Nonlinear indicial response of complex nonstationary oscillations as pulmonary hypertension responding to step hypoxia.
This paper is devoted to the quantization of the degree of nonlinearity of the relationship between two biological variables when one of the variables is a complex nonstationary oscillatory signal. An example of the situation is the indicial responses of pulmonary blood pressure (P) to step changes of oxygen tension (DeltapO2) in the breathing gas. For a step change of DeltapO2 beginning at time t1, the pulmonary blood pressure is a nonlinear function of time and DeltapO2, which can be written as P(t-t1 | DeltapO2). An effective method does not exist to examine the nonlinear function P(t-t1 | DeltapO2). A systematic approach is proposed here. The definitions of mean trends and oscillations about the means are the keys. With these keys a practical method of calculation is devised. We fit the mean trends of blood pressure with analytic functions of time, whose nonlinearity with respect to the oxygen level is clarified here. The associated oscillations about the mean can be transformed into Hilbert spectrum. An integration of the square of the Hilbert spectrum over frequency yields a measure of oscillatory energy, which is also a function of time, whose mean trends can be expressed by analytic functions. The degree of nonlinearity of the oscillatory energy with respect to the oxygen level also is clarified here. Theoretical extension of the experimental nonlinear indicial functions to arbitrary history of hypoxia is proposed. Application of the results to tissue remodeling and tissue engineering of blood vessels is discussed. (+info
NADPH oxidase inhibition does not interfere with low PO2 transduction in rat and rabbit CB chemoreceptor cells.
The aim of the present work was to elucidate the role of NADPH oxidase in hypoxia sensing and transduction in the carotid body (CB) chemoreceptor cells. We have studied the effects of several inhibitors of NADPH oxidase on the normoxic and hypoxia-induced release of [3H]catecholamines (CA) in an in vitro preparation of intact CB of the rat and rabbit whose CA deposits have been labeled by prior incubation with the natural precursor [3H]tyrosine. It was found that diphenyleneiodonium (DPI; 0.2-25 microM), an inhibitor of NADPH oxidase, caused a dose-dependent release of [3H]CA from normoxic CB chemoreceptor cells. Contrary to hypoxia, DPI-evoked release was only partially Ca2+ dependent. Concentrations of DPI reported to produce full inhibition of NADPH oxidase in the rat CB did not prevent the hypoxic release response in the rat and rabbit CB chemoreceptor cells, as stimulation with hypoxia in the presence of DPI elicited a response equaling the sum of that produced by DPI and hypoxia applied separately. Neopterin (3-300 microM) and phenylarsine oxide (0.5-2 microM), other inhibitors of NADPH oxidase, did not promote release of [3H]CA in normoxic conditions or affect the response elicited by hypoxia. On the basis of effects of neopterin and phenylarsine oxide, it is concluded that NADPH oxidase does not appear to play a role in oxygen sensing or transduction in the rat and rabbit CB chemoreceptor cells in vitro and, in the context of the present study, that DPI effects are not related to NADPH oxidase inhibition. (+info
Continuous arterial P(O2) and P(CO2) measurements in swine during nitrous oxide and xenon elimination: prevention of diffusion hypoxia.
BACKGROUND: During nitrous oxide (N2O) elimination, arterial oxygen tension (PaO2) decreases because of the phenomenon commonly called diffusive hypoxia. The authors questioned whether similar effects occur during xenon elimination. METHODS: Nineteen anesthetized and paralyzed pigs were mechanically ventilated randomly for 30 min using inspiratory gas mixtures of 30% oxygen and either 70% N2O or xenon. The inspiratory gas was replaced by a mixture of 70% nitrogen and 30% oxygen. PaO2 and carbon dioxide tensions were recorded continuously using an indwelling arterial sensor. RESULTS: The PaO2 decreased from 119+/-10 mm Hg to 102+/-12 mm Hg (mean+/-SD) during N2O washout (P<0.01) and from 116+/-9 mm Hg to 110+/-8 mm Hg during xenon elimination (P<0.01), with a significant difference (P<0.01) between baseline and minimum PaO2 values (deltaPaO2, 17+/-6 mm Hg during N2O washout and 6+/-3 mm Hg during xenon washout). The PaCO2 value also decreased (from 39.3+/-6.3 mm Hg to 37.6+/-5.8 mm Hg) during N2O washout (P<0.01) and during xenon elimination (from 35.4+/-1.6 mm Hg to 34.9+/-1.6 mm Hg; P< 0.01). The deltaPaCO2 was 1.7+/-0.9 mm Hg in the N2O group and 0.5+/-0.3 mm Hg in the xenon group (P<0.01). CONCLUSION: Diffusive hypoxia is unlikely to occur during recovery from xenon anesthesia, probably because of the low blood solubility of this gas. (+info
Breathing patterns during slow and fast ramp exercise in man.
