Application of flow measurements by magnetic resonance velocity mapping to congenital heart disease.
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Biomedical subjects
Publications and source records attributed to S Rees.
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In this study we have examined structural and functional aspects of nerve fibre development in experimentally growth retarded fetal sheep following restriction of placental growth by carunclectomy in 5 ewes. Measurement of whole-nerve conduction velocity in the peroneal nerve showed, for the most rapidly conducting fibres, a significant slowing from the normal value of 50.3 +/- 1.8 m/s to 33.8 +/- 3.3 m/s (P less than 0.01). Histological examination of nerve sections revealed a deficit of large myelinated fibres in growth retarded fetuses which is consistent with the conduction velocity measurements.
Magnetic resonance is a new method of imaging which is completely non-invasive and is being increasingly applied to the study of the heart. Spin echo images using cardiac gated acquisition have the advantage that moving blood has no signal giving excellent contrast compared to the surrounding soft tissues. Images can be acquired in orthogonal or oblique planes, and up to 16 can be produced within 3 to 4 minutes depending on heart rate. Useful information can be obtained in a variety of conditions including lesions of the myocardium, aorta and pericardium, the detection of tumours and thrombus and the complete display of anatomy in patients with congenital heart disease, both pre- and postoperatively. Although its place in the investigation of heart disease is still being established, already it can be regarded as an imaging technique complementary to echocardiography, which has partially replaced diagnostic invasive angiography and may eventually replace it completely.
The functional maturity of the gastrointestinal system is essential for the survival of the neonate. The effects of reducing placental size and the ensuing fetal growth retardation on the development of the small intestine (SI) of the sheep fetus were investigated. At 140 days of gestation (term is 147 days), fetal body weight, gastrointestinal weight (from the abomasum to the rectum, i.e., the gut), SI weight, and SI length in the growth-retarded fetuses (n = 6) were significantly reduced (p less than 0.05) when compared with age- and breed-matched control fetuses. The SI weight was disproportionately reduced as a fraction of the gut weight or SI length (p less than 0.01). The proximal SI showed marked reductions in the thickness of the wall, muscularis externa, mucosa, villus height, and crypt depth (p less than 0.003). Densities of villi and crypts were also reduced (p less than 0.02). The crypt-to-villus ratio was maintained. Glycogen was accumulated basally in the villus epithelial cells, and their nuclei were located apically. These characteristics are comparable to those of much younger fetuses. In the distal SI, interanimal variation was large; however, the mean thickness of the wall, the muscularis externa, the mucosa, and the villus height were all reduced (p less than 0.05). In this region, the density of villi and crypts, the pattern of glycogen accumulation, and the position of the nuclei did not markedly differ between growth-retarded and control fetuses. Villus cell density was increased (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Thirty-six patients were studied with magnetic resonance (MR) imaging 2-29 years after repair of coarctation of the aorta, and the findings were compared with clinical data and results of echocardiography, catheterization, angiography, and surgery. A satisfactory echocardiographic examination of the isthmus was achieved in 28 patients. Comparison with data from gradient measurements at catheterization and Doppler ultrasound shows that the reduction of lumen diameter correlates well with the gradient and that restenosis at the site of the repair can be suspected when the percentage of stenosis at the isthmus is greater than 50%. MR imaging showed a Dacron patch aneurysm in three patients. Cine MR imaging showed systolic signal loss in the ascending aorta that was presumed to be due, among other factors, to turbulent flow generated from a bicuspid valve. Similar signal loss was seen in the descending aorta distal to the site of the coarctation repair, but this was not related to the presence or absence of a gradient. Aortic compliance measured from transverse MR systolic and diastolic images was abnormally low, suggesting it may be a factor causing systolic hypertension after coarctation repair. MR imaging is a reliable and accurate noninvasive method likely to supersede other methods of assessing the aorta and isthmus following coarctation repair.
