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Biomedical subjects

J L Bert

Publications and source records attributed to J L Bert.

At least 19 recordsLinked to original sources
PubMed2001

Studies on fluid extravasation related to induced hypothermia during cardiopulmonary bypass in piglets.

BACKGROUND: Hypothermia, commonly used for organ protection during cardiopulmonary bypass (CPB), has been associated with changes in plasma volume, hemoconcentration and microvascular fluid shifts. Fluid pathophysiology secondary to hypothermia and the mechanisms behind these changes are still largely unknown. In a recent study we found increased fluid needs during hypothermic compared to normothermic CPB. The aim of the present study was to characterize the distribution of the fluid given to maintain normovolemia. In addition, we wanted to investigate the quantity and quality of the fluid extravasated during hypothermic compared to normothermic CPB. METHODS: Two groups of anesthetized piglets were studied during 2 h of hypothermic (28 degrees C) (n=7) or normothermic (38 degrees C) (n=7) CPB. Net fluid balance (input-output) was recorded. Changes in colloid osmotic pressures of plasma (COPp) and interstitial fluid (COPi), plasma volume (PV), hemoglobin (Hb), hematocrit (HCT), mean corpuscular volume (MCV), s-osmolality, s-albumin and s-total protein was followed throughout the experiments. Fluid extravasation rate was calculated. In addition, total tissue water content was measured and compared with a control group (n=6) (no CPB). RESULTS: During hypothermic compared with normothermic CPB, the average net positive fluid balance from 10-120 min of extracorporeal circulation was 1.35+/-0.06 ml x kg(-1) x min(-1) and 0.33+/-0.03 ml x kg(-1) x min(-1) respectively (P<0.0001). We found a marked increase in fluid extravasation during hypothermic CPB. The extravasation rate during hypothermia was 1.8+/-0.2 ml x kg(-1) x min(-1), (1st hour) and 1.1+/-0.2 ml x kg(-1) x min(-1) (2nd hour) compared with 0.8+/-0.2 ml x kg(-1) x min(-1), and 0.1+/-(0.1) ml x kg(-1) x min(-1) during normothermia, respectively (P<0.01). The total intravascular protein and albumin masses remained constant in both groups. Following hypothermic CPB, the water content increased significantly in all tissues and organs. CONCLUSION: During hypothermic CPB an increased extravasation of fluid from the intravascular to the interstitial space was found. As no leakage of proteins could be demonstrated, based on stable values for albumin and protein masses throughout the experiments, the extravasated fluid contained mainly water and small solutes.

Albumins↗
PubMed2001

A heat transfer model of thermal balloon endometrial ablation.

A heat transfer model was developed for thermal balloon endometrial ablation treatment for menorrhagia. The model includes heat conduction through the uterus wall, cooling due to blood perfusion through the uterine tissue and the contribution of metabolic heat generation. A parameter sensitivity study indicated that metabolic heat generation had a minimal effect, but model predictions were sensitive to blood perfusion rate. However, within the range of expected perfusion rates, the model calculates damage depths (3-6 mm) close to the range for effective treatment. Using a blood perfusion rate of 0.0028 m(3)t m(-3)b s(-1), the predicted burn depth (4 mm) correlated well with experimental measurements (4.2 +/- 0.6 mm) reported elsewhere for a treatment temperature of 92 degrees C and time of 6 mins (Neuwirth, R. S. et al. The endometrial ablator: A new instrument. Obstet. Gynecol. 83:792-796, 1994). If no vaporization of water in the tissue occurs, the model predicts that the same burn depth of 4 mm can be obtained with increased treatment temperature (130 degrees C) and shorter treatment time (1.4 min). Steeper temperature profiles through the uterine wall suggest that, in the absence of other changes due to higher temperatures, the deeper layers of the myometrium and the serosa would be protected from thermal damage when using higher treatment temperatures for a shorter duration. However, if vaporization occurs at 105 degrees C, the model predicts little benefit in using treatment temperatures above 120 degrees C up to 160 degrees C. For further validation of the model, in vivo studies using the high temperature treatments are needed to measure temperature profiles through the uterine wall, blood perfusion rates, and the other effects of temperature on uterine tissue.

Catheterization↗
PubMed2001

Dermal fibroblast morphology is affected by stretching and not by C48/80.

