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Biomedical subjects

J Schaper

Publications and source records attributed to J Schaper.

At least 19 recordsLinked to original sources
PubMed1992

Myocardial dystrophin immunolocalization at sarcolemma and transverse tubules.

Using monoclonal antibodies against two different regions of the helical rod part of dystrophin, we have localized dystrophin on both plasma membrane and transverse tubules in cardiac muscle of man and several animal species. The staining persisted after experimental ischaemia, and was observed in long-standing heart disease. No immunostaining was seen at the intercalated discs. In skeletal muscle the same two antibodies stained only the plasma membrane.

Animals↗
PubMed1992

The extracellular matrix in the failing human heart.

The composition of the extracellular matrix was investigated in eight human hearts explanted at the time of transplantation surgery because of endstage cardiomyopathy. All patients showed clinical signs of heart failure. The tissue was investigated by electron microscopy and immunofluorescence microscopy using monoclonal antibodies against collagen I, III, VI, and IV, fibronectin, laminin, and vimentin. All matrix proteins occurred in increased amounts in the extracellular space separating the myocardial cells by septa of enlarged thickness. Laminin and collagen IV surrounded myocardial and endothelial cells as layers of increased thickness. Vimentin localization was normal in individual cells, but occurred more often and corresponded to the numerous fibroblasts as observed by electron microscopy. It is concluded that an excessive deposition of extracellular matrix material in addition to myocyte degeneration (as reported previously (9)) are the structural correlates of cardiac failure.

Cardiomyopathy, Dilated↗
PubMed1992

Human fetal heart development after mid-term: morphometry and ultrastructural study.

A total of 44 normally developed human fetal hearts aged from 17 to 40 weeks gestation were provided for routine ultrastructural and morphometric studies. For morphometric analysis, the maximal thicknesses of the anterior, lateral and posterior wall of both ventricles and that of interventricular septum were measured and the left-to-right thickness ratios calculated. The cross-sectional areas of both ventricles in the plane of the greatest heart diameter were measured with computerized image analysis system. Data were analyzed using linear regression and one-way analysis of variance. Myofibril formation occurred by attachment of thin filaments into amorphous Z materials which were presented in sarcolemmal plaques, sarcoplasmic condensations, desmosomes and in Z lines. From these Z centers, myofibrils radiated many directions and branched and anastomosed with further development. This pattern of myofibrillar development continued throughout the whole fetal period. A transverse tubule system was clearly evident in later fetal development. It occurred by invagination of sarcolemma into myocardial cells and formation of subsarcolemmal caveolae. Mitochondria, well-developed Golgi complexes, glycogen granules and well-developed microvessels were found throughout the whole fetal period. Binucleated myocytes appeared by 32 weeks gestation and this suggests that myocyte hyperplasia may cease before birth in humans. The growth of both ventricular walls, the interventricular septum and that of both ventricular cross-sectional areas showed linear regression, and the left-to-right wall thickness ratios were nearly constant. Also, there were no differences in morphometric data between the left and right ventricles. In conclusion, development of the myocyte is an ongoing process which may be continued in the post-natal period in humans, and our statistical results do not support the theory of the right ventricular dominance during the fetal period.

Cell Differentiation↗
PubMed1992

Ultrastructural quantitation of mitochondria and myofilaments in cardiac muscle from 10 different animal species including man.

The ultrastructural quantitative composition of normal myocardial cells has been studied in 10 different species: man, dog, pig, cat, rabbit, ferret, guinea-pig, rat, mouse, and bat. Volume densities of mitochondria, myofibrils, and cytoplasm were determined using morphometry. It was found that the content of mitochondria differs in various species ranging between 22.0-37.0%. It is a very specific and constant value for any particular species, the smallest having the highest content. A close correlation exists between the mitochondrial volume density, heart rate and the rate of basal oxygen consumption in any group of animals. The myofibrillar volume density shows no species variability. It was about 60.0% in all species. It is concluded that the mitochondrial volume density is a good indicator of the oxidative capacity of cardiac muscle and that the species specific normal ultrastructural myocyte composition should be a useful baseline in pathophysiological studies of the heart in various animals.

