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Biomedical subjects

J F Cornhill

Publications and source records attributed to J F Cornhill.

At least 55 records · Page 3Linked to original sources

The effect of ischemia on canine carotid endothelial permeability.

The effect of ischemia on arterial endothelial permeability was assessed by surgically interrupting arterial blood flow for 45 min in the left carotid artery of 12 foxhounds. The right carotid artery served as control. Twenty-four hours before sacrificing the animals at 1 day, 1 week, 1 month, and 3 months postoperatively. Evans blue dye (1.5 ml/kg) was administered intravenously. Carotid arteries were harvested, opened, and scanned with a reflectometer to measure Evans blue dye uptake, and scanning electron microscopy was performed on a section of tissue from each harvested vessel. A statistically significant increase in permeability of the ischemic vessel occurred at 1 day (79 +/- 42% (SD], 1 week (186 +/- 75%), and 1 month (229 +/- 125%), but was not present at 3 months (7 +/- 8%) postinjury. Scanning electron microscopic examination of all specimens was essentially normal. This study demonstrates that arterial endothelium has increased permeability at 1 month following a brief ischemic period. What effect this ischemia-induced endothelial dysfunction will have on lipid uptake by the arterial wall will be the subject of future study.

Animals↗

Endothelial surface characteristics in pigeon coronary artery atherosclerosis. I. Cellular alterations during the initial stages of dietary cholesterol challenge.

The early events in coronary artery atherosclerosis in White Carneau pigeons were studied by combined scanning and transmission electron microscopy. Endothelial cells throughout the right coronary artery were elongate in shape, having an axial ratio (width + length) of 0.48 +/- 0.03, and were oriented with the long axis parallel to the direction of blood flow. Deviation in both orientation and morphology were found in control birds in zones of high probability for disease. Endothelial cells in the high predilection zones were less elongate in shape, having an axial ratio of 0.69 +/- 0.04, and had poorly defined margins and a paucity of microvilli. These less elongate cells were on the average 50 per cent larger (surface area of 147.9 +/- 13.3 versus 93.4 +/- 5.5 sq. microns for the typical cell) than the normal endothelial cell. Upon cholesterol challenge, the percentage of elongate cells decreased in the high propensity zones within the first few weeks, and following 8 weeks of cholesterol challenge the less elongate cells were associated with nascent atherosclerotic lesions. In addition to these large irregularly shaped endothelial cells, the early lesions characteristically were encircled by small cells having prominant nuclei and a large number of microvilli clustered over the nuclear area. Continuation of the cholesterol diet beyond 36 weeks resulted in progressive lesion enlargement and the selective binding of blood cells to the lesion periphery. This margination of blood cells was maximal at 36 weeks when the process was evident in 60 per cent of the cholesterol-fed animals. With further prolongation of cholesterol challenge, adherent cells were found in only 25 per cent of the birds. The surface events observed by scanning electron microscopy were correlated with ultrastructural changes in the endothelial glycocalyx. Cholesterol challenge resulted in a significant reduction in both the amount of ruthenium red stain and the number of cationized ferritin particles which were bound to luminal surfaces. In control diet animals, the glycocalyx thickness was in the range of 700 to 1000 A, with the thinnest areas being those in zones of high disease predilection and numerous nonelongate endothelial cells. When analyzed on an individual cell basis, the villus portions of the endothelial surface (glycocalyx thickness, 436 A) averaged 64 per cent thinner than the nonvillus portions of the cell. Upon cholesterol challenge, the glycocalyx was reduced in all arterial zones to 450 A, which approximated the thickness found for microvilli. Our results clearly document changes in endothelial morphology during the early stages of coronary atherosclerosis. These morphologic features are discussed with respect to the role the altered cells may play in disease progression.

Animals↗

Vascular endothelial morphology as an indicator of the pattern of blood flow.

A quantitative study of the en face size and shape of endothelial cells from aortic intercostal ostia has been carried out in rabbits. Photomicrographs were taken from vascular casts of the rabbit aorta and the endothelial cell outlines were analyzed quantitatively using a digitizer and digital computer. The morphology of the endothelial cells was described using 8 calculated parameters (area, perimeter, length, width, angle of orientation, width: length ratio, axis-intersection ratio and shape index). Marked changes in cell morphology were found in the regions proximal and distal to ostia as well as around flow dividers. Cells on the aorta are aligned with the flow direction, and the endothelial cells within the ostia have an angle of orientation of approximately 45 deg to the axis of the vessel. The results obtained to date suggest that endothelial cell morphology and orientation around a branch vessel may be a natural marker or indicator of the detailed features of blood flow.

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Social environment as a factor in diet-induced atherosclerosis.

Rabbits on a 2 percent cholesterol diet were individually petted, held, talked to, and played with on a regular basis. Measurements of aortic affinity for a Sudan stain, serum cholesterol levels, heart rate, and blood pressure were made at the end of the experimental period. Compared to control groups, which were given the same diet and normal laboratory animal care, the experimental groups showed more than a 60 percent reduction in the percentage of aortic surface area exhibiting sudanophilic lesions, even though serum cholesterol levels, heart rate, and blood pressure were comparable.

