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Biomedical subjects

J Schaper

Publications and source records attributed to J Schaper.

At least 145 records · Page 8Linked to original sources
PubMed1985

Effect of reperfusion late in the phase of reversible ischemic injury. Changes in cell volume, electrolytes, metabolites, and ultrastructure.

The acute effects of reperfusion on myocardium reversibly damaged by 15 minutes of severe ischemia in vivo, were studied. Changes in the adenine nucleotide pool, cell volume regulation, myocardial calcium, and ultrastructure were studied at the end of 15 minutes of ischemia and after 0.5, 3.0, and 20 minutes of reflow. Before reperfusion, adenosine triphosphate and the adenylate pool decreased by 63% and 44% of control, respectively, and the adenylate charge was reduced to 0.65. After 3 minutes of reperfusion, the adenylate charge was restored to control by the rephosphorylation of adenosine mono- and diphosphate, but adenosine triphosphate was still reduced by 45%. Mild tissue edema was detected after 0.5 minute of reflow and persisted throughout 20 minutes of reperfusion. The increased tissue water was accompanied by a slight increase in sodium and a marked increase in tissue potassium. Although massive calcium accumulation develops when irreversibly injured tissue is reperfused, no calcium overload was detected during early reperfusion of reversibly injured myocytes. Reperfusion for 3 minutes exaggerated the mitochondrial swelling induced by 15 minutes of ischemia but after 20 minutes of reperfusion, myocardial ultrastructure was essentially normal except for rare swollen, or disrupted, mitochondria. Thus, the cellular abnormalities associated with brief periods of ischemia persist for variable periods of time after reperfusion of reversibly injured myocytes. First: although adenine nucleotide repletion occurs very slowly, the adenylate charge was restored after 3 minutes, indicating rapid resumption of mitochondrial adenosine triphosphate production. Second: calcium overload was not detected, but myocardial edema and increased potassium persisted throughout the 20 minutes of reperfusion. Third: the ultrastructural consequences of ischemia were nearly reversed after 20 minutes of reperfusion.

Adenine Nucleotides↗
PubMed1985

Ultrastructural morphometric analysis of myocardium from dogs, rats, hamsters, mice, and from human hearts.

Volume densities of mitochondria, myofibrils, and unspecified cytoplasm were measured by ultrastructural morphometry in myocardium from dogs, rats, hamsters, mice, and in biopsied tissue from human hearts. Human myocardium was composed of 23% mitochondria, 59% myofibrils, and 18% cytoplasm. Volume densities for mitochondria were 22% for dogs, 28% for rats and hamsters, and 32% for mice. Myofibrillar volume densities were highest in dogs with 63%, 57% for rats and hamsters, and 49% for mice. Differences were significant between all except man and dog, and rat and hamster. In an extensive analysis of canine myocardium, it could be shown that the quantitative composition of tissue from the left ventricular free wall (anterior, lateral, posterior) and the papillary muscles was identical. There were also no differences between subepi- and subendocardium as well as the midmyocardium. Volume densities from longitudinal sections were identical to those from transversal sections. Fixation with glutaraldehyde by perfusion or immersion provided identical results. There were no differences between volume densities in samples from the left ventricular free wall (anterior, lateral, and posterior) in rats, hamsters, and mice. It is concluded that each mammalian species is characterized by a very typical quantitative composition of the myocardium. The increase in mitochondrial volume correlated well with the increase in heart rate and oxygen consumption in smaller animals. These quantitative data are regarded as the morphological correlate of the differing functional capacity of hearts from different species.

Analysis of Variance↗
PubMed1985

The effects of retrograde perfusion of cardioplegic solution in cardiac operations.

