Uncontrolled Hemorrhagic Shock Modeled via Liver Laceration in Mice with Real Time Hemodynamic Monitoring

Abstract

Uncontrolled hemorrhage is an important cause of preventable deaths among trauma patients. We have developed a murine model of uncontrolled hemorrhage via a liver laceration that results in consistent blood loss, hemodynamic alterations, and survival. Mice undergo a standardized resection of the left-middle lobe of the liver. They are allowed to bleed without mechanical intervention. Hemostatic agents can be administered as pre-treatment or rescue therapy depending on the interest of the investigator. During the time of hemorrhage, real-time hemodynamic monitoring via a left femoral arterial line is performed. Mice are then sacrificed, blood loss is quantified, blood is collected for further analysis, and organs are harvested for analysis of injury. Experimental design is described to allow for simultaneous testing of multiple animals. Liver hemorrhage as a model of uncontrolled hemorrhage exists in the literature, primarily in rat and porcine models. Some of these models utilize hemodynamic monitoring or quantify blood loss but lack consistency. The present model incorporates quantification of blood loss, real-time hemodynamic monitoring in a murine model that offers the advantage of using transgenic lines and a high-throughput mechanism to further investigate the pathophysiologic mechanisms in uncontrolled hemorrhage.

Platelet‐derived extracellular vesicles released after trauma promote hemostasis and contribute to DVT in mice

“…Inferior vena cava (IVC) ligation was performed in mice following recovery (24 hours) after tail bleed to model DVT after injury. To mimic traumatic hemorrhage, we used a validated model of uncontrolled hemorrhage in mice . Briefly, mice underwent a midline laparotomy and standard resection of the left middle lobe.…”

“…To mimic traumatic hemorrhage, we used a validated model of uncontrolled hemorrhage in mice. 36 Briefly, mice underwent a midline laparotomy and standard resection of the left middle lobe. Blood loss was quantified (grams).…”

Emerging Therapies for Prehospital Control of Hemorrhage

“…Blood loss was quantified by preweighed absorption triangles that were placed in the abdomen, and animals were sacrificed 20 min after injury. 33,34 Pretreatment with SynthoPlate resulted in significantly less blood loss after liver laceration (0.86 AE 0.16 g control particle versus 0.84 AE 0.13 g normal saline versus 0.68 AE 0.09 g SynthoPlate). 33,34 Rescue therapy with SynthoPlate administered 1 min after injury also resulted in significantly less blood loss (0.89 AE 0.17 g control particle versus 0.92 AE 0.19 g normal saline versus 0.69 AE 0.18 g Syn-thoPlate).…”

“…32 Impressively, animals treated with SynthoPlate had 100% survival at 60 min and 75% survival at 120 min 32 Efficacy of SynthoPlate was further evaluated in their established mouse liver hemorrhage model. 33 This consisted of a laceration of 75% of the left middle lobe of the liver with injection of SynthoPlate particles (30 mg/kg), control particles (30 mg/kg), or saline, either 30 min before injury or 1 min after liver laceration, with surgeons blinded to the treatment group. Blood loss was quantified by preweighed absorption triangles that were placed in the abdomen, and animals were sacrificed 20 min after injury.…”

“…In terms of biodistribution, SynthoPlate particles are mainly distributed in the lung, liver, and injured liver sites. 33,34 SynthoPlate particles represent a promising alternative to platelet transfusion at the site of injury; however, further research is needed, as administration 1 min after injury is not practical in the trauma environment.…”