Biomedical subjects

T Arts

Publications and source records attributed to T Arts.

At least 19 recordsLinked to original sources

PubMed2001

Remodeling by ventricular pacing in hypertrophying dog hearts.

OBJECTIVE: Asynchronous electrical activation of the left ventricle (LV), induced by ventricular pacing (VP), reduces mechanical load in early- and enhances it in late-activated regions. Consequently, chronic VP leads to asymmetric hypertrophy. We investigated whether such locally induced myocardial hypertrophy also occurs in the presence of pressure overload hypertrophy (POH). METHODS: POH was induced by aortic banding in puppies. At age 9 months, seven dogs were paced at the right ventricular (RV) apex at physiological heart rate for 6 months (POH-pace group), while four POH dogs served as POH-control group. Changes in volume of the LV cavity and the total LV wall and of five LV wall sectors were measured by means of 2D-echocardiography and X-ray marker detection. RESULTS: During the last 6 months of the protocol the volume of the five LV wall sectors increased in the POH-control group, ranging from 27+/-9 to 30+/-5% (mean+/-S.D.). In POH-pace animals sector wall volume in the four sectors at intermediate to long distance from the pacing site increased to a similar extent (ranging from 31+/-16 to 35+/-17%), but wall volume in the early-activated apical septum increased significantly less (17+/-21%). In these hearts myocyte diameter was significantly smaller in the apical septum than in the lateral LV wall. The regional difference in wall volume changes (19+/-21%) was significantly smaller in the POH-pace group than in chronically paced, non-hypertrophic, canine hearts in a previous study from our laboratory (43+/-14%). CONCLUSIONS: In hypertrophying hearts chronic pacing at the RV apex suppresses the development of hypertrophy in the early-activated apical septum but does not cause additional hypertrophy in late-activated regions, as is the case in non-hypertrophic hearts. The latter suggests that the local growth response is reduced in hypertrophying hearts.

Analysis of Variance↗

PubMed2000

Detection of leukocytes in contact with the vessel wall from in vivo microscope recordings using a neural network.

Leukocytes play an important role in the host defense as they may travel from the blood stream into the tissue in reacting to inflammatory stimuli. The leukocyte-vessel wall interactions are studied in post capillary vessels by intravital video microscopy during in vivo animal experiments. Sequences of video images are obtained and digitized with a frame grabber. A method for automatic detection and characterization of leukocytes in the video images is developed. Individual leukocytes are detected using a neural network that is trained with synthetic leukocyte images generated using a novel stochastic model. This model makes it feasible to generate images of leukocytes with different shapes and sizes under various lighting conditions. Experiments indicate that neural networks trained with the synthetic leukocyte images perform better than networks trained with images of manually detected leukocytes. The best performing neural network trained with synthetic leukocyte images resulted in an 18% larger area under the ROC curve than the best performing neural network trained with manually detected leukocytes.

Animals↗

PubMed2000

Cardiac mechanoenergetics replicated by cross-bridge model.

The aim of this work is to reproduce the experimentally measured linear dependence of cardiac muscle oxygen consumption on stress-strain area using a model, composed of a three-state Huxley-type model for cross-bridge interaction and a phenomenological model of Ca2+-induced activation. By selecting particular cross-bridge cycling rate constants and modifying the cross-bridge activation model, we replicated the linear dependence between oxygen consumption and stress-strain area together with other important mechanical properties of cardiac muscle such as developed stress dependence on the sarcomere length and force-velocity relationship. The model predicts that (1) the amount of the "passenger" cross bridges, i.e., cross bridges that detach without hydrolyzing ATP molecule, is relatively small and (2) ATP consumption rate profile within a beat and the amount of the passenger cross bridges depend on the contraction protocol.

Actomyosin↗

PubMed1999

An improved isolated, left ventricular ejecting, murine heart model. Functional and metabolic evaluation.

