Relations between physiologic parameters and pulse transit time during loaded breathing

Pulse transit time (PTT) is a non-invasive measure, defined as time taken for the pulse pressure waves to travel from the R-wave of electrocardiogram to a selected peripheral site. Baseline PTT value is known to be influenced by physiologic variables like heart rate (HR), blood pressure (BP) and arterial compliance (AC). However, few quantitative data are available describing the factors which can influence PTT measurements in a child during breathing. The aim of this study was to investigate the effects of changes in breathing efforts on PTT baseline and fluctuations. Two different inspiratory resistive loading (IRL) devices were used to simulate loaded breathing in order to induce these effects. It is known that HR can influence the normative PTT value however the effect of HR variability (HRV) is not well-studied. Two groups of 3 healthy children ( 0.05) HR changes during all test activities. Results showed that HRV is not the sole contributor to PTT variations and suggest that changes in other physiologic parameters are also equally important. Hence, monitoring PTT measurement can be indicative of these associated changes during tidal or increased breathing efforts in healthy children.

The development of an algorithm to track blood pressure accurately based on the pulse transit time method

Oscillometric blood pressure (BP) monitors are currently used to diagnose hypertension both in home and clinical settings. These monitors take BP measurements once every 15 minutes over a 24 hour period and provide a reliable and accurate system that is minimally invasive. Although intermittent cuff measurements have proven to be a good indicator of BP, a continuous BP monitor is highly desirable for the diagnosis of hypertension and other cardiac diseases. However, no such devices currently exist. A novel algorithm has been developed based on the Pulse Transit Time (PTT) method, which would allow non-invasive and continuous BP measurement. PTT is defined as the time it takes the BP wave to propagate from the heart to a specified point on the body. After an initial BP measurement, PTT algorithms can track BP over short periods of time, known as calibration intervals. After this time has elapsed, a new BP measurement is required to recalibrate the algorithm. Using the PhysioNet database as a basis, the new algorithm was developed and tested using 15 patients, each tested 3 times over a period of 30 minutes. The predicted BP of the algorithm was compared to the arterial BP of each patient. It has been established that this new algorithm is capable of tracking BP over 12 minutes without the need for recalibration, using the BHS standard, a 100% improvement over what has been previously identified. The algorithm was incorporated into a new system based on its requirements and was tested using three volunteers. The results mirrored those previously observed, providing accurate BP measurements when a 12 minute calibration interval was used. This new system provides a significant improvement to the existing method allowing BP to be monitored continuously and non-invasively, on a beat-to-beat basis over 24 hours, adding major clinical and diagnostic value.

Metabolite mean transit times in the liver as predicted by various models of hepatic elimination

Predicted area under curve (AUC), mean transit time (MTT) and normalized variance (CV2) data have been compared for parent compound and generated metabolite following an impulse input into the liver, Models studied were the well-stirred (tank) model, tube model, a distributed tube model, dispersion model (Danckwerts and mixed boundary conditions) and tanks-in-series model. It is well known that discrimination between models for a parent solute is greatest when the parent solute is highly extracted by the liver. With the metabolite, greatest model differences for MTT and CV2 occur when parent solute is poorly extracted. In all cases the predictions of the distributed tube, dispersion, and tasks-in-series models are between the predictions of the rank and tube models. The dispersion model with mixed boundary conditions yields identical predictions to those for the distributed tube model (assuming an inverse gaussian distribution of tube transit times). The dispersion model with Danckwerts boundary conditions and the tanks-in series models give similar predictions to the dispersion (mixed boundary conditions) and the distributed tube. The normalized variance for parent compound is dependent upon hepatocyte permeability only within a distinct range of permeability values. This range is similar for each model but the order of magnitude predicted for normalized variance is model dependent. Only for a one-compartment system is the MIT for generated metabolite equal to the sum of MTTs for the parent compound and preformed metabolite administered as parent.

