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Biomedical subjects

J B Gavin

Publications and source records attributed to J B Gavin.

At least 91 records · Page 5Linked to original sources

The effect of ischaemic injury on the fine structure of canine atrial myocardium.

An experimental model for producing a uniformly and maximally ischaemic segment of atrial myocardium has been devised and used in 23 dogs to investigate the effects of severe ischaemia of up to 6 h duration on the fine structure of atrial myocardial cells. Throughout the first 30 min of ischaemia the cells maintained a fine structure comparable with that of control tissue. In the subsequent 2 h they developed morphological alteration at differing rates, despite their uniform deprivation of blood supply. Even at 90 min the ischaemic tissue showed discontinuous change, with many areas differing little from control, and it was only after 3 h that all cells showed well developed and similar alterations. These included glycogen depletion, marked clumping and margination of nuclear chromatin, and the mitochondrial degeneration typically seen in ischaemically injured ventricle. The changes were very severe after 4 and 6 h of ischaemia, when disruption of cellular membrane systems was also evident. At these times the tissue closely resembled ventricular myocardium made ischaemic for similar intervals, except for the persistence of well-preserved 'specific atrial granules'. Atrial muscle cells therefore develop the fine structural changes associated with ischaemia more slowly than ventricular muscle cells and have a more variable response to the initiation of ischaemic injury.

Animals↗

Histological evaluation of transannular autografts of pericardium placed in the right ventricular outflow tract of dogs.

Autografts of pericardium were inserted as patches into incisions across the annulus of the pulmonary valve in 12 adult dogs and 12 pups. In order to accommodate for possible effects of pulmonary hypertension which pertains in many clinical circumstances, constricting teflon bands were placed around the main pulmonary artery in half of the animals. Samples of tissue from the patches were examined by light and scanning electron microscopy from 6 to 14 mth later. The eventual thickness of the insertion site of the patches was found to become 2-14 times greater than the initial autograft due to apposition of layers of collagenous tissue on the endocardial and epicardial surfaces of the autografts. Three pups showed small, angiographically undetected central aneurysms in their patches but the tissue in their base was 5 or more times thicker than control pericardium. Cartilaginous metaplasia was evident at the margins of 57% of the patches, necrotic remnants of parts of the autograft were evident in 38% and foci of dystrophic calcification in 24% of them. Whereas smooth muscle cells sometimes extended into the repair tissue (19%), elastic fibres were not present in the patches. Thus pericardial autografts in the right ventricular outflow tract seem unlikely to develop clinically significant abnormalities.

Animals↗

Study of autologous pericardial patch-grafts in the right ventricular outflow tracts in growing and adult dogs.

The effects of growth and hemodynamic load on autologous pericardial grafts in the right ventricular outflow tract were studied in adult dogs (nine) and pups (12); ten of the 21 also had bands around the main pulmonary artery. All grafts functioned without radiographic evidence of abnormality for up to 14 months. At necropsy small central aneurysms were found in patches in three pups. Fibrous organization extending from the margins and adventitial aspect considerably thickened each patch. Cartilaginous metaplasia was evident in the ingrowing host tissue in many animals (57%). Small foci of necrotic pericardium and dystrophic calcification were evident in half of the grafts in pups but not in those in adult dogs. Patches in animals with normal pressures showed a reduction (p < 0.05) in the axis which lay in the direction of blood flow but no increase in the transverse axis. Only those patches subjected to elevated pressures in adult dogs showed an increase in patch size. These findings indicate that autologous pericardium is a suitable material for use in the surgical enlargement of the right ventricular outflow tract.

Age Factors↗

The pathogenesis of renal allograft rejection: an experimental investigation in sheep.

Fifteen renal allografts and 5 autografts were placed into the necks of bilaterally nephrectomized sheep. Ten of the sheep with allografts were also treated with azathioprine (5 mg/kg) and prednisone(1.5 mg/kg) daily. There were no changes in the distribution of immunoglobulins or of beta lC globulin which could be associated with the rapid decline in glomerular filtration rate observed in untreated allografts after 2 d and in immunosuppressed allografts after 6 d. However, this functional decline was associated with the development of interstitial oedema, lymphocyte infiltration, swelling of tubular and glomerular cells, and necrosis of the outer two-thirds of the renal cortex. Thus the onset of progressive cortical ischaemia appears to be an important event leading to renal allograft failure in sheep.