An improved, isolated, left ventricular-ejecting, murine heart model is described and evaluated. Special attention was paid to the design and impedance characteristics of the artificial aortic outflow tract and perfusate composition, which contained glucose (10 mM plus insulin) and pyruvate (1.5 mM) as substrates. Temperature of the isolated perfused hearts was maintained at 38.5 degrees C. During antegrade perfusion (preload 10 mm Hg, afterload 50 mm Hg, 2.5 mM Ca2+) proper design of the aortic outflow tract provided baseline values for cardiac output (CO), left ventricular developed pressure (LVDP) and the maximum first derivative of left ventricular pressure (LV dP/dtmax) of 11.1+/-1.7 ml min-1, 83+/-5 mm Hg and 6283+/-552 mm Hg s-1, respectively, resembling findings in the intact mouse. During 100 min normoxic antegrade perfusion CO declined non-significantly by less than 10%. Varying pre- and afterloads resulted in typical Frank-Starling relationships with maximal CO values of 18.6+/-1.8 ml min-1 at pre- and afterload pressures of 25 and 50 mm Hg, respectively. Left ventricular function curves were constructed at free [Ca2+] of 1.5 and 2.5 mM in the perfusion medium. Significantly higher values for CO, LVDP and LV dP/dtmax and LV dP/dtmin were obtained at 2.5 mM Ca2+ at all loading conditions investigated. Phosphocreatine and creatine levels remained stable throughout the perfusion period. Despite a small but significant decline in tissue ATP content, the sum of adenine nucleotides did not change during the normoxic perfusion period. The tissue content of glycogen increased significantly.

Adenosine Triphosphate↗

PubMed1999

Kinematic analysis of left ventricular deformation in myocardial infarction using magnetic resonance cardiac tagging.

The Magnetic Resonance (MR) tagging technique provides detailed information about 2D motion in the plane of observation. Interpretation of this information as a reflection of the 3D motion of the entire cardiac wall is a major problem. In finite element models of the mechanics of the infarcted heart, an infarcted region causes motional asymmetry, extending far beyond the infarct boundary. Here we present a method to quantify such asymmetry in amplitude and orientation. For this purpose images of a short-axis cross-section of the ejecting left ventricle were acquired from 9 healthy volunteers and 5 patients with myocardial infarction. MR-tags were applied in a 5 mm grid at end-diastole. The tags were tracked by video-image analysis. Tag motion was fitted to a kinematic model of cardiac motion. For the volunteers and the patients the center of the cavity displaced by about the same amount (p = 0.11) during the ejection phase: 3.8 +/- 1.4 and 3.0 +/- 0.9 mm (mean +/- sd), respectively. Cross-sectional rotation and the decrease in cross-sectional area of the cavity were both greater in the volunteers than in the patients: 6.4 +/- 1.5 vs. 3.0 +/- 0.8 degrees (p < 0.001), and 945 +/- 71 vs. 700 +/- 176 mm2 (p = 0.02), respectively. In the patients, asymmetry of wall motion, as expressed by a sine wave dependency of contraction around the circumference, was significantly enlarged (p = 0.02). The proposed method of kinematic analysis can be used to assess cardiac deformation in humans. We expect that by analyzing images of more cross-sections simultaneously, the 3D location and the degree of infarction can be assessed efficiently.

Biomechanical Phenomena↗

PubMed1999

Maximum likelihood estimation in calibrating a stereo camera setup.

Motion and deformation of the cardiac wall may be measured by following the positions of implanted radiopaque markers in three dimensions, using two x-ray cameras simultaneously. Regularly, calibration of the position measurement system is obtained by registration of the images of a calibration object, containing 10-20 radiopaque markers at known positions. Unfortunately, an accidental change of the position of a camera after calibration requires complete recalibration. Alternatively, redundant information in the measured image positions of stereo pairs can be used for calibration. Thus, a separate calibration procedure can be avoided. In the current study a model is developed that describes the geometry of the camera setup by five dimensionless parameters. Maximum Likelihood (ML) estimates of these parameters were obtained in an error analysis. It is shown that the ML estimates can be found by application of a nonlinear least squares procedure. Compared to the standard unweighted least squares procedure, the ML method resulted in more accurate estimates without noticeable bias. The accuracy of the ML method was investigated in relation to the object aperture. The reconstruction problem appeared well conditioned as long as the object aperture is larger than 0.1 rad. The angle between the two viewing directions appeared to be the parameter that was most likely to cause major inaccuracies in the reconstruction of the 3-D positions of the markers. Hence, attempts to improve the robustness of the method should primarily focus on reduction of the error in this parameter.