Relative dispersions of intra-albumin transit times across rat and elasmobranch perfused livers, and implications for intra- and inter-species scaling of hepatic clearance using microsomal data

It is recognized that vascular dispersion in the liver is a determinant of high first-pass extraction of solutes by that organ. Such dispersion is also required for translation of in-vitro microsomal activity into in-vivo predictions of hepatic extraction for any solute. We therefore investigated the relative dispersion of albumin transit times (CV2) in the livers of adult and weanling rats and in elasmobranch livers. The mean and normalized variance of the hepatic transit time distribution of albumin was estimated using parametric non-linear regression (with a correction for catheter influence) after an impulse (bolus) input of labelled albumin into a single-pass liver perfusion. The mean +/- s.e. of CV2 for albumin determined in each of the liver groups were 0.85 +/- 0.20 (n = 12), 1.48 +/- 0.33 (n = 7) and 0.90 +/- 0.18 (n = 4) for the livers of adult and weanling rats and elasmobranch livers, respectively. These CV2 are comparable with that reported previously for the dog and suggest that the CV2 Of the liver is of a similar order of magnitude irrespective of the age and morphological development of the species. It might, therefore, be justified, in the absence of other information, to predict the hepatic clearances and availabilities of highly extracted solutes by scaling within and between species livers using hepatic elimination models such as the dispersion model with a CV2 of approximately unity.

Relative dispersion of intravascular transit times during isolated human limb perfusions for recurrent melanoma

Aims We have characterized the relative dispersion of vascular and extravascular markers in the limbs of three patients undergoing isolated limb perfusions with the cytotoxic melphalan for recurrent malignant melanoma both before and after melphalan dosing. Methods A bolus of injectate containing [Cr-51] labelled red blood cells, [C-14]-sucrose and [H-3]-water was injected into an iliac or femoral artery and outflow samples collected at 1 s intervals by a fraction collector. The radioactivity due to each isotype was analysed by either gamma [Cr-51] or beta [C-14 and H-3] counting. The moments of the outflow fraction-time profiles were estimated by a nonparametric (numerical integration) method and a parametric model (sum of two inverse Gaussian functions). Results The availability, mean transit time and normalised variance (CV2) obtained for labelled red blood cells, sucrose and water were similar before and after melphalan dosing and with the two methods of calculation but varied between the patients. Conclusions The vascular space is not well-stirred but characterized by a CV2 similar that reported previously for in situ rat hind limb and rat liver perfusions. A flow-limited blood-tissue exchange was observed for the permeating indicators. Administration of melphalan did not influence the distribution characteristics of the indicators.

Optimal perfusion computed tomographic thresholds for ischemic core and penumbra are not time dependent in the clinically relevant time window.

BACKGROUND AND PURPOSE: This study aims to determine whether perfusion computed tomographic (PCT) thresholds for delineating the ischemic core and penumbra are time dependent or time independent in patients presenting with symptoms of acute stroke. METHODS: Two hundred seventeen patients were evaluated in a retrospective, multicenter study. Patients were divided into those with either persistent occlusion or recanalization. All patients received admission PCT and follow-up imaging to determine the final ischemic core, which was then retrospectively matched to the PCT images to identify optimal thresholds for the different PCT parameters. These thresholds were assessed for significant variation over time since symptom onset. RESULTS: In the persistent occlusion group, optimal PCT parameters that did not significantly change with time included absolute mean transit time, relative mean transit time, relative cerebral blood flow, and relative cerebral blood volume when time was restricted to 15 hours after symptom onset. Conversely, the recanalization group showed no significant time variation for any PCT parameter at any time interval. In the persistent occlusion group, the optimal threshold to delineate the total ischemic area was the relative mean transit time at a threshold of 180%. In patients with recanalization, the optimal parameter to predict the ischemic core was relative cerebral blood volume at a threshold of 66%. CONCLUSIONS: Time does not influence the optimal PCT thresholds to delineate the ischemic core and penumbra in the first 15 hours after symptom onset for relative mean transit time and relative cerebral blood volume, the optimal parameters to delineate ischemic core and penumbra.

