, Oxygenation, and Function in a Female Swine Model

Background:Hemorrhagic shock (HS) and rhabdomyolysis (RM) are two important risk factors for acute kidney injury after severe trauma; however, the effects of the combination of RM and HS on kidney function are unknown. The purpose of this study was to determine the impact of RM and HS on renal function, oxygenation, perfusion, and morphology in a pig model.Methods:Forty-seven female pigs were divided into five groups: sham, RM, HS, HS and moderate RM (RM4/HS), and HS and severe RM (RM8/HS). Rhabdomyolysis was induced by intramuscular injection of glycerol 50% with a moderate dose (4 ml/kg for the RM4/HS group) or a high dose (8 ml/kg for the RM and RM8/HS groups). Among animals with HS, after 90 min of hemorrhage, animals were resuscitated with fluid followed by transfusion of the withdrawn blood. Animals were followed for 48 h. Macro- and microcirculatory parameters measurements were performed.Results:RM alone induced a decrease in creatinine clearance at 48 h (19 [0 to 41] vs. 102 [56 to 116] ml/min for RM and sham, respectively; P = 0.0006) without alteration in renal perfusion and oxygenation. Hemorrhagic shock alone impaired temporarily renal microcirculation, function, and oxygenation that were restored with fluid resuscitation. The RM4/HS and RM8/HS groups induced greater impairment of renal microcirculation and function than HS alone at the end of blood spoliation that was not improved by fluid resuscitation. Mortality was increased in the RM8/HS and RM4/HS groups in the first 48 h (73% vs. 56% vs. 9% for the RM8/HS, RM4/HS, and HS groups, respectively).Conclusions:The combination of HS and RM induced an early deleterious effect on renal microcirculation, function, and oxygenation with decreased response to resuscitation and transfusion compared with HS or RM alone. In a female swine model, rhabdomyolysis decreased creatinine clearance without alterations in renal perfusion and oxygenation. Hemorrhagic shock in this experimental model temporarily impaired renal function, microcirculation, and oxygenation that were restored with fluid resuscitation. The combination of rhabdomyolysis and hemorrhagic shock resulted in a greater impairment of renal function that could not be rescued by fluid administration and led to increased mortality.