Actin Cytoskeleton↗
PubMed1992

Ramipril prevents left ventricular hypertrophy with myocardial fibrosis without blood pressure reduction: a one year study in rats.

1. Angiotensin converting enzyme (ACE)-inhibitors have been demonstrated to be effective in the treatment of cardiac hypertrophy when used in antihypertensive doses. The aim of our one year study with an ACE-inhibitor in rats was to separate local cardiac effects produced by a non-antihypertensive dose from those on systemic blood pressure when an antihypertensive dose was used. 2. Rats made hypertensive by aortic banding were subjected to chronic oral treatment for one year with an antihypertensive dose of the ACE inhibitor, ramipril 1 mg kg-1 daily, (RA 1 mg) or received a low dose of 10 micrograms kg-1 daily (RA 10 micrograms) which did not affect high blood pressure. 3. Chronic treatment with the ACE-inhibitor prevented left ventricular hypertrophy in the antihypertensive rats as did the low dose which had no effects on blood pressure. Similar effects were observed on myocardial fibrosis. Plasma ACE activity was inhibited in the RA 1 mg but not in the RA 10 micrograms group although conversion of angiotensin (Ang) I to Ang II in isolated aortic strips was suppressed in both treated groups. Plasma catecholamines were increased in the untreated control group, but treatment with either dose of ramipril normalized the values. The myocardial phosphocreatine to ATP ratio (an indicator of the energy state in the heart) was reduced in the vehicle control group whereas the hearts from treated animals showed a normal ratio comparable to hearts from sham-operated animals. 4. After one year, five animals were separated from each group, treatment withdrawn, and housed for additional six months. In the RA 1 mg group, blood pressure did not reach the value of the control vehicle group and surprisingly, left ventricular hypertrophy and myocardial fibrosis did not recur in animals during withdrawal of treatment.5. These data show that long term ACE inhibitor treatment with ramipril in antihypertensive and non-antihypertensive doses prevented cardiac hypertrophy and myocardial fibrosis. This protective effect was still present after 6 months treatment withdrawal.

Adenosine Triphosphate↗
PubMed1992

The extracellular matrix in human cardiac tissue. Part II: Vimentin, laminin, and fibronectin.

In continuation of our previous work describing the localization of the collagens type I, III, VI, and IV the present study describes the localization of vimentin, laminin, and fibronectin in human myocardium obtained as left ventricular needle biopsies during cardiac surgery. Myocardium from normal pigs served for comparison. Monoclonal antibodies against the various proteins were used on frozen sections, labeled with fluorescein and viewed in the fluorescence microscope. Vimentin, the intermediate filament of mesenchymal cells, is present in fibroblasts, fibrocytes, and endothelial cells. Laminin is observed in the basal membrane of myocytes, smooth muscle and endothelial cells. The staining intensity for the B1-chain is higher in and around myocytes as compared with the B2-chain antibody, but more blood vessels were stained with the latter. The antibody against the A-chain only stained the basal lamina of vascular cells but not that of myocytes. Fibronectin was localized homogeneously throughout the extracellular space as matrix material in which the cellular elements and the various other proteins such as collagens are embedded. Intracellular staining in myocytes (T-tubules) was commonly observed. Both parts of this study show the distribution of extracellular proteins in normal human cardiac tissue and are intended to be the basis for investigations of pathological changes in diseased human myocardium.

Animals↗
PubMed1991

Impairment of the myocardial ultrastructure and changes of the cytoskeleton in dilated cardiomyopathy.

This study was designed to determine the morphological correlate of chronic heart failure. Myocardial tissue from eight patients undergoing transplantation surgery because of end-stage dilated cardiomyopathy was investigated by electron microscopy and immunocytochemistry using monoclonal antibodies against elements of the cytoskeleton: desmin, tubulin, vinculin, and vimentin. The tissue showed hypertrophy, atrophy of myocytes, and an increased amount of fibrosis. Ultrastructural changes consisted of enlargement and varying shape of nuclei, numerous very small mitochondria, proliferation of T tubules, and accumulation of lipid droplets and glycogen. The most obvious ultrastructural alteration was the decrease of myofilaments, ranging from rarefication to complete absence of sarcomeres in cells filled with unspecified cytoplasm. Immunocytochemistry showed that desmin was localized at the Z lines. In diseased myocardium, the amount of desmin was increased, but it was disorderly arranged. Tubulin formed a fine network throughout the myocytes and was significantly increased in cardiomyopathic hearts. Vinculin, a protein closely associated with the cytoskeleton, occurred not only at the sarcolemma and the intercalated disc but also within the myocardial cells. Ultrastructural changes and alterations of the cytoskeleton were severe in about one third of all cells. About one third of all cells showed moderately severe changes, and the remaining cells were normal. Vimentin was present in the interstitial cells and was increased in relation to the increase of fibrosis. We conclude that the increase of fibrosis, the degeneration of hypertrophied myocardial cells, and the alterations of the cytoskeleton are the morphological correlates of reduced myocardial function in chronic heart failure.

