acid-phosphatase and Coronary-Disease

Topics: Acid Phosphatase; Adrenal Cortex Hormones; Animals; Cardiomegaly; Cathepsins; Centrifugation, Density Gradient; Coronary Disease; Fasting; Heart Diseases; Heart Failure; Hormones; Humans; Hyperthyroidism; In Vitro Techniques; Liver; Lysosomes; Myocardial Infarction; Myocardium; Thyroxine

Osteoprotegerin (OPG) inhibits interaction of the receptor-activator of nuclear factor-kappaB (RANK) ligand (RANKL) with its receptor RANK, which is expressed on osteoclasts. OPG appeared to accelerate vascular calcification in vitro by the inhibition of vascular osteoclast-like cells. On the contrary, early-onset arterial calcification was observed in OPG-deficient mice. We measured the coronary artery calcification score (CACS) and abdominal aortic calcification score (AAoCS) by multi-detector computed tomography in 30 pre-dialysis CKD patients (eGFR 20 mL/min on average). Biomarkers were measured, including serum OPG, soluble RANKL (sRANKL) and tartrate-resistant acid phosphatase (TRACP) -5b (the biomarker of osteoclasts independent of renal function). The median values of CACS and AAoCS were 54.4 and 1,088 Agatston units (AU), respectively. Serum OPG was increased and serum sRANKL was decreased. In a multivariate logistic regression analysis using CACS > or = 100 AU as the outcome variable, CACS was found to be positively correlated with serum corrected Ca x iP product and serum OPG, though it was not correlated with serum TRACP-5b. ROC curve analysis showed that the serum OPG cutoff value predicting CACS > or = 100 AU was 5.2 pmol/L (624 pg/mL). In a stepwise regression analysis, log (AAoCS + 1) was positively correlated with serum OPG alone, but it was not correlated with age, eGFR, serum albumin and bone alkaline phosphatase (BAP). No correlation was found between serum OPG and serum TRACP-5b. In conclusion, vascular calcification in pre-dialysis CKD patients was correlated with an increase in OPG, but was independent of serum TRACP-5b. The decrease in serum sRANKL may have been caused by the increase in OPG production.

Topics: Acid Phosphatase; Aorta, Abdominal; Aortic Diseases; Biomarkers; Calcinosis; Coronary Disease; Coronary Vessels; Dialysis; Female; Humans; Isoenzymes; Logistic Models; Male; Osteoclasts; Osteoprotegerin; RANK Ligand; Tartrate-Resistant Acid Phosphatase

Coronary heart disease (CHD) is a major killer worldwide. Atherosclerosis, which is the basis of CHD, is believed to be an inflammatory disorder. Though various aspects of atherosclerosis are extensively studied, leukocytic hydrolytic enzymes are not studied very well with respect to CHD.. This study was planned to assess changes associated with leukocytic hydrolases in CHD patients.. A tertiary care hospital; case-control study.. 106 patients with acute myocardial infarction, 60 patients with unstable angina and 45 healthy controls were included in the study. Acid phosphatase, lysozyme, adenosine deaminase (ADA) and cathepsin-G levels were estimated from leukocytes. Reduced glutathione (GSH) and malondialdehyde (MDA) levels were measured.. Statistical comparison of data was done using student's t-test (unpaired). Correlation difference was calculated by using Pearson correlation coefficient.. Significantly higher levels of acid phosphatase, lysozyme, ADA with lower levels of cathepsin G in leukocytes were observed in CHD group. We also found significantly higher levels of serum MDA with lower concentrations of blood GSH in CHD group. In diabetic CHD group, significantly higher levels of leukocytic acid phosphatase, lysozyme, ADA and serum MDA with lower levels of cathepsin G and blood GSH were observed.. Our study indicates that leukocyte hydrolytic enzymes, mainly acid phosphatase, lysozyme and ADA were more active in CHD patients and may contribute to inflammation related with CHD. Its also indicates that leukocyte cathepsin-G may have antiinflammatory role.

Topics: Acid Phosphatase; Acute Disease; Adult; Angina, Unstable; Cathepsin G; Cathepsins; Coronary Disease; Female; Humans; Leukocytes; Male; Malondialdehyde; Middle Aged; Muramidase; Myocardial Infarction; Serine Endopeptidases

Effect of lignocaine and centbucridine against isoproterenol-induced biochemical changes was studied in the rat. Isoproterenol (40 mg/kg twice) increased the heart weight, level of manolaldehyde (MDA) and activity of acid phosphatase, but decreased the myocardial phospholipid content at 48 h. In addition, increase in plasma triglyceride, cholesterol, MDA and creatine phosphokinase activity was observed. Pretreatment of the animals with lignocaine (10 mg/kg) or centbucridine (1, 3 and 10 mg/kg) protected the animals against these biochemical changes. However, increase in heart weight consequent to isoproterenol treatment could not be prevented. Total protection against creatine phosphokinase release in the blood was also not observed. The results suggest that the two drugs inhibit lipolysis. They may also inhibit phospholipases leading to protection against ischemia-induced changes in the rat.

