Evaluation and management of bleeding during cardiac surgery

Patients undergoing cardiac surgery with and potentially without cardiopulmonary bypass (CPB) are at risk for excessive microvascular bleeding. This bleeding often leads to transfusion of allogeneic blood and blood components as well as reexploration. Excessive bleeding after cardiac surgery occurs because of alterations in the hemostatic system pertaining to dilutional thrombocytopenia, excessive hemostatic activation, and exposure to long-acting antiplatelet or antithrombotic agents. Pharmacologic interventions have been extensively reported as means to attenuate the alterations in the hemostatic system during CPB in an attempt to reduce excessive bleeding, transfusion, and reexploration. Prophylactic administration of agents with antifibrinolytic and antiinflammatory properties can decrease blood loss and transfusion. Aprotinin is the most extensively studied and effective blood conservation agent and has the most potent antifibrinolytic and antiinflammatory effects. Other agents, including the lysine analogues with isolated antifibrinolytic properties, may be effective in low-risk patients. The ability to reduce blood product transfusions and to decrease operative times and reexploration rates favorably affects patient outcomes, availability of blood products, and overall health care costs.     

Muscle temperature and EMG amplitude and frequency during isometric exercise

INTRODUCTION: While muscle temperature is known to vary with environmental temperature and the insulation provided by clothing, little has been published examining the interrelationships between the amplitude and frequency of the electromyogram (EMG), muscle tension, muscle fatigue, and muscle temperature. METHODS: Seven male subjects immersed their arms and legs in water at 24, 27, 34, and 37 degrees C for 20 min. Muscle temperature, strength (maximal voluntary contraction; MVC), endurance for a fatiguing contraction at 40% MVC, and EMG were assessed in the handgrip, biceps brachii, quadriceps, and gastrocnemius muscles. RESULTS: MVC was 44.8% lower for all muscles examined at the coldest muscle temperature. For all temperatures, the relationship between EMG amplitude and tension for brief isometric contractions was nearly linear; however, the increase in the amplitude of the EMG with muscle fatigue was reduced for the coldest muscle temperatures. The frequency components of the EMG and motor unit conduction velocity were largely unaffected by muscle tension but were inversely related to muscle temperature, with a 10 degrees C reduction in temperature resulting in a 32 Hz reduction in the center frequency. During fatiguing contractions at a tension of 40% MVC, the percent reduction in frequency was similar for all muscle temperatures, being reduced by about 20% from the beginning to the end of the contractions. DISCUSSION: EMG amplitude can be used to assess muscle use in most physiological conditions, but the frequency components of the EMG are so related to temperature as to make its use more restricted.     

Metformin-associated respiratory alkalosis

We present an 84-year-old man with a history of chronic obstructive pulmonary disease, type 2 diabetes, hypertension, glaucoma, and bladder cancer who presented to the emergency department after the police found him disoriented and confused. Metformin therapy began 3 days before, and he denied any overdose or suicidal ideation. Other daily medications included glipizide, fluticasone, prednisone, aspirin, furosemide, insulin, and potassium supplements. In the emergency department, his vital signs were significant for hypertension (168/90), tachycardia (120 bpm), and Kussmaul respirations at 24 breaths per minute. Oxygen saturation was 99% on room air, and a fingerstick glucose was 307 mg/dL. He was disoriented to time and answered questions slowly. Metformin was discontinued, and by day 3, the patient's vital signs and laboratory test results normalized. He has been asymptomatic at subsequent follow-up visits. Metformin-associated lactic acidosis is a well-known phenomenon. Respiratory alkalosis may be an early adverse event induced by metformin prior to the development of lactic acidosis.     

Macrophages from lupus-prone MRL mice are characterized by abnormalities in Rho activity, cytoskeletal organization, and adhesiveness to extracellular matrix proteins

Macrophages (mphi) from prediseased mice of the major murine models of lupus have an identical defect in cytokine expression that is triggered by serum and/or apoptotic cells. It is striking that cytokine expression in the absence of serum and apoptotic cells is equivalent to that of nonautoimmune mice. Here, we show that mphi from prediseased lupus-prone MRL/MpJ (MRL/+) or MRL/MpJ-Tnfrsf6(lpr) (MRL/lpr) mice also have reversible abnormalities in morphology, cytoskeletal organization, and adhesive properties. In the presence of serum, MRL mphi adhered in increased numbers to a variety of extracellular matrix proteins compared with mphi from two nonautoimmune strains. However, in the absence of serum, adhesion by MRL mphi was similar to that of nonautoimmune mphi. Increased adhesion by MRL mphi was also observed in the presence of apoptotic, but not necrotic, cells. The morphology and actin-staining pattern of adherent MRL mphi were consistent with reduced activity of Rho, a cytoskeletal regulator. Indeed, MRL mphi cultured in the presence of serum had markedly decreased levels of active Rho compared with nonautoimmune mphi. It is remarkable that when cultured in the absence of serum, MRL mphi displayed normal Rho activity and cytoskeletal morphology. Addition of a Rho inhibitor to normal mphi reproduced the morphologic and cytoskeletal abnormalities observed in MRL mphi. Taken together, our findings support the hypothesis that mphi from MRL and other systemic lupus erythematosus-prone mice have an apoptotic, cell-dependent, autoimmune phenotype that affects a broad range of mphi functions, including cytokine gene expression and Rho-dependent cytoskeletal regulation.