Biomedical subjects

K R Rajagopal

Publications and source records attributed to K R Rajagopal.

At least 19 recordsLinked to original sources

PubMed2006

A theoretical model of enlarging intracranial fusiform aneurysms.

The mechanisms by which intracranial aneurysms develop, enlarge, and rupture are unknown, and it remains difficult to collect the longitudinal patient-based information needed to improve our understanding. We submit, therefore, that mathematical models hold promise by allowing us to propose and test competing hypotheses on potential mechanisms of aneurysmal enlargement and to compare predicted outcomes with limited clinical information--in this way, we may begin to narrow the possible mechanisms and thereby focus experimental studies. In this paper, we present a constrained mixture model of evolving thin-walled, fusiform aneurysms and compare multiple competing hypotheses with regard to the production, removal, and alignment of the collagen that provides the structural integrity of the wall. The results show that this type of approach has the capability to infer potential means by which lesions enlarge and whether such changes are likely to produce a stable or unstable process. Such information can better direct the requisite histopathological examinations, particularly on the need to quantify collagen orientations as a function of lesion geometry.

Animals↗

PubMed2005

Heat-induced changes in the finite strain viscoelastic behavioir of a collaagenous tissue.

Supra-physiological temperatures are increasingly being used to treat many different soft need for injuries. To identify improved clinical treatments, however, there is a need for better information on the effect of the mechanics on the thermal damage process as well as the effect of the incurred damage on the subsequent mechanical properties. In this paper we report the first biaxial data on the stress relaxation behavior of a collagenous tissue before and after thermal damage. Based on a two-dimensional finite strain viscoelastic model, which incorporates an exponential elastic response, it is shown that the thermal damage can significantly decrease the characteristic time for stress relaxation and the stress residual.

Animals↗

PubMed2005

A model for the formation and lysis of blood clots.

Both biochemical and mechanical factors have to be taken into account if a meaningful model for the formation, growth, and lysis of clots in flowing blood is to be developed. Most models that are currently in use neglect one or the other of these factors. We have previously reported a model [J Theoret Med 2003;5:183-218] that we believe is a step in this direction, incorporating many of the crucial biochemical and rheological factors that play a role in the formation, growth, and lysis of clots. While this model takes into account the extrinsic pathway of coagulation, it largely ignores the intrinsic pathway. Here, we discuss some of the general issues with respect to mathematical modeling of thrombus formation and lysis, as well as specific aspects of the model that we have developed.

Blood Coagulation↗

PubMed2003

A constrained mixture model for arterial adaptations to a sustained step change in blood flow.

A sustained change in blood flow results in an arterial adaptation that can be thought to consist of two general steps: an immediate vasoactive response that seeks to return the wall shear stress to its homeostatic value, and a long-term growth and remodeling process that seeks to restore the intramural stresses and, if needed, the wall shear stress toward their homeostatic values. Few papers present mathematical models of arterial growth and remodeling in general, and fewer yet address flow-induced changes. Of these, most prior models build upon the concept of "kinematic growth" proposed by Skalak in the early 1980s (Skalak R (1981) In: Proceedings of the IUTAM Symposium on finite elasticity. Martinus Nijhoff, The Hague, pp 347-355). Such approaches address important consequences of growth and remodeling, but not the fundamental means by which such changes occur. In this paper, therefore, we present a new approach for mathematically modeling arterial adaptations and, in particular, flow-induced alterations. The model is motivated by observations reported in the literature and is based on a locally homogenized, constrained mixture theory. Specifically, we develop a 3-D constitutive relation for stress in terms of the responses of the three primary load-bearing constituents and their time-varying mass fractions, with the latter accounting for the kinetics of the turnover of cells and extracellular matrix in changing, stressed configurations. Of particular importance is the concept that the natural configurations of the individual constituents can evolve separately and that this leads to changes in the overall material properties and empirically inferred residual stress field of the vessel. Potential applications are discussed, but there is a pressing need for new, theoretically motivated data to allow the prescription of specific functional forms of the requisite constitutive relations and the values of the associated material parameters.

Adaptation, Physiological↗

PubMed2003

Gas mixing for achieving suitable conditions for single point aerosol sampling in a straight tube: experimental and numerical results.