The effects of continuous retrograde coronary perfusion of a cardioplegic solution were investigated in 42 patients. From each patient, a needle biopsy was taken on the anterior left ventricular free wall during cardiac operations and investigated by electron microscopy. With the use of our well-standardized ultrastructural criteria of ischemic injury, we found that the retrograde perfusion technique provides cardiac protection of a quality superior to that of antegrade perfusion. This finding applied to the state of the myocardial cells. The cardiac microvessels, on the other hand, were more severely injured by retrograde perfusion, and extracellular edema occurred more frequently. It is concluded, therefore, that the retrograde perfusion of a crystalline cardioplegic solution during cardiac operation has beneficial effects on the preservation of myocardial cells in comparison to the antegrade application. Unfortunately, we also conclude that the occurrence of extracellular edema and of microvascular damage represents a serious drawback in the clinical use of this method. This technique, therefore, needs to be improved before it may routinely be applied in patients undergoing cardiac operations.

Glucose↗
PubMed1984

Increased myocardial capillary density in dogs with experimental emphysema.

In the hearts of control beagle dogs, capillary density in the right ventricle was found to be similar to that of the subendocardium of the left ventricle but lower than that of the subepicardium of the left ventricle. In emphysematous animals, 6 months after the exposure to papain (the emphysema-inducing agent), capillary density in the right ventricle and in the subendocardium of the left ventricle increased significantly, reaching values similar to that of the subepicardium of the left ventricle, which remained constant. These morphologic changes are considered to be an adaptation to a prolonged condition of increased myocardial oxygen demand and/or may represent an early stage of a developing cardiac hypertrophy.

Animals↗
PubMed1983

Reperfusion of ischemic myocardium: ultrastructural and histochemical aspects.

The effects of reperfusion on ischemic myocardium generally depend on the severity of the preceding ischemic injury. Reperfusion of myocardium, irreversibly injured by ischemia, produces further progression of myocardial necrosis that is accompanied by simultaneously occurring stimulation of interstitial cell proliferation resulting in scar formation. Reperfusion of reversibly injured myocardium leads to structural improvement and reorganization. Thus, it may be stated from the ultrastructural part of this study that reperfusion of ischemic myocardium induces 1) slow structural recuperation after reversible injury, and 2) accelerated cellular destruction and symptoms of scar formation after irreversible ischemic injury. We observed that the reduced tissue content of nicotinamide adenine dinucleotide (NAD), rather than reduced dehydrogenase activity, is the basis of histochemical reactions employing tetrazolium salts. Directly measured NAD tissue content in ischemic tissue correlated well with the degree of ultrastructural injury and with macroscopic differential staining. Occlusion of two small coronary arteries in the same heart followed by reperfusion of only one artery (identical occlusion times for both arteries) showed identical infarct sizes for reperfused and nonreperfused myocardium for occlusion times of 3 and 6 hours. When the effects of occlusion times of less than 3 hours are studied with tetrazolium salts, a difficult technical problem arises: during that time, tissue-NAD concentrations have not decreased enough to enable differential staining. Reperfusion leads to washout of NAD, thus producing differential staining; this may be a harmful effect of reperfusion. However, because early reperfusion leads to significant structural and functional recovery and to small infarcts, reperfusion injury is unlikely to occur. Both ultrastructural and histochemical evidence suggest that reperfusion is beneficial for reversibly injured tissue but accelerates the decay of irreversibly injured tissue.

Animals↗
PubMed1983

Ultrastructural correlates of reduced cardiac function in human heart disease.

The ultrastructural correlates of a decrease in cardiac function resulting in heart failure are unknown. For this reason, transmural needle biopsies were taken during cardiac surgery from patients with aortic valve disease (AD, n = 143) and coronary heart disease (CHD, n = 136) and examined by electron microscopy. Ultrastructural features were: occurrence of abnormal but still viable nuclei and mitochondria combined with lack of myofibrils in greatly enlarged myocardial cells plus an increased amount of fibrosis in patients with AD. In CHD most myocardial cells were of normal size or atrophic, reduced in number and showed signs of subcellular degeneration. Fibrosis was greatly increased. These findings were confirmed in both groups of patients by quantitative analysis (morphometry). Cardiac failure was diagnosed and clinically treated in about 25% of all patients investigated in this study. The loss of specific myocardial cellular components or loss of entire cells are the morphological correlates of cardiac failure in different types of heart disease.