Gastrointestinal transit of extruded or pelletized diets in pacu fed distinct inclusion levels of lipid and carbohydrate

The objective of this work was to evaluate the effect of pelletized or extruded diets, with different levels of carbohydrate and lipid, on the gastrointestinal transit time (GITT) and its modulation in pacu (Piaractus mesopotamicus). One hundred and eighty pacu juveniles were fed with eight isonitrogenous diets containing two carbohydrate levels (40 and 50%) and two lipid levels (4 and 8%). Four diets were pelletized and four were extruded. Carbohydrate and lipid experimental levels caused no changes to the bolus transit time. However, the bolus permanence time was related to diet processing. Fish fed pelletized diets exhibited the highest gastrointestinal transit time. Regression analysis of bolus behavior for pelletized and extruded diets with 4% lipid depicted different fits. GITT regression analysis of fish fed 8% lipid was fitted to a cubic equation and displayed adjustments of food permanence, with enhanced utilization of the diets, either with extruded or pelletized diets. GITT of fish fed extruded diets with 4% lipid was adjusted to a linear equation. The GITT of pacu depends on the diet processing and is affected by dietary levels of lipid and carbohydrate.

Ambient solar wind's effect on ICME transit times

Most empirical and numerical models of Interplanetary Coronal Mass Ejection (ICME) propagation use the initial CME velocity as their primary, if not only, observational input. These models generally predict a wide spread of 1 AU transit times for ICMEs with the same initial velocity. We use a 3D coupled MHD model of the corona and heliosphere to determine the ambient solar wind's effect on the propagation of ICMEs from 30 solar radii to 1 AU. We quantitatively characterize this deceleration by the velocity of the upstream ambient solar wind. The effects of varying solar wind parameters on the ICME transit time are quantified and can explain the observed spread in transit times for ICMEs of the same initial velocity. We develop an adjustment formula that can be used in conjunction with other models to reduce the spread in predicted transit times of Earth-directed ICMEs.

Predictions of the arrival time of coronal mass ejections at 1AU: an analysis of the causes of errors

Three existing models of Interplanetary Coronal Mass Ejection (ICME) transit between the Sun and the Earth are compared to coronagraph and in situ observations: all three models are found to perform with a similar level of accuracy (i.e. an average error between observed and predicted 1AU transit times of approximately 11 h). To improve long-term space weather prediction, factors influencing CME transit are investigated. Both the removal of the plane of sky projection (as suffered by coronagraph derived speeds of Earth directed CMEs) and the use of observed values of solar wind speed, fail to significantly improve transit time prediction. However, a correlation is found to exist between the late/early arrival of an ICME and the width of the preceding sheath region, suggesting that the error is a geometrical effect that can only be removed by a more accurate determination of a CME trajectory and expansion. The correlation between magnetic field intensity and speed of ejecta at 1AU is also investigated. It is found to be weak in the body of the ICME, but strong in the sheath, if the upstream solar wind conditions are taken into account.

Validation of a priori CME arrival predictions made using real-time heliospheric imager observations

Between December 2010 and March 2013, volunteers for the Solar Stormwatch (SSW) Citizen Science project have identified and analyzed coronal mass ejections (CMEs) in the near real-time Solar Terrestrial Relations Observatory Heliospheric Imager observations, in order to make “Fearless Forecasts” of CME arrival times and speeds at Earth. Of the 60 predictions of Earth-directed CMEs, 20 resulted in an identifiable Interplanetary CME (ICME) at Earth within 1.5–6 days, with an average error in predicted transit time of 22 h, and average transit time of 82.3 h. The average error in predicting arrival speed is 151 km s−1, with an average arrival speed of 425km s−1. In the same time period, there were 44 CMEs for which there are no corresponding SSW predictions, and there were 600 days on which there was neither a CME predicted nor observed. A number of metrics show that the SSW predictions do have useful forecast skill; however, there is still much room for improvement. We investigate potential improvements by using SSW inputs in three models of ICME propagation: two of constant acceleration and one of aerodynamic drag. We find that taking account of interplanetary acceleration can improve the average errors of transit time to 19 h and arrival speed to 77 km s−1.

