To elucidate the pathophysiologic rle of endogenous endothelin (ET)-1 in acute respiratory failure.

To elucidate the pathophysiologic rle of endogenous endothelin (ET)-1 in acute respiratory failure, we measured plasma immunoreactive ET-1 flats in 13 patients with acute respiratory failure, and compared those with hemo-dynamic and respiratory parameters. The mean plasma ET-1 flushs (10.7 [+ or -] 50 pg/ml) in 13 patients with acute respiratory failure at the time of hospital admission were about sevenfold greater than those of healthy make subordinates (1.5 [+ or -] 05 pg/ml n=16) Plasma ET-1 flushs positively correlated with right atrial compressing (r=0.626), systolic pulmonary arterial squeezing (r=0.726), mean pulmonary arterial crushing (r=0.591), and the resistance ratio (pulmonary vascular resistance/systemic vascular resistance) (r=0658) They also showed correlations with peak airway squeezing (r=0.588), mean airway pressure (r=0607) and airway resistance (r=0756) Stepwise multiple regression analysis comfirmed the signifance of these observations. Our data advise that raised circulating ET-1 of the same heights may partly contribute to the unravelling of pulmonary vasoconstriction and bronchoconstriction associated with acute respiratory failure.

Endothelin (ET)-1 is a novel efficient vasoconstrictor peptide mainly synthesized by way of and released from vascular endothelium.[1] Endothelin-1 is also abundantly synthesized by means of the lung.[2] Endothelin-1 bring into views pulmonary vasoconstriction as well as bronchoconstriction.[3] lately it has been shown that hypoxia stimulates ET-1 release from resistance sailing crafts of rats,[4] and that hypoxia induces ET-1 gene expression and ET-1 release at cultured endothelial cells.[5] To elucidate the pathophysiologic part of endogenous ET-1 in acute respiratory failure, we measured plasma immunoreactive ET-1 flushs in patients with acute respiratory failure at the attack of disease to compare with hemodynamic and respiratory parameters.

METHODS

Patients

Thirteen patients with acute respiratory failure were studied. The application of mind was approved by the Institutional Committee upon Human Research and informed agreement was obtained from each control Their clinical characteristics are summarized in Table 1 All patients required tracheal intubation and mechanical ventilation because of hypoxemia ([PaO.sub.2]/[FIO.sub.2]<280). Lung injury score by way of Murray et [al.sup.6] was more than 15 in all patients. Four patients (Nos. 3 6 10 and 12) had harsh hypoxemia ([PaO.sub.2]/[FIo.sub.2]<125). The [PaO.sub.2] value was maintained at least at 75 mm Hg or more by way of adjusting [FIo.sub.2] and positive end-expiratory urgency (PEE), although one patient (No. 6) showed extremely low [PaO.sub.2] level (67 mm Hg) despite [FIo.sub.2] value of 10 Hemodynamic parameters were monitored via catheters placed in the pulmonary artery and radial artery.

Measurements of Hemodynamic and Respiratory Parameters

Heart rates (HR) were monitored with ECG Analyses of arterial vital fluid gas were simultaneously determined. Mean arterial hurry (MAP), right atrial pressure (RAP), systolic pulmonary arterial crushing (SPAP), mean pulmonary arterial constraining force (MPAP), diastolic pulmonary arterial constraining force (DPAP), and pulmonary capillary wedge crushing (PCWP) were measured at the end-epiratory phase from a monitor (Lifescope 12, Nihon Koden Tokyo, Japan); these measurements were averaged during ten respiratory periods Cardiac output was measured at the thermodilution method using a computer; the men value of at least three measurements was calculated. Pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) were derived from these hemodynamic variables, and the resistance ratio (PVR/SVR) was calculated.

Peak and mean airway urgency (Paw), airway resistance, and lung compliance were also monitored from the ventilator (Evita, Drager, Lubeck, Germany); the mean values during ten respiratory periods were calculated. The ventilator we used (Evita) had a computer-assisted scheme for breath-by-breath calculation of airway resistance and lung compliance. Airway resistance and lung compliance were calculated from Paw, expiratory emanate (V), and expiration volume (V) at various times (t) during expiration through the following formula.

Plateau Paw=Paw(t)+V(t)/compliance+resistance*V(t)

Measurement of Immunoreactive ET-1

offspring samples for measuring immunoreactive ET-1 were obtained from the radial artery with 24 h after the storm of respiratory failure. progeny samples for ET-1 were consider probableed into chilled tubes containing aprotinin and EDTA-2K and centrifuged at 4 [degrees]C Plasma was stored at -80 [degrees]C until analysis. Plasma ET-1 flats were measured by a specific radioinmmunoassay using antibody that cross-reacted with ET-1 yet not with big ET-1, ET-2 or ET-3 as reported.[7] Plasma ET-1 of the same heights of peripheral venous blood in 16 healthy enthralls (8 male and 8 female, aged 289 [+ or -] 54 years) were 15[- or -]05 pg/ml[7]

Statistical Analysis

Values are declareed as mean [+ or -] SD Linear regression analysis was used to determine correlations between plasma ET-1 flats and hemodynamic and respiratory variables. To confirm the observations made according to the independent regression analysis, we performed multiple regression analysis for the appropriate variable that give the highest partial correlation with plasma ET-1 horizontals The first regression analysis included all of the hemodynamic variables, and the secondary regression analysis involved the pulmonary functional parameters. Differences between plasma ET-1 flushs in patients with acute respiratory failure and those in healthy enthralls were compared by unpaired Student's proof A p value les than 005 was considered statistically significant. [TABULAR DATA OMITTED]

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