Topics: Acid Phosphatase; Anesthetics, Local; Animals; Coronary Disease; Isoproterenol; Lidocaine; Lipolysis; Male; Phospholipids; Rats; Tacrine

The effect of NCO-700 (1), a protease inhibitor, on subcellular distribution of lysosomal enzymes was studied in the ischemic perfused rat heart. Ischemia was induced by lowering the afterload pressure of the working heart preparation. The subcellular distribution of lysosomal enzymes was estimated by the ratio of the activities of cathepsin D, beta,N-acetylglucosaminidase, and acid phosphatase in the cytoplasm to the total enzyme activities. Ischemia caused subcellular redistribution of lysosomal enzymes from the lysosomes to the cytoplasm, indicating the rupture of lysosomes. Compound 1 (1.75 x 10(-4) M) was provided for the heart 5 min before the onset of ischemia. Compound 1 appeared to inhibit the rupture of lysosomes being caused by ischemia. The mechanism by which 1 protects the myocardium against ischemic injury may involve the inhibition of lysosomal rupture in the ischemic myocardium.

Topics: Acetylglucosaminidase; Acid Phosphatase; Animals; Cathepsin D; Coronary Disease; In Vitro Techniques; Lysosomes; Male; Myocardium; Piperazines; Protease Inhibitors; Rats; Rats, Inbred Strains; Subcellular Fractions

Cytochemical investigations were carried out of the activity of peroxidase, nitroblue tetrazolium test and level of cationic proteins in patients with infectious-allergic and myocarditis cardiosclerosis. The activity of peroxidase was reduced in patients with infectious-allergic myocarditis. Patients with infectious-allergic myocarditis and myocarditic cardiosclerosis revealed an increase of the level of cationic proteins. The nitroblue tetrazolium test showed elevated values in the neutrophils and lymphocytes in patients with infectious-allergic myocarditis. In myocarditic cardiosclerosis 15 patients showed an increase of the activity of nitroblue tetrazolium test in lymphocytes. The employed cytochemical methods are of value for the diagnosis of infectious-allergic myocarditis and myocarditic cardiosclerosis.

Topics: Acid Phosphatase; Adolescent; Adult; Alkaline Phosphatase; Blood Proteins; Coronary Disease; Female; Histocytochemistry; Humans; Leukocytes; Male; Middle Aged; Myocarditis; Peroxidase

The acid phosphatase and cathepsin D activities and cAMP and cGMP levels in isolated perfused rat heart were investigated during various periods of ischaemic myocardial injury and postischaemic reperfusion. The effect of phosphodiesterase inhibitor--caffeine was also studied. Free acid hydrolases activities and cyclic nucleotide content were increased under 40 and 60 min ischemia and 20 min postischaemic reperfusion. Addition of 50 microM caffeine to perfusion solution after 30 min of ischaemia resulted in increase of cAMP level, cAMP/cGMP ratio, lysosomal bound activities of acid hydrolase and decrease of free acid hydrolase activities. The obtained results suggested that defect in cAMP synthesis might be present in lysosomal membranes labilization in cardiomyocytes injured during ischaemic conditions. Addition of such agents, as caffeine, which increased heart cAMP level, may be effective in lysosomal membranes stabilization under reversible heart ischaemia and reperfusion.

Topics: Acid Phosphatase; Animals; Caffeine; Cathepsin D; Coronary Disease; Cyclic AMP; Cyclic GMP; Male; Myocardial Reperfusion; Myocardium; Rats; Time Factors

Lysosomal changes have been implicated as one of the major factors contributing to the progression and complications of atherosclerosis, and recently foam cell formation has been correlated with increases in several acid hydrolases. To explore at the subcellular level relationships among lesion progression, cellular lipid accumulation, and lysosomal change, atherosclerotic lesions from hypercholesterolemic White Carneau pigeons have been studied through combined ultrastructural cytochemistry and stereo (three-dimensional) high-voltage electron microscopy. Lysosomal enzyme activity in the prelesion intima and in foam cells of early lesions was in discrete lysosomes of macrophage foam cells. Foam cell lipid at the early stages was primarily (72%) in cytoplasmic droplets, which formed a three-dimensional network with the small (0.25-0.8 microM in diameter), reaction-positive lysosomes suspended at the vertices of a cytoplasmic lattice that delineated individual lipid pools. Concomitant with lesion progression and increasing complexity, foam cell lysosome number, size, and complexity increased. The complexity was characterized by lysosome lipid accumulation (60% of cell lipid) and the fusion of lysosomes to form multilobulated organelles in which the acid phosphatase reaction product typically was circumferential to the lysosomal lipid core. The involvement of lysosomes climaxed in the more advanced region of lesions with foam cells in which the bulk of cytoplasmic volume was occupied by large (15-20 microM in diameter), multicompartmental, lipid-containing lysosomes. It is suggested that this progressive involvement of lysosomes is responsible for cell and tissue necroses characteristic of advanced lesions.

