Effects of epinephrine, norepinephrine, and phenylephrine on microcirculatory blood flow in the gastrointestinal tract in sepsis

OBJECTIVE: The use of vasopressors for treatment of hypotension in sepsis may have adverse effects on microcirculatory blood flow in the gastrointestinal tract. The aim of this study was to measure the effects of three vasopressors, commonly used in clinical practice, on microcirculatory blood flow in multiple abdominal organs in sepsis. DESIGN: Random order, cross-over design. SETTING: University laboratory. SUBJECTS: Eight sedated and mechanically ventilated pigs. INTERVENTIONS: Pigs were exposed to fecal peritonitis-induced septic shock. Mesenteric artery flow was measured using ultrasound transit time flowmetry. Microcirculatory flow was measured in gastric, jejunal, and colon mucosa; jejunal muscularis; and pancreas, liver, and kidney using multiple-channel laser Doppler flowmetry. Each animal received a continuous intravenous infusion of epinephrine, norepinephrine, and phenylephrine in a dose increasing mean arterial pressure by 20%. The animals were allowed to recover for 60 mins after each drug before the next was started. MEASUREMENTS AND MAIN RESULTS: During infusion of epinephrine (0.8 +/- 0.2 mug/kg/hr), mean arterial pressure increased from 66 +/- 5 to 83 +/- 5 mm Hg and cardiac index increased by 43 +/- 9%. Norepinephrine (0.7 +/- 0.3 mug/kg/hr) increased mean arterial pressure from 70 +/- 4 to 87 +/- 5 mm Hg and cardiac index by 41 +/- 8%. Both agents caused a significant reduction in superior mesenteric artery flow (11 +/- 4%, p < .05, and 26 +/- 6%, p < .01, respectively) and in microcirculatory blood flow in the jejunal mucosa (21 +/- 5%, p < .01, and 23 +/- 3%, p < .01, respectively) and in the pancreas (16 +/- 3%, p < .05, and 8 +/- 3%, not significant, respectively). Infusion of phenylephrine (3.1 +/- 1.0 mug/kg/min) increased mean arterial pressure from 69 +/- 5 to 85 +/- 6 mm Hg but had no effects on systemic, regional, or microcirculatory flow except for a 30% increase in jejunal muscularis flow (p < .01). CONCLUSIONS: Administration of the vasopressors phenylephrine, epinephrine, and norepinephrine failed to increase microcirculatory blood flow in most abdominal organs despite increased perfusion pressure and-in the case of epinephrine and norepinephrine-increased systemic blood flow. In fact, norepinephrine and epinephrine appeared to divert blood flow away from the mesenteric circulation and decrease microcirculatory blood flow in the jejunal mucosa and pancreas. Phenylephrine, on the other hand, appeared to increase blood pressure without affecting quantitative blood flow or distribution of blood flow.

Evaluating Esophageal Bolus Transit by Impedance Monitoring

The function of the esophagus is transporting nutrients from the oropharyngeal cavity to the stomach. This is achieved by coordinated contractions and relaxation of the tubular esophagus and the upper and lower esophageal sphincter. Multichannel intraluminal impedance monitoring offers quantification of esophageal bolus transit and/or retention without the use of ionizing radiation. Combined with conventional or high-resolution manometry, impedance measurements complement the quantification of esophageal body contraction and sphincter relaxation, offering a more comprehensive evaluation of esophageal function. Further studies evaluating the utility of quantifying bolus transit will help clarify the role and position of impedance measurements.

Parkinson's disease and gastrointestinal dysfunctions: morphological, neurochemical and functional modifications of the enteric nervous system associated with central dopaminergic impairment

Parkinson’s disease (PD) is frequently associated with gastrointestinal (GI) symptoms, mostly represented by abdominal distension, constipation and defecatory dysfunctions. Despite GI dysfunctions have a major impact on the clinical picture of PD, there is currently a lack of information on the neurochemical, pathological and functional correlates of GI dysmotility associated with PD. Moreover, there is a need of effective and safe pharmacological therapies for managing GI disturbances in PD patients. The present research project has been undertaken to investigate the relationships between PD and related GI dysfunctions by means of investigations in an animal model of PD induced by intranigral injection of 6-hydroxydopamine (6-OHDA). The use of the 6-OHDA experimental model of PD in the present program has allowed to pursue the following goals: 1) to examine the impact of central dopaminergic denervation on colonic excitatory cholinergic and tachykininergic neuromotility by means of molecular, histomorphologic and functional approaches; 2) to elucidate the role of gut inflammation in the onset and progression of colonic dysmotility associated with PD, characterizing the degree of inflammation and oxidative damage in colonic tissues, as well as identifying the immune cells involved in the production of pro-inflammatory cytokines in the gut; 3) to evaluate the impact of chronic treatment with L-DOPA plus benserazide on colonic neuromuscular activity both in control and PD animals. The results suggest that central nigrostriatal dopaminergic denervation is associated with an impaired excitatory cholinergic neurotransmission and an enhanced tachykininergic control, resulting in a dysregulated smooth muscle motor activity, which likely contributes to the concomitant decrease in colonic transit rate. These motor alterations might result from the occurrence of a condition of gut inflammation associated with central intranigral denervation. The treatment with L-DOPA/BE following central dopaminergic neurodegeneration can restore colonic motility, likely through a normalization of the cholinergic enteric neurotransmission, and it can also improve the colonic inflammation associated with central dopaminergic denervation.