Biomechanical Phenomena↗

PubMed1999

Feasibility of minimally invasive intrauterine fetal access in a monkey model.

PURPOSE: We evaluated new intervention techniques and surgical instruments in a fetal monkey model to determine improvements that would be useful for early intrauterine intervention. Our findings may be helpful in the future for treating select cases of severe prenatal obstructive uropathology. MATERIALS AND METHODS: In a series of experiments on 18 pregnant rhesus monkeys (Macaca mulatta) at mid trimester we assessed various endoscopic intra-amniotic access techniques as well as morbidity, mortality and possibilities for fetoscopy. RESULTS: In all 18 fetuses adequate fetoscopy was possible with no maternal mortality. Of the 18 pregnancies 14 went to term with no early or late postoperative complications. Technical improvements changed the intrauterine access technique from open placement of trocars to the use of the Seldinger technique, gun introduction of needles with small caliber sheets and small caliber introduction trocars, resulting in minimal amniotic membrane separation. Various rigid and flexible endoscopes were evaluated for fetoscopy and up to 3 cannulas were placed. No change in the fetal growth pattern was observed on postoperative ultrasound. Subsequent pregnancies occurred during this study period, and there were no acceptance problems of the newborns by the mothers. CONCLUSIONS: New techniques have led to improved intrauterine fetal access. Morbidity mainly depends on the disruption of amniotic membranes, which has an important preterm role. Adapted endoscopes and other instruments offer new possibilities for fetal diagnosis and therapy in the future. Our primate model seems to be suitable for evaluating these new techniques before they are used in a clinical setting.

Animals↗

PubMed1998

Asynchronous electrical activation induces asymmetrical hypertrophy of the left ventricular wall.

BACKGROUND: Asynchronous electrical activation, induced by ventricular pacing, causes regional differences in workload, which is lower in early- than in late-activated regions. Because the myocardium usually adapts its mass and structure to altered workload, we investigated whether ventricular pacing leads to inhomogeneous hypertrophy and whether such adaptation, if any, affects global left ventricular (LV) pump function. METHODS AND RESULTS: Eight dogs were paced at physiological heart rate for 6 months (AV sequential, AV interval 25 ms, ventricular electrode at the base of the LV free wall). Five dogs were sham operated and served as controls. Ventricular pacing increased QRS duration from 47.2+/-10.6 to 113+/-16.5 ms acutely and to 133.8+/-25.2 ms after 6 months. Two-dimensional echocardiographic measurements showed that LV cavity and wall volume increased significantly by 27+/-15% and 15+/-17%, respectively. The early-activated LV free wall became significantly (17+/-17%) thinner, whereas the late-activated septum thickened significantly (23+/-12%). Calculated sector volume did not change in the LV free wall but increased significantly in the septum by 39+/-13%. In paced animals, cardiomyocyte diameter was significantly (18+/-7%) larger in septum than in LV free wall, whereas myocardial collagen fraction was unchanged in both areas. LV pressure-volume analysis showed that ventricular pacing reduced LV function to a similar extent after 15 minutes and 6 months of pacing. CONCLUSIONS: Asynchronous activation induces asymmetrical hypertrophy and LV dilatation. Cardiac pump function is not affected by the adaptational processes. These data indicate that local cardiac load regulates local cardiac mass of both myocytes and collagen.

Animals↗

PubMed1998

Estimates of regional work in the canine left ventricle.

Assessment of the magnitude of regional myocardial work requires knowledge of regional fiber stress and fiber shortening. The theoretical development and experimental validation of a method is presented which used values of estimated active and passive fiber stress according to a fluid-fiber model, and measured fiber strain values. This enables the construction of regional stress-strain diagrams, a regional analog of the pressure-volume area model by Suga and co-investigators, which can be linked to regional oxygen consumption. In the left ventricle, either normally or asynchronously activated, the method yields reliable data on strain and active and passive fiber stress. The relation between estimated regional work and myocardial oxygen demand is in quantitative agreement with previously reported relations between global oxygen demand and measured pressure-volume area. During coronary artery occlusion, however, these values were less reliable, which might be due to inaqdequate knowledge of the (passive) material properties of the myocardium.