Topics: Acid Phosphatase; Animals; Arteriosclerosis; Columbidae; Coronary Disease; Coronary Vessels; Diet, Atherogenic; Lipids; Lysosomes; Microscopy, Electron

Effect of diltiazem on subcellular distribution of lysosomal enzymes, high-energy phosphate metabolism and mechanical function in the ischemic heart was studied. Ischemia was induced by lowering the afterload pressure of the perfused working rat heart. The activities of cathepsin D, beta,N-acetylglucosaminidase and acid phosphatase were determined in the nonsedimentable and sedimentable fractions after centrifugation of the tissue extract to assess the subcellular distribution of lysosomal enzymes. After ischemia, decreases in the mechanical function and the tissue level of high-energy phosphates were observed. In addition, ischemia caused subcellular redistribution of lysosomal enzymes from the lysosomes to the cytoplasm. Reperfusion of the ischemic heart did not restore the mechanical function and the level of high-energy phosphates completely. Diltiazem (2.21 X 10(-6), 1.11 X 10(-5) and 2.21 X 10(-5) M) was provided for the heart 5 min before the onset of ischemia. Diltiazem preserved high-energy phosphates in the ischemic heart, and inhibited the subcellular redistribution of lysosomal enzymes being caused by ischemia, depending on its concentration. Reperfusion after ischemia with diltiazem recovered the mechanical function that had been decreased by ischemia. These results may indicate that diltiazem can protect the myocardium against ischemic damage.

Topics: Acetylglucosaminidase; Acid Phosphatase; Adenosine Triphosphate; Animals; Cathepsin D; Coronary Disease; Diltiazem; Lysosomes; Male; Myocardium; Perfusion; Phosphocreatine; Rats; Rats, Inbred Strains

Cholesterol ester storage disease is a rare, inherited metabolic disorder of lipid associated with acid cholesteryl ester hydrolase deficiency. Thus far, 15 cases have been reported in the world literature. Reported here is the autopsy study of the oldest patient with this disease. The lipid storage occurred in the forms of birefringent needle-shaped crystals limited to hepatocytes and non-birefringent autofluorescent granules accumulated within the foam cells of the hepatic portal triads, duodenum, and ovaries. The cholesterol content of the liver was 16 times normal, primarily caused by increased cholesterol ester. Only trace cholesteryl ester hydrolase activity was demonstrated in the liver. An additional unique finding in our case was the presence of mesenteric lipodystrophy. Whether these two rare disorders observed in our patient represent unrelated conditions or have an etiologic association remains unknown.

Topics: Acid Phosphatase; Cholesterol Esters; Coronary Disease; Female; Humans; Lipid Metabolism, Inborn Errors; Liver; Liver Cirrhosis; Mesentery; Middle Aged; Portal System; Sterol Esterase; Whipple Disease

Alterations in the localization and the intensity of acid phosphatase activity were studied electron microscopically in acute ischemic myocardial cells in the dog, in relation to processes of cellular degradation. In normal myocardial cells, the acid phosphatase activity was concentrated in the terminal cisternae, the longitudinal elements and the subsarcolemmal cisternae of the sarcoplasmic reticulum and the primary lysosomes. Activity was moderate in the secondary lysosomes, residual bodies and Golgi apparatus. As early as 15 min after coronary ligation the intensity of acid phosphatase activity increased in the enlarged lysosomes and the sarcoplasmic reticulum of the ischemic myocardial cells. Fine deposits of the reaction product were distributed in the sarcoplasm around lysosomes and the sarcoplasmic reticulum after 30 min, and the activity began to decrease in lysosomes and in the sarcoplasmic reticulum. One to 3 hours after ligation, intramitochondrial dense deposits appeared, and the reaction product decreased both in lysosomes and the sarcoplasmic reticulum. The fine reaction product, which leaked from lysosomes and the sarcoplasmic reticulum, was scattered in the sarcoplasm and was accompanied by fine structural changes indicating cellular necrosis. From these findings it is strongly suggested that acid hydrolases in lysosomes and the sarcoplasmic reticulum are closely related to the necrotic process in ischemic myocardial cells.