Guidelines on building design and operation to minimize air quality impacts from major roads in transit oriented development

Poor air quality has a huge detrimental effect, both economic and on the quality of life, in Australia. Transit oriented design (TOD), which aims to minimise urban sprawl and lower dependency on vehicles, leads to an increasing number of buildings close to transport corridors. This project aims at providing guidelines that are appropriate to include within City Plan to inform future planning along road corridors, and provide recommendations on when mitigation measures should be utilised.

Modelling urban public transit users' route choice behaviour: review and outlook

This paper reviews the main development of approaches to modelling urban public transit users’ route choice behaviour from 1960s to the present. The approaches reviewed include the early heuristic studies on finding the least cost transit route and all-or-nothing transit assignment, the bus common line problem and corresponding network representation methods, the disaggregate discrete choice models which are based on random utility maximization assumptions, the deterministic use equilibrium and stochastic user equilibrium transit assignment models, and the recent dynamic transit assignment models using either frequency or schedule based network formulation. In addition to reviewing past outcomes, this paper also gives an outlook into the possible future directions of modelling transit users’ route choice behaviour. Based on the comparison with the development of models for motorists’ route choice and traffic assignment problems in an urban road area, this paper points out that it is rewarding for transit route choice research to draw inspiration from the intellectual outcomes out of the road area. Particularly, in light of the recent advancement of modelling motorists’ complex road route choice behaviour, this paper advocates that the modelling practice of transit users’ route choice should further explore the complexities of the problem.

Investigation into Travel of Transit Oriented Development Residents’ of Kelvin Grove Urban Village

Travel surveys were conducted for collecting data related to residents’ travel at Kelvin Grove Urban Village (KGUV). Currently, KGUV has residents living in the affordable apartments, apartments, townhouses and student accommodation. As a part of data collection process, travel surveys were undertaken for residents living in apartments, affordable apartments and student accommodation. This document contains the questionnaire form used to collect the demographic and travel data related to residents at KGUV. A mail back survey technique was used to collect data for residents living in affordable apartment and apartments, and an intercept surveys was conducted for residents living in student accommodation.

Modelling urban public transit users’ route choice behaviour : a review and outlook

Public transport is one of the key promoters of sustainable urban transport. To encourage and increase public transport patronage it is important to investigate the route choice behaviours of urban public transit users. This chapter reviews the main developments of modelling urban public transit users’ route choice behaviours in a historical perspective, from the 1960s to the present time. The approaches re- viewed for this study include the early heuristic studies on finding the least-cost transit route and all-or- nothing transit assignment, the bus common lines problem, the disaggregate discrete choice models, the deterministic and stochastic user equilibrium transit assignment models, and the recent dynamic transit assignment models. This chapter also provides an outlook for the future directions of modelling transit users’ route choice behaviours. Through the comparison with the development of models for motorists’ route choice and traffic assignment problems, this chapter advocates that transit route choice research should draw inspiration from the research outcomes from the road area, and that the modelling practice of transit users’ route choice should further explore the behavioural complexities.

Investigation into travel of transit oriented development : school students’ travel survey of Kelvin Grove Urban Village

Travel surveys were conducted for collecting data related to school students’ travel at Kelvin Grove Urban Village (KGUV). Currently, KGUV has school students studying at grade 10 to 12. As a part of data collection process, travel surveys were undertaken for school students studying. This document contains the questionnaire form used to collect the demographic and travel data related to school students at KGUV. The surveys forms were hand delivered to the school and the responses were collected back via reply paid envelop provided with the questionnaire form.

Dwell-time and run-time control for DC mass rapid transit railways

Dwell times at stations and inter-station run times are the two major operational parameters to maintain train schedule in railway service. Current practices on dwell-time and run-time control are that they are only optimal with respect to certain nominal traffic conditions, but not necessarily the current service demand. The advantages of dwell-time and run-time control on trains are therefore not fully considered. The application of a dynamic programming approach, with the aid of an event-based model, to devise an optimal set of dwell times and run times for trains under given operational constraints over a regional level is presented. Since train operation is interactive and of multi-attributes, dwell-time and run-time coordination among trains is a multi-dimensional problem. The computational demand on devising trains' instructions, a prime concern in real-time applications, is excessively high. To properly reduce the computational demand in the provision of appropriate dwell times and run times for trains, a DC railway line is divided into a number of regions and each region is controlled by a dwell- time and run-time controller. The performance and feasibility of the controller in formulating the dwell-time and run-time solutions for real-time applications are demonstrated through simulations.