Biomedical subjects

W J Karlon

Publications and source records attributed to W J Karlon.

8 recordsLinked to original sources

PubMed2000

Structural and mechanical factors influencing infarct scar collagen organization.

Although large collagen fibers in myocardial infarct scar are highly organized, little is known about mechanisms controlling this organization. The preexisting extracellular matrix may act as a scaffold along which fibroblasts migrate. Conversely, deformation within the ischemic area could guide fibroblasts so new collagen is oriented to counteract the stretch. To investigate these potential mechanisms, we infarcted three groups of pigs. Group 1 served as infarct controls. Group 2 had the endocardium slit longitudinally to alter local systolic deformation. Group 3 had a plug sectioned from ischemic tissue and rotated 90 degrees. The slit altered systolic deformation in the infarcted tissue, changing circumferential strain from expansion to compression and increasing radial strain and shears and the variability of collagen fiber angles but not the mean angle. In the plug pigs, when deformation, matrix orientation, and continuity are altered in the infarct area, the result is complete disarray in the organization of collagen within the infarct scar.

Animals↗

PubMed2000

Regional dysfunction correlates with myofiber disarray in transgenic mice with ventricular expression of ras.

A hallmark of certain cardiac diseases such as familial hypertrophic cardiomyopathy is focal myofiber disarray. Regional ventricular dysfunction occurs in human subjects with hypertrophic cardiomyopathy; however, no direct evidence exists to correlate regional dysfunction with myofiber disarray. We used a transgenic mouse, which exhibits regional myofiber disarray via ventricular expression of the human oncogene ras, to investigate the relationship between myofiber disarray and septal surface strain. An isolated ejecting mouse heart preparation was used to record deformation of markers on the septal surface and to determine nonhomogeneous septal surface strain maps. Myofiber disarray made in histological tissue sections was correlated with gradients in surface systolic shortening. Significantly smaller maximum principal shortening was associated with disarray located near the right ventricle (RV) septal surface. There was also significantly smaller surface shear strain associated with disarray located either near the RV surface or at the midwall. Because surface shear is a local indicator of torsion, we conclude that myofiber disarray is associated with reduced septal torsion and reduced surface shortening.

Animals↗

PubMed1998

Protection against myocardial dysfunction after a brief ischemic period in transgenic mice expressing inducible heat shock protein 70.

Brief ischemic periods lead to myocardial dysfunction without myocardial infarction. It has been shown that expression of inducible HSP70 in hearts of transgenic mice leads to decreased infarct size, but it remains unclear if HSP70 can also protect against myocardial dysfunction after brief ischemia. To investigate this question, we developed a mouse model in which regional myocardial function can be measured before and after a temporary ischemic event in vivo. In addition, myocardial function was determined after brief episodes of global ischemia in an isolated Langendorff heart. HSP70-positive mice and transgene negative littermates underwent 8 min of regional myocardial ischemia created by occlusion of the left descending coronary artery, followed by 60 min of reperfusion. This procedure did not result in a myocardial infarction. Regional epicardial strain was used as a sensitive indicator for changes in myocardial function after cardiac ischemia. Maximum principal strain was significantly greater in HSP70-positive mice with 88+/-6% of preischemic values vs. 58+/-6% in transgene-negative mice (P < 0.05). Similarly, in isolated Langendorff perfused hearts of HSP70-positive and transgene-negative littermates exposed to 10 min of global ischemia and 90 min of reperfusion, HSP70 transgenic hearts showed a better-preserved ventricular peak systolic pressure. Thus, we conclude that expression of HSP70 protects against postischemic myocardial dysfunction as shown by better preserved myocardial function.

Animals↗

PubMed1998

Automated measurement of myofiber disarray in transgenic mice with ventricular expression of ras.

Quantitative assessment of myofiber disarray associated with diseases such as familial hypertrophic cardiomyopathy (FHC) can be performed by estimating local angular deviation of fiber orientation in histologic sections. The large number of measurements required to estimate angular deviation prohibits manual measurement. We describe methods for automated measurement of local orientation and angular deviation in tissue sections from transgenic mice with ventricular expression of ras, proposed as a model of FHC. Images of histologic tissue sections from normal and transgenic mice were analyzed using image processing techniques to estimate local orientation of myofibers. Results from the automated methods were compared with manual measurements. Automated methods estimated differing mean orientation in 7-20% of normal sections and 17-29% of transgenic tissue sections with differing dispersions in 23-30% of normal sections and 25% of transgenic tissue sections. Automated methods estimate 24.47+/-13.03% of total ventricular mass affected by disarray that is comparable to a previous estimate of 21.7% in the same mouse model. Automated methods are a rapid and accurate alternative to manual measurement for estimation of mean orientation and angular deviation in myocardial tissue sections. Differences between manual and automated methods may be attributed to the substantially larger number of measurements made by automated methods. Automated methods are particularly appropriate for use in determining local variation in orientation such as focal myofiber disarray associated with FHC. The generality of these methods suggests they may have use in other biological fields such as quantifying cellular alignment.