Topics: Acid Phosphatase; Acute Disease; Animals; Arterial Occlusive Diseases; Coronary Disease; Dogs; Histocytochemistry; Lysosomes; Mitochondria, Heart; Myocardium; Sarcoplasmic Reticulum

Alterations in myocardial acid hydrolases in acute ischemia were studied in relation to the evolution of cardiac cellular necrosis by the determination of cathepsin D, acid phosphatase (AcPase), and beta-glucuronidase activities of the myocardial fractions and by electron microscopic cytochemical studies on AcPase in the canine heart. In the normal myocardium, the same level of activity of acid hydrolases was found in sarcoplasmic reticulum (SR) as in the lysosome fraction. In electron microscopy, AcPase reaction products were observed markedly in SR and moderately in lysosomes, in residual bodies, and in Golgi apparatus. In the ischemic myocardium, at 20 to 30 min after coronary ligation, activation of these enzymes was observed in both SR and lysosomes, and at 60 to 90 min they were decreased in the particles and, in turn, increased in the cytoplasm accompanying the ischemic fine structural changes. At 2 to 3 hr those acid hydrolase activities in the cytosol were decreased, indicating the loss of enzymes from necrotic myocardial cells. Acid hydrolases are the most important factor for the evolution of ischemic myocardial necrosis by being activated not only in lysosomes but also in SR and by being released to the cytoplasm to disintegrate the cellular structures.

Topics: Acid Phosphatase; Animals; Cathepsins; Coronary Disease; Dogs; Glucuronidase; Lysosomes; Microsomes; Mitochondria, Heart

Glutathion (GSH) plays an important role in maintenance of the redox state of the myocardium and acts as the membrane stabilizer. Seventeen patients who underwent cardiac surgery were subjected to cardiopulmonary bypass (CPB) and ischemic cardioplegia. The effect of GSH on ischemic myocardium was evaluated by serum lysosomal enzymes (acid phosphatase, beta-glucuronidase), isoenzymes of creatine phosphokinase (MB-CPK) and aspartate aminotransferase (m-GOT). standard CPB was instituted and systemic hypothermia was employed. GSH was administered to 8 patients in a dose of 200 mg/kg i.v. prior to institution of CPB. Mixed venous blood was sampled before administration of GSH, 10 min after institution of CPB and 0, 1, 6, 24 and 48 hr of reperfusion period following cardioplegia. Activity of acid phosphatase and beta-glucuronidase were significantly suppressed in the GSH-treated group compared to the non-treated group at 24 hours of reperfusion and immediately after aortic unclamping, respectively. Serum MB-CPK levels remained stable during reperfusion, but in the non-treated group, the level increased significantly at 6 hours of reperfusion. Increment of serum m-GOT levels was significantly suppressed at 1, 6 and 24 hours of reperfusion, compared to the non-treated group. These data suggest that pretreatment of GSH can protect the myocardium subjected to CPB from ischemic insult.

Topics: Acid Phosphatase; Aspartate Aminotransferases; Cardiopulmonary Bypass; Coronary Disease; Creatine Kinase; Glucuronidase; Glutathione; Heart Arrest, Induced; Humans; Hypothermia, Induced; Isoenzymes; Lysosomes; Middle Aged

Activities and subcellular distributions of acid hydrolases, cathepsin D, acid phosphatase and beta-glucuronidase in myocardial subfractions were determined serially with reference to the initiation of myocardial necrosis in dog hearts with acute ischemia. The following results were obtained: 1) In the normal myocardium, respectable activities of three enzymes were obtained either in the sarcoplasmic reticulum or in the lysosome-containing fraction. 2) Thirty min after coronary ligation, an increase in the activities was observed in both lysosome and sarcoplasmic reticulum fractions of the ischemic heart muscle. After 60 to 90 min these activities were decreased rapidly in both fractions to about 70% of those of the normal myocardium with an increase in the cytosolic activity. Two to 3 hours after ligation, the reduction in the cytosolic activity was noted, indicating an escape of the enzymes from the necrotic myocardium. The subcellular distribution of these enzymes was further altered in the ischemic heart muscle for 12 to 14 hours reflecting an infiltration of the interstitial cells. These findings suggest that activation and release of acid hydrolases not only in lysosomes but also in the sarcoplasmic reticulum are one of the primary and the earliest factors for the evolution of ischemic myocardial injury which leads to necrosis.

Topics: Acid Phosphatase; Animals; Cathepsin D; Cathepsins; Coronary Disease; Dogs; Glucuronidase; Hydrolases; Lysosomes; Mitochondria, Heart; Myocardium; Necrosis

Protective action of aprotinin froom ischemic myocardial damage was evaluated in 9 patients compared to non-treated 18 patients, who underwent open heart surgery (22 ACB, 3 AVR and 2 MVR) with respect to the alterations of beta-glucronidase, acid-phosphatase, MB-CPK and m-GOT. Cold cardioplegia with glucose-insulin-potassium solution was used in this investigation. Average arrest time was 78.6 +/- 4.9 minutes associated with hypothermia between 25 and 28 degrees C in rectal temperature. Aprotinin was administered in 9 patients intravenously with 5,000 KIU/Kg 30 minutes prior to CPB and then 5,000 KIU/Kg in the prime solution. Activity of beta-glucronidase was significantly suppressed in the aprotinin-treated group compared to the non-treated group following cardioplegia and in the reperfusion period up to 6 hours, however, acid-phosphatase failed to demonstrate significant difference among two groups. Serum MB-CPK and m-GOT levels in the aprotinin-treated group did not elevate the beginning of reperfusion following cardioplegia. These data suggest that aprotinin add myocardial protection to cold cardioplegia.