Antibodies, Monoclonal↗
PubMed1991

Coronary capillaries in patients with congestive cardiomyopathy or angina pectoris with patent main coronary arteries. Ultrastructural morphometry of endomyocardial biopsy samples.

BACKGROUND: The coronary microvasculature may be abnormal even in the presence of angiographically normal epicardial arteries. Abnormalities of small coronary vessels have been invoked as a cause of angina. METHODS AND RESULTS: To quantitatively evaluate the morphology of capillaries in patients with idiopathic dilated cardiomyopathy (DCM) or the syndrome of angina and small vessel disease (SVD), we performed electron microscopic morphometry of capillaries in right ventricular biopsy samples taken from 32 patients. Ten had angina, normal epicardial coronary arteries, and evidence for SVD; 12 had DCM; and 10 had normal hearts. In patients with DCM, the ratio of microvessels to myocytes was not different than that of controls (0.49 +/- 0.06 versus 0.51 +/- 0.05). Mean cross-sectional areas of the capillaries (lumen plus wall) and lumen were significantly greater than those of controls (45.3 +/- 15.1 versus 22.7 +/- 8.3 micron 2, p less than 0.001; 17.6 +/- 6.9 versus 11.6 +/- 6.2 micron 2, p less than 0.05, respectively). Fibrous content of the myocardium, as assessed by quantitative light microscopy, was significantly increased (16.3 +/- 3.3% versus 5.0 +/- 2.4%, p less than 0.001). In contrast, in patients with SVD, the capillary-to-myocyte ratio was reduced (0.33 +/- 0.08, p less than 0.001). Although mean cross-sectional areas of the entire capillary (32.4 +/- 19.7 micron 2) and the lumen (8.9 +/- 7.8 micron 2) were not statistically different than those of controls, there was an absence of capillaries less than 15 micron 2 in cross-sectional area, and the frequency distribution of the lumen area was skewed to the left. Swollen endothelial cells frequently encroached upon the lumen. There was a mild increase in fibrous content (9.5 +/- 3.7%, p less than 0.05). CONCLUSIONS: Enlarged capillaries and a normal ratio of capillaries to myocytes appear to be features of DCM. Of the patients with SVD, there was both a relative lack of capillaries and capillary lumen narrowing from swollen endothelium. These changes may induce ischemia and angina and may result in mild fibrosis.

Adult↗
PubMed1991

Effect of increasing degrees of ischemic injury on myocardial oxidative metabolism early after reperfusion in isolated rat hearts.

The present investigation studied the effect of increasing severities of ischemic injury on recovery of oxidative metabolism after reperfusion in isolated rat hearts perfused retrogradely with erythrocyte-containing medium. Hearts subjected to 60 minutes of low-flow ischemia (5% of control perfusion) exhibited delayed but sustained recovery of left ventricular pressure development during reperfusion and preservation of ultrastructure delineated with electron microscopy. Immediately after reperfusion, myocardial oxygen consumption returned to control values, well before left ventricular pressure development recovered. Early after reperfusion release of 14CO2 from [1-14C]palmitate was reduced (-53%, p less than 0.01). Conversely, release of 14CO2 from [U-14C]glucose was increased (+131%, p less than 0.05). After 60 minutes of reperfusion 14CO2 release had completely returned to normal for both labeled substrates. Pulse-labeling experiments indicated that during transient depression of [1-14C]palmitate oxidation more tracer was incorporated into myocardial lipid esters, primarily triglycerides. In contrast to hearts subjected to low-flow ischemia, hearts subjected to 60 minutes of no-flow ischemia exhibited poor recovery of contractile function during the reperfusion period. Electron microscopic examination of reperfused hearts showed advanced myocyte damage consistent with irreversible injury. Interestingly, myocardial oxygen consumption in this group also recovered to control values. The substrate pattern during the early reperfusion period was similar to that of hearts subjected to low-flow ischemia. After 120 minutes of no-flow ischemia, recovery of oxidative metabolism was virtually absent. The results indicate a pronounced dissociation between recovery of oxidative metabolism and of contractile function in reperfused myocardium. The oxidative metabolic rate was disproportionately high compared with contractile function, not only in reversibly "stunned" hearts, but also in severely damaged hearts exhibiting signs of irreversible injury.

