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Conventional inhaled NO systems deliver NO by synchronized injection or continuous NO flow in the ventilator circuitry. Such methods can lead to variable concentrations during inspiration that may differ from desired dosing. NO concentrations in these systems are generally monitored through electrochemical methods that are too slow to capture this nuance and potential dosing error. A novel technology that reduces NO2 into NO via low-resistance ascorbic-acid cartridges just prior to inhalation has recently been described. The gas volume of these cartridges may enhance gas mixing and reduce dosing inconsistency throughout inhalation. The impact of the ascorbic-acid cartridge technology on NO concentration during inspiration was characterized through rapid chemiluminescence detection during volume control ventilation, pressure control ventilation, synchronized intermittent mandatory ventilation and continuous positive airway pressure using an in vitro lung model configured to simulate the complete uptake of NO. Two ascorbic acid cartridges in series provided uniform and consistent dosing during inspiration during all modes of ventilation. The use of one cartridge showed variable inspiratory concentration of NO at the largest tidal volumes, whereas the use of no ascorbic acid cartridge led to highly inconsistent NO inspiratory waveforms. The use of ascorbic acid cartridges also decreased breath-to-breath variation in SIMV and CPAP ventilation. The ascorbic-acid cartridges, which are designed to convert NO2 (either as substrate or resulting from NO oxidation during injection) into NO, also provide the benefit of minimizing the variation of inhaled NO concentration during inspiration. It is expected that the implementation of this method will lead to more consistent and predictable dosing., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Clinical right ventricular (RV) impairment can occur with left ventricular assist device (LVAD) use, thereby compromising the therapeutic effectiveness. The underlying mechanism of this RV failure may be related to induced abnormalities of septal wall motion, RV distension and ischemia, decreased LV filling, and aberrations of LVAD flow. Inhaled nitric oxide (NO), a potent pulmonary vasodilator, may reduce RV afterload, and thereby increase LV filling, LVAD flow, and cardiac output (CO). To investigate the mechanisms associated with LVAD-induced RV dysfunction and its treatment, we created a swine model of hypoxia-induced pulmonary hypertension and acute LVAD-induced RV failure and assessed the physiological effects of NO. Increased LVAD speed resulted in linear increases in LVAD flow until pulse pressure narrowed. Higher speeds induced flow instability, LV collapse, a precipitous fall of both LVAD flow and CO. Nitric oxide (20 ppm) treatment significantly increased the maximal achievable LVAD speed, LVAD flow, CO, and LV diameter. Nitric oxide resulted in decreased pulmonary vascular resistance and RV distension, increased RV ejection, promoted LV filling and improved LVAD performance. Inhaled NO may thus have broad utility for the management of biventricular disease managed by LVAD implantation through the effects of NO on LV and RV wall dynamics.

Inhaled nitric oxide (NO) selectively dilates pulmonary blood vessels, reduces pulmonary vascular resistance (PVR), and enhances ventilation-perfusion matching. However, existing modes of delivery for the treatment of chronic pulmonary hypertension are limited due to the bulk and heft of large tanks of compressed gas. We present a novel system for the generation of inhaled NO that is based on the initial heat-induced evaporation of liquid N2O4 into gas phase NO2 followed by the room temperature reduction to NO by an antioxidant, ascorbic acid cartridge just prior to inhalation. The biologic effects of NO generated from liquid N2O4 were compared with the effects of NO gas, on increased mean pulmonary artery pressure (mPAP) and PVR in a hypoxemic (FiO2 15%) swine model of pulmonary hypertension. We showed that NO concentration varied directly with the fixed cross sectional flow of the outflow aperture when studied at temperatures of 45, 47.5 and 50°C and was independent of the rate of heating. Liquid N2O4-sourced NO at 1, 5, and 20 ppm significantly reduced the elevated mPAP and PVR induced by experimental hypoxemia and was biologically indistinguishable from gas source NO in this model. These experiments show that it is feasible to generate highly purified NO gas from small volumes of liquid N2O4 at concentrations sufficient to lower mPAP and PVR in hypoxemic swine, and suggest that a miniaturized ambulatory system designed to generate biologically active NO from liquid N2O4 is achievable., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Patients with type I diabetes nearly always need therapy with insulin. The most desirable treatment would be to mimic the operation of a normal pancreas. In this work a patient affected with this pathology is modeled and identified with a neural network, and a control strategy known as Nonlinear Model Predictive Control is evaluated as an approach to command an insulin pump using the subcutaneous route. A method for dealing with the problems related with the multiple insulin injections simulation and a multilayer neural network identification of the patient model is presented. The controller performance of the proposed strategy is tested under charge and reference disturbances (setpoint). Simulating an initial blood glucose concentration of 250 mg/dl a stable value of 97.0 mg/dl was reached, with a minimum level of 76.1 mg/dl. The results of a simulated 50 g oral glucose tolerance test show a maximum glucose concentration of 142.6 mg/dl with an undershoot of 76.0 mg/dl. According to the simulation results, stable close-loop control is achieved and physiological levels are reached with reasonable delays, avoiding the undesirable low glucose levels. Further studies are needed in order to deal with noise and robustness aspects, issues which are out of the scope of this work.

