Journal of applied physiology
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Comparative Study
Vigilance state-dependent attenuation of hypercapnic chemoreflex and exaggerated sleep apnea in orexin knockout mice.
Exogenous administration of orexin can promote wakefulness and respiration. Here we examined whether intrinsic orexin participates in the control of breathing in a vigilance state-dependent manner. Ventilation was recorded together with electroencephalography and electromyography for 6 h during the daytime in prepro-orexin knockout mice (ORX-KO) and wild-type (WT) littermates. ⋯ Hypoxic responses during wake and sleep periods were not different between the genotypes. Spontaneous but not postsigh sleep apneas were more frequent in ORX-KO than in WT littermates during both SWS and REM sleep. Our findings suggest that orexin plays a crucial role both in CO(2) sensitivity during wakefulness and in preserving ventilation stability during sleep.
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Mechanical ventilation (MV) is associated with diaphragmatic oxidative stress that contributes to both diaphragmatic atrophy and contractile dysfunction. However, the pathways responsible for oxidant production in the diaphragm during MV remain unknown. To address this issue, we tested the hypothesis that diaphragmatic nitric oxide synthase (NOS) activity is elevated during MV, resulting in nitration of diaphragmatic proteins. ⋯ Moreover, prolonged MV did not elevate diaphragmatic levels of S-nitrosothiols, nitrate, or nitrite. Finally, prolonged MV significantly reduced diaphragmatic levels of GSH, which is consistent with diaphragmatic oxidative stress. Collectively, these data reveal that MV-induced oxidative stress in the diaphragm is not due to increases in nitric oxide production by NOS.
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Mechanisms of burn-related cardiac dysfunction may involve defects in mitochondria. This study determined 1) whether burn injury alters myocardial mitochondrial integrity and function; and 2) whether an antioxidant vitamin therapy prevented changes in cardiac mitochondrial function after burn. Sprague-Dawley rats were given a 3 degrees burn over 40% total body surface area and fluid resuscitated. ⋯ In burn animals, lipid peroxidation in cardiac mitochondria increased 30-50%, suggesting burn-induced oxidative stress. Antioxidant vitamin therapy prevented burn-related loss of membrane integrity and antioxidant defense in myocardial mitochondria and prevented cardiac dysfunction. These data suggest that burn-mediated mitochondrial dysfunction and loss of reactive oxygen species defense may play a role in postburn cardiac dysfunction.
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To evaluate the role of pulmonary surfactant in the prevention of lung injury caused by mechanical ventilation (MV) at low end-expiratory volumes, lung mechanics and morphometry were assessed in three groups of eight normal, open-chest rabbits ventilated for 3-4 h at zero end-expiratory pressure (ZEEP) with physiological tidal volumes (Vt = 10 ml/kg). One group was left untreated (group A); the other two received surfactant intratracheally (group B) or aerosolized dioctylsodiumsulfosuccinate (group C) before MV on ZEEP. Relative to initial MV on positive end-expiratory pressure (PEEP; 2.3 cmH(2)O), quasi-static elastance (Est) and airway (Rint) and viscoelastic resistance (Rvisc) increased on ZEEP in all groups. ⋯ Lung edema developed in group C (wet-to-dry ratio = 7.1), but not in the other groups. Relative to group D, both groups A and C, but not B, showed histological indexes of bronchiolar injury, whereas all groups exhibited an increased number of polymorphonuclear leukocytes in alveolar septa, which was significantly greater in group C. In conclusion, administration of exogenous surfactant largely prevents the histological and functional damage of prolonged MV at low lung volumes, whereas surfactant dysfunction worsens the functional alterations, also because of edema formation and, possibly, increased inflammatory response.