Acetates↗
PubMed1991

The extracellular matrix in human myocardium: Part I: Collagens I, III, IV, and VI.

The composition of the extracellular matrix in normal human myocardium obtained at open-heart surgery was investigated using monoclonal antibodies against the collagens I, III, IV, and VI, and fluorescence microscopy. The aim of the study was to provide information on normal myocardium that could be used in the evaluation of pathological changes. Porcine myocardium was used for comparison, and both tissues showed a perfect agreement of the results, apart from collagen IV. This was negative in pig myocardium, due to the species specificity of the antibody. Collagens I and III were localized in the extracellular space as either coarse or fine fibrillar structures; the cellular elements of the interstitium, except for the endothelial cells, were also stained. Labeling for collagen VI was much finer than for the other collagens, and was present throughout the interstitium. Collagen IV stained the basement membranes of myocytes and capillary endothelial cells, and also labeled the T-tubular system in the myocytes. The second part of this communication will describe the localization of fibronectin, laminin and vimentin in normal human myocardium.

Animals↗
PubMed1990

Molecular biologic concepts of coronary anastomoses.

The discovery that collateral development after progressive coronary stenosis proceeds by means of DNA synthesis, mitosis and proliferation of endothelial and smooth muscle cells in preformed small interconnecting arterioles (canine heart) and capillaries (porcine heart) has stimulated research into the molecular mechanisms of vascular growth. Growth is tightly controlled under physiologic conditions, and several factors must act in concert to overcome control. Because the result of growth is a much larger orderly structure of complex design, we expect the existence of a genetic blueprint for its construction. Peptide growth factors have recently been isolated from a variety of organs, including the heart. We have provided experimental evidence that the heparin-binding growth factor beta-ECGF shows an increased transcription in growing pig collateral vessels. Because the chain of events probably originates in the ischemic cardiac myocyte, it appears logical to search there for the initiating factor. In addition to local production, growth factors can also be transported into ischemic myocardium by blood-borne cells. Monocytes adhere to altered endothelium in a potentially ischemic region and start to produce growth factors in situ. Platelets are rich sources of transforming growth factor-beta (TGF-beta), platelet-derived endothelial cell growth factor (PDECGF) and platelet-derived growth factor (PDGF), all of which are known angiogenic factors or mitogens.

Adaptation, Physiological↗
PubMed1990

[Multiple aneurysms of unknown etiology in childhood--complications and diagnostic possibilities].

A 6.5-year old boy with already known multiple aneurysms of all major arteries presented with acute abdominal pain. As demonstrated by ultrasound a big aneurysm of the left renal artery thrombosed in the course of three days. As a result, the left kidney developed severe ischaemia. Although computed tomography and scintigraphy were applied, a plan for a definitive therapeutic procedure could be established only by arterial angiography. Both Ehlers-Danlos' syndrome and Kawasaki's syndrome were excluded. There were no facts suggesting an infective aetiology. Four other cases with multiple aneurysms of unknown aetiology in childhood have so far been described in literature.

Aneurysm↗
PubMed1990

[Tuberous sclerosis--rare pulmonary manifestations].

We report on a twenty year old female patient with pulmonary involvement in tuberous sclerosis. According to the literature these patients seem to represent a unique subtype of tuberous sclerosis because of female predominance, age at diagnosis and especially the course of the disease, which comes to an end by the pulmonary changes.