Experimental measurements of velocity and tracer gas concentration are taken in a straight tube to evaluate the effectiveness of mixing in achieving conditions as required by ANSI N13.1-1999 for single point extractive sampling from stacks and ducts of nuclear facilities. Mixing is evaluated for inlet turbulent intensities of 1.5%, 10%, and 20%, achieved by introducing various bi-plane grids, and for conditions generated by a commercial static gas mixer. The data obtained (at Reynolds number = 15,000) highlight the importance of inlet turbulence intensity in the process of turbulent dispersion of a dilute gas. The gas mixer does not introduce significant pressure losses and unlike bi-plane grids, the turbulence downstream of the mixer is not homogenous. A judicious choice of the release location that uses the large scale eddies and inhomogeneity of the turbulence ensures that the specified ANSI N13.1-1999 criteria are attained within 7 diameters downstream of the duct inlet. This is significantly more effective than a bi-plane grid where even with 20% inlet intensity the criteria are met only at 21 diameters downstream. The predictions of a proposed semi-empirical correlation match favorably with data. For example, at 18 diameters downstream with inlet intensities of 1.5% and 10%, the predicted coefficients of variation (COVs) of 150% and 65% are close to the actual values of 154% and 50%; where the COV of a set of measurements is the ratio of the standard deviation of the set to its mean value. The corresponding results obtained using commercially available software are 141% and 12%. Results from a particle-tracking model show good qualitative trends, but they should not be used to determine compliance with the requirements of the ANSI standard.

Aerosols↗

PubMed1998

Lung function during moderate hypobaric hypoxia in normal subjects and patients with chronic obstructive pulmonary disease.

BACKGROUND: We sought to describe changes in spirometric variables and lung volume subdivisions in healthy subjects and patients with chronic obstructive pulmonary disease (COPD) during moderate acute hypobaric hypoxia as occurs during air travel. We further questioned whether changes in lung function may associate with reduced maximum ventilation or worsened arterial blood gases. METHODS: Ambulatory patients with COPD and healthy adults comprised the study populations (n = 27). We obtained baseline measurements of spirometry, lung volumes and arterial blood gases from each subject at sea level and repeated measurements during altitude exposure to 8000 ft (2438 m) above sea level in a man-rated hypobaric chamber. RESULTS: Six COPD patients and three healthy subjects had declines in FVC during altitude exposure greater than the 95% confidence interval (CI) for expected within day variability (p < 0.05). Average forced vital capacity (FVC) declined by 0.123 +/- 0.254 L (mean +/- SD; 95% CI = -0.255, -0.020; p < 0.05) for all subjects combined. The magnitude of decline in FVC did not differ between groups (p > 0.05) and correlated with increasing residual volume (r = -0.455; <0.05). Change in maximum voluntary ventilation (MVV) in the COPD patients equaled -1.244 +/- 4.797 L x min(-1) (95% CI = -3.71, 1.22; p = 0.301). Decline in maximum voluntary ventilation (MVV) in the COPD patients correlated with decreased FVC (r = 0.630) and increased RV (r = -0.546; p < 0.05). Changes in spirometric variables for patients and controls did not explain significant variability in the arterial blood gas variables PaO2, PaCO2 or pH at altitude. CONCLUSIONS: We observed a decline in forced vital capacity in some COPD patients and normal subjects greater than expected for within day variability. Spirometric changes correlated with changes in reduced maximum voluntary ventilation in the patients but not with changes in resting arterial blood gases.

Adult↗

PubMed1996

A single integral finite strain viscoelastic model of ligaments and tendons.

A general continuum model for the nonlinear viscoelastic behavior of soft biological tissues was formulated. This single integral finite strain (SIFS) model describes finite deformation of a nonlinearly viscoelastic material within the context of a three-dimensional model. The specific form describing uniaxial extension was obtained, and the idea of conversion from one material to another (at a microscopic level) was then introduced to model the nonlinear behavior of ligaments and tendons. Conversion allowed different constitutive equations to be used for describing a single ligament or tendon at different strain levels. The model was applied to data from uniaxial extension of younger and older human patellar tendons and canine medial collateral ligaments. Model parameters were determined from curve-fitting stress-strain and stress-relaxation data and used to predict the time-dependent stress generated by cyclic extensions.

