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Biomedical subjects

S Lindal

Publications and source records attributed to S Lindal.

52 records · Page 3Linked to original sources
PubMed1991

Myopathy in Marinesco-Sjögren syndrome: an electrophysiological study.

Electrophysiological studies were performed in 7 patients with Marinesco-Sjögren syndrome in order to search for neuromuscular involvement in this multiorgan disorder. In 6 patients muscle biopsies were also obtained. Light microscopic examinations of the biopsies showed extensive myopathic changes, and in two patients ragged red fibers were found. Electron microscopy showed subsarcolemmal accumulation of abnormal mitochondria in all. Concentric needle EMG revealed unequivocal myopathic changes, more extensive in the anterior tibial than in the biceps brachii muscle. Motor and sensory conduction velocities in the peripheral nerves were normal. There were remarkably high amplitudes of sensory responses. Macro EMG studies in the biceps brachii muscle in four patients showed increased amplitude and area of the macro MUPs. This may be due to abnormal membrane function. Both electrophysiological and morphological findings confirm myopathic features of Marinesco-Sjögren syndrome.

Adolescent↗
PubMed1990

Amelioration of reperfusion injury following hypothermic, ischemic cardioplegia in isolated, infarcted rat hearts.

The left coronary artery was ligated and myocardial infarction developed in 28 rats. Three weeks later, the hearts were excised and mounted in an apparatus for perfusion of non-working isolated hearts (Langendorff). Hypothermic (15 degrees C), ischemic cardioplegia was induced for either 2 or 3 1/2 h followed by reperfusion for 45 min. Half of the hearts were reperfused with an initially gradual rise in temperature and pressure of the perfusion fluid, whereas the other half was reperfused directly with the perfusate at 37 degrees C and 100 cm H2O pressure. The hearts were examined by transmission electron microscopy and randomized for stereological analysis based on point counting on electron micrographs. Cardioplegia of 2 h duration was tolerated better than cardioplegia for 3 1/2 h (interstitial edema; P = 0.03, fraction of altered mitochondria; P = 0.001). Particularly in the hearts undergoing the longest cardioplegia, myocardial injury was less severe following a gentle reperfusion as compared with those exposed to the clinically common abrupt technique (fraction of mitochondria in the myocyte; P = 0.03, fraction of altered mitochondria; P = 0.008). In the interstitium, the luminal area of capillaries was significantly increased and the endothelial swelling less pronounced in the groups undergoing the gentle reperfusion technique, (luminal/endothelial fraction; P = 0.01). The study shows that previously infarcted hearts are susceptible to ischemic damage even after 2 h of regular hypothermic, ischemic cardioplegia and that a gentle reperfusion technique significantly ameliorates reperfusion injury.

Animals↗
PubMed1990

Early mitochondrial changes in chronic progressive ocular myopathy.

Two sisters with chronic progressive external ophthalmoplegia (CPEO) and their in all 7 healthy children were investigated. Both ophthalmoplegic patients had histopathological changes typical of mitochondrial myopathy. The same type of muscular pathology was also found among the healthy children. The most common muscular changes were subsarcolemmal accumulation of pathological mitochondria, including vacuoles, abnormal cristae and sometimes also inclusion bodies. Biochemical studies showed partial complex III deficiency, with low succinate-cytochrome c reductase activity in 1 of the ophthalmoplegic patients. These findings suggest that CPEO is a slowly progressive muscle disease, starting early in life. The widespread occurrence among the children may indicate maternal inheritance.

Adolescent↗
PubMed1990

Ultrastructural changes in rat hearts following cold cardioplegic ischemia of differing duration and differing modes of reperfusion.