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Localization of atherosclerotic lesions in the human basilar artery.

The topography of atherosclerotic lesions in the human basilar arteries has been studied quantitatively by digitizing images of the excised vessels and producing contour probability maps. Fifteen basilar arteries were obtained at autopsy (age--61 +/- 2; males--6, females--9; black--6, white--9), fixed in formalin, opened along the ventral aspect and stained grossly with Sudan IV to delineate fat-containing lesions. Photographs of the flattened arteries were analyzed and the presence or absence of sudanophilic lesions was determined at approximately 1000 identical sites on all vessels. The probability of finding a lesion at each site was determined and a contour probability map was constructed. Fifty-two percent of the area of the mean contour map was involved with lesions. The extent of the sudanophilic lesions decreased as one proceeded distally from the origin of the basilar artery at the confluence of the vertebral branches (i.e. proximal 1/3--56%; middle 1/3--49%; distal 1/3--43%; P less than 0.04). Significantly more sudanophilic material was observed on the ventral (outer curvature) as opposed to the dorsal (inner curvature) surfaces (55%, 43% respectively; P less than 0.03). These data suggest that hemodynamic forces associated with confluent flow and curvature may be important in the localization of sudanophilic lesions in the proximal and ventral aspects of the human basilar artery.

Adolescent↗

Quantitative study of the localization of sudanophilic coeliac lesions in the White Carneau pigeon.

Polar coordinate mapping was used to determine the rate of progression of spontaneous sudanophilic coeliac lesions on the aortic wall in White Carneau pigeons. Three age groups of 5 pigeons were studied (approximately 1, 4 approximately 4 and approximately 6.5 years). Serum cholesterol was found to decrease with age (r = 0.69, P less than 0.01). Lesion area was found to increase with both age (r = 0.86, P less than 0.01) and the age--serum cholesterol product (r = 0.92, P less than 0.01). Lesions developed initially in the proximal sector (270 degrees leads to 90 degrees) with two relative maxima (approximately 20 degrees and approximately 320 degrees). Lesions then grow proximally and radially. The immediately proximal inflow region (340 degrees leads to 360 degrees) was spared in all 3 age groups. Little sudanophilic material was observed on the distal flow divider (90 degrees leads to 270 degrees) even in the oldest birds. The mode of spontaneous coeliac sudanophilic lesion development in the White Carneau pigeon is in sharp contrast to that observed both in spontaneous lesions in human infants and in experimental lesions in the hypercholesterolemic rabbit where lesion development is in the distal sector (90 degrees leads to 270 degrees).

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Quantitative study of the rabbit aortic endothelium using vascular casts.

A quantitative study of the en face size and shape of rabbit endothelial cells from the ventral mid-thoracic and ventral infrarenal abdominal aorta has been carried out in 6 rabbits. Photomicrographs were taken from vascular casts of the rabbit aorta and the endothelial cell outlines were analyzed quantitatively using a digitizer and digital computer. The morphology of the endothelial cells was described using 8 calculated parameters (area, perimeter, length, width, angle of orientation, width:length ratio, axis intersection ratio and shape index). The endothelial cells in both locations had the same surface area (P greater than 0.30); however, the cells in the abdominal aorta were longer (P less than 0.01) and narrower (P less than 0.01) than those in the thoracic aorta. This fact is reflected by the smaller value for the shape index and width : length ratio in the abdominal aorta (P less than 0.01). Cells in both the thoracic and abdominal aorta were aligned with the flow direction.

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Alterations in gastrointestinal contents induced by elemental diets.

The effects of elemental diets on selected aspects of the rat colon were studied. Forty young male Sprague-Dawley rats were divided into 4 diet groups of 10 rats each: Purina Rat Chow (control); Flexical; Precision L-R; and Vivonex. All diets were fed ad lib to rats housed in pairs in wire-bottom cages. Two weeks after weight stabilization had been achieved all rats were killed and colon contents were collected for culture and short-chain fatty acid analysis on the Perkins-Elsoner 3920 gas chromatograph. Colon fecal butyric/acetic acid ratios of the rats in the 4 groups were: Rat Chow, 2.56; Flexical, 0.28; Precision L-R, 0.16; and Vivonex, 0.26. Bacterial cultures showed increased coliform and enterococcal species in the rats consuming elemental diets.

Acetates↗

Vascular casting. A new method for the study of the arterial endothelium.

Vascular casts of the rat aorta were made using modified Batson's No. 17 anatomical corrosion compound. The outline of the silver-stained endothelial cell boundaries were clearly visible on the cast when examined using both scanning electron and light microscopy. The physical properties of the injectate were determined. The exothermic nature of the polymerization of the injectate did not grossly damage the endothelial cells. A method was developed for recovery, without damage, of the arterial tissue surrounding the cast. The technique of vascular casting appears to be a powerful tool for the study of the arterial endothelium which avoids shrinkage artifacts and maintains 3-dimensional geometry.