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Adult male rats were treated for 24 or 48 h with harmaline which selectively activates neurones in the inferior olivary nucleus which give rise to climbing fibres projecting to the cerebellar vermis. Electrophysiological studies have shown that harmaline-induced climbing fibre activity completely blocks the responses of the Purkinje cell to parallel fibre input. Morphometric analysis of the ultrastructure of climbing and parallel fibre synapses revealed no significant differences in morphology between vermis (experimental) and hemisphere (control). These findings indicate that the decreased responsiveness of Purkinje cells to parallel fibre inputs induced by increased climbing fibre activity over 24 or 48 h is not accompanied by any observable structural changes in the cerebellar cortex.
Harmaline has been used to produce long-term activation of the climbing fibre projection to the cerebellar cortex and the effects on parallel fibre transmission to Purkinje cells were studied electrophysiologically. The climbing fibre activation produced a profound depression in parallel fibre transmission which could be sustained for a period of more than two days. It was found that ongoing climbing fibre activity was necessary to maintain the depression at the synaptic junctions because transmission returned to normal within a matter of minutes if the climbing fibre input to the Purkinje cell was removed. This finding suggests that climbing fibre impulses do not induce permanent modifications in the efficacy of parallel fibre synapses.
The Mustard operation in infancy and childhood has successfully palliated many patients with transposition of the great arteries who have now survived to adulthood. Right ventricular dysfunction and tricuspid regurgitation are important determinants of late morbidity and mortality. The value of noninvasive magnetic resonance imaging (MRI) in the assessment of cardiac function and anatomy 9 to 20 years after this procedure has been investigated, and compared with findings on echocardiography, radionuclide ventriculography and angiography in 17 adult patients. Ejection fractions measured by MRI were higher compared with radionuclide ventriculography. The correlation for the left ventricle was closer (r = 0.75) than for the right ventricle (r = 0.49). Tricuspid regurgitation was assessed by Doppler echocardiography and by MRI using the right/left ventricular stroke volume ratio. The mean stroke volume ratio in those with Doppler evidence of tricuspid regurgitation was 1.6:1 compared to 1.1:1 in those without, and this difference reached significance (p less than 0.01). The anatomy of the great arteries was clearly visible in all patients. Five patients had a residual ventricular septal defect which, with the exception of 1 small defect, was easily visualized. The intraatrial baffle was best seen in transverse slices, and the systemic venous connection showed as a relatively narrow channel lying in the posterior part of the cavity. In general, baffle anatomy was easier to assess on 2-dimensional echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS)
In an experimental model of growth retardation which involves the reduction of placental mass in sheep, we have investigated the effects of intrauterine deprivation on synaptogenesis, synaptic ultrastructure and mitochondrial formation in the cerebral and cerebellar cortices of fetal sheep (140 days gestation). In the growth-retarded fetus, the numerical density of synapses in layer I of the visual cortex was reduced by 17% (P less than 0.05) compared with controls but there was no detectable difference between the two groups in the density of parallel fibre-Purkinje cell synapses in the molecular layer of the cerebellum. The length and curvature of the postsynaptic density at synapses in both regions were not affected in growth retardation but the synaptic cleft was 13% wider in the cerebellum (P less than 0.05) in growth retardation compared with controls. The number of mitochondrial profiles per unit area of neuropil in the visual cortex was increased by 20% (P less than 0.01) in growth retardation and the electron density of the inner matrix increased but the average profile area was not affected. These findings show that intrauterine growth retardation affects some aspects of synaptic development in the cerebellum and the visual cortex. The increase in the number of mitochondrial profiles in the visual cortex of growth-retarded fetuses might be an attempt by the cortical neurons to compensate for the reduced efficiency of aerobic metabolism in individual mitochondria.
