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Biomedical subjects

D R Boughner

Publications and source records attributed to D R Boughner.

At least 19 recordsLinked to original sources

Stunned myocardium and myocardial collagen damage: differential effects of single and repeated occlusions.

It has been suggested that collagen loss and damage is responsible for the dysfunction seen in stunned myocardium. To test this hypothesis we compared collagen in canine hearts stunned by repeated occlusion with collagen in hearts stunned by a single occlusion. Regional contractile function was equally depressed in both groups: segment shortening at 1 hour after reperfusion averaged 37% +/- 9% versus 32% +/- 9% of preocclusion values in repeated and single occlusion models, respectively. Midmyocardial collagen content was not different in either single occlusion (10.5% +/- 0.4%) or repeated occlusion models (9.5% +/- 0.7%) when compared with nonischemic hearts (8.5 +/- 0.8%). Collagen damage, which was revealed with polarized light microscopy, was seen in 5 of 6 dogs after repeated occlusion but was not apparent after a single occlusion. Thus although both models of stunned myocardium produce similar dysfunction, there was no apparent collagen loss. Furthermore, collagen damage was only seen after repeated occlusion. Therefore it appears unlikely that collagen damage is a primary mechanism of stunned myocardium.

Animals

Cardiac function in aneurysmal subarachnoid haemorrhage: a study of electrocardiographic and echocardiographic abnormalities.

Electrocardiographic (ECG) changes are reported frequently after subarachnoid haemorrhage (SAH). The aim of this study was to investigate the functional significance of ECG changes by echocardiographic assessment of cardiac function. Forty-five patients with intracranial aneurysms were studied. All patients had a 12-lead ECG and a two-dimensional echocardiogram. After patients with an history of chronic cardiac disease (n = 4) were excluded, only four patients were found to have wall motion abnormalities. These patients had only minor ECG abnormalities, but severe neurological dysfunction. Conversely, patients with other ECG abnormalities including the deep inverted T waves associated usually with SAH, had normal echocardiograms. We conclude that the ECG is not an accurate predictor of myocardial function after SAH and that myocardial dysfunction is related more closely to severity of neurological condition.

Adolescent

Role of collagen in acute myocardial infarct expansion.

BACKGROUND: We sought to determine if damage to the myocardial collagen network was the cause of infarct expansion. METHODS AND RESULTS: Using polarized light microscopy, we examined sections from rat hearts obtained at 1, 2, 3, and 4 days after permanent coronary artery occlusion. Three features of the collagen network likely to be important in resisting infarct expansion were assessed: collagen quality, collagen quantity, and collagen organization. We observed a decrease in the number of normally birefringent collagen fibers in the infarct as early as 1 day after infarction. This decrease correlated significantly with time (r = -0.989, p less than 0.001). In addition, we found that the fewer normally birefringent collagen fibers present, the greater the degree of infarct expansion (assessed by measurement of total left ventricular cross-sectional area). At 4 days after infarction, we noted a loss of intermyocyte collagen struts and loss of interstitial space. These changes coincided with the onset of pronounced infarct expansion. The loss of collagen struts is consistent with the concept that expansion proceeds via slippage of myocytes previously tethered by the struts. The loss of interstitial space may represent the resolution of interstitial edema, which could further weaken the ventricular wall. CONCLUSIONS: The correlation of infarct expansion with collagen damage and the loss of support provided by collagen struts suggest that collagen is important in maintaining structural integrity after acute myocardial infarction.

Animals

Quantitative assessment of the age of fibrotic lesions using polarized light microscopy and digital image analysis.

Reliable histologic methods for gauging the maturity of fibrotic lesions are limited, making interventions in the healing process difficult to assess. As collagen ages there is enhanced birefringence due to increased molecular and fibrillar organization. The purpose of this study was to develop a microscopal technique to quantify this process and to determine its ability to distinguish scars of varying ages. Fibrosis in the rat gracilis muscle was studied 5 to 63 days after superficial injury. Sections were stained with picrosirius red and illuminated with monochromatic, polarized light. The microscope fields were digitized using a computer-video system yielding an image in which noncollagenous material was dark (gray level 0) and collagen was depicted by grey levels 1 to 255. In the fibrosis model used, the collagen area fraction plateaued at 80% by day 21. The median collagen grey level increased progressively as the scar aged. It is concluded that this histologic, nondestructive technique can reliably quantify age-related optical properties of fibrotic collagen and that this could be used to determine the maturity of fibrotic lesions.

