Journal of applied physiology
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Concomitant smoke inhalation trauma in burn patients is a serious medical problem. Previous investigations in our sheep model revealed that these injuries lead to significant airway hyperemia, enhanced pulmonary fluid extravasation, and severely impaired pulmonary function. However, the pathophysiological mechanisms are still not fully understood. ⋯ Furthermore, the treatment significantly attenuated abnormalities in respiratory gas exchange. The data suggest that calcitonin gene-related peptide contributes to early airway hyperemia, transvascular fluid flux, and respiratory malfunction following ovine burn and smoke inhalation injury. Future studies will be needed to clarify the potential therapeutic benefit for patients with this injury.
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The ubiquitin-proteasome system is a key proteolytic pathway activated during skeletal muscle atrophy. The proteasome, however, cannot degrade intact myofibrils or actinomyosin complexes. In rodent models of diabetes mellitus and uremia, caspase-3 is involved in actinomyosin cleavage, generating fragments that subsequently undergo ubiquitin-proteasome-mediated degradation. ⋯ In contrast, there was an increase in TdT-mediated dUTP nick end label-positive nuclei in the denervated muscle of wild-type compared with caspase-3-knockout mice. Apoptotic signaling upstream of caspase-3 remained intact, with equivalent mitochondrial Bax translocation and cytochrome c release and caspase-9 activation in the denervated gastrocnemius muscle of wild-type and caspase-3-knockout mice. In contrast, diminished poly(ADP-ribose) polymerase cleavage in the denervated muscle of caspase-3-knockout compared with wild-type mice revealed that apoptotic signaling downstream of caspase-3 was impaired, suggesting that the absence of caspase-3 protects against denervation-induced muscle atrophy by suppressing apoptosis as opposed to ubiquitin-proteasome-mediated protein degradation.
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Comment Letter
Muscle oxygenation by near-infrared-based tissue oximeters.
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Noninvasive, continuous measurements in vivo are commonly used to make inferences about mechanisms controlling internal and external respiration during exercise. In particular, the dynamic response of muscle oxygenation (Sm(O(2))) measured by near-infrared spectroscopy (NIRS) is assumed to be correlated to that of venous oxygen saturation (Sv(O(2))) measured invasively. However, there are situations where the dynamics of Sm(O(2)) and Sv(O(2)) do not follow the same pattern. ⋯ In contrast, model simulations of venous oxygen concentration show an exponential decrease under both conditions due to the imbalance between oxygen delivery and consumption at the onset of exercise. Also, model simulations that distinguish the dynamic responses of oxy-and deoxygenated Hb (HbO(2), HHb) and Mb (MbO(2), HMb) concentrations (C(oxy) = HbO(2) + MbO(2); C(deoxy) = HHb + HMb) show that Hb and Mb contributions to the NIRS signal are comparable. Analysis of NIRS signal components during exercise with a mechanistic model of oxygen transport and metabolism indicates that changes in oxygenated Hb and Mb are responsible for different patterns of Sm(O(2)) and Sv(O(2)) dynamics observed under normoxia and hypoxia.
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At birth, the initiation of pulmonary gas exchange is dependent on air entry into the lungs, and recent evidence indicates that pressures generated by inspiration may be involved. We have used simultaneous plethysmography and phase-contrast X-ray imaging to investigate the contribution of inspiration and expiratory braking maneuvers (EBMs) to lung aeration and the formation of a functional residual capacity (FRC) after birth. Near-term rabbit pups (n = 26) were delivered by cesarean section, placed in a water plethysmograph, and imaged during the initiation of spontaneous breathing. ⋯ The incidence of EBMs was rare early during lung aeration, with most (>80%) occurring after >80% of max FRC was achieved. Although EBMs were associated with an overall increase in FRC, 34.8 +/- 5.3% of EBMs were associated with a decrease in FRC. We conclude that lung aeration is predominantly achieved by inspiratory efforts and that EBMs help to maintain FRC following its formation.