Animals↗

PubMed1997

Tissue remodeling with micro-structurally based material laws.

Cardiomyocytes and the extracellular collagen matrix which holds them together respond to changes in their mechanical environment by adapting their orientation, size and composition. We examine local mechanical feedback mechanisms affecting the fiber orientation, sheet orientation and passive fiber direction stiffness, using an axisymmetric finite element model of the left ventricle (LV), with material constitutive laws based on the fibrous-sheet microstructure of myocardium.

Animals↗

PubMed1997

Tracking markers with missing data by lower rank approximation.

Motion and deformation of an object may be quantified by following attached markers in video or cine frame sequences. When recording cardiac motion by video (256 x 256 pixels, 50 Hz), generally no more than approximately 20 markers can be followed due to difficulties in proper identification of marker images. In the present study we developed the lower rank (LR) tracking method which can automatically follow considerably more than 20 markers. The performance of the method was evaluated in computer simulations of naturally moving myocardial markers observed in a sequence of 60 video frames. White noise was added to the marker coordinates. Realistic loss of data due to detection failure was simulated by deleting a generated marker image when the distance to another marker image was below a given minimum value. In a test, realistic values were substituted for the noise level sigma (0.5 pixel) and the minimum marker distance dm (4 pixels). For numbers of markers ranging from 50 to 100, 95-90% of the detected marker images was correctly tracked. Less than 0.7% was part of a false track, i.e. a track containing images of different markers. Under less favourable conditions (sigma = 1 pixel; dm = 8 pixels) the method was robust: for 75 markers with 40% of the marker images missing, still 70% of the detected images was correctly tracked, while the fraction in false tracks did not increase. The LR tracking method appears reliable for automatic tracking of large amounts of moving markers in a sequence of video or cine frames.

Algorithms↗

PubMed1997

Relation between torsion and cross-sectional area change in the human left ventricle.

During the ejection phase, motion of the left ventricular (LV) wall is such that all myocardial fibers shorten to the same extent. In a mathematical model of LV mechanisms it was found that this condition could be satisfied only if torsion around the long axis followed a unique function of the ratio of cavity volume to wall volume. When fiber shortening becomes non-uniform due to cardiac pathology, this pathology may be reflected in aberration of the torsional motion pattern. In the present study we investigated whether the predicted regular motion pattern could be found in nine healthy volunteers, using Magnetic Resonance Tagging. In two parallel short-axis cross-sections, displacement, rotation, and area ejection were derived from the motion of tags, attached non-invasively to the myocardium. Information from both sections was combined to determine area ejection, quantified as the change in the logarithm of the ratio of cavity area to wall area, and torsion, represented by the shear angle on the epicardium. Linear regression was applied to torsion as a function of area ejection. The slope thus found (-0.173 +/- 0.024 rad, mean +/- S.D.) was similar to the slope as predicted by the model of LV mechanics (-0.194 +/- 0.026 rad). In conclusion, the relation between area ejection and torsion could be assessed noninvasively in humans. In healthy volunteers, the relation was close to what was predicted by a mathematical model of LV mechanics, and also close to what was found earlier in experiments on animals.

Algorithms↗

PubMed1997

Optimization of cardiac fiber orientation for homogeneous fiber strain at beginning of ejection.

Mathematical models of left ventricular (LV) wall mechanics show that fiber stress depends heavily on the choice of muscle fiber orientation in the wall. This finding brought us to the hypothesis that fiber orientation may be such that mechanical load in the wall is homogeneous. Aim of this study was to use the hypothesis to compute a distribution of fiber orientation within the wall. In a finite element model of LV wall mechanics, fiber stresses and strains were calculated at beginning of ejection (BE). Local fiber orientation was quantified by helix (HA) and transverse (TA) fiber angles using a coordinate system with local r-, c-, and l-directions perpendicular to the wall, along the circumference and along the meridian, respectively. The angle between the c-direction and the projection of the fiber direction on the cl-plane (HA) varied linearly with transmural position in the wall. The angle between the c-direction and the projection of the fiber direction on the cr-plane (TA) was zero at the epicardial and endocardial surfaces. Midwall TA increased with distance from the equator. Fiber orientation was optimized so that fiber strains at BE were as homogeneous as possible. By optimization with TA = 0 degree, HA was found to vary from 81.0 degrees at the endocardium to -35.8 degrees at the epicardium. Inclusion of TA in the optimization changed these angles to respectively 90.1 degrees and -48.2 degrees while maximum TA was 15.3 degrees. Then the standard deviation of fiber strain (epsilon f) at BE decreased from +/- 12.5% of mean epsilon f to +/- 9.5%. The root mean square (RMS) difference between computed HA and experimental data reported in literature was 15.0 degrees compared to an RMS difference of 11.6 degrees for a linear regression line through the latter data.