Aortic Valve Insufficiency↗
PubMed1982

Coronary collateral vessels: their significance for left ventricular histologic structure.

Whether coronary collateral vessels protect the left ventricular myocardium is unknown. Light microscopic morphometry was carried out on myocardial tissue samples from 56 surgically treated patients with coronary artery disease. Transmural biopsy of the myocardium perfused by the left anterior descending coronary artery was obtained during open heart surgery. In initial reproducibility studies of biopsy samples of 17 patients a sampling error for evaluation of myocardium was defined and differences in transmural fibrosis exceeding +/- 6.2 percent were considered biologically significant. Stenosis of the left anterior descending artery was determined from preoperative angiography. Group A (control group) comprised patients with less than 75 percent area reduction of the left anterior descending coronary artery (mean +/- standard deviation 65 +/- 10 percent). Patients in group B (more than 95 percent area reduction [mean 99 +/- 2 percent] without collateral supply on arteriography) were compared with patients in group C (identical stenosis [mean 99 +/- 2 percent] but with collateral supply). Fibrosis averaged 17 percent in group A, 68 percent in group B (p less than 0.001 versus group A) and 29 percent in group C (p greater than 0.05 versus group A, p less than 0.001 versus group B). Thus, in severe coronary stenosis myocardium supplied by collateral vessels shows less fibrosis on biopsy sample than does myocardium without collateral supply.

Adult↗
PubMed1982

The effects of global ischemia and reperfusion on human myocardium: quantitative evaluation by electron microscopic morphometry.

During open-heart operation, myocardial biopsies were taken from 31 patients undergoing aortic valve replacement during total cardiopulmonary bypass. The first needle biopsy was taken before induction of cardiac arrest (Kirsch cardioplegia), the second at the end of global ischemia, and the third during the reperfusion period. Teh tissue was investigated by electron microscopy, in both a qualitative and a quantitative manner (morphometry). Ultrastructural morphometry revealed cellular and especially mitochondrial swelling that occurred during the reperfusion phase, but not after ischemia alone. On the basis of morphological measurements, this study shows the occurrence of postischemic cellular and mitochondrial edema that possibly might be avoided by the use of improved techniques of myocardial protection during operation.

Aortic Valve↗
PubMed1982

DNA synthesis in coronary collaterals after coronary artery occlusion in conscious dog.

With [3H]thymidine, DNA synthetic activity in coronary collateral arterioles was assessed in dogs subjected to progressive stenosis of the left circumflex coronary artery for different periods (36 h-5 days). Coronary flow, reactive hyperemia, and pressure gradient (aortic pressure, peripheral coronary pressure) were measured. Normal animals and animals with sham operations served as controls. Labeling of nuclei was seen in seven of the constricted dogs. Proliferative activity was highest at the level of the smallest diameters of the collateral vessels (midzone). There was heavy labeling in intima and media. Adventitial and myocardial mesenchymal cells also incorporated [3H]thymidine. No radioactive DNA was found in control animals. The data suggest that the active growth process in collaterals after constriction of the left circumflex coronary artery appears early, as there is evidence of collateral growth after 36 h of constriction. Peak growth as evidenced by [3H]thymidine incorporation was reached when the occlusion period was 4 days.

Animals↗
PubMed1982

A six-month study of the evolution of papain-induced emphysema in the dog.