Topics: Acid Phosphatase; Aprotinin; Aspartate Aminotransferases; Cardiopulmonary Bypass; Coronary Disease; Creatine Kinase; Heart Arrest, Induced; Humans; Hypothermia, Induced; Isoenzymes; Lysosomes

Rabbit hearts perfused under hypoxic conditions underwent progressive subcellular damage, which becomes irreversible by one hour. During the first 20 minutes of perfusion, minor dilation of mitochondria and condensation of nuclear chromatin were the only salient features of cell injury. By 40 minutes moderate mitochondrial swelling was evident in hypoxic myocytes. Moreover, an increase in degenerating mitochondria and autophagic vacuoles was apparent. Reperfusion after either 20 or 40 minutes of hypoxia restored contractility, and injured myocytes underwent a cellular repair process that involved a dramatic increase in lysosomal autoplagy. One hour of hypoxia yielded irreversibly injured myocytes. Upon reoxygenation, some of these cells displayed typical changes of necrosis, but others apparently underwent an abortive repair process involving the formation of large, probably nonfunctional lysosomes. These observations suggest that lysosomal autophagy is important in the efforts at repair that cardiac cells initiate during and after hypoxia.

Topics: Acid Phosphatase; Animals; Autolysis; Coronary Disease; Disease Models, Animal; Hydrolases; Hypoxia; In Vitro Techniques; Lysosomes; Male; Mitochondria, Heart; Myocardium; Oxygen Consumption; Rabbits

Prolonged starvation produces dramatic changes both in the lysosomal properties of the heart and in its energy stores and, therefore, might be expected to alter some of the characteristic cardiac responses to ischemia. To test this possibility we ligated the circumflex coronary artery of rabbits that had been fed normally or starved for 6 days. Ultrastructural evidence of myocytic damage following 30 to 120 minutes of ischemia was much less severe in the starved animals than in the normally fed group. The development of signs of irreversible injury (e.g., osmiophilic densities in mitochondria) was delayed for 1 hour or more by starvation. A similar delay occurred in the biochemical redistribution of cathepsin D activity and in the cytoplasmic release of acid hydrolases from lysosomes and sarcoplasmic reticulum. These results indicate a marked protective effect of starvation against myocardial ischemia. In addition, both in starved and in fed animals, ischemically induced release of lysosomal enzymes was closely linked temporally to the development of subcellular damage.

Topics: Acid Phosphatase; Animals; Cathepsins; Coronary Disease; Histocytochemistry; Lysosomes; Male; Myocardium; Rabbits; Sarcoplasmic Reticulum; Starvation

Topics: Acid Phosphatase; Animals; Coronary Disease; Disease Models, Animal; Dogs; Indomethacin; Intracellular Membranes; Lysosomes; Male; Myocardium; Nucleotides, Cyclic; Prostaglandins

The conducting system was studied in an in situ perfused swine heart preparation with reduced coronary flow (ischemia) using perfusate containing high and low levels of glucose (26.6 versus 8.6mM) with and without insulin. Coronary flow was maintained at normal levels for 60 minutes in control hearts. In ischemic hearts flow was reduced to about 50 percent of control levels for 30 minutes. Ultrastructural studies documented only subtle modifications of Purkinje fibers in ischemic hearts. Glycogen depletion and disruption of cell junctions were observed in some fibers. One consistent finding was the activation of the lysosomal system. The outer membranes of primary lysosomes appeared herniated and in some cases disrupted, and small vesicles containing hydrolytic enzymes were seen in association with the Golgi apparatus and larger primary lysosomes. Specimens prepared for the demonstration of acid phosphatase indicated a redistribution of hydrolytic enzymes in Purkinje fibers with a depostion of acid hydrolases in smaller lysosomal vesicles, the transverse and side-to-side junctions between cells, and occasionally in the sarcoplasmic reticulum. Enriched perfusate containing high levels of glucose with insulin appeared to have no therapeutic effects in terms of the structure of the Purkinje fibers. The results suggest that alterations in the lysosomal system may be one of the earliest structural changes which occur in oxygen-deficient hearts.