Adult↗

PubMed1995

Identification of elastic properties of homogeneous, orthotropic vascular segments in distension.

Characterization of the constitutive behavior of normal and pathological blood vessel segments could provide the clinician with a means to predict the onset and assess the severity of certain vascular maladies. Many of the constitutive models that have been proposed to date either fail to properly consider certain features of the anatomic structure and function of vascular tissue or are so mathematically complex that their utilization is intractable. We have developed a material identification technique that first required the adaptation and validation of a constitutive law describing the nonlinear, three-dimensional behavior of orthotropic, compressible, hyperelastic vascular segments. By coupling a nonlinear finite element program and experimental data with a robust nonlinear least-squares regression algorithm, a set of elastic parameters (moduli) is obtained. Regressions on data for a canine carotid artery and rabbit infrarenal aorta yielded coefficients of variation of 0.21 and 0.08, respectively. The estimated moduli demonstrated certain trends found by other investigators: both the canine carotid artery and rabbit aorta were found to be stiffer radially than circumferentially, and the former was found to be stiffer circumferentially than longitudinally. Using these material constants and measured arterial pressures, the stress distribution was computed for each specimen. The predicted radial stress was consistent with a transmural variation of approximately--p (applied luminal pressure) to approximately zero in both specimens, while the circumferential stresses ranged from 2.2p to 0.7p for the canine carotid, and from 6.4p to 3.7p for the rabbit aorta. The stress distributions qualitatively agreed with those reported in previous investigations, as well as with certain physiologic observations. Based on the results of our two sample cases, we believe that our technique could be beneficial to the assessment of the three-dimensional, anisotropic behavior of vascular tissue.

Animals↗

PubMed1995

A mathematical model for shear-induced hemolysis.

The time-varying history of stress exposure within a rotary blood pump makes it difficult to arrive at a quantifiable design criterion for predicting cell traumatization. Constant stress experiments have revealed that there is a threshold stress level above which damage to blood cells occurs depending upon the time of exposure. The shear stress history experienced by cells within a rotary blood pump, however, is highly unsteady. In order to better predict cell trauma under these realistic conditions, a mathematical damage model based on a concept of "damage accumulation" has been developed. This model is evaluated within the context of red cell trauma. Experimental results support the hypothesis that the rate of damage accumulation increases nonlinearly with the stress level as well as the age of the cell.

Erythrocytes↗

PubMed1993

Hemodynamic effects of altitude exposure and oxygen administration in chronic obstructive pulmonary disease.

PURPOSE: Cardiovascular events are the leading cause of death during air travel. Because patients with chronic obstructive pulmonary disease (COPD) develop severe hypoxemia at altitude, we sought to determine whether changes in systemic hemodynamics may contribute to health risks during hypobaric hypoxia. PATIENTS AND METHODS: We recorded radial artery catheter blood pressure, cardiac frequency, and cardiac ectopy in 18 men (aged 68 +/- 6 years, mean +/- SD) with severe COPD (forced expiratory volume in 1 second 0.97 L +/- 0.32 L) at sea level, after 45 minutes of steady-state hypobaric hypoxia at 2,438 m in a hypobaric chamber, and after oxygen supplementation at 2,438 m. RESULTS: Mean arterial pressure (mm Hg), systolic blood pressure (SBP), diastolic blood pressure, and pulsus paradoxus during acute hypobaric exposure did not differ from baseline. During oxygen supplementation, SBP declined (p = 0.028). Decreases in pulsus paradoxus and pulse pressure were noted on oxygen (p < 0.05). We found no changes in cardiac frequency. Cardiac ectopy was uncommon; for one subject, ectopy increased with hypobaric hypoxia and decreased with oxygen administration. CONCLUSION: Vasopressor responses to hypoxia do not add to the risk of air travel in patients with severe COPD. Supplemental oxygen may cause beneficial hemodynamic changes in patients with COPD during acute hypobaric exposure.

Aerospace Medicine↗

PubMed1992

Oxygen supplementation during air travel in patients with chronic obstructive lung disease.