Both stretching and C48/80 have been hypothesized to cause disruption of cell-matrix adhesions and thereby affect the dynamics of fluid balance in tissues. We investigated the effect of sinusoidal stretching and/or C48/80 on the morphology of fibroblasts in skin excised from the backs of Wistar-Möller rats in order to assess how these stimuli affect cellular interactions in tissues. Tissue samples were either soaked in Krebs' buffer with and without C48/80, or sinusoidally stretched (20% strain) in buffer with and without C48/80. Control skin was fixed immediately after excision. All tissues were processed for transmission electron microscopy. Morphometric analyses demonstrated that sinusoidal stretching of the skin results in the retraction or disruption of fibroblast cytoplasmic extensions, rounding up of the cell bodies and subsequently in increased tissue water content. C48/80 had no apparent effect on fibroblast morphology and adherence in tissues.

Animals↗
PubMed2000

A model of fluid and solute exchange in the human: validation and implications.

In order to understand better the complex, dynamic behaviour of the redistribution and exchange of fluid and solutes administered to normal individuals or to those with acute hypovolemia, mathematical models are used in addition to direct experimental investigation. Initial validation of a model developed by our group involved data from animal experiments (Gyenge, C.C., Bowen, B.D., Reed, R.K. & Bert, J.L. 1999b. Am J Physiol 277 (Heart Circ Physiol 46), H1228-H1240). For a first validation involving humans, we compare the results of simulations with a wide range of different types of data from two experimental studies. These studies involved administration of normal saline or hypertonic saline with Dextran to both normal and 10% haemorrhaged subjects. We compared simulations with data including the dynamic changes in plasma and interstitial fluid volumes VPL and VIT respectively, plasma and interstitial colloid osmotic pressures PiPL and PiIT respectively, haematocrit (Hct), plasma solute concentrations and transcapillary flow rates. The model predictions were overall in very good agreement with the wide range of experimental results considered. Based on the conditions investigated, the model was also validated for humans. We used the model both to investigate mechanisms associated with the redistribution and transport of fluid and solutes administered following a mild haemorrhage and to speculate on the relationship between the timing and amount of fluid infusions and subsequent blood volume expansion.

Animals↗
PubMed2000

Mechanical properties of the tracheal mucosal membrane in the rabbit. I. steady-state stiffness as a function of age.

Airway responsiveness is exaggerated in infancy and declines with maturation. These age-related differences (R.S. Tepper, T. Du, A. Styhler, M. Ludwig, and J.G. Martin. Am. J. Respir. Crit. Care Med. 151: 836-840, 1995; R.S. Tepper, S.J. Gunst, C.M. Doerschuk, Y. Shen, and W. Bray. J. Appl. Physiol. 78: 505-512, 1995; R.S. Tepper, J. Stevens, and H. Eigen. Am. J. Respir. Crit. Care Med. 149: 678-681, 1994) could be due to changes in the smooth muscle, the lung, and/or the airway wall. Folding of the mucosal membrane can provide an elastic load (R.K. Lambert, J. Appl. Physiol. 71: 666-673, 1991), which impedes smooth muscle shortening. We hypothesized that increased stiffness of the mucosal membrane occurs during aging, causing an increased mechanical load on airway smooth muscle and a decrease in airway responsiveness. Forty female New Zealand White rabbits between 0.75 and 35 mo of age were studied. Rectangular mucosal membrane strips oriented both longitudinally and circumferentially to the long axis of the trachea were dissected, and the stress-strain relationships of each strip were tested. The results showed that the membrane was stiffer in the longitudinal than in the circumferential direction of the airway. However, there was no significant change with age in either orientation. We conclude that the mechanical properties of the airway mucosal membrane did not change during maturation and were not likely to influence age-related changes in airway responsiveness.

Aging↗
PubMed2000

Mechanical properties of the tracheal mucosal membrane in the rabbit. II. Morphometric analysis.

Folding of the airway mucosal membrane provides a mechanical load that impedes airway smooth muscle contraction. Mechanical testing of rabbit tracheal mucosal membrane showed that the membrane is stiffer in the longitudinal than in the circumferential direction of the airway. To explain this difference in the mechanical properties, we studied the morphological structure of the rabbit tracheal mucosal membrane in both longitudinal and circumferential directions. The collagen fibers were found to form a random meshwork, which would not account for differences in stiffness in the longitudinal and circumferential directions. The volume fraction of the elastic fibers was measured using a point-counting technique. The orientation of the elastic fibers in the tissue samples was measured using a new method based on simple geometry and probability. The results showed that the volume fraction of the elastic fibers in the rabbit tracheal mucosal membrane was approximately 5% and that the elastic fibers were mainly oriented in the longitudinal direction. Age had no statistically significant effect on either the volume fraction or the orientation of the elastic fibers. Linear correlations were found between the steady-state stiffness and the quantity of the elastic fibers oriented in the direction of testing.

