Branch Mode Selection during Early Lung Development

Many organs of higher organisms, such as the vascular system, lung, kidney, pancreas, liver and glands, are heavily branched structures. The branching process during lung development has been studied in great detail and is remarkably stereotyped. The branched tree is generated by the sequential, non-random use of three geometrically simple modes of branching (domain branching, planar and orthogonal bifurcation). While many regulatory components and local interactions have been defined an integrated understanding of the regulatory network that controls the branching process is lacking. We have developed a deterministic, spatio-temporal differential-equation based model of the core signaling network that governs lung branching morphogenesis. The model focuses on the two key signaling factors that have been identified in experiments, fibroblast growth factor (FGF10) and sonic hedgehog (SHH) as well as the SHH receptor patched (Ptc). We show that the reported biochemical interactions give rise to a Schnakenberg-type Turing patterning mechanisms that allows us to reproduce experimental observations in wildtype and mutant mice. The kinetic parameters as well as the domain shape are based on experimental data where available. The developed model is robust to small absolute and large relative changes in the parameter values. At the same time there is a strong regulatory potential in that the switching between branching modes can be achieved by targeted changes in the parameter values. We note that the sequence of different branching events may also be the result of different growth speeds: fast growth triggers lateral branching while slow growth favours bifurcations in our model. We conclude that the FGF10-SHH-Ptc1 module is sufficient to generate pattern that correspond to the observed branching modesComment: Initially published at PLoS Comput Bio

Correlations between capnographic waveforms and peak flow meter measurement in emergency department management of asthma

BACKGROUND The usual method for initial assessment of an acute asthma attack in the emergency room includes the use of peak flow measurement and clinical parameters. Both methods have their own disadvantages such as poor cooperation/effort from patients (peak flow meter) and lack of objective assessment (clinical parameters). We were looking into other methods for the initial asthma assessment, namely the use of capnography. The normal capnogram has an almost square wave pattern comprising phase 1, slope phase 2, plateau phase 3, phase 4 and angle alpha (between slopes 2 and 3). The changes in asthma include decrease in slope of phase 2, increase in slope 3 and opening of angle alpha. AIMS Our objective was to compare and assess the correlation between the changes in capnographic indices and peak flow measurement in non-intubated acute asthmatic patients attending the emergency room. METHODS We carried out a prospective study in a university hospital emergency department (ED). One hundred and twenty eight patients with acute asthma were monitored with peak flow measurements and then had a nasal cannula attached for microstream sampling of expired carbon dioxide. The capnographic waveform was recorded onto a PC card for indices analysis. The patients were treated according to departmental protocols. After treatment, when they were adjudged well for discharge, a second set of results was obtained for peak flow measurements and capnographic waveform recording. The pre-treatment and post-treatment results were then compared with paired samples t-test analysis. Simple and canonical correlations were performed to determine correlations between the assessment methods. A p value of below 0.05 was taken to be significant. RESULTS Peak flow measurements showed significant improvements post-treatment (p < 0.001). On the capnographic waveform, there was a significant difference in the slope of phase 3 (p < 0.001) and alpha angle (p < 0.001), but not in phase 2 slope (p = 0.35). Correlation studies done between the assessment methods and indices readings did not show strong correlations either between the measurements or the magnitude of change pre-treatment and post-treatment. CONCLUSION Peak flow measurements and capnographic waveform indices can indicate improvements in airway diameter in acute asthmatics in the ED. Even though the two assessment methods did not correlate statistically, capnographic waveform analysis presents several advantages in that it is effort independent and provides continuous monitoring of normal tidal respiration. They can be proposed for the monitoring of asthmatics in the ED

The Abdominal Circulatory Pump

Blood in the splanchnic vasculature can be transferred to the extremities. We quantified such blood shifts in normal subjects by measuring trunk volume by optoelectronic plethysmography, simultaneously with changes in body volume by whole body plethysmography during contractions of the diaphragm and abdominal muscles. Trunk volume changes with blood shifts, but body volume does not so that the blood volume shifted between trunk and extremities (Vbs) is the difference between changes in trunk and body volume. This is so because both trunk and body volume change identically with breathing and gas expansion or compression. During tidal breathing Vbs was 50–75 ml with an ejection fraction of 4–6% and an output of 750–1500 ml/min. Step increases in abdominal pressure resulted in rapid emptying presumably from the liver with a time constant of 0.61±0.1SE sec. followed by slower flow from non-hepatic viscera. The filling time constant was 0.57±0.09SE sec. Splanchnic emptying shifted up to 650 ml blood. With emptying, the increased hepatic vein flow increases the blood pressure at its entry into the inferior vena cava (IVC) and abolishes the pressure gradient producing flow between the femoral vein and the IVC inducing blood pooling in the legs. The findings are important for exercise because the larger the Vbs the greater the perfusion of locomotor muscles. During asystolic cardiac arrest we calculate that appropriate timing of abdominal compression could produce an output of 6 L/min. so that the abdominal circulatory pump might act as an auxiliary heart

Quantitative modeling of the physiology of ascites in portal hypertension

Although the factors involved in cirrhotic ascites have been studied for a century, a number of observations are not understood, including the action of diuretics in the treatment of ascites and the ability of the plasma-ascitic albumin gradient to diagnose portal hypertension. This communication presents an explanation of ascites based solely on pathophysiological alterations within the peritoneal cavity. A quantitative model is described based on experimental vascular and intraperitoneal pressures, lymph flow, and peritoneal space compliance. The model's predictions accurately mimic clinical observations in ascites, including the magnitude and time course of changes observed following paracentesis or diuretic therapy