The objective of this study was to quantitate the effects of O2 supplementation by nasal cannula (NC) and Venturi mask (VM) on PaO2 in patients with chronic obstructive pulmonary disease (COPD) during acute hypobaric exposure, simulating a commercial jet aircraft cabin. We conducted a crossover intervention trial in which subjects served as their own controls in an ambulatory outpatient pulmonary disease service of a tertiary care military medical center and a hypobaric research facility. The subjects were a volunteer sample of 18 men with stable severe COPD, not requiring long-term O2 therapy, and uncomplicated by hypercapnea or cardiac disease. Mean age was 68 years, and mean FEV1 was 0.97 L (31.3 percent predicted). We exposed patients to conditions equivalent to 8,000 feet in a hypobaric chamber. Radial artery catheters provided blood samples at ground level and 8,000 feet. O2 was sequentially administered at 8,000 feet by NC at 4 L/min and 24 percent or 28 percent VM. We describe changes in blood gas data from baseline values and between interventions. O2 at 4 L/min NC flow at 8,000 feet caused PaO2 to increase from 47.4 +/- 6.3 mm Hg to 82.3 +/- 14 mm Hg (n = 18), an increase of 34.9 +/- 14.8 mm Hg. Supplementation of O2 by 24 percent VM caused PaO2 at 8,000 feet to increase by 12.7 +/- 3.8 mm Hg. Twenty-eight percent VM caused PaO2 at 8,000 feet to increase by 19.7 +/- 8.2 mm Hg. Changes in PaO2 with 4 L/min NC were greater than those with either VM. The increase with 28 percent VM was greater than that caused by 24 percent VM (p less than 0.05). Compared with ground level, 4 L/min NC increased mean PaO2 by 9.9 +/- 12.6 mm Hg; 24 percent and 28 percent VM did not cause mean PaO2 to increase above ground level values. We describe a range of capability of familiar O2 therapy devices to increase PaO2 to levels that will maintain tissue oxygenation of patients during acute altitude exposure.

Aged↗

PubMed1992

Sensitivity and specificity of bronchial provocation testing. An evaluation of four techniques in exercise-induced bronchospasm.

The thresholds used to define a positive result for bronchial provocation challenges (BPC) are arbitrary. Requiring smaller decrements in expired flow to define a positive study would capture more cases of reactive airways (increased sensitivity) but would include some "normal" responses (decreased specificity). To examine the relationship between threshold definition and the ability to correctly classify subjects as either normal or as having airways hyperresponsiveness (AHR), four different BPC tests were administered on different days to 20 patients with a clinical diagnosis of exercise-induced bronchospasm (EIB) and 20 control subjects. The four BPC tests were indoor exercise on a cycle ergometer, methacholine inhalation challenge (MIC), eucapnic voluntary hyperventilation (EVH) with dry gas, and EVH with cold gas. Our results indicate that the thresholds which best separate the two groups are different for each of the four BPC techniques. For methacholine inhalation (MIC), a fall in FEV1 (d%FEV1) of 15 percent or greater at 188 cumulative breath units was 100 percent specific for AHR but had a sensitivity of only 55 percent. Eucapnic voluntary hyperventilation (EVH) with room temperature dry gas was 100 percent specific at a d%FEV1 of 11 percent, but, at that threshold, sensitivity was only 50 percent. EVH with cold air was 100 percent specific at a d%FEV1 of 12 percent but sensitivity was only 35 percent. The bicycle ergometer challenge was far too insensitive to be of value in evaluating AHR. Based on their respective receiver operating characteristic curves, the best separation of the two subject groups occurred at a d%FEV1 of 5 percent and 12 percent for the two EVH techniques and MIC, respectively. An individual's response to one test was highly correlated with the response to either of the other two (r = 0.66, p less than 0.001 for dry vs cold gas EVH; r = 0.56, p less than 0.001 for dry gas EVH vs methacholine; and r = 0.69, p less than 0.001 for cold gas EVH vs methacholine). Thus, MIC and EVH techniques are equally useful in defining AHR and each has its optimal threshold for a positive test result.

Adult↗

PubMed1992

Exercise responses prior to pregnancy and in the postpartum state.