Topics: Acid Phosphatase; Animals; Coronary Disease; Female; Glucose; Golgi Apparatus; Heart Conduction System; Hydrolases; Insulin; Lysosomes; Male; Mitochondria, Heart; Myocardium; Myofibrils; Perfusion; Purkinje Fibers; Sarcoplasmic Reticulum; Swine

Topics: Acid Phosphatase; Animals; Cell Membrane; Coronary Disease; In Vitro Techniques; Male; Myocardium; Rats; Sarcoplasmic Reticulum

Topics: Acid Phosphatase; Alkaline Phosphatase; Coronary Disease; Enzyme Activation; Glycogen; Humans; Leukocytes; Lipids; Oxidoreductases

Topics: Acetylglucosaminidase; Acid Phosphatase; Animals; Cathepsins; Coronary Disease; Cytosol; Lysosomes; Male; Organoids; Rabbits; Solubility; Time Factors

Topics: Acid Phosphatase; Animals; Arylsulfatases; Coronary Disease; Golgi Apparatus; Lysosomes; Male; Microscopy, Electron; Mitochondrial Swelling; Myocardium; Necrosis; Rabbits; Time Factors

Occlusion of the circumflex coronary artery induced a profound redistribution in ischemic rabbit myocardium of several lysosomal acid hydrolases, including cathepsin D, B-acetylglycosaminidase, and acid phosphatase. 30-45 min after ligation non-sedimentable cathepsin D activity rose from 36% of the total activity to 42-48%, and in immunohistochemical preparations cathepsin D appeared to have diffused from lysosomes into the cytosol of injured cells. A pharmacologic dose of methylprednisolone (50mg/kg) significantly delayed the subcellular redistribution of cathepsin D and the other hydrolases in ischemic heart. Thus, in treated hearts the nonsedimentable activity of cathepsin D rose to only 38% after 30 min of ischemia and 42% after 45 min (P is less than 0.05 compared to untreated ischemia at each time). Similarly, unlike untreated hearts, noevidence of enzyme diffusion from lysosomes could be demonstrated immunohistochemically in corticosteroid-treated ischemic hearts for over 45 min. After 1-2 h of ischemia, however, steroid-protected myocytes deteriorated and the biochemical activity and anatomical distribution of cathepsin D were indistinguishable from untreated ischemic hearts. This study demonstrates that corticosteroid pretreatment does not prevent alterations in cardiac lysosomes during severe ischemia indefinitely, but does delay their development significantly.

Topics: Acetylglucosaminidase; Acid Phosphatase; Animals; Cathepsins; Coronary Disease; Disease Models, Animal; Lysosomes; Male; Methylprednisolone; Myocardium; Rabbits; Time Factors

Topics: Acid Phosphatase; Cells, Cultured; Coronary Disease; Lysosomes; Permeability

Topics: Acid Phosphatase; Animals; Coronary Disease; Heart Arrest; Intercellular Junctions; Lysosomes; Male; Myocardium; Organoids; Rats

It has been proposed that administration of pharmacologic doses of glucocorticoids may be beneficial in the setting of acute myocardial ischemia because of their ability to stabilize lysosomal membranes and thereby to prevent the leakage of proteolytic enzymes into the cytoplasm and interstitium. We collected cardiac lymph in anesthetized open-chest dogs in successive 2-h periods and used acid phosphatase as our marker lysosomal enzyme. In group 1 (n=5), we studied the effect of time alone. In these dogs, the total amount of acid phosphatase decreased (P less than 0.05). In group 2 (n=5), methylprednisolone, 30 mg/kg iv, was given. This drug did not change any variable we measured. Ligation of the circumflex coronary artery in group 3 (n=7), produced a significant increase (P less than 0.05) in the amount of acid phosphatase drained from the heart compared to group 1. In the dogs of group 4 (n=5), methylprednisolone did not reduce, and may have augmented, the total amount of acid phosphatase draining from the heart. Thus glucocorticoids do not appear to reduce the amount of acid phosphatase released by the ischemic myocardium into the cardiac lymph.

Topics: Acid Phosphatase; Animals; Coronary Disease; Dogs; Lymph; Lymphatic System; Lysosomes; Methylprednisolone; Myocardium; Time Factors

A new experimental model for the study of two important aspects of ischemia, namely, oxygen and substrate deprivation, is proposed: the intact, beating fetal mouse heart in organ culture. This model offers long-term stability, ease and reproducibility of preparation, and the ability to manipulate experimental conditions. Hearts deprived of oxygen and glucose ceased beating immediately. After 3-4 hr of deprivation, biochemical and ultrastructural changes consistent with ischemic injury were evident. These include depletion of ATP and glycogen levels, loss of cytoplasmic enzymes, and extensive swelling and disruption of mitochondrial structure. Glucose and insulin partially protected against ATP depletion. Upon resupply of oxygen and glucose , beating resumed immediately, ATP levels rapidly increased to control levels and, consistent with this, mitochondrial structure returned toward normal. During the recovery phase autophagic vacuoles containing damaged mitochondria and myofibrils were seen, indicating that repair mechanisms were activated. Consistent with this, the proportion of lysosomal enzymes that were present in the nonsedimentable fraction of the tissue homogenate increased. We conclude that the cultured fetal mouse heart is a model useful for studying myocardial responses to anoxia and/or substrate deprivation and for assessing interventions designed to limit damage or to stimulate repair after ischemic injury.

