A computer model of the artificially ventilated human respiratory system in adult intensive care.

A multi-technique approach to modelling artificially ventilated patients on the adult general intensive care unit (ICU) is proposed. Compartmental modelling techniques were used to describe the mechanical ventilator and the flexible hoses that connect it to the patient. 3D CFD techniques were used to model flow in the major airways and a Windkessel style balloon model was used to model the mechanical properties of the lungs. A multi-compartment model of the lung based on bifurcating tree structures representing the conducting airways and pulmonary circulation allowed lung disease to be modelled in terms of altered V/Q ratios within a lognormal distribution of values and it is from these that gas exchange was determined. A compartmental modelling tool, Bathfp, was used to integrate the different modelling techniques into a single model. The values of key parameters in the model could be obtained from measurements on patients in an ICU whilst a sensitivity analysis showed that the model was insensitive to the value of other parameters within it. Measured and modelled values for arterial blood gases and airflow parameters are compared for 46 ventilator settings obtained from 6 ventilator dependent patients. The results show correlation coefficients of 0.88 and 0.85 for the arterial partial pressures of the O(2) and CO(2), respectively (p<0.01) and of 0.99 and 0.96 for upper airway pressure and tidal volume, respectively (p<0.01). The difference between measured and modelled values was large in physiological terms, suggesting that some optimisation of the model is required.

Quantification of lung injury using ventilation and perfusion distributions obtained from gamma scintigraphy.

This paper explores the potential of isotope V/Q lung scans to quantify lung disease. Areas of restricted perfusion in subjects with a pulmonary embolus (PE) were identified in 3D reconstructions of V/Q images achieved using anatomical data from the Visible Human Project. From these, the extent of lung damage was quantified. Significant differences in the values of both LogSD V and LogSD Q (p > 0.05) obtained from plots of V and Q against Log(V/Q) were found between normal subjects and subjects with a PE, but no correlation was found between either of these parameters and the degree of lung damage in subjects with a PE (p > 0.05). Whilst V/Q values were log normally distributed, the V/Q distributions from the subjects with a PE failed to show the bimodal distribution predicted from theoretical considerations and MIGET measurements previously reported. There was a statistically significant difference in the mean and standard deviation values of the V/Q distributions between normal subject and subjects with a PE (p < 0.05) but not in the median values (p > 0.05). There was no correlation between the mean, median and standard deviation of the distributions from the subjects with a PE and the percentage of damage present (p > 0.05).

Expression of phosphodiesterase 4D (PDE4D) is regulated by both the cyclic AMP-dependent protein kinase and mitogen-activated protein kinase signaling pathways. A potential mechanism allowing for the coordinated regulation of PDE4D activity and expression in cells.

Multiple families of cyclic nucleotide phosphodiesterases (PDE) have been described, and the regulated expression of these genes in cells is complex. Although cAMP is known to control the expression of certain PDE in cells, presumably reflecting a system of feedback on cAMP signaling, relatively little is known about the influence of non-cAMP signaling systems on PDE expression. In this study, we describe a novel mechanism by which activators of the protein kinase C (PKC)-Raf-MEK-ERK cascade regulate phosphodiesterase 4D (PDE4D) expression in vascular smooth muscle cells (VSMC) and assess the functional consequences of this effect. Whereas a prolonged elevation of cAMP in VSMC resulted in a protein kinase A (PKA)-dependent induction of expression of two PDE4D variants (PDE4D1 and PDE4D2), simultaneous activation of both the cAMP-PKA and PKC-Raf-MEK-ERK signaling cascades blunted this cAMP-mediated increase in PDE4D expression. By using biochemical, molecular biological, and pharmacological approaches, we demonstrate that this PDE4D-selective effect of activators of the PKC-Raf-MEK-ERK cascade was mediated through a mechanism involving altered PDE4D mRNA stability and markedly attenuated the cAMP-mediated desensitization that results from prolonged activation of the cAMP signaling system in cells. The data are presented in the context of activators of the PKC-Raf-MEK-ERK cascade having both short and long term effects on PDE4D activity and expression in cells that may influence cAMP signaling.

Computer simulation of counterlungs.

We have developed a computer model of chest-mounted counterlungs, which accounts for counterlung shape, effective volume, and pressure centroid. The model has been validated and the principles are applicable to other counterlung systems. The highly non-linear and discontinuous behavior of a counterlung is predicted by use of a sophisticated numerical integration method that computes variables such as pressure and volume in the time domain. Three separate stiffness (reciprocal of compliance) terms have been used which contribute to the diver's work of breathing: material elastic stiffness, "gas" stiffness, and "hydrostatic" stiffness. The model provides a significant advance in the understanding of counterlung behavior, allowing the performance of practical equipment to be predicted.

A Comparison of SIR-B Directional Ocean Wave Spectra with Aircraft Scanning Radar Spectra.

Directional ocean wave spectra derived from Shuttle Imaging Radar-B (SIR-B) L-band imagery collected off the coast of southern Chile on 11 and 12 October 1984 were compared with independent spectral estimates from two airborne scanning radars. In sea states with significant wave heights ranging from 3 to 5 meters, the SIR-B-derived spectra at 18 degrees and 25 degrees off nadir yielded reasonable estimates of wavelengths, directions, and spectral shapes for all wave systems encountered, including a purely azimuth-traveling system. A SIR-B image intensity variance spectrum containing predominantly range-traveling waves closely resembles an independent aircraft estimate of the slope variance spectrum. The prediction of a U.S. Navy global spectral ocean wave model on 11 October 1984 exhibited no significant bias in dominant wave number but contained a directional bias of about 30 degrees espect to the mean of the aircraft and spacecraft estimates.

Dynamic radiography. An evaluation of cardiac motion by the analysis of scattered radiation during fluoroscopy.

A non-invasive technique, utilizing scattered radiation, has been developed to monitor and measure the motion of the epicardial surface during fluoroscopy. A number of dogs were studied using a monitoring device which consists of an X-Ray beam collimator, collimated sodium iodide dectetors and their associated electronics. The detector signals are computer processed to obtain frequency fingerprints of epicardial motion that may, in the future, indicate the condition of the myocardium.