Heart↗

PubMed1996

Use of fluorescent in situ hybridization to detect aneuploidy in cervical dysplasia.

Fluorescent in situ hybridization (FISH) with alpha satellite DNA probes for chromosomes 11 and X were applied to normal, atypical, and dysplastic cervical-vaginal cytology smears to evaluate the detection of hyperploidy in suspected abnormal cells. Forty-six cases were obtained from fixed archival material. Eight cases with a morphological diagnosis of within normal limits (WNL) were directly selected to use as controls. The other 38 cases were blinded as study cases. These included five WNL, six ASCUS, six SIL-LG, 16 SIL-HG, four invasive squamous cell carcinomas, and one case of adenocarcinoma of the cervix. Cells with chromosome copy numbers suggesting hyperploidy (3-4 signals per chromosome specific probe) were found more often in higher grade dysplasia (Bethesda class SIL-HG) cases and less often in lower grade lesions (SIL-LG). All cases morphologically diagnosed as WNL were found to have normal copy number except for one control case which was hyperploid and, upon reexamination of the original slides, was upgraded from normal to atypical squamous cells of undetermined significance (ASCUS). Our FISH results are similar to those of previous studies involving flow cytometry and morphometric cytometry in which changes in ploidy correlated with progression toward higher grade lesions. However, FISH with enumeration probes offers a higher resolution view of the genome than is possible with flow cytometry or morphometry by allowing detection of specific chromosome changes in small numbers of affected cells in a routine cervical smear, and it may have the capacity to detect those cases in which progression toward high grade dysplasias is more likely.

Adenocarcinoma↗

PubMed1996

Endoscopic intrauterine fetal therapy: a monkey model.

OBJECTIVES: Prenatal ultrasonographic investigations have led to an increasing number of prenatally detected abnormalities, of which a large number involves the urogenital tract. This study was performed to evaluate if endoscopic intra-amniotic access is possible in primates. METHODS: In 10 midtrimester rhesus monkeys (Macaca mulatta), endoscopic intrauterine fetoscopy was performed with three access cannulas. Using a Seldinger technique, a vascular access system, and a pediatric laparoscopy set, intra-amniotic inspection was attempted. Fetal growth throughout pregnancy was monitored by ultrasonographic measurements of fetal biometry. RESULTS: Intrauterine access could successfully be achieved in 10 rhesus monkeys with three cannulas. After partial amniotic fluid exchange, adequate fetoscopy was always possible. Two monkeys aborted on the second and sixth postoperative days. Serial ultrasonographic investigations for fetal biometry showed no disturbance of the intrauterine growth patterns in the remaining 8 monkeys. CONCLUSIONS: We currently conclude that the rhesus monkey model for experimental intrauterine endoscopic surgery may be suitable for study of the developmental abnormalities of the genitourinary tract.

Animals↗

PubMed1996

Optimization of left ventricular fibre orientation of the normal heart for homogeneous sarcomere length during ejection.

UNLABELLED: During the ejection phase of the cardiac cycle, left ventricular muscle fibres shorten while generating force. It was hypothesized that fibres are oriented in the wall such that the amount of shortening is the same for all fibres. We evaluated this hypothesis for the equatorial region of the left ventricle. In a finite element model of left ventricular wall mechanics fibre orientation was quantified by a helix angle which varied linearly from the inner to the outer wall. Fibre length was characterized by sarcomere length, set at 1.95 microns everywhere in the passive state of 0 transmural pressure. For a cavity pressure of 15 kPa, considered representative for ejection, inhomogeneity in mechanical loading was expressed by the variance of the sarcomere length. The variance was minimized by adapting the transmural course of fibre angle. First, only the slope was optimized and in a second optimization this was done for both slope and intercept. Optimal helix fibre angles were 69.6 degrees endocardially, 0 degree at the middle of the wall and -69.6 degrees epicardially for the first optimization and 78.2 degrees, 20.7 degrees and, -36.7 degrees respectively for the second. Sarcomere length changed from 1.95 to 1.975 +/- 0.012 and 1.981 +/- 0.004 microns (mean +/- SD) respectively. CONCLUSION: After optimization calculated helix fibre angles were in the physiological range. Describing the transmural course of fibre angle with slope and intercept significantly improved homogeneity in mechanical load.