Aging

Fibrosis in the transplanted heart and its relation to donor ischemic time. Assessment with polarized light microscopy and digital image analysis.

Long-distance procurement of cardiac allografts is commonly used to increase the supply of donor organs but has recently been associated with the development of impaired diastolic function. Therefore, the effect of the total ischemic duration on myocardial fibrosis was quantitatively evaluated in 36 cardiac transplant recipients in whom the ischemic time ranged from 70 to 363 (mean, 189 +/- 83) minutes. Interstitial collagen was quantified with polarization microscopy and digital image analysis in 115 endomyocardial biopsy specimens taken 5-10 days after surgery. The technique, developed for this study, showed excellent correlation with hydroxyproline analysis (r = 0.98, p less than 0.001). Collagen volume fraction in biopsy specimens from the transplanted hearts was significantly greater than that in biopsy samples from seven normal, age-matched autopsy hearts (4.7 +/- 1.9% vs. 2.9 +/- 0.6%, p less than 0.02). The degree of fibrosis correlated with the total ischemic time (r = 0.60, p less than 0.001). Donor age ranged from 10 to 51 years and did not correlate with the degree of fibrosis. No relation was found between the corresponding collagen content and right atrial pressure, pulmonary artery wedge pressure, or cardiac output measured at the time of biopsy. Myocyte damage was observed in eight of the 36 patients and was characterized by a striking loss of muscle birefringence. We conclude that cardiac allograft fibrosis may be identified shortly after transplantation and is dependent on the total ischemic duration.

Adult

The bovine pericardial xenograft: I. Effect of fixation in aldehydes without constraint on the tensile viscoelastic properties of bovine pericardium.

Tensile testing of tissue strips has been used to examine the effect of simple fixation in glutaraldehyde and formaldehyde on the viscoelastic properties of bovine pericardium. To assess tissue anisotropy, tissue strips were cut at 0 degree, 30 degrees, 60 degrees, and 90 degrees relative to the base-to-apex direction. Fresh anterior pericardium was modestly anisotropic, being least extensible in the base-to-apex direction; however, fixation removed this anisotropy. Fixation also produced a marked change in the response of the material to initial cyclic loading during preconditioning. Overall extensibility of the fixed material was significantly greater than that for the fresh tissue, consistent with a 10.7% shrinkage in aldehydes calculated from strain at fracture data. Reductions in stress relaxation and creep after fixation were noted as well, consistent with intrafibrillar crosslinking. Cyclic hysteresis and ultimate tensile strength were unaffected. Since the observed changes in the stress-strain response were largely attributable to shrinkage, control of shrinkage by physical means would allow for engineering modification of bovine pericardial mechanics for controlled anisotropy.

Aldehydes

An improved method for detecting and quantifying cardiac muscle disarray in hypertrophic cardiomyopathy.

The presence of muscle disarray in hypertrophic cardiomyopathy (HC), although well established, has only been semiquantitatively assessed. A quantitative method that uses polarized light microscopy is described. Hematoxylin and eosin-stained sections of ventricular septa from six HC patients and six normal hearts were examined. Cell orientations were measured in five regions from each section using a polarizing microscope with a rotating stage. Histograms of cell orientation angles were plotted and the mean and angular deviation of each sample were calculated. In normal hearts, cells were predominantly aligned parallel to each other. Orientation distributions were sharply peaked, with angular deviations ranging from 4 to 13 degrees. For HC, the sharp peak was lacking and angular deviations varied from 7 to 37 degrees; some distributions were bimodal. Areas in HC septa that appeared normal by gross inspection had abnormal orientation distributions. Polarized light microscopy provides an improved method of detecting and quantifying cellular disorganization in HC.

Cardiomyopathy, Hypertrophic

Measurements from light and polarised light microscopy of human coronary arteries fixed at distending pressure.