Increased women in the work force and requirements for maximal employee productivity have necessitated examination of the optimal time for parturients to resume normal activities. This prospective study was designed to determine whether prepregnancy measures of aerobic capacity are regained by 4-8 wk postpartum. Weight, percent body fat, recall energy expenditure, and exercise responses via a stage 1, graded cycle ergometer exercise test were determined in 11 subjects (mean age = 27.56 +/- 2.2) in a postabsorptive state prior to pregnancy and 4-8 wk postpartum. Subject characteristics were compared by the Student's t-test and differences across workloads and time by analysis of variance with repeated measures. Prepregnant weight (mean = 58.80 +/- 7.26 kg) was significantly less (P less than 0.05) than postpartum weight (mean = 62.81 +/- 9.12 kg), and prepregnant energy expenditure (1352 +/- 453 kJ) per day was significantly higher (P less than 0.05) than in the postpartum period (274 +/- 333 kJ). Maximal oxygen uptake was significantly higher (35.2 +/- 0.7 vs 30.5 +/- 2.0 ml.kg-1min-1) in the prepregnant as compared with the postpartum period. Further, heart rate at 125 and 150 W was significantly lower prepregnancy as compared with postpregnancy. Results support a detraining effect in the early postpartum period. Whether this detraining is an inevitable factor associated with pregnancy or whether exercising throughout pregnancy can ameliorate the decline in aerobic capacity postpartum is uncertain.

Adult↗

PubMed1991

Expiratory muscle recruitment during inspiratory flow-resistive loading and exercise.

Both exercise and inspiratory flow-resistive loading may cause recruitment of expiratory muscles. To evaluate the extent of recruitment in combined exercise and flow-resistive loading, and to estimate the effect on inspiratory muscle work, we studied five men, 26 to 39 yr of age, during mild exercise with different degrees of inspiratory flow-resistive loading. Each subject performed four 1-h exercise runs at 30% of their maximal oxygen consumption on different days while inspiring through an external resistor of either 1.4, 14.5, 19.9, or 30.6 cm H2O/s/L. Mouth and esophageal pressure, inspiratory flow rate, and abdominal and rib cage motion were recorded continuously. Abdominal expansion tended to lead and rib cage expansion tended to lag the start of inspiration as judged from the beginning of negative pressure development at the mouth. These time differences increased as resistive load increased. Plots of abdominal versus rib cage motion also showed increase in phase shift, with the abdomen leading the rib cage on inspiration. For all subjects, the esophageal pressure at the end of expiration became less negative as the resistive load increased, indicating that the end-expiratory volume decreased with increasing resistive load. We conclude that there was increasing use of expiratory muscles as the resistive load increased, and that the initial expansion of the abdomen at high resistive loads represented elastic recoil of structures that had been compressed below the volume at FRC by the expiratory muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

PubMed1991

Urinary desmosine excretion as a marker of lung injury in the adult respiratory distress syndrome.

Desmosine, the intermolecular and intramolecular cross link between the chains of elastin polypeptide, may be useful as a marker of a lung injury in adult respiratory distress syndrome (ARDS). A radioimmunoassay for rabbit antibody developed against desmosine, conjugated to bovine serum albumin, can detect as little as 100 pg of desmosine in plasma or urine. Desmosine is not metabolically absorbed, reused, or catabolized by the body, but rather eliminated unchanged in the urine as low molecular weight peptides. The lung is relatively rich in elastin, and we reasoned that a timed collection could be used as an index of elastin degradation in vivo. A 2-h collection of urine for desmosine assay was obtained at the time of Swan-Ganz catheter insertion in 41 consecutive patients. On the basis of clinical and initial Swan-Ganz catheter data, the patients were assigned to one of three groups: an ARDS group (n = 12); a cardiogenic pulmonary edema (CPE) group (n = 12); and a critically ill, nonpulmonary edema group (NPE, n = 17). The mean urine desmosine concentration (mg/L) for the ARDS group (0.728 +/- 0.22 SE) differed from the CPE group (0.149 +/- 0.07; p less than 0.001). The total excretion (microgram/2 h) was 64.95 +/- 24.7 in the ARDS group and 24.71 +/- 11.7 in the CPE group (p less than 0.05). Urine desmosine concentration/serum creatinine index for the ARDS group (0.78 +/- 0.28) was greater than in the CPE group (0.07 +/- 0.04; p = 0.019). Desmosine excretion was increased in the NPE group compared with CPE and ARDS groups, possibly reflecting heterogeneity in this group. In the differentiation of ARDS from CPE, we conclude that substantial increases in urinary desmosine excretion favor a diagnosis of ARDS.

