Injectable and rapidly expandable thrombin-decorated cryogels achieve rapid hemostasis and high survival rates in a swine model of lethal junctional hemorrhage

Effective therapies are urgently needed to stabilize patients with marginally compressible junctional hemorrhage long enough to get them to the hospital alive.Herein,we report injectable and rapidly expandable cryogels consisting of polyacrylamide and thrombin(AT cryogels)created by cryo-polymerization for the efficient management of lethal junctional hemorrhage in swine.The produced cryogels have small pore sizes and highly interconnected porous architecture with robust mechanical strength.The cryogels exhibit rapid shape memory properties and prove to be resilient against fatigue.These cryogels also show high water/blood absorption capacity,fast blood clotting effect,and enhanced adhesion of red blood cells and platelets in vitro.Further,in vivo,hemostatic efficacy tests in a lethal swine junctional hemorrhage model suggest that treatment with AT cryogels,especially AT-2 cryogels,achieves the least blood loss and the highest survival rate(100%)compared to currently employed products such as XStat®and combat gauze.The high hemostatic performance of the cryogels may be attributed to highly interconnected porous architecture with small pore size and the use of thrombin as a pro-coagulant agent.Collectively,injectable and rapidly expandable thrombin-decorated polyacrylamide-based cryogels show significant promise as hemostatic material,offering effective management of marginally compressible junctional hemorrhages in prehospital settings.

Effect of SAM junctional tourniquet on respiration when applied in the axilla: A swine model

Purpose:SAM junctional tourniquet(SJT)has been applied to control junctional hemorrhage.However,there is limited information about its safety and efficacy when applied in the axilla.This study aims to investigate the effect of SJT on respiration when used in the axilla in a swine model.Methods:Eighteen male Yorkshire swines,aged 6-month-old and weighing 55-72 kg,were randomized into 3 groups,with 6 in each.An axillary hemorrhage model was established by cutting a 2 mm transverse incision in the axillary artery.Hemorrhagic shock was induced by exsanguinating through the left carotid artery to achieve a controlled volume reduction of 30% of total blood volume.Vascular blocking bands were used to temporarily control axillary hemorrhage before SJT was applied.In Group I,the swine spontaneously breathed,while SJT was applied for 2 h with a pressure of 210 mmHg.In Group II,the swine were mechanically ventilated,and SJT was applied for the same duration and pressure as Group I.In Group III,the swine spontaneously breathed,but the axillary hemorrhage was controlled using vascular blocking bands without SJT compression.The amount of free blood loss was calculated in the axillary wound during the 2 h of hemostasis by SJT application or vascular blocking bands.After then,a temporary vascular shunt was performed in the 3 groups to achieve resuscitation.Pathophysiologic state of each swine was monitored for 1 h with an infusion of 400 mL of autologous whole blood and 500 mL of lactated ringer solution.Tb and T0 represent the time points before and immediate after the 30% volume-controlled hemorrhagic shock,respectively.T30,T60,T90 and T120,denote 30,60,90,and 120 min after T0(hemostasis period),while T150,and T180 denote 150 and 180 min after T0(resuscitation period).The mean arterial pressure and heart rate were monitored through the right carotid artery catheter.Blood samples were collected at each time point for the analysis of blood gas,complete cell count,serum chemistry,standard coagulation tests,etc.,and thromboelastography was conducted subsequently.Movement of the left hemidiaphragm was measured by ultrasonography at Tb and T0 to assess respiration.Data were presented as mean±standard deviation and analyzed using repeated measures of two-way analysis of variance with pairwise comparisons adjusted using the Bonferroni method.All statistical analyses were processed using GraphPad Prism software.Results:Compared to Tb,a statistically significant increase in the left hemidiaphragm movement at T0 was observed in Groups I and II(bothp<0.001).In Group III,the left hemidiaphragm movement remained unchanged(p=0.660).Compared to Group I,mechanical ventilation in Group II significantly alleviated the effect of SJT application on the left hemidiaphragm movement(p<0.001).Blood pressure and heart rate rapidly increased at T0 in all three groups.Respiratory arrest suddenly occurred in Group I after T120,which required immediate manual respiratory assistance.PaO_(2) in Group I decreased significantly at T120,accompanied by an increase in PaCO_(2)(both p<0.001vs.Groups II and III).Other biochemical metabolic changes were similar among groups.However,in all 3 groups,lactate and potassium increased immediately after 1 min of resuscitation concurrent with a drop in pH.The swine in Group I exhibited the most severe hyperkalemia and metabolic acidosis.The coagulation function test did not show statistically significant differences among three groups at any time point.However,D-dimer levels showed a more than 16-fold increase from T120 to T180 in all groups.Conclusion:In the swine model,SJT is effective in controlling axillary hemorrhage during both spontaneous breathing and mechanical ventilation.Mechanical ventilation is found to alleviate the restrictive effect of SJT on thoracic movement without affecting hemostatic efficiency.Therefore,mechanical ventilation could be necessary before SJT removal.