Animals↗
PubMed1999

Occupational risk factors for prostate cancer mortality in British Columbia, Canada.

BACKGROUND: Although prostate cancer is the most common life-threatening cancer among males in North America, relatively little is known about its etiology. We have conducted a proportional mortality study to generate hypotheses concerning occupational risk factors for the disease. METHODS: Age standardized proportional mortality ratios (PMR) for prostate cancer were calculated for a total of 216 occupations and 88 industries. Separate calculations were done for all male deaths age 20 and up and for deaths that occurred during men's working lifetime (age 20-65). RESULTS: Elevated mortality from prostate cancer was seen among business owners and managers (PMR = 110; 95% CI = 101-118), brokers (PMR = 184; 95% CI = 122-266), farmers and farm managers (PMR = 112; 95% CI = 105-120), and school teachers (PMR = 133; 95% CI = 101-174). Evaluation by industry shows elevated prostate cancer mortality in agriculture (PMR = 110; 95% CI = 103-118), financial institutions (PMR = 138, 95% CI = 112-170), and transportation equipment manufacture (PMR = 136; 95% CI = 109-168). CONCLUSIONS: The findings suggest that workers in a number of occupations have elevated risks of prostate cancer including farmers and teachers. More detailed cohort and case-control studies, evaluating specific exposures are required before primary prevention programs in the workplace are feasible.

Adult↗
PubMed1999

Transport of fluid and solutes in the body I. Formulation of a mathematical model.

A compartmental model of short-term whole body fluid, protein, and ion distribution and transport is formulated. The model comprises four compartments: a vascular and an interstitial compartment, each with an embedded cellular compartment. The present paper discusses the assumptions on which the model is based and describes the equations that make up the model. Fluid and protein transport parameters from a previously validated model as well as ionic exchange parameters from the literature or from statistical estimation [see companion paper: C. C. Gyenge, B. D. Bowen, R. K. Reed, and J. L. Bert. Am. J. Physiol. 277 (Heart Circ. Physiol. 46): H1228-H1240, 1999] are used in formulating the model. The dynamic model has the ability to simulate 1) transport across the capillary membrane of fluid, proteins, and small ions and their distribution between the vascular and interstitial compartments; 2) the changes in extracellular osmolarity; 3) the distribution and transport of water and ions associated with each of the cellular compartments; 4) the cellular transmembrane potential; and 5) the changes of volume in the four fluid compartments. The validation and testing of the proposed model against available experimental data are presented in the companion paper.

Animals↗
PubMed1999

Transport of fluid and solutes in the body II. Model validation and implications.

A mathematical model of short-term whole body fluid, protein, and ion distribution and transport developed earlier [see companion paper: C. C. Gyenge, B. D. Bowen, R. K. Reed, and J. L. Bert. Am. J. Physiol. 277 (Heart Circ. Physiol. 46): H1215-H1227, 1999] is validated using experimental data available in the literature. The model was tested against data measured for the following three types of experimental infusions: 1) hyperosmolar saline solutions with an osmolarity in the range of 2,000-2,400 mosmol/l, 2) saline solutions with an osmolarity of approximately 270 mosmol/l and composition comparable with Ringer solution, and 3) an isosmotic NaCl solution with an osmolarity of approximately 300 mosmol/l. Good agreement between the model predictions and the experimental data was obtained with respect to the trends and magnitudes of fluid shifts between the intra- and extracellular compartments, extracellular ion and protein contents, and hematocrit values. The model is also able to yield information about inaccessible or difficult-to-measure system variables such as intracellular ion contents, cellular volumes, and fluid fluxes across the vascular capillary membrane, data that can be used to help interpret the behavior of the system.

Animals↗
PubMed1998

Ultrastructure and tensile properties of human tracheal cartilage.