Animals↗

Late failure of porcine valve heterografts in children.

Heterograft porcine valves have gained wide acceptance in replacement of diseased cardiac valves, and their clinical performance in adults has been very satisfactory over follow-up periods of up to 8 years. Valve replacement in children is relatively infrequent and experience with porcine xenografts is necessarily small. Our combined experience at three university hospitals has been with 25 children, 17 months to 16 years of age, who have been followed for 10 to 54 months (mean follow-up 33 months). Porcine valves were used to replace the aortic valve in nine, the mitral valve in seven, both valves in two, the tricuspid valve in two, and the pulmonary valve in five patients. Severe bioprosthetic valve dysfunction has occurred in five (20%) of these patients so far and necessitated replacement because of severe stenosis in mitral (two) or aortic (three) valve prostheses at 18 to 45 months after implantation; one postoperative death occurred among the five reoperations. Pathological examination showed extensive fragmentation of collagen with focal heavy calcification and degeneration. In addition we have encountered deterioration and calcification of two porcine valves in 23 valved conduits followed for 12 to 70 months (mean 43 months), requiring removal and replacement of the valves 65 and 67 months after implantation. This experience indicates a disquietingly high incidence of relatively early failure of porcine xenograft valves in children. This is significantly higher than the failure rate observed in adult patients. The failure rate is not consistently related to the small size of an implanted valve which becomes relatively narrow with the growth of the patient, leading to excessive turbulence and trauma to the prosthesis. Other factors, including increased turnover of calcium and accelerated rejection in growing children, may contribute to these failures and should be examined in order to improve long-term results. A satisfactory performance would make heterografts the ideal valvular prosthesis in children, since anticoagulation is avoided.

Adolescent↗

A quantitative study of the development of sudanophilic lesions in the aorta of rabbits fed a low-cholesterol diet for up to six months.

Eighteen New Zealand white rabbits were placed on a diet containing 0.25% cholesterol and 6% corn oil for periods of up to 6 months. The animals were divided into 4 gours and sacrificed after 2, 3, 4, and 6 months. The aortae were removed, stained with Sudan III, and analyzed with the polar coordinate technique. While the periorificial lesions developed more slowly on this diet than on the diet with 2% cholesterol and 6% corn oil we had used previously, there was no differences in either the location or the shape of the lesions. In the descending thoracic aorta, lesions developed initially distal to orifices; however, significant lateral and proximal components were observed as atherogenesis progressed. The coronary lesions completely surrounded the ostia in all stages of development. The total area of the lesions was more related to time (r = 0.74, P less than 0.01), than to serum cholesterol (r - 0.51, P less than 0.05) or to cholesterol-time product (r = 0.69, P less than 0.01).

Animals↗

An aortic--left ventricular pulse duplicator used in testing prosthetic aortic heart valves.

A pulse duplicator for the testing of prosthetic valves has been produced which accurately simulates physiological pressure and flow wave forms in the left ventricle and ascending aorta. The model consists of two components--the ventricle and the artificial systemic circulation. The ventricle is a collapsible bag which is externally pressurized and produces an accurate ventricular pressure-time history. The artificial circulation is externally pressurized and produces an accurate ventricular pressure-time history. The artificial circulation is a development of the lumped parameter model of Westerhof13 in which the physiological input impedance is modeled by a characteristic resistance, a capacitance, and a peripheral resistance connected in series. The model allows for a wide range of heart rates, systolic-diastolic ratios, mean pressures, flow rates, and fluid viscosity. A Fourier analysis of the model pressure and flow waves shows excellent quantitative agreement with physiological data, as does the vascular input impedance. The Oxford aortic heart valve exhibited a regurgitation of 1.9 per cent and no measureable pressure drop or power loss.

Aorta↗

The effect of the duration of cholesterol feeding on the development of sudanophilic lesions in the rabbit aorta.

Polar coordinate mapping was used to determine the rate of growth of individual sudanophilic lesions on the aortic wall around several major branches of the aortae of cholesterol fed rabbits. Four groups, with 6 8-month old male albino white rabbits in each, were used in the study. One group served as a control and the remaining 3 were fed a diet of 2% cholesterol and 6% heated corn oil mixed with ground rabbit pellets for 4, 8, and 10 weeks each. Animals were sacrificed, the aortae removed, stained with Sudan III, pinned at in vivo dimensions, and mapped by the polar coordinate method. No sudanophilic lesions were observed in the control animals. In the experimental groups, the early lesions, except the coronaries, were almost entirely distal to the orifices, and maintained roughly the same contour while spreading around the orifice. The coronary lesions completely encircled the orifices as described previously. As lesions progressed, they became elevated and often granular, so that the lesions themselves may have affected flow profiles around the orifices. Lesions around adjacent orifices were fused in 48% of the cases after 10 weeks on the diet, as opposed to 2% after 4 weeks on the diet. More prolonged experiments were not possible with this diet as the animals developed jaundice and diarrhea. Hemodynamically, these results suggest that early sudanophilic lesions in cholesterol-fed rabbits develop on the aortic wall in areas of high shear stress.

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