With the long term goal of improving our understanding of the mechanisms involved in coronary artery spasm, we have undertaken a two part study of the artery structure. We have made a comparison of the relative proportions of the different layers in proximal and distal regions of the main coronary arteries, and have quantitatively assessed their three dimensional structural fabric. Major coronary arteries from nine hearts were prepared for histological examination after fixation at a transmural pressure of 120 mm Hg. Measurements from 14 proximal and distal pairs of the cross sectioned arteries showed a dominant subendothelial layer, which diminished in thickness distally, with a small fraction of muscle cells interspersed with collagen. Three dimensional orientation measurements of the collagen and muscle components, which are birefringent, were obtained from one pair of segments from each of the left anterior descending, circumflex and right coronary arteries, using the polarising light microscope and Universal stage. Findings showed (1) a single circumferential order of adventitial collagen, with a mean circular standard deviation (CSD) of 22.3 degrees; (2) very highly ordered medial smooth muscle, mean CSD of 5.0 degrees (both findings are quantitatively similar between proximal and distal segments of artery, and between arteries); and (3) a multilayered fabric of collagen in the subendothelium in all vessel segments. The principal contributor to functional differences between proximal and distal regions may be the prominent and structurally varied subendothelial layer of the coronary arteries.

Adult

Analysis of healing after myocardial infarction using polarized light microscopy.

To better understand the healing process after permanent coronary artery occlusion in a canine model, the authors used polarized light microscopy. At 6 weeks after occlusion the scar collagen was mainly type I. Some regions of the scar contained a fiber lattice which appeared to be type III collagen. Collagen orientation was measured using a universal stage; subepicardial collagen was obliquely aligned (-14.0 +/- 3.5 degrees), midmyocardial collagen circumferentially aligned (1.4 +/- 0.4 degrees) and subendocardial collagen obliquely aligned (12.7 +/- 2.1 degrees). The molecular organization of scar collagen increased from 1 to 6 weeks after occlusion. Muscle cell disarray, similar to that in hypertrophic cardiomyopathy, was seen in the viable muscle adjacent to the scar. Such abnormal organization extended as far as 1 cm from the edge of the scar. The ability of polarized light microscopy to assess these different parameters from histologic sections demonstrates that it is a useful adjunct to other methods commonly used to study myocardial healing.

Animals

Quantitative structural analysis of collagen in chordae tendineae and its relation to floppy mitral valves and proteoglycan infiltration.

Imbibition analysis, a polarised light microscopy technique, was used to examine the molecular organisation of collagen in normal and diseased mitral valve chordae tendineae. A single strut chorda from each of 23 valves (14 from necropsy specimens and nine from valve replacement surgery) was studied. The degree of molecular organisation of collagen in unstained 7 micron sections of the chordae was assessed by measuring the retardation of polarised light by the sample. Sections from each tendon were examined, after staining with Movat's pentachrome, for the presence of proteoglycan infiltration and classified as normal or abnormal on that basis. The imbibition analysis results were grouped accordingly. The retardation in the collagen in the seven chordae with proteoglycan infiltration was significantly lower than in the 16 normal chordae, indicating decreased molecular organisation. Five of the seven abnormal chordae with proteoglycan infiltration and decreased retardation were from patients with floppy mitral valves; the other two were from normal necropsy specimens. Although proteoglycan infiltration may not be a specific marker for floppy valve disease, its presence is associated with decreased molecular organisation of collagen in the chordae. Degradation of the ground substance bound to the collagen is the most plausible explanation for the measured optical changes.

Adult

Cardiac and arterial lesions in carotid transient ischemic attacks.

Two hundred fifty consecutive patients with carotid transient ischemic attacks (TIAs) and no previous stroke were assessed with cerebral angiography (95%), two-dimensional echocardiography (86%), electrocardiography (100%), and Holter monitoring (99 selected patients). Angiography disclosed a lesion appropriate to the TIAs in 84%. Lesions also occurred in the asymptomatic carotid artery, but stenosis of more than 75% of the lumen diameter and ulcers were significantly more frequent on the symptomatic side. Twenty-three percent of the patients had a potential source of emboli from the heart, usually in the context of symptomatic heart disease. Among the 205 patients who underwent full angiographic and cardiac investigations, 6% had an isolated potential cardiac source of emboli and 19% had a potential cardiac source of emboli associated with appropriate carotid disease. The search for a potential cardiac source of emboli is strongly indicated in patients with carotid TIAs and known heart disease. In the patients with no history of heart disease, the yield of this search is low, but our results suggest that at least 14 of such patients have an undetected potential cardiac source of emboli. Cardiac and arterial lesions commonly coexist in carotid TIAs.

