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Biomedical subjects

J Schaper

Publications and source records attributed to J Schaper.

At least 127 records · Page 7Linked to original sources
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↗
PubMed1987

Delay of development of transmural irreversible ischaemic injury in canine myocardium.

During the course of experimentally induced myocardial ischaemia affected tissue initially suffers reversible ischaemic injury or, if ischaemia persists, injury of increasing severity before becoming irreversibly damaged. This state is characterized by tissue necrosis and referred to as myocardial infarction. The purpose of this study was to investigate whether it is possible to delay or perhaps even prevent the development of irreversible ischaemic injury. Ischaemia was induced by coronary artery occlusion (CAO) in canine hearts for 90 min or 24 h. The drug used for intervention was hyaluronidase. Ischaemic damage was assessed by p-NBT staining and ultrastructural evaluation of tissue biopsies. Development of irreversible ischaemic damage was prevented during 90 min of CAO. However, progression of reversible to irreversible ischaemic injury could not be prevented during 24 h of CAO. In conclusion, it is possible to prevent the development of irreversible ischaemic injury by a suitable intervention during the early stages of ischaemia in the canine heart and thus to gain time for additional intervention in the early treatment of myocardial infarction.

Animals↗
PubMed1987

Hypertension and atherosclerosis in cholesterol-fed rabbits. II. One-kidney, one clip Goldblatt hypertension treated with nifedipine.

Eight groups of New Zealand white rabbits were used to study the effects of moderate chronic one-kidney, one clip hypertension (HT) and long-term nifedipine therapy on atherogenesis. Four groups were fed a normal diet (ND) over an 8-month study period; two groups, one of which was given nifedipine, remained normotensive (NT) throughout the study. Of the two HT groups, one remained hypertensive for 7 months; the blood pressure of the other group was normalized after 2 months with nifedipine. The other four groups of animals were similarly constructed except that they were fed a 0.1% cholesterol diet (CD). The results showed that: although scattered fibromuscular vascular lesions were present in the aortas of normal-diet, HT animals no atheroma was observed; neither moderate chronic HT nor abrupt, short-term HT exacerbated atherogenesis in the CD-animals; nifedipine therapy had no suppressive effect on either fibromuscular lesions or atherogenesis; nifedipine therapy reduced the aorta weight of the normotensive ND and CD groups; the aortic triglyceride content of both dietary groups was reduced by nifedipine; cholesterol content was unaffected; left ventricular hypertrophy was evident only in HT-untreated groups; and only the weight of the left ventricle of the ND-NT-treated group was significantly reduced, but the mitochondria volume per unit volume of left ventricle myocardial cells was reduced only in the NT-CD group treated with nifedipine. It is concluded that an antihypertensive dosage of nifedipine administered to animals with atherosclerosis does not suppress subsequent atherogenesis.

Animals↗
PubMed1987

Relation between reversal of diastolic creep and recovery of systolic function after ischemic myocardial injury in conscious dogs.

Although prolonged functional abnormalities after transient myocardial ischemia have been well described, the interrelationship between postischemic systolic and diastolic alterations remains controversial. Therefore, 24 chronically instrumented conscious dogs were studied with left ventricular and pleural micromanometers, ultrasonic dimension transducers in the left anterior descending (LAD) coronary distribution, and vena caval and coronary artery occluders. The LAD was occluded for 15 minutes and reperfused for 24 hours while vena caval occlusions were performed at intervals to measure myocardial segment length at 0 mm Hg transmural diastolic left ventricular pressure (L0). Coronary occlusion produced an immediate fall in systolic function as assessed by ejection shortening and stroke work and also induced a 16 +/- 4% increase in L0, which was termed diastolic creep. Throughout reperfusion, reversal of diastolic abnormalities correlated strongly with recovery of segmental shortening and stroke work (p less than 0.001). Correlation between systolic dysfunction and diastolic creep was also observed during alteration of inotropic state by dopamine, during initial reperfusion hyperfunction, and during pharmacologic manipulation of afterload. In 5 additional dog hearts fixed in diastole by rapid glutaraldehyde infusion after coronary occlusion, myocardial creep measured by the segment length transducers paralleled sarcomere elongation measured by electron microscopy. Thus, the direct correlation between diastolic creep and systolic dysfunction throughout reperfusion and during hemodynamic alterations suggests that diastolic properties of postischemic myocardium may not be entirely passive and that systolic and diastolic dysfunction induced by ischemia may have a common basis at the cellular level.