Animals↗

The value of smears in the diagnosis of gonorrhoea in the female.

Of 332 consecutive patients attending the female venereal disease clinic, Auckland Hospital, 74 patients had gonorrhoea confirmed by culture, but gram stained slides were positive in only 36 of these patients. Five other patients had positive gram stained smears but were culture negative. The study showed the value of gram stained smear in the rapid diagnosis of gonorrhoea in the female.

Bacteriological Techniques↗

The effect of ischaemia on the function and fine structure of the microvasculature of myocardium.

Seventeen mongrel dogs were subjected to ligation of the circumflex branch of the left coronary artery. At intervals from 10 to 300 minutes after ligation, 10 ml of a sodium fluorescein and colloidal thorium hydroxide solution were injected via an intra-arterial catheter placed distal to the ligature. Up to 20 minutes after ligation this tracer solution evenly perfused the left ventricular wall including the posterior papillary muscle (PPM). During 25 to 50 minutes there was a progressive patchy loss of perfusion into the PPM although the sub-epicardial region was evenly perfused. After 60 or more minutes of ischaemia it was not possible to inject this tracer solution into the subendocardial region. Electron microscopic examination indicated that this loss of vascular competence was possibly due to vasospasm of some vessels in the marginal zone between the perfused and non-perfused areas and was unlikely to be due to intravascular thrombosis, endothelial cell swelling, or to compression of vessels due to cell or tissue oedema.

Animals↗

An association between the onset of rigor and loss of vascular competence in early myocardial infarcts.

Experimental myocardial ischaemia was induced in 12 anaesthetized mongrel dogs by ligation of the circumflex branch of the left coronary artery. Twenty minutes after ligation 1% sodium fluorescein injected into the artery distal to the ligature evenly perfused the left ventricular wall in the vicinity of the posterior papillary muscle (PPM) but, when injected 90 minutes after ligation, the PPM and adjacent subendocardial myocardium was not perfused by this tracer. Measurements with a linear variable transducer and standard load demonstrated that after 20 minutes ischaemia, the PPM had a similar percentage compressibility to the corresponding unaffected anterior papillary muscle but, after 90 minutes, the compressibility of the PPM was significantly reduced. Scanning electron microscopy of the marginal zone between the perfused and unperfused parts of the myocardium revealed many collapsed vessels which contained small groups of tightly packed erythrocytes indicating that the loss of vascular competence was probably due to the plugging of small vessels by erythrocytes.

Animals↗

The effect of rigor mortis on the passage of erythrocytes and fluid through the myocardium of isolated dog hearts.

The effect of normal and artificially induced rigor mortis on the vascular passage of erythrocytes and fluid through isolated dog hearts was studied. Increased rigidity of 6-mm thick transmural sections through the centre of the posterior papillary muscle was used as an indication of rigor. The perfusibility of the myocardium was tested by injecting 10 ml of 1% sodium fluorescein in Hanks solution into the circumflex branch of the left coronary artery. In prerigor hearts (20 minute incubation) fluorescein perfused the myocardium evenly whether or not it was preceded by an injection of 10 ml of heparinized dog blood. Rigor mortis developed in all hearts after 90 minutes incubation or within 20 minutes of perfusing the heart with 50 ml of 5 mM iodoacetate in Hanks solution. Fluorescein injected into hearts in rigor did not enter the posterior papillary muscle and adjacent subendocardium whether or not it was preceded by heparinized blood. Thus the vascular occlusion caused by rigor in the dog heart appears to be so effective that it prevents flow into the subendocardium of small soluble ions such as fluorescein.

Animals↗

A scanning electron microscopic study of wear in the plastic components of prosthetic knee and hip joints.

The polyethylene surfaces of four metal on plastic prosthetic knee joints were compared with those of four hip joint replacements, by the use of scanning electron microscopy. The acetabular components of the hip joints showed concentric machining marks, but were generally smooth, and in some areas plastic deformation of the articular surface was evident after 24 months' use. In contrast, the tibial components of knee joints removed after 12 to 22 months showed deep scoring and pitting near the centre of their articular surfaces. This appeared to be due to abrasion by a third material, possibly fragments of cement, which sometimes became embedded in the joint surface. These results indicate that wear in prosthetic knee joints may be much more rapid than in hip joint replacements made from similar materials.

Hip Joint↗

The distribution of dextran macromolecules in the glomeruli of normal and nephrotoxic rats.