Morphologic consequences of prolonged global hypothermic (15 degrees C), cardioplegic ischemia and two reperfusion techniques were studied in Langendorff-perfused rat hearts. A 'gentle' reperfusion technique, with gradual rise in perfusate temperature and pressure to physiologic levels over 30 min, was used for 12 hearts following 2-hour or 3 1/2-hour (6 in each group) ischemia. Abrupt reperfusion, with perfusate at 37 degrees C and 70 mmHg, was performed on 13 hearts (6 ischemic for 2 hours and 7 for 3 1/2 hours). Six nonischemic, perfused hearts served as controls. Randomly selected specimens from the left ventricle after 45-60 min reperfusion were prepared for transmission electron microscopy. Volume fractions of myocardial structural components were calculated from stereologic point-counting on the electron micrographs. Two-way analysis of variance revealed that interstitial edema developed with increasing ischemic time and was not influenced by reperfusion technique. The degree of endothelial damage was independent of ischemic time, but was lessened by 'gentle' reperfusion. Both mitochondrial injury and myocyte edema were less when perfusate temperature and pressure were slowly raised after 3 1/2-hour ischemia.

Animals↗
PubMed1988

Effects of endotoxin on the pancreatic ultrastructure.

Intravenous administration of Escherichia coli endotoxin caused a state of shock with increased serum cationic trypsin-like immunoreactivity (CTLI) in a porcine model. The pancreatic acinar cells revealed focal changes, including intracellular oedema, appearance of membrane-bound vacuoles and breaks in the plasma membrane. In the micro circulatory vessels, there was swelling of endothelial cells. Similar changes have been observed in hemorrhagic and cardiogenic shock. This study demonstrates severe ultrastructural changes in the pancreas during E. coli endotoxin shock.

Acute Disease↗
PubMed1988

Endothelial cells of the cardiac microvasculature during and after cold cardioplegic ischaemia. Comparison of endothelial and myocyte damage.

Ultrastructural changes in endothelial cells of the myocardial microvasculature were studied in 18 patients who underwent aortocoronary bypass surgery under cold ischaemic cardioplegia. Biopsy specimens for electron microscopy were taken from the right atrium before and at the end of aortic cross-clamping and after 20 and 60 min of reperfusion. At the end of the cold ischaemic cardioplegia, the endothelial cells showed reduced numbers of pinocytotic vesicles, moderate intracellular oedema and slight nuclear changes. During reperfusion the endothelial changes became more pronounced and interstitial oedema developed. These changes persisted, or even increased in the first 60 min of reperfusion, in contrast to the myocytic changes, which tended to regress. The endothelial cells of the myocardial microvasculature thus appeared to be more vulnerable than the myocytes to cold ischaemic cardioplegia and reperfusion. Focally reduced blood reperfusion due to endothelial swelling and interstitial oedema did not seem to be the main cause of the focal postischaemic myocytic damage.

Adult↗
PubMed1986

Reversible and irreversible changes in the dog heart during acute left ventricular failure due to experimental multifocal ischaemia.

Acute left ventricular (LV) failure was induced in closed-chest pentobarbital anaesthetized dogs (n = 15), by injection of 50 micron plastic microspheres into the main left coronary artery. There were marked reductions of cardiac output and peak LV dp/dt after the embolization, while LV end-diastolic pressure (LVEDP) increased markedly. Biopsies were taken 1, 2, 3, 4, 6, 8, 10, 36, 48 hours, 7 and 14 days after injection of microspheres. Histological examination of the left ventricle revealed multiple ischaemic lesions distributed throughout the are supplied by the left main coronary artery. Oilred O staining revealed deposition of fine lipid droplets in the ischaemic cardiac muscle cells bordering on the necrotic areas. Ultrastructurally the lipid-containing cells showed numerous vacuoles localized in association with the mitochondria. The vacuoles could be observed already 1 hour after embolization and increased in number up to 48 hours. At the end of the observation period at two weeks, the number of lipid droplets was markedly reduced and the heart regained its functional activity. It is concluded that the myocardial lesions induced by coronary embolization of plastic microspheres were associated with acute left ventricular pump failure and consist of multiple foci of damaged myocardium with a central core of necrotic tissue. In the periphery of these lesions there were myocytes with lipids and other signs of light and moderate ischaemic injury. Our suggestion is that these cells represent a region of intermediate injury of "border zone" cells that are a potentially salvageable myocardium.