Topics: Acetylglucosaminidase; Acid Phosphatase; Adenosine Triphosphate; Animals; Cathepsins; Coronary Disease; Disease Models, Animal; Female; Fetus; Gestational Age; Glucose; Lysosomes; Mice; Microscopy, Electron; Myocardium; Organ Culture Techniques; Oxygen Consumption; Pregnancy; Time Factors

The present study was undertaken to determine the involvement of cardiac lyososomes in injury to the myocardium after cardiopulmonary bypass. Twenty conditioned mongrel dogs, weighing 15 to 18 kilograms, were fasted overnight, anesthetized with sodium pentobarbital (30 mg. per kilogram), intubated, and maintained on positive-pressure ventilation. The femoral artery and femoral vein were cannulated for pressure measurements. After median sternotomy, intravenous heparin was administered (3 mg. per kilogram) before the aorta and the superior and inferior venae cavae were cannulated for bypass. Bypass was instituted with a Travenol modular pump and a Bentley pediatric bubble oxygenator and heat exchanger. The ultrastructural effects on the myocardium and the acid phosphatase activity in the left ventricle were compared in dogs exposed to bypass for 1 hour with varying types of myocardial support: perfusion of the coronary arteries, normothermic ischemic arrest, or selective cardiac hypothermia. The morphology of control hearts and hearts fixed after 1 hour of coronary perfusion were similar. The distribution and structure of subcellular lysosomes were the same and showed identical patterns of acid phosphatase activity. Normothermic ischemic arrest was associated with a loss of glycogen stores, disrupted sarcoplasmic reticulum and T tubules, vacuolization and decrease in matrix density of mitochondria, and separation of the intercalated discs. Lysosomal activity was absent except for occasional residual bodies in the nuclear pole zone of the myocardial cells. Selective cardiac hypothermia produced results superior to those from normothermic ischemic arrest. Although these hearts showed proliferation of the lysosomal compartment, the organelles responsible for excitation-contraction coupling were spared.

Topics: Acid Phosphatase; Animals; Cardiopulmonary Bypass; Coronary Disease; Dogs; Extracorporeal Circulation; Glycogen; Heart Arrest; Heart Diseases; Lysosomes; Mitochondria, Muscle; Myocardium; Sarcoplasmic Reticulum; Time Factors

Early changes in lysosomal enzymes must occur if their role is significant in irreversible myocardial injury. Therefore, we ligated the anterior descending coronary artery in 14 dogs and after 60 min excised epicardial and endocardial samples from the ischemic and adjacent normal heart. The collateral flow measured with radioactive microspheres in the endocardial samples averaged 19% of control. The muscle was disrupted and fractionated by ultracentrifugation into nuclear pellet (NP), heavy lysosomal pellet (HL), light lysosomal pellet (LL), microsomal pellet (M) and supernate (S). Electron microscopy demonstrated changes characteristic of sichemia in whole tissues and sedimented fractions. Acid phosphatase reaction product was present in residual bodies in the HL fraction and membrane-bound vesicles in the LL fraction and in the intact tissue. Significant decreases in the specific activity of N-acetyl-beta-glucosaminidase and beta-glucuronidase occurred in the endocardial LL fraction, while significant increases in both were found in the ts fraction (P less than 0.05). Losses of acid phosphatase occurred in both LL and S fractions. Moreover, decreases of total N-acetyl-beta-glucosaminidase in the HL fraction and of total beta-glucuronidase and acid phosphatase in the LL fraction were positively correlated (P less than 0.01) with the degree of ischemia measured with radioactive microspheres. Only insignificant enzymatic changes were found when the collateral flow was greater than 40%, and the differences were less significant in epicardial samples where the flow averaged 29%. The early loss of enzymes from the lysosomal fractions in severe ischemia suggests a role for lysosomal hydrolases in the necrosis that follows coronary occlusion.

