Anesthesia and analgesia
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The mechanisms of general anesthesia by volatile drugs remain largely unknown. Mitochondrial dysfunction and reduction in energy levels have been suggested to be associated with general anesthesia status. 2-Deoxy-D-glucose (2-DG), an analog of glucose, inhibits hexokinase and reduces cellular levels of adenosine triphosphate (ATP). 3-Nitropropionic acid is another compound which can deplete ATP levels. In contrast, idebenone and L-carnitine could rescue deficits of energy. We therefore sought to determine whether 2-DG and/or 3-nitropropionic acid can enhance the anesthetic effects of isoflurane, and whether idebenone and L-carnitine can reverse the actions of 2-DG. ⋯ These results from our pilot studies have established a system and generated a hypothesis that 2-DG enhances anesthetic effects via reducing energy levels. These findings should promote further studies to investigate anesthesia mechanisms.
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Anesthesia and analgesia · Feb 2015
Propofol-Induced Electroencephalographic Seizures in Neonatal Rats: The Role of Corticosteroids and γ-Aminobutyric Acid Type A Receptor-Mediated Excitation.
An imbalance between excitation and inhibition in the developing central nervous system may result in a pathophysiological outcome. We investigated the mechanistic roles of endocrine activity and γ-aminobutyric acid type A receptor (GABAAR)-mediated excitation in electroencephalographic seizures caused by the GABAAR-selective anesthetic propofol in neonatal rats. ⋯ Propofol increases systemic corticosteroid levels in neonatal rats, which along with GABAAR-mediated excitation appear to be required for propofol-induced neonatal electroencephalographic seizures. Enhancement of GABAAR activity alone may not be sufficient to elicit neonatal electroencephalographic seizures.
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Anesthesia and analgesia · Feb 2015
Excessive Postoperative Bleeding and Outcomes in Neonates Undergoing Cardiopulmonary Bypass.
Neonates undergoing cardiac surgery are especially prone to the hemostatic alterations of cardiopulmonary bypass (CPB) and are at high risk for post-CPB bleeding. An immature coagulation system, significant hemodilution from the CPB prime, long CPB times at low temperatures, and extensive suture lines increase neonates' susceptibility to bleeding after CPB. In this study, we examined the relationship between excessive bleeding in neonates after CPB and major postoperative adverse events. ⋯ Excessive postoperative bleeding in neonates after CPB is independently associated with increased adverse events, specifically the need for postoperative dialysis and ECMO support. Our findings in neonates are congruent with other recent research that also has found increasing transfusion requirements after pediatric CPB to be independently associated with an increase in major postoperative adverse events. Our results may aid clinicians in anticipating potential adverse events after neonatal bypass and in allocating the resources necessary to manage these events.
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Anesthesia and analgesia · Feb 2015
The Effects of Exogenous Surfactant Treatment in a Murine Model of Two-Hit Lung Injury.
Because pulmonary endogenous surfactant is altered during acute respiratory distress syndrome, surfactant replacement may improve clinical outcomes. However, trials of surfactant use have had mixed results. We designed this animal model of unilateral (right) lung injury to explore the effect of exogenous surfactant administered to the injured lung on inflammation in the injured and noninjured lung. ⋯ Exogenous surfactant administration to an acid-injured right lung improved gas exchange and whole respiratory system compliance. However, markers of inflammation increased in the right (injured) lung, although this result was not found in the left (uninjured) lung. These data suggest that the mechanism by which surfactant improves lung function may involve both uninjured and injured alveoli.
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Anesthesia and analgesia · Feb 2015
Acute Ketamine Impairs Mitochondrial Function and Promotes Superoxide Dismutase Activity in the Rat Brain.
Ketamine is often associated with altered mitochondrial function and oxidative stress. Nevertheless, limited data are still available regarding the in vivo action of ketamine in mitochondrial bioenergetics and redox state. Accumulating evidence supports a role for nitric oxide (NO) as a possible modulator of ketamine's side effects. In the present study, we investigated the role of NO modulation on ketamine anesthesia at the level of brain mitochondrial function and redox status. ⋯ Acute ketamine administration impaired the function of mitochondrial complex I leading to increased mtNOS activity, increased generation of hydrogen peroxide and NO, resulting in superoxide dismutase triggering, and improved antioxidant activity. The present findings clarify the role of NO modulation in ketamine anesthesia, providing new data on a relevant clinical mechanism.