Animals↗
PubMed1987

Human mitochondrial aldehyde dehydrogenase: mRNA expression in different tissues using a specific probe isolated from a cDNA expression library.

Using monospecific antibodies against mitochondrial aldehyde dehydrogenase (ALDH I), cDNA clones were isolated from a human liver cDNA library constructed in the plasmid expression vector pEX. Two overlapping clones pEXAL21 and pEXAL43 containing inserts of 861 bp and 1180 bp respectively, code for the carboxy-terminal end of ALDH I as confirmed by sequence analysis. The messenger RNA of ALDH I was estimated by Northern blot analysis to contain approximately 2350 nucleotides. RNA hybridizations revealed that the ALDH I gene transcription is generally low in fetal tissues. Especially, transcription in the adult liver is up to 5-fold higher than in the fetal liver.

Adult↗
PubMed1986

Ultrastructure of the human myocardium after intermittent ischemia compared to cardioplegia.

A lot of reports informed about the detrimental effects of intermittent ischemia nevertheless this method is still used during coronary surgery. We investigated the myocardial protection due to cardioplegic arrest compared to intermittent ischemia in 120 patients undergoing coronary surgery. In all patients we took myocardial biopsies from the left ventricle before and after ischemia. Electron microscopic studies of all biopsies were performed and the degree of ultrastructural alteration was determined. The ischemic period in the cardioplegic group was 61 +/- 15 minutes and in the group with intermittent ischemia the total ischemic time was 45 +/- 21 minutes. After ischemia the myocardium showed most time only damage of moderate or light degree, while after intermittent ischemia the most biopsies showed severe ultrastructural damage. From our results we conclude, that intermittent ischemia is unable to protect the myocardium in a sufficient amount and should therefore no longer be used as a method of myocardial protection.

Biopsy↗
PubMed1986

Hypertension and atherosclerosis in cholesterol-fed rabbits. Part 1. Mild, two-kidney, one-clip Goldblatt hypertension treated with enalapril.

Ten groups of New Zealand white rabbits were used to study the effects of mild, chronic two-kidney, one-clip hypertension (HT) and long-term antihypertensive therapy on atherogenesis. Five groups were fed a normal diet (ND) over the 8-month study period; 2 groups, one of which was given enalapril, remained normotensive (NT) throughout the study. Of the 3 HT groups, one was hypertensive for 7 months; the blood pressures of the other groups were normalized after 2 months with enalapril, or by removal of the clipped kidney. The other 5 groups were similar except that they were fed at 0.1% cholesterol diet (CD). The results showed that: neither mild chronic HT nor abrupt, short-term HT exacerbated atherogenesis in the CD-animals; although fibromuscular vascular lesions were present in the aorta of normal-diet, HT animals no atheroma was observed; enalapril therapy had no effect on atherogenesis; enalapril therapy reduced the total weight and the cholesterol and triglyceride content of the aorta of the ND groups regardless of blood pressure history; the aortic triglyceride content, but not the cholesterol content, of the CD group, was reduced by enalapril; and although heart size was unaffected by either diet or blood pressure levels, the mitochondria volume per unit volume of the left ventricle was reduced in both NT-ND and HT-CD groups treated with enalapril.

Animals↗
PubMed1986

Ultrastructural changes of the myocardium in regional ischaemia and infarction.