Breathing frequency (fb), tidal volume (VT), and respiratory timing during slow (SR, 8 W min-1) and fast (FR, 65 W min-1) ramp exercise to exhaustion on a cycle ergometer was examined in seven healthy male subjects. Expiratory ventilation (VE), pulmonary gas exchange (VO2 and VCO2) and end-tidal gas tensions (PET,O2 and PET,CO2) were determined using breath-by-breath techniques. Arterialized venous blood was sampled from a dorsal hand vein at 2 min intervals during SR and 30 s intervals during FR and analysed for arterial plasma PCO2 (PaCO2). PET,CO2 increased with increasing work rates (WRs) below the ventilatory threshold (VT); at WRs > or = 90% VO2,max, PET,CO2 was reduced (P < 0.05) below 0 W values in SR but not in FR.fb and VT were similar for SR and FR at all submaximal WRs, resulting in a similar VE. At exhaustion VE was similar but fb was higher (P < 0.05) and VT was lower (P < 0.05) in SR (fb, 51 +/- 10 breaths min-1; VT, 2590 +/- 590 ml) than in FR (fb, 42 +/- 8 breaths min-1; VT, 3050 +/- 470 ml). The time of expiration (TE) decreased with increasing WR, but there was no difference between SR and FR. The time of inspiration (TI) decreased at exercise intensities > or = VT; at exhaustion, TI was shorter (P < 0.05) during SR (0.512 +/- 0.097 s) than during FR (0.753 +/- 0.100 s). The TI to total breath duration (TI/TTot) and the inspiratory flow (VT/TI) were similar during SR and FR at all submaximal exercise intensities; at VO2,max, TI/TTot was lower (P < 0.05) and VT/TI was higher (P < 0.05) during SR (TI/TTot, 0.473 +/- 0.030; VT/TI, 5.092 +/- 0.377 l s-1) than during FR (TI/TTot, 0.567 +/- 0.050; VT/TI, 4.117 +/- 0.635 l s-1). These results suggest that during progressive exercise, breathing pattern and respiratory timing may be determined, at least at submaximal work rates, independently of alveolar and arterial PCO2. (+info
Electrocardiographic signs of chronic cor pulmonale: A negative prognostic finding in chronic obstructive pulmonary disease.
BACKGROUND: Chronic cor pulmonale (CCP) is a strong predictor of death in chronic obstructive pulmonary disease (COPD). The aims of this study were to assess the prognostic role of individual ECG signs of CCP and of the interaction between these signs and abnormal arterial blood gases. METHODS AND RESULTS: Two hundred sixty-three patients (217 men) with COPD, mean age 67+/-9 years, were grouped according to whether they had no ECG signs (group 1, n=100) or >/=1 ECG signs (group 2, n=163) of CCP and were followed up for 13 years after an exacerbation of respiratory failure. The median survival was significantly shorter in group 2 than in group 1 (2.58 versus 3. 45 years, respectively; Mantel-Cox test, 9.58; P=0.002). The Cox regression analysis identified S1S2S3 pattern, right atrial overload (RAO), and alveolar-arterial oxygen gradient (PAO2-PaO2) >48 mm Hg during oxygen therapy as the strongest predictors of death, with hazard rate (HR)=1.81 (95% CI, 1.22 to 2.69), HR=1.58 (95% CI, 1.15 to 2.18), and HR=1.96 (95% CI, 1.19 to 3.25), respectively. The median survivals of patients having both S1S2S3 pattern and RAO (n=14) and of patients having either S1S2S3 pattern or RAO (n=77) were 1.33 and 2.70 years, respectively (P=0.022). Group 2 patients had a 3-year survival of 18% or 53%, depending on whether their PAO2-PaO2 during oxygen therapy was or was not >48 mm Hg. CONCLUSIONS: Some ECG signs of CCP and PAO2-PaO2 >48 mm Hg during oxygen therapy qualified as a simple and inexpensive tool for targeting subsets of COPD patients with severe or very severe short-term prognosis. (+info
Spin-lattice relaxation of laser-polarized xenon in human blood.