Analysis of heart rate variability (HRV) is a valuable, non-invasive method for quantifying autonomic cardiac control in humans. Frequency-domain analysis of HRV involving myocardial ischaemic episodes should take into account its non-stationary behaviour. The wavelet transform is an alternative tool for the analysis of non-stationary signals. Fourteen patients have been analysed, ranging from 40 to 64 years old and selected from the European Electrocardiographic ST-T Database (ESDB). These records contain 33 ST episodes, according to the notation of the ESDB, with durations of between 40s and 12 min. A method for analysing HRV signals using the wavelet transform was applied to obtain a time-scale representation for very low-frequency (VLF), low-frequency (LF) and high-frequency (HF) bands using the orthogonal multiresolution pyramidal algorithm. The design and implementation using fast algorithms included a specially adapted decomposition quadrature mirror filter bank for the frequency bands of interest. Comparing a normality zone against the ischaemic episode in the same record, increases in LF (0.0112 +/- 0.0101 against 0.0175 +/- 0.0208 s2 Hz(-1); p<0.1) and HF (0.0011 +/- 0.0008 against 0.00 17 +/- 0.0020 s2 Hz(-1); p<0.05) were obtained. The possibility of using these indexes to develop an ischaemic-episode classifier was also tested. Results suggest that wavelet analysis provides useful information for the assessment of dynamic changes and patterns of HRV during myocardial ischaemia.

Viscoelastic properties determine the dynamic behaviour of the arterial wall under pulsatile pressure and flow, suggesting time- or frequency-dependent responses to changes in wall stress and strain. The objectives of the present study were: (i) to develop a simplified model to derive simultaneously the elastic, viscous and inertial wall moduli; (ii) to assess Young's modulus as a function of frequency, in conscious, chronically instrumented dogs. Parametric discrete time models were used to characterise the dynamics of the arterial system based on thoracic aortic pressure (microtransducer) and diameter (sonomicrometry) measurements in control steady state and during activation of smooth muscle with the alpha-adrenoceptor agonist phenylephrine (5 microg kg(-1) min(-1), I.V.), in eight conscious dogs. The linear autoregressive model and a physically motivated non-linear model were fitted to the input-output (stress-strain) relationship. The aortic buffering function (complex Young's modulus) was obtained in vivo from the identified linear model. Elastic, viscous and inertial moduli were significantly increased from control state ((44.5 +/- 7.7) x 10(4) Pa; (12.3 +/- 4.7) x 10(4) Pa s; (0.048 +/- 0.028) x 10(4) Pa s(2) ) to active state ((85.3 +/- 29.5) x 10(4) Pa, P < 0.001; (22.4 +/- 8.3) x 10(4) Pa s, P < 0.05; (0.148 +/- 0.060) x 10(4) Pa s(2), P < 0.05). These moduli, obtained using the linear model, did not present significant differences compared with those derived using the non-linear model. In control conditions, the magnitude of the normalised complex Young's modulus was found to be similar to that reported in previous animal studies ranging from 1 to 10 Hz. During vascular smooth muscle activation, this modulus was found to be increased with regard to control conditions (P < 0.01) in the frequency range used in this study. The frequency-dependent Young's modulus of the aortic wall was obtained for the first time in conscious, unsedated dogs. The parametric modelling approach allows us to verify that vascular smooth muscle activation increases the elastic, viscous and inertial moduli with the advantage of being able to track their time evolution. Furthermore, under activation, the aortic wall remains stiff in the physiological frequency range, suggesting the impairment of the arterial buffering function. Experimental Physiology (2001) 86.4, 519-528.