Mechanism of warmed malate ringer’s solution in fluid resuscitation in improving the lethal triad of severe trauma

To explore the role and mechanism of warm malate ringer’s solution (MR) in resuscitation of the lethal triad caused by severe trauma.

A rat model of severe trauma was established in SPF-grade SD rats (half male and half female, weighing 200~220 g) using combined multiple injuries and hemorrhagic shock, and the rats were randomly divided into 8 groups (n=8): Sham group, only arterial and venous catheterization; Trauma (Tra) groups with different time points (10, 30, 60, 90, 120, 180 min) and a Trauma group that were observed without any treatment for 180 min after model establishment. The changes of activated clotting time (ACT), reaction time (R), maximum amplitude (MA), and rate of blood clot formation (Angle) at different time points were detected by using thromboelastography, and tail bleeding, core body temperature and arterial blood gas parameters, were also observed and detected. The plasma von Willebrand Factor (vWF) level, mitochondrial respiratory control ratio in pulmonary venous endothelium, and expression levels of vascular endothelial cadherin (VE-Cadherin), peroxisome proliferator activating receptor gamma coactivator 1α (PGC1α), dynamin-related protein 1 (Drp1), p-Drp1, and mitofusin 2 (Mfn2) were detected to evaluate the vascular endothelial injury and mitochondrial dysfunction. Another group of SD rats were randomly divided into severe trauma group (no treatment for 180 min after injury), and MR solution at room temperature and at 37 ℃ groups. MR solution at room temperature or at 37 ℃ was given to the rats using a medical blood transfusion apparatus at 60 min post-trauma. Above indicators were observed and detected to investigate the resuscitation effect of the MR solution.

Compared with the Sham group, the severely traumatic rats at 180 min after injury had significantly prolonged ACT and R values (P<0.05), shortened MA and decreased Angle values (P<0.05), extended tail bleeding time (P<0.05), lower partial pressure of carbon dioxide (PCO₂) and HCO₃^- and base excess (BE) levels (P<0.05), and continuously increasing K⁺ (P<0.05) and decreasing Na⁺ (P<0.05) and Ca²⁺ levels (P<0.05). Additionally, plasma vWF level (P<0.05) and protein levels of VE-cadherin, PGC1α and Mfn2 in pulmonary vein endothelium were significantly reduced (P<0.05), the expression of p-Drp1 was enhanced and the mitochondrial respiration control rate was declined in the rats at 180 min after injury (P<0.05). MR solution resuscitation shortened tail bleeding time (P<0.05), increased core body temperature (P<0.05), elevated plasma vWF level (P<0.05), increased protein levels of VE-cadherin, PGC1α and Mfn2 (P<0.05), and decreased that of p-Drp1 protein expression (P<0.05) when compared with the rats at 180 min after severe traumatic injury. The above effects were more significant in the rats infused with the solution at 37 ℃ than those at room temperature.

Warm MR solution significantly improves the lethal triad in rats after severe trauma, which may be associated with its improving mitochondrial function and attenuating vascular endothelial damage.