The nuclear spin polarization of 129Xe can be enhanced by several orders of magnitude by using optical pumping techniques. The increased sensitivity of xenon NMR has allowed imaging of lungs as well as other in vivo applications. The most critical parameter for efficient delivery of laser-polarized xenon to blood and tissues is the spin-lattice relaxation time (T1) of xenon in blood. In this work, the relaxation of laser-polarized xenon in human blood is measured in vitro as a function of blood oxygenation. Interactions with dissolved oxygen and with deoxyhemoglobin are found to contribute to the spin-lattice relaxation time of 129Xe in blood, the latter interaction having greater effect. Consequently, relaxation times of 129Xe in deoxygenated blood are shorter than in oxygenated blood. In samples with oxygenation equivalent to arterial and venous blood, the 129Xe T1s at 37 degrees C and a magnetic field of 1.5 T were 6.4 s +/- 0.5 s and 4.0 s +/- 0.4 s, respectively. The 129Xe spin-lattice relaxation time in blood decreases at lower temperatures, but the ratio of T1 in oxygenated blood to that in deoxygenated blood is the same at 37 degrees C and 25 degrees C. A competing ligand has been used to show that xenon binding to albumin contributes to the 129Xe spin-lattice relaxation in blood plasma. This technique is promising for the study of xenon interactions with macromolecules. (+info
Randomised controlled trial of aminophylline for severe acute asthma.
OBJECTIVES: To determine whether children with severe acute asthma treated with large doses of inhaled salbutamol, inhaled ipratropium, and intravenous steroids are conferred any further benefits by the addition of aminophylline given intravenously. STUDY DESIGN: Randomised, double blind, placebo controlled trial of 163 children admitted to hospital with asthma who were unresponsive to nebulised salbutamol. RESULTS: The placebo and treatment groups of children were similar at baseline. The 48 children in the aminophylline group had a greater improvement in spirometry at six hours and a higher oxygen saturation in the first 30 hours. Five subjects in the placebo group were intubated and ventilated after enrollment compared with none in the aminophylline group. CONCLUSIONS: Aminophylline continues to have a place in the management of severe acute asthma in children unresponsive to initial treatment. (+info
Randomised trial of three doses of inhaled nitric oxide in acute respiratory distress syndrome.
BACKGROUND: Inhaled nitric oxide (iNO) is a potential therapeutic agent for the management of acute respiratory distress syndrome (ARDS). Concerns remain, however, regarding the potential toxicity from iNO and/or its oxidative derivatives and methaemoglobinaemia. AIMS: To determine the risk of toxicity from iNO, which includes worsening of lung injury, a prospective study evaluating the acute effects of three concentrations of iNO on gas exchange and haemodynamics in 12 children with ARDS was performed in a tertiary paediatric intensive care unit. INTERVENTION: iNO was administered for one hour at three concentrations (1, 10, and 20 parts per million (ppm)) in a random order of possible dosing schedules to avoid dose accumulation bias. Arterial blood gas, methaemoglobin concentrations, and haemodynamic parameters were obtained at baseline before commencement of iNO, at the end of each study hour, and after iNO was discontinued. Nitric oxide and nitrogen dioxide concentrations were continuously monitored during the study. RESULTS: iNO significantly improved the oxygenation ratio (Pao2/Fio2) from a mean (SEM) baseline of 11.9 (1.7) kPa to 20 (3.9) kPa, 24 (4.5) kPa, and 21.6 (3.9) kPa at 1, 10, and 20 ppm iNO, respectively. There was no significant difference in the improvement in oxygenation achieved between the three concentrations. Correspondingly, there was a significant improvement in oxygenation index (pre-iNO 28.3 (5) v post-iNO 18 (3) (1 ppm), 15 (3) (10 ppm), 16 (3) (20 ppm)). No toxicity from methaemoglobinaemia or nitrogen dioxide was seen during iNO administration. CONCLUSION: The results show that a low concentration of iNO (1 ppm) is as effective as higher concentrations (10 and 20 ppm) in improving oxygenation in children with ARDS and may be important in minimising toxicity during iNO use. (+info