The development of the fetal sheep cerebellum at 80, 100, 120 and 140 days gestation (term = 146 days) and 3 months postnatally was studied using Nissl stained sections and rapid Golgi preparations. The most rapid expansion of the Purkinje cell dendritic tree occurred between 100 and 120 days of gestation (5-6 fold increase in area). By 140 days it had acquired its adult form after which time growth continued mainly in the vertical direction. The effects of intrauterine growth retardation on the growth of granule and Purkinje cell dendrites in the cerebellar cortex of fetal sheep (140 days) were investigated in Golgi preparations. Compared with control cerebella the length (but not the number) of granule cell dendrites was reduced by 14% (P less than 0.01); the area of the Purkinje cell dendritic field was reduced by 20% (P less than 0.01); the branching density was reduced by 8% (P less than 0.01); the total branch length was reduced by 27% (P less than 0.002); the density of dendritic spines per row was not affected. These factors resulted in a decrease of 26% (P less than 0.002) in the total number of dendritic spines per row per Purkinje cell. These findings show that the growth of granule cell dendrites and the Purkinje cell dendritic tree have been significantly affected by chronic intrauterine deprivation. Such structural abnormalities could affect the pattern of neuronal connectivity and could be associated with functional deficits.
A quantitative morphometric study of brain development has been made in growth-retarded fetal sheep. Intrauterine growth retardation was induced by removal of endometrial caruncles in the ewe prior to conception thereby reducing the size of the placenta in a subsequent pregnancy. Total brain and cerebellar weights were reduced by 21% (P less than 0.002) and the cerebrum by 20% (P less than 0.05) in the growth-retarded fetuses at 139 +/- 1 day (term = 146 days) compared with age matched control fetuses. Measurements of mean neuronal diameters were made on Purkinje cells, cerebellar granule cells, cortical cells in the motor and visual areas and hippocampal pyramidal cells; none were significantly different from control values. In growth-retarded fetuses compared with controls, there was a significant reduction in the thickness of the motor and visual cortices and the numerical density of neurones was significantly higher in these areas. In the cerebellar vermis, the number of Purkinje cells per unit surface area of Purkinje cell layer was higher, the numerical density of granule cells was significantly higher concomitant with a reduction in the area of the inner granular layer, and the area of the molecular layer was also reduced. In the hippocampal formation, the numerical density of pyramidal neurones was higher and the width of the stratum moleculare (dentate gyrus) was reduced. Migration of pyramidal neurones from the germinal layer to stratum pyramidale was not affected. These findings indicate that intrauterine growth retardation does not markedly affect cell size or neuronal migration (in the hippocampus) but does cause a significant reduction in the growth of the neuropil in the cerebellum, motor and visual cortices and the hippocampal formation.
We have examined the reversibility of the biochemical and pathological changes induced in the spleen, kidney and lung of the suramin-treated rat which we have previously proposed as a useful model of the human condition, mucopolysaccharidosis (MPS). Rats were injected with a single intravenous dose of suramin (250 mg/kg) and allowed to survive for periods of up to 6 months. The organs were examined for suramin content, pathological changes, biochemical storage of glycosaminoglycans (GAGs) and for the blockage of the relevant hydrolytic enzymes. The extent and rate of suramin accumulation and the retention of the drug varied considerably between organs with the greatest concentration of suramin (4,000 micrograms/g) occurring in the kidney 2 weeks after injection. Suramin persisted at gradually decreasing levels in all organs for the duration of the experiment, remaining at the highest level (1,150 micrograms/g) in the kidney. The concentration of GAGs peaked 10-18 days after administration of the drug, in all organs. Within 6 months the level had returned to normal in the liver, spleen and lung, but remained elevated in the kidney. The activities of beta-glucuronidase and acid phosphatase were decreased in all organs at diminishing levels throughout the experiment. There was a significant increase in the activity of arylsulphatase B, except in the kidney, where the predominant effect was a reduction of activity. Recovery from the morphological changes was evident in all organs except the lung within 6 months of suramin administration. The reversibility of the biochemical and pathological changes in the various tissues is discussed and compared with the earlier results described for the liver (Rees et al. 1986) and the implications of using suramin for the treatment of human trypanosomiasis, onchocerciasis and AIDS are considered.