Animals↗
PubMed1983

Progression of myocardial damage following coronary microembolization in dogs.

The aim of the present study was to determine whether induction of ischaemic heart failure by micro-embolization leads to only a single episode of myocardial injury or whether it sets up a vicious cycle of progressive myocardial damage. Acute left ventricular (LV) failure was produced in 15 closed-chest anaesthetized dogs by injection of 50 microns plastic microspheres into the left main coronary artery. The dogs showed signs of severely depressed LV function; there was a marked increase in LV end-diastolic pressure and a marked decrease in stroke volume. Myocardial lactate uptake decreased or reversed to production. Six dogs with very high LV end-diastolic pressure died during the subsequent 3 days and autopsy revealed pulmonary edema. The LV function was re-examined in four dogs at 2 and 4 weeks after embolization. Except for a modest elevation of LV end-diastolic pressure there were no haemodynamic or metabolic signs of myocardial dysfunction. Gross and light microscopic examination of the heart in dogs 8 hours to 6 weeks following microsphere injections revealed numerous small infarcts or focal areas of granulation or scar tissue throughout the entire left ventricle. At 1 to 6 weeks close to the infarcts there were scattered myocytes with strong eosinophilia and pyknosis or loss of nuclei, interpreted as myocytolysis. In two dogs killed at six weeks after the embolization there were areas of granulation tissue, similar to a recent infarction about 1 week old. Thus, in spite of apparent functional restoration there were morphological signs of repeated and progressive myocardial injury several weeks after coronary embolization.

Animals↗
PubMed1983

Morphologic changes in atrial myocardial cells after cold cardioplegic standstill and during reperfusion in coronary bypass surgery.

Changes in the morphology of myocardial cells during reperfusion after long cardiac ischemia were studied as a sensitive indicator of myocardial damage. Observations were made by light and electron microscopy on specimens of atrial myocardium from 20 patients undergoing uneventful coronary bypass surgery with global hypothermic (less than 18 degrees C) cardioplegic protection. The findings in biopsy specimens taken before and immediately after cardiac arrest and following 20 and 60 min of reperfusion were arbitrarily graded in a semiquantitative scoring system. More than 60 min of cold cardioplegic arrest resulted in foci of altered myocardial structure, as seen in biopsies prior to reperfusion. After 20 min of reflow, intracellular and interstitial edema was found and no regression of the subcellular changes had taken place. (Worsening was observed in 7 cases.) After 60 min of reperfusion the myocardial ultrastructure had normalized in all the patients who had had ischemic cardiac arrest for less than two hours. In two hearts with longer ischemia (120 and 140 min), scattered areas of myocytes undergoing progressive changes were seen, although the postoperative myocardial performance was normal. Provided that the observed atrial changes were representative of left and right ventricle, the study indicates that reperfusion per se may enhance edema and cellular derangement, and that reperfusion for more than 20 min is usually necessary for normalization of the myocardium after more than one hour of ischemia.

Adult↗
PubMedDate not supplied

Ultrastructural alterations during the critical phase of reperfusion: a stereological study in buffer-perfused isolated rat hearts.