Biomechanical Phenomena↗

PubMed1996

Regional wall mechanics in the ischemic left ventricle: numerical modeling and dog experiments.

The mechanics of the ischemic left ventricle during a complete cardiac cycle were simulated using a finite-element model accounting for the thick-walled ventricular geometry, the fibrous nature of the myocardial tissue, and the dependency of active muscle fiber stress on time, strain, and strain rate. Ischemia was modeled by disabling the generation of active stress in a region comprising approximately 12% of total wall volume. In the model simulations, the approximately 12% reduction in the amount of normally contracting tissue resulted in an approximately 25% reduction in stroke work compared with the normal situation. The more-than-proportional loss of stroke work may partly be attributed to storage of elastic energy in the bulging ischemic region. Furthermore the mechanical performance in the nonischemic border zone deteriorated because of reduced systolic fiber stress (if fibers were in series with those in the ischemic region) or reduced fiber shortening (if fibers were parallel). The deformation pattern of the ventricle was asymmetric with respect to the ischemic region because of the anisotropy of the myocardial tissue. Epicardial fiber shortening in and around the ischemic region, as predicted from the model simulations, was in qualitative agreement with shortening, as measured in four dogs in which ischemia was induced by occlusion of the distal part of the left anterior interventricular coronary artery.

Animals↗

PubMed1996

Regional electrical activation and mechanical function in the partially ischemic left ventricle of dogs.

During normoxia, asynchronous electrical activation of the left ventricle significantly affects regional mechanical performance. Regional fiber strain and external work during the ejection phase are found to be lower in early-activated than in late-activated regions. Because electrical activation is known to be delayed during ischemia, the present study was designed to investigate the influence of this electrical asynchrony on regional fiber strain, if any, during moderate and severe myocardial ischemia. Regional electrical activation time (t(ea)) and fiber strain during the ejection phase (ef,e) were measured in the epicardial layers of the left ventricular anterior wall during normoxia and after 15 min of total occlusion (n = 5) or 30, 60, 120, and 180 min of partial occlusion of the left anterior interventricular coronary artery (LAICA; n = 11). Myocardial blood flow (MBF) was assessed with radioactive microspheres. Blood gases, pH, and lactate and Pi contents were determined in arterial, local venous, and coronary sinus blood. During normoxia, t(ea) and ef,e were similar in various epicardial regions of the left ventricular anterior wall. During total LAICA occlusion, in the ischemic area, subepicardial MBF decreased from 0.86 +/- 0.36 (SD) to 0.18 +/- 0.09 ml.g-1.min-1 and subepicardial ef,e decreased from -0.11 +/- 0.02 to -0.01 +/- 0.01, whereas the delay in t(ea) between the normoxic basal-lateral and ischemic apical-medial areas increased slightly but significantly from 1.9 +/- 8.0 to 7.5 +/- 8.0 ms. After a 180-min partial occlusion of the LAICA, in the ischemic area, subepicardial MBF decreased from 0.62 +/- 0.17 to 0.49 +/- 0.18 ml.g-1.min-1 and ef,e decreased from -0.08 +/- 0.01 to -0.03 +/- 0.01. No significant change in the difference in t(ea) between the normoxic and ischemic areas could be detected (5.1 +/- 4.8 and 5.2 +/- 5.8 ms in the control situation and after 180-min partial occlusion, respectively). These findings indicate that in the ischemic epicardium 1) mechanical function is more affected than electrical impulse conduction and 2) delayed activation, if any, is accompanied by decreased instead of increased fiber strain, as found in the normoxic left ventricle.

Animals↗