and its downstream targets of the AMP-activated protein kinase family are important regulators of many aspects of skeletal muscle cell function, including control of mitochondrial content and capillarity. LKB1 deficiency in skeletal and cardiac muscle (mLKB1-KO) greatly impairs exercise capacity. However, cardiac dysfunction in that genetic model prevents a clear assessment of the role of skeletal muscle LKB1 in the observed effects. Our purposes here were to determine whether skeletal musclespecific knockout of LKB1 (skmLKB1-KO) decreases exercise capacity and mitochondrial protein content, impairs accretion of mitochondrial proteins after exercise training, and attenuates improvement in running performance after exercise training. We found that treadmill and voluntary wheel running capacity was reduced in skmLKB1-KO vs. control (CON) mice. Citrate synthase activity, succinate dehydrogenase activity, and pyruvate dehydrogenase kinase content were lower in KO vs. CON muscles. Three weeks of treadmill training resulted in significantly increased treadmill running performance in both CON and skmLKB1-KO mice. Citrate synthase activity increased significantly with training in both genotypes, but protein content and activity for components of the mitochondrial electron transport chain increased only in CON mice. Capillarity and VEGF protein was lower in skmLKB1-KO vs. CON muscles, but VEGF increased with training only in skmLKB1-KO. Three hours after an acute bout of muscle contractions, PGC-1␣, cytochrome c, and VEGF gene expression all increased in CON but not skmLKB1-KO muscles. Our findings indicate that skeletal muscle LKB1 is required for accretion of some mitochondrial proteins but not for early exercise capacity improvements with exercise training. liver kinase B1; adenosine 5=-monophosphate-activated prokine kinase; mitochondria; exercise training; skeletal muscle EXERCISE TRAINING RESULTS IN A HOST OF ADAPTATIONS in skeletal muscle that contribute to an enhanced capacity for subsequent exercise performance. Among the most significant of these is an increase in mitochondrial content and enzyme activity (14). Although the mechanisms involved in mitochondrial biogenesis are not fully defined, existing evidence suggests that AMPactivated protein kinase (AMPK) plays an important role in promoting this process (1, 51). AMPK is potently activated under conditions of low cellular energy, when ATP levels decline and AMP/ADP levels rise (4, 52). In skeletal muscle, this occurs during exercise or muscle work (50). Upon activation, AMPK generally signals the allocation of cellular resources to catabolism and energy production while reducing growth and proliferation signals. In line with these broad functions, chronic activation of AMPK, using the AMP mimetic AICAR, increases mitochondrial enzyme protein content and activity (18,51). This is likely due, at least in part, to increased peroxisome proliferator-activated receptor-␥ coactivator 1␣ (PGC-1␣) content (18, 27) and phosphorylationmediated PGC-1␣-dependent transcr...

Fibrinolysis is a natural physiologic process that maintains homeostasis by regulating clot formation and degradation. This balance allows for clot remodeling and prevents diffuse thrombosis formation. Fibrinolysis is largely mediated by tissue plasminogen activator (tPA), which cleaves plasminogen into plasmin, ultimately leading to fibrin degradation and clot dissolution. Fibrinolysis can be measured quantitatively via thromboelastography (TEG) and rotational thromboelastometry (ROTEM). Detection of fibrinolysis via these assays and others allows for directed therapy and potential pharmaceutical inhibition of fibrinolysis. This pharmaceutical inhibition, also termed antifibrinolytic therapy, is most commonly performed with medications such as aprotinin, aminocaproic acid, and tranexamic acid. Antifibrinolytic therapy may be indicated in the setting of significant hemorrhage or excessive fibrinolysis (known as hyperfibrinolysis). Because of this, antifibrinolytic therapy has become commonly used in many clinical settings, including trauma, surgery, and cardiopulmonary bypass. When considering initiation of antifibrinolytic therapy, the benefit of decreased hemorrhage and anti-inflammatory effects must be weighed against the theoretical risk of unchecked thrombus formation.

Regular exercise training leads to increased mitochondrial protein content in skeletal muscle. The necessity of liver kinase B1 (LKB1) for this adaptation is unknown. Our purpose here was to determine whether skeletal muscle LKB1 is required for exercise training‐induced increases in mitochondrial protein content. To test this, skeletal muscle‐specific LKB1 knockout (KO) and littermate control (C) mice (n=8–9) were either sedentary (SED) or treadmill trained (TRN) 4 days/week, twice per day for 3 weeks. Exercise intensity and duration for both WT and KO mice were determined as tolerated by the KO mice such that the training stimulus was identical for both genotypes. Gastrocnemius (GAST) of TRN C mice had a significant (p ≤ 0.05) increase in the content of the mitochondrial proteins cytochrome‐C and complex I of the electron transport chain (ETC) as well as a trend (p=0.14) for an increase in core 2 of complex III of the ETC. vs. SED C mice. These training adaptations did not occur in TRN KO GAST. We conclude that LKB1 is necessary for increases in some mitochondrial proteins after moderate intensity exercise training. This work was funded by NIAMSD Grant AR‐51928.

Massive hemorrhage is a major complication of traumatic injury and many surgical operations. Early detection of hemorrhage and appropriate resuscitation is essential to improve outcomes during recovery from the inciting event. Traumatic injury, surgical exposure, and large-volume resuscitation can cause physiologic derangements that result in alterations of the normal coagulation cascade and formation of thrombin clot. Careful balancing of resuscitation using appropriate ratios of packed red blood cells (pRBCs), fresh frozen plasma (FFP), and platelets as well as avoiding crystalloid solutions have been shown to decrease mortality, likely due to improved hemostasis. Additionally, careful evaluation of laboratory values, patient history and pharmacologic exposure can further guide resuscitation efforts and provide information for potential pharmacological intervention.

Hemorrhagic shock is a significant cause of morbidity and mortality in trauma and surgical patients. Hemodynamically significant hemorrhage, when coupled with the physiologic derangements associated with trauma and surgery, results in oxygen debt, acidosis, organ dysfunction, coagulopathy, and ultimately death if not treated aggressively. Early detection of hemorrhagic shock allows for the prompt initiation of resuscitation and supportive care, mitigating these risks. Volume expansion via transfusion of whole blood or a balanced ratio of blood products is the intervention proven to have the most significant impact toward improving patient outcomes and should be employed to prolong life while patients await definitive surgical, endoscopic, or angiographic control of hemorrhage. Careful physical examination coupled with use of available laboratory tests and imaging techniques can aid in the development of a plan for resuscitation.