Adult↗
PubMed1989

Total ischemia III: Effect of inhibition of anaerobic glycolysis.

The effect of inhibition of glycolysis with sodium iodoacetate (IAA) on the changes induced by total ischemia was studied in canine left ventricle. Hearts were excised from phenobarbital anesthetized dogs and the circumflex (LCC) and anterior descending (LAD) branches of the left coronary artery were perfused in order to expose the LCC region to 48 mumol of IAA (about 1.5 mumol/g wet wt). The LAD regions of the same hearts served as untreated control myocardium. Hearts then were subjected to total ischemia in vitro at 37 degrees C. Metabolites, ultrastructure, and the capacity of thin incubated slices of heart to maintain volume and ion gradients were studied in the control and IAA-treated regions. Depletion of ATP to levels of 3-4% of control occurred in only 4-5 min of ischemia in the IAA-treated myocardium, but similar depletion required 90 min of total ischemia in untreated myocardium. These low levels of ATP were associated with marked contracture-rigor. Depletion of ATP in the IAA treated region was accompanied by a marked increase in adenosine levels in the tissue at the onset of rigor (approximately 5 min); at this time, as much as 50% of the adenine nucleotide pool (sigma Ad) was in the form of adenosine. In contrast, inosine was the predominant catabolite at 5 min in control myocardium, and only composed 16% of the sigma Ad pool. Thus, pretreatment with IAA produced an enormous acceleration in the rate at which the sigma Ad pool was consumed in totally ischemic myocardium. Lactate, the principal glycolytic intermediate which accumulates in totally ischemic tissue, was not formed in the IAA-treated heart. Moreover, IAA treatment did not accelerate the rate at which ultrastructural evidence of lethal injury developed in the poisoned myocytes. Thus, in a setting in which lactate accumulation did not occur, totally ischemic myocytes tolerated a very low level of high energy phosphate for a longer period of time than did untreated tissue before ultrastructural signs of cell death developed. The results indicate that marked ATP depletion, pe se, does not necessarily cause prompt sarcolemmal disruption.

Adenine Nucleotides↗
PubMed1988

Time course of myocardial necrosis.

The time course of myocardial ischemia was studied in canine myocardium by electron microscopy. Ischemia of the myocardium produces ultrastructural alterations of mitochondria, nuclei, contractile apparatus, and the SR- and T-tubular system that are accompanied by loss of glycogen and intracellular edema. These changes are more pronounced with increasing severity of ischemia, and they allow the differentiation between different stages of reversible and of irreversible injury. Reperfusion of reversibly injured tissue leads to structural recovery; reperfusion of irreversibly injured tissue produces further deterioration. On the basis of ultrastructural data, it was found that in a dog, after 45 minutes of coronary artery occlusion, subendocardial infarction was present in 20% of all animals. Transmural infarction was present in 24% of all dogs after 90 minutes of coronary artery occlusion and in 53% after 24 hours. The individual variability in the speed of development of infarction is caused by the rate of oxygen consumption at the time of occlusion and by the amount of collateral flow. Intermittent ischemia is much better tolerated than permanent ischemia of the same duration. Species differences are evident. The course of development of myocardial necrosis, therefore, depends on time, rate of oxygen consumption, collateral flow, mode of ischemia, and on the species investigated.

Coronary Disease↗
PubMed1988

Effects of multiple ischaemic events on human myocardium--an ultrastructural study.

Chronically ischaemic myocardium from patients with coronary heart disease was investigated by light and electron microscopy using tissue biopsies taken during cardiac surgery. Light microscopy showed a significantly increased amount of fibrotic material, cell size was variable. By electron microscopy, the most obvious alterations were abnormalities of nuclei, mitochondria, and a reduction of contractile material. This was confirmed by ultrastructural morphometry. The subendocardium was more severely altered than the subepicardium. It is concluded that repeated episodes of reversible ischaemic injury produce cellular degeneration and significant loss of myofibrils. Even though these patients do not exhibit gross histologic evidence of myocardial infarction, the cardiac tissues slowly deteriorates with loss of myocytes and an increased amount of fibrosis. These findings are interpreted as the morphologic correlate of functional disturbances, especially of hypokinesia of the affected area.

Coronary Disease↗