Adult

Clinical predictors of cardiac and arterial lesions in carotid transient ischemic attacks.

In 205 patients with carotid transient ischemic attacks (TIAs) who underwent full angiographic and cardiac investigations, we found that ipsilateral carotid bruit and triggering of TIA by exertion or standing up suggested a carotid lesion. Angina pectoris or palpitations at onset of TIA suggested a cardiac source of emboli. Patients with only one TIA, multiple identical attacks, progression of symptoms over minutes, and appropriate infarct on computed tomograms (28%) were likely to show a potential arterial or cardiac cause for the TIAs in subsequent investigations. Transient monocular blindness correlated with carotid occlusion, but the severity of the carotid lesion did not influence the duration and repetition of attacks. Transient ischemic attacks in multiple territories, identical attacks, and multiple or silent infarcts on computed tomograms occurred equally in the patients with arterial lesions and those with cardiac lesions. These findings suggest that only a few, albeit important, conclusions regarding etiology can be drawn from the clinical characteristics of TIAs.

Adult

Physical conditioning effects on cardiac dimensions: a review of echocardiographic studies.

Echocardiographic studies related to chronic exercise effects on cardiac dimensions were reviewed. Sources of error in M-mode echocardiography include its resolving power, changes in transmission velocity in a nonhomogeneous medium, subjective analysis of records, and assumptions to predict ventricular volume and mass from one-dimensional data. Existing studies document larger values for left ventricular internal diastolic dimension (LVIDd) in endurance athletes, and for septal and posterior wall thicknesses (ST, PWT) in endurance, strength-type and anaerobic-type athletes compared to nonathletes. Values for the athletes were lower than in cardiac disease states. Short-term conditioning studies generally reported unimpressive changes in ventricular dimensions. Existing literature also does not clearly support a relationship between training intensity and the degree of cardiac enlargement, or changes in the heart's trainability with age. Hereditary and/or familial factors appear to influence heart size to some degree and a correlation with anthropometric variables may exist. Further study concerning hereditary and long-term conditioning effects is recommended.

Adolescent

A multipurpose tissue bending machine.

A unique tissue bending machine was developed to test the bending properties of normal and bioprosthetic heart valve material. It can be operated in air or in a tissue bath and can measure bending torques with an accuracy in excess of 1.0 microN m. Three contrasting substances were tested to compare their stiffness and to demonstrate the machine.

Biophysics

Mechanical properties of human pericardium. Differences in viscoelastic response when compared with canine pericardium.

Whereas most experiments on the mechanical function of the pericardium have been performed on dogs, very little is known about the applicability of those data to humans. To examine the tensile viscoelastic properties of fresh human pericardium, we have used the methods from our previous study of canine pericardium. Although the mechanical responses of canine and human pericardium were qualitatively similar, human pericardium displayed a significantly greater viscous character. Human pericardium was 7.3 times thicker than canine pericardium, but was more extensible in stress-strain tests, with lower stiffness at a given strain. The static (elastic) stiffness of human pericardium seems identical to that of canine pericardium; lower stiffness per unit thickness of the human tissue at predicted physiological stresses was almost exactly compensated by the greater wall thickness. This effect was also seen in data on fracture strength and stiffness. However, human pericardium displayed greater viscous responses than the canine tissue. This was seen in doubled cyclic hysteresis losses, and greater stress relaxation and creep. Our results suggest that experiments on the viscoelastic properties of canine pericardium may not be directly applicable to humans, especially where dynamic mechanical properties are most important: i.e., in studies of ventricular function and the time-course of pericardial effusions.

Adult

Evaluation of commercially available heart rate monitors.

The accuracy and tracking ability of nine commercially available heart rate monitors were assessed. The heart rate of 16 young healthy men was continuously monitored by a single-lead electrocardiograph while they exercised on a stationary bicycle ergometer. Readings were obtained from the devices during exercise. The devices that measured the cardiac electrical potential with a three-electrode system or that incorporated a light transmission device attached to the earlobe were the most accurate and provided suitable monitoring of the heart rate during exercise.

Adult