Fixed Volume or Fixed Pressure: A Murine Model of Hemorrhagic Shock

Abstract

It is common knowledge that severe blood loss and traumatic injury can lead to a cascade of detrimental signaling events often resulting in mortality. 1,2,3,4,5 These signaling events can also lead to sepsis and/or multiple organ dysfunction (MOD). 6,7,8,9 It is critical then to investigate the causes of suppressed immune function and detrimental signaling cascades in order to develop more effective ways to help patients who suffer from traumatic injuries. 10 This fixed pressure Hemorrhagic Shock (HS) procedure, although technically challenging, is an excellent resource for investigation of these pathophysiologic conditions. 11,12,13 Advances in the assessment of biological systems, i.e. Systems Biology have enabled the scientific community to further understand complex physiologic networks and cellular communication patterns. 14 HemorrhagicShock has proven to be a vital tool for unveiling these cellular communication patterns as they relate to immune function. 15,16,17,18 This procedure can be mastered! This procedure can also be used as either a fixed volume or fixed pressure approach. We adapted this technique in the murine model to enhance research in innate and adaptive immune function. 19,20,21 Due to their small size HS in mice presents unique challenges. However due to the many available mouse strains, this species represents an unparalleled resource for the study of the biologic responses. The HS model is an important model for studying cellular communication patterns and the responses of systems such as hormonal and inflammatory mediator systems, and danger signals, i.e. DAMP and PAMP upregulation as it elicits distinct responses that differ from other forms of shock. 22,23,24,25 The development of transgenic murine strains and the induction of biologic agents to inhibit specific signaling have presented valuable opportunities to further elucidate our understanding of the up and down regulation of signal transduction after severe blood loss, i.e. HS and trauma 26,27,28,29,30 .There are numerous resuscitation methods (R) in association with HS and trauma. 31,32,33,34 A fixed volume resuscitation method of solely lactated ringer solution (LR), equal to three times the shed blood volume, is used in this model to study endogenous mechanisms such as remote organ injury and systemic inflammation. 35,36,38 This method of resuscitation is proven to be effective in evaluating the effects of HS and trauma 38,39 .

Toll-Like Receptor 4 Regulates Platelet Function and Contributes to Coagulation Abnormality and Organ Injury in Hemorrhagic Shock and Resuscitation

“…23 Briefly, bilateral inguinal dissections were performed, a small femoral arteriotomy was made, and the femoral arteries were cannulated with sterile PE-10 catheter. Animals were hemorrhaged to a mean arterial pressure (MAP) of 25 mmHg for 120 min.…”

Milk fat globule epidermal growth factor-factor 8 mitigates inflammation and tissue injury after hemorrhagic shock in experimental animals

“…A model of hemorrhagic shock was conducted as previously described 19 . Animals were kept on a 12-hour light-dark cycle with free access to food and water in a temperature-controlled room.…”

Establishment of an Experimental Mouse Model of Trauma-Hemorrhagic Shock

“…however, the procedures can be used with either a fixed pressure or fixed volume hemorrhage approach, and the animal can remain in ThS for 0.5-3 h, which has excellent potential for the investigation of pathophysiological conditions in mice [2]. Our ThS model could also be an important model for studying cellular communication patterns and the responses of systems such as hormonal and inflammatory mediator systems, and danger signals, as it elicits distinct responses that differ from other forms of shock [7,15]. Moreover, the development of knockout and transgenic murine strains and the induction of biologic agents to inhibit specific signaling have presented valuable opportunities to further elucidate our understanding of the up-and downregulation of signal transduction after ThS [14,19].…”

“…hemorrhagic shock following critical trauma is associated with high morbidity and mortality [23,24]. The establishment of a standard experimental model of trauma-hemorrhagic shock (ThS) is necessary to understand the pathophysiological effects of traumatic tissue injury and hemorrhagic shock, to investigate the causes of suppressed immune function and detrimental signaling cascades, and to develop more effective ways of helping those patients who suffer from traumatic injuries [15,17].…”