Changes in regional blood flow and pCO2 gradients during isolated abdominal aortic blood flow reduction

Objective: pCO2 gradients are used for the assessment of splanchnic regional and local mucosal blood flow changes in experimental and clinical research. pCO2 gradients may not parallel blood flow changes because of concomitant changes in metabolism, hemoglobin, temperature, and the Haldane effect. Design and setting: A randomized, controlled animal experiment in a university experimental research laboratory. Interventions: An extracorporeal shunt with reservoir and roller pump was inserted between the proximal and the distal abdominal aorta in 16 pigs. In animals randomized to the low-flow group (n=8) splanchnic perfusion was reduced by running the roller pump. At baseline and after 45min of stable shunt flow superior mesenteric artery, celiac trunk, spleen artery, and portal vein blood flows and regional venous-arterial and jejunal and gastric mucosal-arterial pCO2 gradients were measured, and the respective regional O2 consumption rates (VO2) calculated. Measurements and results: In the low-flow group all regional blood flows and the associated VO2 decreased to roughly 50% of baseline values, and hemoglobin decreased from 7.3 (4.4-9.6) g/dl to 5.7 (4.1-8.9) g/dl. Decreasing regional blood flows were consistently associated with increasing regional and mucosal pCO2 gradients. Conclusions: During isolated reduction in abdominal aortic blood flow there is no preferential distribution to any splanchnic vascular bed and changes in regional pCO2 gradients reflect consistently the associated blood blow change

Change in stroke volume in response to fluid challenge: assessment using esophageal Doppler

Abstract.: Objective: To compare two methods of assessing a change in stroke volume in response to fluid challenge: esophageal Doppler and thermodilution with the pulmonary artery catheter. Design: Prospective study. Setting: Department of Intensive Care of a university medical center. Patients: 19 adult patients, intubated and sedated, with a pulmonary catheter and a clinical indication for a fluid challenge. Interventions: Two examiners independently assessed the effect of a fluid challenge on stroke volume and cardiac output with esophageal Doppler. Thermodilution performed by an independent clinician was used as the reference. Between-method variation and interobserver variability of the Doppler method were assessed. Measurements and results: There were no differences in stroke volume and cardiac output before volume challenge when measured with either of the two methods or by the two examiners using the esophageal Doppler. Despite a small bias between the methods and the two examiners using the esophageal Doppler (overall bias for cardiac output 0.3l/min), the precision was poor (1.8l/min). Conclusions: The esophageal Doppler method is a non-invasive alternative to the pulmonary artery catheter for the assessment of stroke volume in critically ill patients. Measurement of stroke volume response to fluid challenge using esophageal Doppler shows substantial interobserver variability. Despite the poor precision between methods and investigators, similar directional changes in stroke volume can be measure

Thermodynamic stability, unfolding kinetics, and aggregation of the N-terminal actin-binding domains of utrophin and dystrophin.

Muscular dystrophy (MD) is the most common genetic lethal disorder in children. Mutations in dystrophin trigger the most common form of MD, Duchenne, and its allelic variant Becker MD. Utrophin is the closest homologue and has been shown to compensate for the loss of dystrophin in human disease animal models. However, the structural and functional similarities and differences between utrophin and dystrophin are less understood. Both proteins interact with actin through their N-terminal actin-binding domain (N-ABD). In this study, we examined the thermodynamic stability and aggregation of utrophin N-ABD and compared with that of dystrophin. Our results show that utrophin N-ABD has spectroscopic properties similar to dystrophin N-ABD. However, utrophin N-ABD has decreased denaturant and thermal stability, unfolds faster, and is correspondingly more susceptible to proteolysis, which might account for its decreased in vivo half-life compared to dystrophin. In addition, utrophin N-ABD aggregates to a lesser extent compared with dystrophin N-ABD, contrary to the general behavior of proteins in which decreased stability enhances protein aggregation. Despite these differences in stability and aggregation, both proteins exhibit deleterious effects of mutations. When utrophin N-ABD mutations analogous in position to the dystrophin disease-causing mutations were generated, they behaved similarly to dystrophin mutants in terms of decreased stability and the formation of cross-β aggregates, indicating a possible role for utrophin mutations in disease mechanisms

Increasing abdominal pressure with and without PEEP: effects on intra-peritoneal, intra-organ and intra-vascular pressures

Intra-organ and intra-vascular pressures can be used to estimate intra-abdominal pressure. The aim of this prospective, interventional study was to assess the effect of PEEP on the accuracy of pressure estimation at different measurement sites in a model of increased abdominal pressure

Increasing abdominal pressure with and without PEEP: effects on intra-peritoneal, intra-organ and intra-vascular pressures

Intra-organ and intra-vascular pressures can be used to estimate intra-abdominal pressure. The aim of this prospective, interventional study was to assess the effect of PEEP on the accuracy of pressure estimation at different measurement sites in a model of increased abdominal pressure

Increasing abdominal pressure with and without PEEP: effects on intra-peritoneal, intra-organ and intra-vascular pressures

Abstract Background Intra-organ and intra-vascular pressures can be used to estimate intra-abdominal pressure. The aim of this prospective, interventional study was to assess the effect of PEEP on the accuracy of pressure estimation at different measurement sites in a model of increased abdominal pressure. Methods Catheters for pressure measurement were inserted into the stomach, urinary bladder, peritoneal cavity, pulmonary artery and inferior vena cava of 12 pigs. The pressures were recorded simultaneously at baseline, during 10 cm H20 PEEP, external abdominal pressure (7 kg weight) plus PEEP, external abdominal pressure without PEEP, and again under baseline conditions. Results (mean ± SD) PEEP alone increased diastolic pulmonary artery and inferior vena cava pressure but had no effect on the other pressures. PEEP and external abdominal pressure increased intraperitoneal pressure from 6 ± 1 mm Hg to 9 ± 2 mm Hg, urinary bladder pressure from 6 ± 2 mm Hg to 11 ± 2 mm Hg (p = 0.012), intragastric pressure from 6 ± 2 mm Hg to 11 ± 2 mm Hg (all p ≤ 0.001), and inferior vena cava pressure from 11 ± 4 mm Hg to 15 ± 4 mm Hg (p = 0.01). Removing PEEP and maintaining extraabdominal pressure was associated with a decrease in pulmonary artery diastolic but not in any of the other pressures. There was a significant correlation among all pressures. Bias (-1 mm Hg) and limits of agreement (3 to -5 mm Hg) were similar for the comparisons of absolute intraperitoneal pressure with intra-gastric and urinary bladder pressure, but larger for the comparison between intraperitoneal and inferior vena cava pressure (-5, 0 to -11 mm Hg). Bias (0 to -1 mm Hg) and limits of agreement (3 to -4 mm Hg) for pressure changes were similar for all comparisons Conclusions Our data suggest that pressure changes induced by external abdominal pressure were not modified by changing PEEP between 0 and 10 cm H20. </p