The present study focuses on myocardial ultrastructural alterations during the early phase of reperfusion. Isolated buffer-perfused rat hearts were exposed to standard perfusion (control group,n = 10); 60 min of global ischemia (n = 10); 60 min of global ischemia followed by 2 min of reperfusion (n = 10); or 60 min of global ischemia followed by 10 min of reperfusion (n = 10). The hearts were perfusion-fixed for electron microscopy, and ultrastructural evaluation was performed using stereological technique in order to obtain an estimate of the volume fraction and absolute volume of different tissue components. EFFECT OF ISCHEMIA: Neither the ventricular nor the myocytic volume differed significantly from the respective control values. Both the myocytic mitochondrial volume (135+/-8 vs control 89+/-6 microl) and the volume of myocytic clear space (35+/-6 vs control 10+/-2 microl) were significantly increased. The capillary volume (22+/-4 vs control 58+/-6 microl) and the volume of the capillary lumen (15+/-3 vs control 48+/-5 microl) were significantly decreased. The volume of the capillary wall, however, was not altered after exposure to ischemia (7+/-3 vs control 10+/-1 microl). ADDITIVE EFFECT OF ISCHEMIA AND REPERFUSION: Both the ventricular volume (755+/-28 vs control 600+/-32 microl) and the myocytic volume (396+/-24 vs control 287+/-16 microl) were significantly increased after 10 min of reperfusion. EFFECT OF REPERFUSION: The ischemic-induced myocytic mitochondrial swelling and increase of clear space were not reinforced during reperfusion. Furthermore, the volume of the capillary lumen and the capillary wall did not alter significantly in the groups exposed to reperfusion compared to the ischemic hearts. In conclusion, stereological evaluation did not reveal significant aggravation of ischemic-induced myocardial injury during the early phase of reperfusion.

Actin Cytoskeleton↗
PubMedDate not supplied

Microvascular perturbations in rats receiving the maximum tolerated dose of methotrexate or its major metabolite 7-hydroxymethotrexate.

Methotrexate (MTX) is a clinically important cytostatic antifolate. The study describes the acute effects of maximum tolerated doses of MTX or its major metabolite 7-hydroxymethotrexate (7-OH-MTX) on the ultrastructure of rat liver and kidneys. The ultrastructural changes in rats receiving MTX or 7-OH-MTX were, in principle, indistinguishable and their severity and extension increased with time of survival or doses of medication. All lesions were focal, microvascular, or parenchymal. Microvascular changes were more severe in nature when blood cells were present. The endothelial cells were swollen with loss of pinocytotic vesicles, their luminal plasma membrane formed blebs or were disrupted. Partly detached endothelial cells or deendothelialized areas, various types of white blood cells, in particular, neutrophil granulocytes, were observed in the microcirculation. Single platelets or small platelet aggregates were found either in the lumen or adhering to deendothelialized areas of injured endothelial cells. Hepatocytes exhibited steatosis, edema, and manifest single cell necrosis. There were also nuclear changes, marked proliferation of smooth endoplasmatic reticulum, increased amounts of intracellular lipid vacuoles, and a decrease in glycogen particles in hepatocytes. The kidney presented the major changes in the tubules and in the interstitial part. MTX and 7-OH-MTX acute toxicity may primarily be related to microvascular perturbation.

Animals↗
PubMedDate not supplied

The initial phase of myocardial reperfusion is not associated with aggravation of ischemic-induced ultrastructural alterations in isolated rat hearts exposed to prolonged global ischemia.

The present study focuses on the qualitative and sequential development of myocardial ultrastructural changes during the first 10 min of reperfusion in isolated rat hearts exposed to 60 min of global ischemia. The frequency of and the association between ultrastructural changes were examined by semiquantitative morphometry using the micrograph as unit. In each micrograph the subcellular components of the myocytes (sarcolemma, mitochondria, myofilaments and nucleus) and the endothelial cells were evaluated and graded as slightly, moderately, or severely altered. Ischemia alone induced moderate to severe ultrastructural alterations. The myocytes revealed sarcolemmal disattachment or rupture. The myocytic mitochondria had a clear matrix with abundant broken cristae and amorphous matrix densities. The myofilamental pattern was irregular or even disrupted, and most nuclei had reduced density and showed margination of chromatin. The endothelium showed vacuolization, rupture of the plasma membrane, and extracellular accumulation of cellular debris. During the first 2 min of reperfusion severe ultrastructural alterations were partly reversed. After 10 min of reperfusion both the frequency and grade of myocardial ultrastructural alternations were similar to that observed after ischemia. Cristal adhesions occurred predominately during reperfusion and were associated with moderately and severely altered myocytic mitochondrial alterations. In conclusion, the results showed that ischemic-induced ultrastructural alterations were transiently improved upon reperfusion. With exception of the development of cristal adhesions, the acute phase of reperfusion was not associated with additional ultrastructural changes in isolated buffer-perfused rat hearts exposed to prolonged ischemia.

