BACKGROUND: Calculation of physiologic dead space (dead space divided by tidal volume [V D / V T ]) using the Enghoff modification of the Bohr equation requires measurement of the partial pressure of mean expired CO 2 (P E CO 2 ) by exhaled gas collection and analysis, use of a metabolic analyzer, or use of a volumetric CO 2 monitor. The Dräger XL ventilator is equipped with integrated volumetric CO 2 monitoring and calculates minute CO 2 production (V CO 2 ). We calculated P E CO 2 and V D /V T from ventilator derived volumetric CO 2 measurements of V CO 2 and compared them to metabolic analyzer and volumetric CO 2 monitor measurements. METHODS: A total of 67 measurements in 36 subjects recovering from acute lung injury or ARDS were compared. Thirty-one ventilator derived measurements were compared to measurements using 3 different metabolic analyzers, and 36 ventilator derived measurements were compared to measurements from a volumetric CO 2 monitor. RESULTS: There was a strong agreement between ventilator derived measurements and metabolic analyzer or volumetric CO 2 monitor measurements of P E CO 2 and V D /V T. The correlations, bias, and precision between the ventilator and metabolic analyzer measurements for P E CO 2 were r ‫؍‬ 0.97, r 2 ‫؍‬ 0.93 (P < .001), bias ؊1.04 mm Hg, and precision ؎ 1.47 mm Hg. For V D /V T the correlations were r ‫؍‬ 0.95 and r 2 ‫؍‬ 0.91 (P < .001), and the bias and precision were 0.02 ؎ 0.04. The correlations between the ventilator and the volumetric CO 2 monitor for P E CO 2 were r ‫؍‬ 0.96 and r 2 ‫؍‬ 0.92 (P < .001), and the bias and precision were ؊0.19 ؎ 1.58 mm Hg. The correlations between the ventilator and the volumetric CO 2 monitor for V D /V T were r ‫؍‬ 0.97 and r 2 ‫؍‬ 0.95 (P < .001), and the bias and precision were 0.01 ؎ 0.03. CONCLUSIONS: P E CO 2 , and therefore V D /V T , can be accurately calculated directly from the Dräger XL ventilator volumetric capnography measurements without use of a metabolic analyzer or volumetric CO 2 monitor.

Aging is associated with chronic oxidative stress and inflammation that impact the tissue repair and regeneration capacity. MG53 is a TRIM family protein that facilitates repair of cell membrane injury in a redox-dependent manner. Here we demonstrate that the expression of MG53 is reduced in failing human heart and aging mouse heart, concomitant with elevated NFκB activation. We evaluate the safety and efficacy of longitudinal, systemic administration of recombinant human MG53 (rhMG53) protein in aged mice. Echocardiography and pressure-volume loop measurements reveal beneficial effects of rhMG53 treatment in improving heart function of aging mice. Biochemical and histological studies demonstrate the cardioprotective effects of rhMG53 are linked to suppression of NFκB-mediated inflammation, reducing apoptotic cell death and oxidative stress in the aged heart. Repetitive administrations of rhMG53 in aged mice do not have adverse effects on major vital organ functions. These findings support the therapeutic value of rhMG53 in treating age-related decline in cardiac function.

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Introduction: Aging is associated with chronic oxidative stress and inflammation that affect the tissue repair and regeneration capacity. MG53 is a TRIM family protein that facilitates repair of cell membrane injury in a redox-dependent manner. However, it is not clear how MG53 regulates cardiac inflammation during aging. Hypothesis: We hypothesize that the expression of MG53 is associated with age-related heart failure, and treatment with recombinant human MG53 (rhMG53) protein in aged mice might have beneficial effect on the age-related decline of heart function. Methods: qPCR and Western blots were conducted for targeted genes/proteins in non-failing and failing human left ventricular tissues, and mouse heart tissues. A total of sixty mice (24 months, 30 male and 30 female) were enrolled for treatment with rhMG53 (6 mg/kg, subcutaneous, daily for 6 weeks) or saline as control, and subjected to cardiac functional measurement with echocardiography and pressure-volume loop, and cardiac apoptotic and ROS assays. Blood were collected to quantify the serum levels of biomarkers for liver and cardiovascular injury. Results: We demonstrate that the expression of MG53 is reduced in failing human heart and aging mouse heart, concomitant with elevated NFκB activation. We evaluate the safety and efficacy of longitudinal, systemic administration of recombinant human MG53 (rhMG53) protein in aged mice. Echocardiography and pressure-volume loop measurements reveal beneficial effects of rhMG53 treatment in improving heart function of aging mice. Biochemical and histological studies demonstrate the cardioprotective effects of rhMG53 are linked to suppression of NFκB-mediated inflammation, reducing apoptotic cell death and oxidative stress in the aged heart. Repetitive administration of rhMG53 in aged mice does not have adverse effects on immune response and major vital organ functions. Conclusions: In this study, we showed decreased expression of MG53 and increased NFκB activation in both failing human hearts and aging mouse hearts. Moreover, longitudinal administration of rhMG53 mitigated the heart dysfunction in the aged mice. These findings support the therapeutic value of rhMG53 in treating age-related decline in cardiac function.