Adult↗

PubMed1991

Accuracy of oxyhemoglobin saturation monitors during simulated altitude exposure of men with chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) are at risk for hypoxemia during air travel. We assessed the comparative performance of oxyhemoglobin saturation (%O2Hb) monitors on these patients during hypobaric exposure. We measured %O2Hb by arterial catheter blood co-oximetry (COOX) and compared these values to those from a transmittance ear oximeter and a reusable digital pulse oximeter. Additionally, we examined the effect of oxygen supplementation (4 L/min) on %O2Hb. A total of 18 ambulatory males with severe COPD were exposed to 8,000 ft (565 mm Hg) in a hypobaric chamber. Multiple measures of %O2Hb were made with each monitor at sea level and at 8,000 ft, with and without supplemental oxygen. By COOX, %O2Hb fell at altitude to clinically significant levels, and was subsequently corrected with supplemental oxygen. Saturations measured by the transmittance ear oximeter were very close to the COOX, underestimating the true value by only 0.6% at altitude (p less than 0.05), while the reusable digital pulse oximeter over-estimated %O2Hb alinearly by a mean of 3.8% at altitude.

Aged↗

PubMed1990

Respiratory failure in rapidly progressing pulmonary lymphoma. Role of immunophenotyping in diagnosis.

An asymptomatic man was found to have bilateral small pulmonary infiltrates on a preoperative chest roentgenogram. Over a 4-wk period there was rapid progression of the infiltrates with a clinical picture suggestive of adult respiratory distress syndrome. Open lung biopsy showed a high grade lymphoma filling and distorting the pulmonary parenchyma. Flow cytometry of pleural fluid showed an aberrant phenotype consistent with T cell lymphoma. The patient died of progressive respiratory failure 6 wk after the first radiographic abnormalities were detected. With further experience, immunophenotyping of pleural fluid may secure definitive diagnoses in certain clinical situations, obviating more invasive procedures.

Antigens, Differentiation↗

PubMed1989

Hypoxemia during air travel in patients with chronic obstructive pulmonary disease.

STUDY OBJECTIVE: To quantitate and identify determinants of the severity of hypoxemia during air travel in patients with chronic obstructive pulmonary disease. DESIGN: Prospective study of physiologic variables before and during intervention. SETTING: Referral-based pulmonary disease clinic at a U.S. Army medical center. PATIENTS: Eighteen ambulatory retired servicemen (age 68 +/- 6 [SD] years) with severe chronic obstructive pulmonary disease (forced expiratory volume in the first second [FEV1] 31% +/- 10% of predicted). INTERVENTION: Altitude simulation equivalent to 2438 meters (8000 feet) above sea level in a hypobaric chamber. MEASUREMENTS AND MAIN RESULTS: Radial artery catheter blood oxygen tension in the patients declined from a ground value (PaO2G) at sea level of 72.4 +/- 9 mm Hg to an altitude value (PaO2Alt) of 47.4 +/- 6 mm Hg after 45 minutes of steady state hypobaric exposure. The PaO2G correlated with PaO2Alt (r = 0.587; P less than 0.01). Multiple regression analysis revealed that the preflight FEV1 reduced the variability in PaO2Alt not explained by PaO2G in the equation: PaO2Alt = 0.453 [PaO2G] + 0.386 [FEV1% predicted] + 2.440 (r = 0.847; P less than 0.001). Residuals from two previously published formulas using PaO2G also correlated with FEV1 (r greater than or equal to 0.765; P less than 0.001). CONCLUSIONS: Arterial blood oxygen tension declined to clinically significant levels in most patients during hypobaric exposure. When combined with the preflight arterial PO2 at ground level (PaO2G), the measurement of the preflight FEV1 improved prediction of PaO2 at altitude (PaO2Alt) in patients with severe chronic obstructive pulmonary disease.

Adult↗