Topics: Acetylglucosaminidase; Acid Phosphatase; Acute Disease; Anaerobiosis; Animals; Collateral Circulation; Coronary Circulation; Coronary Disease; Disease Models, Animal; Dogs; Endocardium; Hydrolases; Hydrolysis; Lysosomes; Myocardium; Polyethylene Glycols; Proteins

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Coronary Disease; Erythrocytes; Female; Humans; Male; Middle Aged

Topics: Acid Phosphatase; Acute Disease; Adult; Aged; Alkaline Phosphatase; Angina Pectoris; Aspartate Aminotransferases; Butyrates; Carbonic Anhydrases; Catalase; Ceruloplasmin; Cholinesterases; Clinical Enzyme Tests; Coronary Disease; Female; Humans; Male; Middle Aged; Myocardial Infarction

Topics: Acid Phosphatase; Adenosine Monophosphate; Adenosine Triphosphatases; Adolescent; Adult; Aged; Alkaline Phosphatase; Arteriosclerosis; Autopsy; Coronary Disease; Coronary Vessels; Dihydrolipoamide Dehydrogenase; Esterases; Glutamate Dehydrogenase; Glycerolphosphate Dehydrogenase; Histocytochemistry; Humans; L-Lactate Dehydrogenase; Leucyl Aminopeptidase; Lipase; Malate Dehydrogenase; Middle Aged; Oxidation-Reduction; Oxidoreductases; Phosphoric Monoester Hydrolases; Succinate Dehydrogenase

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Aorta; Arteriosclerosis; Blood Vessels; Child; Chronic Disease; Coronary Disease; Coronary Vessels; Esterases; Female; Humans; Hyperthyroidism; Lipase; Lipid Metabolism; Liver Cirrhosis; Male; Middle Aged; Pneumonia; Tuberculosis, Pulmonary

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Arteriosclerosis; Coronary Disease; Dihydrolipoamide Dehydrogenase; Enzyme Induction; Esterases; Extracellular Space; Humans; L-Lactate Dehydrogenase; Lipase; Lipid Metabolism; Muscle, Smooth; Succinate Dehydrogenase

Topics: Acid Phosphatase; Animals; Aspartate Aminotransferases; Carbon Dioxide; Coronary Disease; Esterases; Esters; Isoenzymes; L-Lactate Dehydrogenase; Myocardium; Rabbits; Time Factors

Topics: Acid Phosphatase; Animals; Coronary Disease; Coronary Vessels; Dogs; Female; Glucuronidase; Glycogen; Heart Ventricles; In Vitro Techniques; Ligation; Lysosomes; Male; Muscles; Myocardial Infarction; Papillary Muscles; Potassium; Time Factors

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Arteriosclerosis; Carbamates; Cholesterol; Coronary Disease; Diethylstilbestrol; Esterases; Fructose-Bisphosphate Aldolase; Glucosephosphate Dehydrogenase; Glucosyltransferases; Glucuronidase; Histocytochemistry; L-Lactate Dehydrogenase; Lipase; Nucleotidases; Pyridines; Rabbits; Succinate Dehydrogenase

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Coronary Disease; Esterases; Glucosephosphate Dehydrogenase; Histocytochemistry; L-Lactate Dehydrogenase; Male; Microcirculation; Monoamine Oxidase; Myocardium; Nucleotidyltransferases; Rats; Succinate Dehydrogenase; Time Factors

Topics: Acid Phosphatase; Adult; Alanine Transaminase; Alkaline Phosphatase; Blood Cell Count; Blood Glucose; Clinical Enzyme Tests; Coronary Disease; Diet; Dietary Fats; Fasting; Fatty Liver; Hematocrit; Hemoglobins; Humans; L-Lactate Dehydrogenase; Life Support Systems; Male; Metals; Osmolar Concentration; Time Factors; Triglycerides

Topics: Acid Phosphatase; Alanine Transaminase; Alcohol Oxidoreductases; Alkaline Phosphatase; Amylases; Animals; Aorta; Arteries; Arteriosclerosis; Aspartate Aminotransferases; Blood Cell Count; Blood Glucose; Calcium; Cholesterol; Cholinesterases; Coronary Disease; Fatty Acids; Fatty Acids, Nonesterified; Female; Hematocrit; Hemoglobins; L-Lactate Dehydrogenase; Leucyl Aminopeptidase; Lipids; Lipoprotein Lipase; Lipoproteins; Liver; Myocardium; Nicotine; Phospholipids; Potassium; Rabbits; Smoking; Sodium; Time Factors; Urea

Topics: Acid Phosphatase; Alkaline Phosphatase; Capillaries; Coronary Disease; Coronary Vessels; Dihydrolipoamide Dehydrogenase; Electron Transport Complex IV; Esterases; Glycogen; Heart Conduction System; Heart Neoplasms; Histocytochemistry; Humans; Hypertension; Lipase; Methods; Myocardial Infarction; NAD; NADP; Regional Blood Flow; Succinate Dehydrogenase

Topics: Acid Phosphatase; Acute Disease; Aged; Alkaline Phosphatase; Chronic Disease; Coronary Disease; Electron Transport Complex IV; Esterases; Heart Neoplasms; Histocytochemistry; Humans; Lipase; Methods; Middle Aged; Myocardium; NAD; NADP; Peritonitis; Succinate Dehydrogenase; Uremia

Topics: Acid Phosphatase; Black People; Coronary Disease; Embolism; Humans