The incorporation of intravenously injected dextran molecules (molecular weight 500,000 & 2,000,000) by the glomeruli of laboratory rats was studied by electron microscopy. In normal rats some dextran molecules were observed 12 minutes after injection in vesicles and invaginations of both endothelial and mesangial cells. Rats with nephrotoxic serum nephritis showed extensive separation of endothelial cells from the glomerular basement membrane. These subendothelial spaces contained irregular granular material, cytoplasmic extensions of mesangial cells and, in animals injected with dextran, dense accumulations of dextran molecules. There was no apparent difference in distribution of the two test samples of dextran. These findings demonstrated the involvement of both endothelial and mesangial cells in the glomerular localization of circulating material and indicated that immunologically inactive macromolecules can be incorporated into subendothelial deposits following immunological injury to the glomerulus.

Animals↗

Fine structural changes in dog myocardium exposed to lowered pH in vivo.

A surgical preparation that allows chemical alteration of the blood supplied to specific area of the intact heart was used to investigate the effects of lowered tissue pH on the fine structure of myocardial cells. Controlled infusion of isotonic saline acidified with HCl to a pH value between 1.0 and 2.0 produced a lowering of blood pH to values of less than 7.0. This drop in the pH of the perfusing blood resulted in a corresponding decrease in pH of the relevant area of myocardium. When this decrease occurred without a concomitant increase in tissue lactate level, the myocardial cells of the acid-perfused area showed focal glycogen depletion, moderate relaxation of myofibrils and clumping of nuclear chromatin, and mild mitochondrial change, which did not include marked swelling although intramitochondrial electron-dense inclusions were often detectable. When the fall in pH was accompanied by a large increase in lactate concentration, however, the cells showed more severe glycogen depletion and clumping of nuclear chromatin, and mitochondrial change, which did include marked swelling, together with the presence of well developed inclusions.

Animals↗

The surface morphology and the cell cycle of mastocytoma target cells: no apparent effect on cell-mediated killing.

Mastocytoma cells (P-185) have been separated by velocity sedimentation into fractions which were highly enriched for cells at discrete stages of the cell cycle. By scanning electron microscopy it was shown that the surface morphology of the majority of cells in each fraction was characteristic of that fraction. No difference could be detected between isolated fractions and unfractionated cells in their ability to be lysed by cytotoxic lymphocytes.

Animals↗

The electron microscopic localization of nephrotoxic antibodies in isolated glomeruli.

Scanning electron microscopy showed that most glomeruli isolated by sieving from normal and nephrotoxic rats were cleanly decapsulated and undisrupted. An anti-IgG antibody-horesradish peroxidase conjugate was applied to such isolated glomeruli and also to slices of renal cortex which were sebsequently embedded in epoxy resin. Linear staining along the glomerular basement membranes of nephrotoxic rats was evident and subendothelial electron-dense deposits were shown to contain anti-glomerular basement membrane antibody. Whereas the linear reaction was faint and limited to superficial parts of glomeruli in tissue slices, it was intense and present in most regions of all of the isolated glomeruli. Thus, the fine details of the distribution of intraglomerular antibody are more clearly and consistently demonstrated in isolated glomeruli than in kidney slices.

Animals↗

Experimental autoimmune glomerulonephritis in the rat. I. Factors influencing induction.

Albino Holtzman, albino Wistar and hooded HS rats were injected fortnightly for 14 weeks with human glomerular basement membrane (GBM) emulsified in Freund's complete adjuvant. Half of the rats were pretreated with Freund's complete adjuvant and some were unilaterally nephrectomized. Anti-GBM antibody glomerulonephritis, characterized by proteinuria (greater than 100 mg/16 h) and a diffuse linear deposition of host immunoglobulin along the glomerular basement membrane, was first detected in Holtzman rats 4 weeks after treatment with GBM had begun, and had developed in 69% of these rats by 15 weeks. In contrast, none of the similarly treated Wistar or HS rats became proteinuric at any time, although a few showed weak glomerular fluorescence at the end of the experiment. Thus Holtzman rats are susceptible, and HS and Wistar rats are resistant to experimental anti-GBM antibody glomerulonephritis. Pretreatment with Freund's complete adjuvant apparently shortened the induction period of the experimental disease in the Holtzman rats whereas unilateral nephrectomy appeared to decrease their susceptibility to it.

Animals↗