This study describes ultrastructural changes observed in experimental myocardial ischaemia and infarction in the dog heart. In myocardial cells, the evaluation of the state of mitochondria, nuclei and myofilaments by electron microscopy allows the differentiation of reversible versus irreversible ischaemic injury. Other subcellular symptoms such as glycogen loss, lipid deposition or occurrence of cytoplasmic proteinous substances are indicative of metabolic disturbances in ischaemia. The microvasculature shows degenerative as well as regenerative processes; a close interaction of the endothelium with platelets and leucocytes is evident. The extravascular space shows necrosis of interstitial cells as well as proliferation indicating early preparations for scar formation. Blood cells in the tissue are found to be typical of an early unspecific inflammatory response. Regional ischaemia seems to provoke a whole cascade of events on the subcellular level which are apparently closely linked with each other.

Animals↗
PubMed1986

Increase in number and decrease in size of mitochondrial profiles in myocytes of the right ventricle of dogs with experimental emphysema.

An ultrastructural study of the myocardium in control dogs and in dogs with papain-induced emphysema of 6 months duration without signs of right ventricular hypertrophy was undertaken to determine the number, size, and relative volume of the mitochondria. In the right ventricle of the emphysematous dogs, the number of mitochondrial profiles was greater per unit area of tissue (46.18 +/- 1.28/100 micron 2 versus 41.20 +/- 1.60/100 micron 2, p less than 0.05), but the mitochondria were smaller in size (mean mitochondrial profile area: 0.39 +/- 0.01 micron 2 versus 0.46 +/- 0.02 micron 2, p less than 0.05; mean mitochondrial "diameter": 0.65 +/- 0.01 micron versus 0.71 +/- 0.02 micron, p less than 0.05) than in control dogs. A highly significant negative correlation was found in the right ventricle of control and emphysematous dogs between the number per unit area and the size (area) of the mitochondrial profiles (r = -0.92; p less than 0.001). The increase in number but decrease in size of the mitochondrial profiles resulted in an unchanged relative volume of mitochondria in the right ventricle of the emphysematous dogs. In the subendocardium and in the subepicardium of the left ventricle of the papain-treated dogs, these changes were smaller and did not reach significance. These ultrastructural changes in the myocardium of the emphysematous animals are considered to be a response to a situation of prolonged increase in work of the right ventricle and may represent an early stage of a developing right ventricular hypertrophy.

Animals↗
PubMed1986

Ultrastructural study comparing the efficacy of five different methods of intraoperative myocardial protection in the human heart.

The quality of myocardial protection during cardiac arrest in cardiac operations was investigated in 310 patients. Eighty patients underwent aortic valve replacement and 230 had coronary artery bypass grafting. Four different cardioplegic solutions (Kirsch, Bretschneider, St. Thomas' Hospital, and Hamburg) and the method of induced fibrillation were tested by ultrastructural analysis of the degree of ischemic injury at the end of the cardiac arrest period. Hypothermia was identical in all five groups. In this study, subendocardial and subepicardial needle biopsies were evaluated by a standardized scoring system. Chemical cardioplegia produced mainly moderate ultrastructural injury independent of the time of ischemia. Kirsch cardioplegia and the intermittent fibrillation procedure produced ischemic injury of greater and unpredictable severity. Only with Kirsch cardioplegia was a correlation observed between the duration of intraoperative arrest and the degree of injury, which is indicative of a lack of myocardial protection. The tolerance to ischemia was significantly better in patients undergoing bypass grafting than in those with aortic valve disease and therefore longstanding hypertrophy. In conclusion, the Bretschneider, St. Thomas' Hospital, and Hamburg solutions provide satisfactory myocardial protection but are not able to completely prevent myocardial ischemic injury. Kirsch cardioplegia and the intermittent fibrillation procedure provide insufficient myocardial protection. Patients with left ventricular hypertrophy are at a greater risk during cardiac operations than patients undergoing coronary bypass operations.

Aortic Valve↗