Transit times – the link between hydrology and water quality at the catchment scale

In spite of trying to understand processes in the same spatial domain, the catchment hydrology and water quality scientific communities are relatively disconnected and so are their respective models. This is emphasized by an inadequate representation of transport processes, in both catchment-scale hydrological and water quality models. While many hydrological models at the catchment scale only account for pressure propagation and not for mass transfer, catchment scale water quality models are typically limited by overly simplistic representations of flow processes. With the objective of raising awareness for this issue and outlining potential ways forward we provide a non-technical overview of (1) the importance of hydrology-controlled transport through catchment systems as the link between hydrology and water quality; (2) the limitations of current generation catchment-scale hydrological and water quality models; (3) the concept of transit times as tools to quantify transport and (4) the benefits of transit time based formulations of solute transport for catchment-scale hydrological and water quality models. There is emerging evidence that an explicit formulation of transport processes, based on the concept of transit times has the potential to improve the understanding of the integrated system dynamics of catchments and to provide a stronger link between catchment-scale hydrological and water quality models.

AC Biosusceptometry as a Tool for Monitoring the Gastrointestinal Transit of Multiparticulate Drug Delivery System

Drug delivery systems based on natural polysaccharides, such as chitosan (CS) and pectin (PC), rather than on synthetic polymers, have been widely studied. Some reasons for that are low toxicity and costs and high biodegradability of the formers. A multiparticulate system based on CS and PC was developed in our laboratories, including the addition of an enteric polymer, cellulose acetate phtalate (CAP). Such improvement promoted stronger gastric and enteric resistances, as assessed in vitro, making the systems more selective to enzymatic degradation in the colon. Although in vitro dissolution tests can simulate some properties concerning the gastrointestinal transit (GT), collaborating to characterize the systems behavior in the biological fluids, frequently they do not result in satisfactory in vitro/in vivo correlations. The objective of this work was to follow in vivo the GT of the particles developed by means of AC biosusceptometry (ACB), a non-invasive and of low cost methodology. The particles containing ferrite in powder form were prepared by complex coacervation using an ideal 3:1:1 mass ratio for PC:CS:CAP. The magnetic particles were administered to healthy volunteers by oral route. The GT was monitored by using multi-sensor ACB system and the signal acquisition was performed every IS min until the colonic region was reached. By means of ACB technique, it was possible to acquiring images generated by the magnetic particles within the whole gastrointestinal tract including the colonic region. Variable particles transit times were observed among the volunteers, but without interference on the mapping of the particles until the colonic region. The particles were able to produce magnetic field strong enough to generate signals adequate for mapping the particles. The results suggest that integral particles reached the colon, after they resisted against gastric and enteric media. Studies associating transit time and in vivo drug release are in development in order to confirm the efficiency of the systems.

The influence of sour taste and cold temperature in pharyngeal transit duration in patients with stroke

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of a muscarinic type-2 antagonist on cardiorespiratory function and intestinal transit in horses anesthetized with halothane and xylazine

Objective-To evaluate the cardiorespiratory and intestinal effects of the muscarinic type-2 (M-2) antagonist, methoctramine, in anesthetized horses.Animals-6 horses.Procedure-Horses were allocated to 2 treatments in a randomized complete block design. Anesthesia was maintained with halothane (1% end-tidal concentration) combined with a constant-rate infusion of xylazine hydrochloride (1 mg/kg/h, IV) and mechanical ventilation. Hemodynamic variables were monitored after induction of anesthesia and for 120 minutes after administration of methoctramine or saline (0.9% NaCl) solution (control treatment). Methoctramine was given at 10-minute intervals (10 mug/kg, IV) until heart rate (HR) increased at least 30% above baseline values or until a maximum cumulative dose of 30 mug/kg had been administered. Recovery characteristics, intestinal auscultation scores, and intestinal transit determined by use of chromium oxide were assessed during the postanesthetic period.Results-Methoctramine was given at a total cumulative dose of 30 mug/kg to 4 horses, whereas 2 horses received 10 mug/kg. Administration of methoctramine resulted in increases in HR, cardiac output, arterial blood pressure, and tissue oxygen delivery. Intestinal auscultation scores and intestinal transit time (interval to first and last detection of chromium oxide in the feces) did not differ between treatment groups.Conclusions and Clinical Relevance-Methoctramine improved hemodynamic function in horses anesthetized by use of halothane and xylazine without causing a clinically detectable delay in the return to normal intestinal motility during the postanesthetic period. Because of their selective positive chronotropic effects, M-2 antagonists may represent a safe alternative for treatment of horses with intraoperative bracycardia.