American journal of physiology. Regulatory, integrative and comparative physiology
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Sep 2014
Randomized Controlled TrialTissue oxygen saturation during hyperthermic progressive central hypovolemia.
During normothermia, a reduction in near-infrared spectroscopy (NIRS)-derived tissue oxygen saturation (So2) is an indicator of central hypovolemia. Hyperthermia increases skin blood flow and reduces tolerance to central hypovolemia, both of which may alter the interpretation of tissue So2 during central hypovolemia. This study tested the hypothesis that maximal reductions in tissue So2 would be similar throughout normothermic and hyperthermic central hypovolemia to presyncope. ⋯ Pre-LBNP, tissue So2 was similar (P = 0.654) between normothermia (74 ± 5%) and hyperthermia (73 ± 7%). Tissue So2 decreased (P < 0.001) throughout LBNP, but the reduction from pre-LBNP to presyncope was greater during normothermia (-10 ± 6%) than during hyperthermia (-6 ± 5%; P = 0.041). Contrary to our hypothesis, these findings indicate that hyperthermia is associated with a smaller maximal reduction in tissue So2 during central hypovolemia to presyncope.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Sep 2014
Effect of antigen sensitization and challenge on oscillatory mechanics of the lung and pulmonary inflammation in obese carboxypeptidase E-deficient mice.
Atopic, obese asthmatics exhibit airway obstruction with variable degrees of eosinophilic airway inflammation. We previously reported that mice obese as a result of a genetic deficiency in either leptin (ob/ob mice) or the long isoform of the leptin receptor (db/db mice) exhibit enhanced airway obstruction in the presence of decreased numbers of bronchoalveolar lavage fluid (BALF) eosinophils compared with lean, wild-type mice following antigen (ovalbumin; OVA) sensitization and challenge. To determine whether the genetic modality of obesity induction influences the development of OVA-induced airway obstruction and OVA-induced pulmonary inflammation, we examined indices of these sequelae in mice obese as a result of a genetic deficiency in carboxypeptidase E, an enzyme that processes prohormones and proneuropeptides involved in satiety and energy expenditure (Cpe(fat) mice). ⋯ However, OVA challenge enhanced airway obstruction and pulmonary inflammation in Cpe(fat) compared with wild-type mice. These results demonstrate that OVA sensitization and challenge enhance airway obstruction in obese mice regardless of the genetic basis of obesity, whereas the degree of OVA-induced pulmonary inflammation is dependent on the genetic modality of obesity induction. These results have important implications for animal models of asthma, as modeling the pulmonary phenotypes for subpopulations of atopic, obese asthmatics critically depends on selecting the appropriate mouse model.
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Am. J. Physiol. Regul. Integr. Comp. Physiol. · Sep 2014
Apolipoprotein A-I mimetic peptide 4F attenuates kidney injury, heart injury, and endothelial dysfunction in sepsis.
Kidney injury, heart injury, and cytokine-induced vascular hyperpermeability are associated with high rates of morbidity and mortality in sepsis. Although the mechanism remains unknown, apolipoprotein A-I (apoA-I) mimetic peptide 4F reduces inflammation and protects HDL levels, which are reduced in sepsis. We hypothesized that 4F also protects kidneys and hearts in a rat model of cecal ligation and puncture (CLP). ⋯ In CLP+4F rats, baroreflex sensitivity and cardiac function were completely protected from the effects of CLP, as was glomerular filtration; heart mitochondria morphology was improved; sepsis-induced changes in serum cholesterol, LDL, HDL, and apoA-I were less common; all cytokines were lower than in CLP rats; and expression of Slit2, Robo4, and eNOS was completely restored. Administration of 4F inhibits inflammatory responses and strengthens the vascular barrier, protecting kidneys and hearts in an HDL-dependent manner. To determine the extent of the protective effect of 4F, further studies are needed.