The development of papain-induced emphysema and the effect of structural changes of the lung on pulmonary hemodynamics were investigated in the dog in a 6-month study. Papain was administered as an aerosol at the beginning of the study and at Day 21; control animals received saline. At 3 or at 6 months, hemodynamic investigations were carried out in the awake animal (sedated with piritramide). The dogs were then killed and the lungs processed for morphometric evaluation. Arterial blood gases were analyzed at regular intervals for the duration of the study. In the papain-treated dogs, mean linear intercept (Lm) and internal surface area of the lungs corrected to an arbitrary lung volume of 2L (ISA2) were significantly different from control dogs both at 3 and at 6 months. No progression of the structural changes of the lung occurred between these two time intervals. Arterial blood oxygenation was normal throughout the study. In the papain-treated group at 6, but not at 3, months, mean pulmonary arterial blood pressure (PAPm) and pulmonary arteriolar resistance (PAR) were significantly augmented when compared with the control group. A significant correlation was found at 6 months between the Lm and ISA2 on one side, and PAPm and PAR on the other side, suggesting that the structural changes of the lung were responsible for pulmonary hemodynamic alterations.

Aerosols↗
PubMed1981

[Ultrastructural changes in human myocardium with hypertrophy due to aortic valve disease and their relationship to left ventricular mass and ejection fraction (author's transl)].

Biopsies from hypertrophied left ventricles were obtained intraoperatively from patients undergoing valve replacement for aortic valve disease. The tissue was immediately fixed in glutaraldehyde and, after appropriate preparation, examined by light and electron microscopy. Morphologic characterization was carried out with respect to 1. qualitative alterations within myocytes, mostly degenerative, 2. measurement of cell diameter and the percentage of interstitial tissue volume within the total myocardium, 3. determination of volume densities of mitochondria, myofibrils, and cytoplasm in myocardial cells by morphometric techniques. Data from hypertrophied hearts were compared with those from normal hearts (control group). Analysis of morphologic and clinical data yielded the following results: 1. The increase in the clinically determined left ventricular muscle mass due to hypertrophy in aortic valve disease is caused by an increase in cellular diameter as well as an increase in interstitial tissue; 2. The morphologic correlate of the reduction of left ventricular function (EF) with increasing degrees of hypertrophy consists of an increase in interstitial tissue, i.e. fibrosis, and a marked relative loss of myofibrillar components from hypertrophied myocardial cells which is accompanied by an increase in cytoplasm-filled areas.

Aortic Valve Insufficiency↗
PubMed1981

[Quantitative ultrastructural findings of the myocardium in the failing heart. I. Aortic valve insufficiency (author's transl)].

Quantitative ultrastructural changes of the left ventricular (LV) myocardium and contractile function were studied in 9 symptomatic patients with severe aortic insufficiency (AI). The volume fractions of myofibrils, sarcoplasm, and mitochondria in myocardial cells were determined by electron microscopic morphometry in small LV tissue samples. Interstitial fibrosis was measured by light microscopic morphometry. Transmural biopsies of the LV free wall perfused by the left anterior descending coronary artery (LAD) were obtained during aortic valve replacement. Biopsies from the LAD-perfusion area of 10 surgical patients with coronary artery disease but moderate LAD-stenosis and normal regional motion of LAD-area were taken as controls for morphometric data. LV-function was analyzed from preoperative heart catheterization. In initial reproducibility studies of biopsy samples of 17 patients a sampling error for evaluation of myocardium was defined and differences exceeding 6.2% transmural fibrosis and 6.5% myofibrils were considered biologically significant differences. Patients with AI had higher LV end-diastolic volume (180 versus 77 ml/m2, p less than 0.001), and lower LV ejection fraction (51 versus 69%, p less than 0.001) than 10 control individuals. The volume fraction of myofibrils was lower in AI than in controls (44 versus 53%, p less than 0.01), and sarcoplasm was higher (33 versus 21%, p less than 0.01). Mitochondria and interstitial fibrosis did not differ between groups (p greater than 0.05). Thus reduction in the volume fraction of myofibrils was the major ultrastructural finding in LV biopsy samples of patients with heart failure due to aortic insufficiency.

Adult↗