Rats treated with the trypanocidal drug suramin, a potent inhibitor of several lysosomal enzymes, develop a storage disorder which mimics the features of mucopolysaccharidosis (Constantopoulos et al. 1983). In this paper we have examined the reversibility of the biochemical and pathological changes induced in the liver of the suramin-treated rat. Rats were injected with a single intravenous dose of suramin (250 mg/kg) and allowed to survive for periods of up to 6 months. The liver was examined for suramin content, pathological changes, biochemical storage of glycosaminoglycans (GAGs) and for the blockade of the relevant hydrolytic enzymes. GAG storage in the liver peaked at approximately 14 days after administration of suramin when there was a five-fold increase in the GAG content. Thereafter GAGs decreased in parallel with the fall of suramin concentrations so that within 6 months the content had returned to control levels. The activity of most of the enzymes tested had also returned to control levels within 6 months. The pathological changes which are evident in the liver 1-2 weeks after administration of the drug had diminished considerably within 6 months. These results indicate that significant reversibility of both the biochemical and pathological changes induced by suramin occurs and they support the suitability of the suramin treated rat as a model to assess the value of therapeutic treatments of mucopolysaccharidosis.
Young adult male rats were anaesthetised with urethane and exposed to either 24 h of silence or 24 h of repetitive 77 dB tones in a sound-proofed anechoic chamber. The influence of these two conditions on the ultrastructure of the synaptic appositions made by auditory afferents in the anterior ventral cochlear nucleus (end bulbs of Held) was compared. Both the cross-sectional area and the mean thickness of the postsynaptic density (PSD) in the rats exposed to tones were significantly reduced when compared with rats maintained in silence. Similarly, the degree of curvature of the apposition was significantly reduced. The results of these experiments provide further evidence that the postsynaptic density material is a plastic structure significantly influenced by the amount of activity in the presynaptic element.
Various anatomical and functional features of hypertrophic cardiomyopathy are analyzed in view of the data provided by two-dimensional echocardiography. Measurement of septal thickness is crucial, and is best done by a combination of M-Mode and 2-D echo. Two types of systolic anterior movement of the mitral valve (SAM) are observed and are related to the degree of subvalvular gradient. The specificity of these patterns of SAM is analyzed. The functional anatomy of the mitral valve in relation to the presence and degree of mitral regurgitation shows that although the presence and type of SAM are important, there are other causes of mitral regurgitation in hypertrophic cardiomyopathy unrelated to SAM. We emphasize the fact the 2-D echo cannot "diagnose" hypertrophic cardiomyopathy except when cardiac hypertrophy plus SAM involving the body of the mitral valve is seen; in the remaining cases, 2-D echo confirms/suggests the clinical diagnosis.
Tetramethyl lead in an oily vehicle was administered to rats at weekly intervals during gestation and early postnatal life, raising the total lead concentration in the brain to about 1 microgram/g. Birth weight was unaffected, but postnatal body growth was stimulated more than brain growth, resulting in a higher body:brain weight ratio. Histological measures of brain myelination, dendritic growth, granule cell production, and retinal receptor development showed no deficit. We conclude that the body:brain weight ratio is the most sensitive of the parameters measured for detecting the effect on development of exposure to a low concentration of tetramethyl lead. The latter is neurotoxic at higher concentrations, and the stimulating effect on body growth of a low concentration is an example of "hormesis," a phenomenon which has been noted with other toxins.
To assess the mechanism of mitral regurgitation in ventricular dilatation, 24 patients with dilated cardiomyopathy (13 with and 11 without mitral regurgitation) and 10 normal individuals were studied by two-dimensional echocardiography. Left ventricular dimensions and mitral ring diameters in systole and diastole were measured in the long-axis section, and systolic interpapillary muscle distance in the short-axis section. The results showed: Mitral ring diameter is increased in most patients with dilated cardiomyopathy. Neither increased ring diameter, reduced ring contraction, nor decreased interpapillary muscle distance determine the presence of mitral regurgitation. The only difference between those patients with and without mitral regurgitation was the degree of left ventricular dilatation (p less than 0.05).