The cartilage of the walls of the trachea and bronchi acts to keep these airways open despite intrathoracic pressure differences during breathing that would otherwise collapse them and limit air flow. Changes in biomechanical properties and composition of airway cartilage may contribute to altered lung function in obstructive lung diseases. To investigate the relationship between collagen organization and equilibrium tensile modulus within the structure of airway cartilage, we used scanning electron microscopy (SEM), histochemistry and equilibrium tensile testing to analyze tracheal cartilage from 10 humans aged 17-81 yr. We show that the surfaces of tracheal cartilage matrix are collagen-rich and surround a proteoglycan-rich core. Collagen fibrils in the superficial zones are oriented in the plane of the cartilage surface. In deeper layers of the cartilage, collagen fibrils are oriented less regularly. Equilibrium tensile modulus of 100 microm thick strips of cartilage was measured and was found to decrease with depth; from 13.6 +/- 1.5 MPa for the ablumenal superficial zone to 4.6 +/- 1.7 MPa in the middle zone (means +/- S.D., n = 10, p < 0.001). Stress-strain curves were linear for strains up to 10% with minimal residual strain. This is consistent with a model in which collagen fibres in the outer layers of the cartilage resist tensile forces, and hydrated proteoglycans in the central zone resist compression forces as the cartilage crescent bends.

Adolescent↗
PubMed1997

Pressure-volume relationship for rat dermis: compression studies.

The relationship between tissue hydrostatic pressure and fluid content is an important determinant of the response of the microvascular exchange system to perturbations. However, only a limited number of studies relating these parameters have been reported. To add to this body of information, fully swollen rat dermis in vitro was subjected to successive compressive loads in an apparatus in which tissue thickness changes were monitored. At steady-state the mechanical load on the tissue was balanced by the interstitial fluid pressure within the tissue while the fluid content of the tissue was determined from the unstressed tissue fluid content and changes in tissue thickness. The range of conditions investigated was from moderate overhydration through normal tissue fluid content to significant dehydration. From the relationship between interstitial fluid pressure and tissue fluid content (expressed as mass of fluid per mass of fat-free dry tissue) the tissue compliance was determined. Compliance, defined as the rate of change of the tissue fluid content with changes in interstitial pressure, increased with tissue hydration. The compliance determined using compressive loads and steady-state response of tissue thickness compares favourably with the limited amount of information available about this tissue property which is critical in the determination of tissue fluid balance. Compliance ranged over one order of magnitude for the conditions studied and at normal hydration, tissue fluid volume changed by about 6.6% per mmHg in tissue hydrostatic pressure.

Animals↗
PubMed1997

Fast Fourier transform analysis of dynamic data: sine wave stress-strain analysis of biological tissue.

We propose an improvement to the dynamic oscillation method using as an example the measurement of the tensile stiffness of the rabbit tracheal mucosal membrane. A sine wave oscillation technique was used to study the tissue mechanical properties. A mathematical model was developed using fast Fourier analysis. After mathematically eliminating the machine response, this analysis reveals the tissue frequency response over a wide range of frequencies. This study addresses the advantages of using Fourier analysis to interpret dynamic properties of biological tissue and provides a complete description of how to obtain the pure tissue response.

Animals↗
PubMed1995

A model of human microvascular exchange.

A compartmental model consisting of the circulation, a general interstitium, and the lymphatics, is formulated to describe the transport and distribution of fluid and plasma proteins (albumin) in the human microvascular exchange system. Transcapillary mass exchange is assumed to occur via a coupled Starling mechanism. Unknown or poorly quantified model parameters are estimated by statistical fitting of simulation predictions to five different sets of experimental data. The data consist of steady-state and transient plasma and interstitial volumes and colloid osmotic pressures measured under laboratory or clinical conditions for normal humans and for patients with nephrotic syndrome or mild heart disease. In all cases, it is assumed that the system response to perturbations imposed either artificially or through illness is due to changes in the Starling driving forces. The three best-fit parameters were found to be normal capillary hydrostatic pressure, Pc,o = 11.0 mm Hg; albumin reflection coefficient, sigma = 0.99; and lymph flow sensitivity, LS = 43.1 ml/mm Hg.hr. Three other parameters, which were unknown but related to the estimated parameters through steady-state mass balance equations, were determined to be fluid filtration coefficient, KF = 121.1 ml/mm Hg.hr; albumin permeability-surface area product, PS = 73.0 ml/hr; and normal lymph flow, JL,o = 75.7 ml/hr. The fully described model was validated by comparisons between (1) simulation predictions and data used in parameter estimation, (2) estimated transport parameters and available literature values, and (3) model predictions and an additional set of experimental data.

Cardiac Output, Low↗
PubMed1995

A model of fluid resuscitation following burn injury: formulation and parameter estimation.