Animals↗
PubMedDate not supplied

Mitochondrial diseases and myopathies: a series of muscle biopsy specimens with ultrastructural changes in the mitochondria.

From 1986 to 1991, 472 muscle biopsy specimens from patients from different hospitals in Norway were examined. Of these, 364 were embedded for electron microscopy, and 194 were examined with electron microscopy. Ultrastructural alterations in the mitochondria were detected in 49 of these specimens. Characteristic electron microscopic findings included subsarcolemmal accumulation of abnormal mitochondria of various shapes and sizes, often containing electron-dense granules and sometimes lipid vacuoles in the mitochondria and diffusely electron-lucent matrix space. Paracrystalline inclusion bodies were seldom seen in specimens from young patients, but in some cases mitochondrial electron-dense granules at the cristae were found. These amorphous densities are consistent with lipoproteins, suggesting that they may represent an early stage of paracrystalline inclusions. Biochemical and genetic exploration of the patients with biopsy specimens suggesting mitochondrial disease indicated maternally genetic inheritance and an enzyme defect in the respiratory chain in 21 patients in two families. Three patients had MELAS syndrome, 7 Marinesco-Sjögren syndrome, and 2 Kearns-Sayre syndrome. Five family members had ptosis, cardiomyopathy, mild myopathy, and increased lactate in cerebrospinal fluid and serum. In addition to the diseases mentioned above, changes in the mitochondria were detected in other conditions such as Rett's syndrome (n = 1), ornithine transcarbamylase deficiency (n = 2), and hypothyroidism (n = 2) as well as in 3 patients with clinical and laboratory results indicative of inflammatory myopathy and 3 patients with clinical and laboratory findings consistent with peripheral neuropathy. It is concluded that, although ultrastructural changes in the mitochondria may represent unspecific findings, electron microscopic examination of muscle biopsy specimens is a useful screening method to select specimens for further biochemical analysis and to obtain an early and more precise diagnosis of the disease.

Biopsy↗
PubMedDate not supplied

The effects of two different crystalloid cardioplegic solutions on cultured human endothelial cells.

The effects on cultured human endothelial cells of incubation with two standard crystalloid cardioplegic solutions (St. Thomas' and Bretschneider's) for one or five hours at 10 degrees C or 20 degrees C were studied. The cells were prelabelled with 51Cr and cell injury was measured by release of 51Cr, cell detachment, and by electron microscopy. The injury was also studied after a rewarming period of 35 minutes in cell culture medium at 37 degrees C. Endothelial cells incubated with cell culture medium, but otherwise treated in a similar way, served as controls. Both cardioplegic solutions caused significantly greater release of 51Cr than cell culture medium when incubated at 10 degrees C or 20 degrees C. The Bretschneider's solution induced slightly more release of 51Cr than did the St. Thomas' solution. The cells did not become detached during incubation. Electron microscopy of the cells after 5 hours with the cardioplegic solutions at 10 degrees C revealed contraction of the cells, mild intracellular oedema, swelling of mitochondria, and blebs or craters on the luminal surface of the cells. After rewarming in culture medium for 35 min the cells were not contracted and showed only minimal signs of injury, indicating a rapid and nearly complete reversibility of the changes. The present observations indicate that cultured endothelial cells get some protection, albeit not optimal, from the two crystalloid cardioplegic solutions tested. The presence of procaine-CL increased the injurious effect of the solutions.

Bicarbonates↗