Animals↗

PubMed1994

Finite element models of thoracic conductive anatomy: sensitivity to changes in inhomogeneity and anisotropy.

A moderately detailed 3-D finite element model of the conductive anatomy of a canine thorax was used to examine the sensitivity of the results obtained during simulated transthoracic defibrillation to variations in skeletal muscle anisotropy and differing degrees of model inhomogeneity. Our results suggest that the myocardial current density distribution is not particularly sensitive to the method used to model skeletal muscle anisotropy. However, anisotropy variations caused defibrillation parameters such as paddle to paddle impedance and threshold current to change by as much as 50%. We found a greater sensitivity in the myocardial current density and the defibrillation parameters to variations in model inhomogeneity. The changes observed in both depended substantially on paddle placement. This sensitivity to paddle placement highlights the difficulty in predicting how a reduction in anatomical detail will affect the myocardial current density distribution. In general, we found the defibrillation parameters to be more sensitive than the myocardial current density distribution to the variations in anatomical detail we examined.

Animals↗

PubMed1993

Effects of paddle placement and size on defibrillation current distribution: a three-dimensional finite element model.

A realistic three-dimensional finite element model of the conductive anatomy of a canine thorax was constructed for use in the study of transthoracic electrical defibrillation. The model was constructed from a series of 21 cross-sectional CT scans of a 14.5 kg beagle, each separated by 0.82 cm. The electrical conductive properties of 8 distinct tissues were incorporated, including the anisotropic properties of skeletal muscle. Current density distributions were obtained for six paddle pairings and two paddle sizes. A quantitative basis for comparing the resulting distributions was formulated. Our results suggest that placing one or both of the paddles near the heart delivers a higher fraction of current to the heart. However, such paddle placements also produce a less uniform myocardial current density distribution and thus have a higher potential for causing damage. We found that some paddle positions can produce myocardial current densities close to the threshold for damage in successful defibrillations. Results obtained for 8 and 12 cm paddles indicate that 12 cm paddles may offer modest advantages over 8 cm paddles in clinical defibrillation. Comparison of our results to available in vivo experimental data confirm the validity of the finite element method for examining continuum field variables pertinent to electrical defibrillation.

Animals↗

PubMed1992

Test of four defibrillation dosing strategies using a two-dimensional finite-element model.

The most widely used defibrillation dosing strategy is that adopted by the American Heart Association in 1986. However, several alternative dosing strategies have been proposed to match delivered energy to the individual requirements of defibrillation subjects. In this study, two-dimensional finite element methods are used to investigate the performance of four of these dosing strategies applied to three thoracic models representative of men and women of different thoracic aspect ratios. From the resulting current density distributions, the relative effectiveness of the following dosing strategies are evaluated and compared: constant current; current proportional to body weight; constant energy; energy proportional to body weight. Our results show that the strategy of applying current proportional to subject body weight with a current dose of 0.58 A kg-1 was able to defibrillate all three subjects with only minimal overexposure of any one of them. None of the other dosing strategies examined could be made to successfully defibrillate all three subjects without significantly overexposing at least one.

Adult↗

PubMedDate not supplied

Measurement of orientation and distribution of cellular alignment and cytoskeletal organization.

Endothelial cells elongate and align with the direction of applied fluid shear stress. Previously, automated methods for analysis of cell orientation distribution have used Fourier- or fractal-based methods. We used intensity gradients in images of control and sheared endothelial cells to measure orientation distributions. Automated measurements of mean orientation and angular deviation compared favorably with manual measurements. There was a significantly greater angular deviation in images of control cells compared with sheared cells. Automated methods were also used to quantify organization of cytoskeletal fibers using the local angular deviation and a measure of the local coalignment of fibers called the coalignment ratio. The local angular deviation of microtubules and microfilaments was significantly smaller in sheared cells compared with control. The coalignment of cytoskeletal fibers was significantly greater in sheared cells. We conclude that image intensity gradients can be used rapidly, accurately, and objectively to measure cell orientation distributions and cytoskeletal filament organization.

Algorithms↗