A dynamic compartmental model is developed to describe the redistribution of fluid and albumin between the circulation and the intact and injured interstitia following burn injury in humans. Transcapillary fluid and albumin exchange is described by a coupled Starling mechanism, while the effect of the burn is represented by time-dependent perturbations to all three compartments. The unknown model parameters are determined for two groups of patients, having less than and greater than 25% total body surface area burns, by statistical fitting of model predictions to patient data from two sources. The parameters include the perturbations to the fluid filtration coefficients in uninjured and injured tissue, GkF,Tl and GkF,BT, respectively, the relaxation coefficient, r, which describes the exponential decay of the perturbations, and the exudation factor, EXFAC, which relates the protein concentration in the exudate to that in the injured tissue. Perturbations to other parameters, including the membrane permeability-surface area product and the albumin reflection coefficient in the injured and uninjured tissues, are determined based on interrelationships with GkF,Tl and GkF,BT. The values of GkF,BT, when corrected for tissue destruction and decreased post-injury perfusion, are in reasonable agreement with the limited experimental data available from the literature. The model and its parameters are further validated by comparing the simulated patient responses to the clinical data used in the parameter estimation as well as to data available from two additional sources.

Body Fluid Compartments↗
PubMed1993

A model of human microvascular exchange: parameter estimation based on normals and nephrotics.

A mathematical model is formulated and used to describe the distribution and transport of fluid and albumin in the human circulation, interstitium and lymphatics. Two transcapillary mass exchange mechanisms are investigated: a homoporous 'coupled Starling model', in which transcapillary albumin diffusion and convection occur within the same pathway, and a heteroporous 'plasma leak model', in which variations in structure and pressure are permitted along the length of the capillary. Parameters used in the transport models are determined based on statistical fitting of simulation predictions to experimental data from normal humans and nephrotic patients. The data consists of interstitial fluid volumes and interstitial colloid osmotic pressures as functions of plasma colloid osmotic pressure. Model validation is carried out based on comparison of (i) simulation predictions with experimental data used in parameter estimation, (ii) estimated transport parameters with experimentally determined values, and (iii) simulation predictions with a set of dynamic data from an albumin infusion study. While both models with their best-fit parameter estimates provide a good representation of experimental data, the drawbacks of the plasma leak model are three-fold: it requires more estimated parameters than the coupled Starling model, little experimental information exists with which to compare these parameters and, with the best fit values obtained, the plasma leak mechanism becomes insignificant. The model that employs a Starling-type exchange mechanism will therefore be favoured in future applications.

Arteries↗
PubMed1992

Modeling transient exchange in mesentery.

In this paper, a mathematical model of interstitial transport and microvascular exchange within a rigid mesenteric tissue segment is employed to simulate the transient exchange of fluid and plasma proteins following two systemic disturbances: hypoproteinemia and venous congestion. In each case, the model system behavior is studied as a function of interstitial plasma protein transport mechanisms and mesothelial transport properties. Plasma protein washout was generally predicted in cases of hypoproteinemia. However, following venous congestion, the transient change in interstitial plasma protein content also depended on the relative sieving properties of the filtering and draining boundaries. When these boundaries display similar sieving characteristics, the interstitial plasma protein content increases following the disturbance. Such behavior may have some bearing on transient exchange in the hepatic microcirculation during venous congestion.

Biological Transport↗
PubMed1992

Mechanical properties of human tracheal cartilage.

Biomechanical changes in airway cartilage could influence the mechanics of maximal expiratory flow and cough and the degree of shortening of activated airway smooth muscle. We examined the tensile stiffness of small samples of human tracheal cartilage rings in specimens obtained at autopsy from 10 individuals who ranged in age from 17 to 81 yr. The tensile properties of the cartilage were compared with its content of water (%water), glycosaminoglycans (chondroitin sulfate equivalents, mg/mg dry wt), and hydroxyproline content (mg hydroxyproline/mg dry weight). The average values for tensile stiffness ranged between 1 and 15 MPa and increased significantly with increasing age [tensile stiffness = 0.19 x (age in yr) + 2.02; r = 0.83, P less than 0.05]. The outermost layer of cartilage was the most stiff in all individuals, and the deeper layers were progressively less stiff. Water content and hydroxyproline content both decreased with increasing age. Thus tensile stiffness correlated inversely with water content and hydroxyproline content [tensile stiffness = -0.83 x (%water) + 16.4; r = 0.82, P less than .05 and tensile stiffness = -342 x (hydroxyproline content) + 25; r = 0.87, P less than 0.05]. Total tissue content of glycosaminoglycans did not change with age, although changes in glycosaminoglycan type and proteoglycan structure with increasing age have been described. We conclude that there are age-related changes in the biomechanical properties and biochemical composition of airway cartilage that could influence airway dynamics.

Adolescent↗