Cardiac Muscle Necrosis Research Articles

Mitochondrial Myopathy inSenna occidentalis-Seed-Fed Chicken

Plants of the genusSenna(formerlyCassia) have been recognized as the cause of a natural and experimental syndrome of muscle degeneration frequently leading to death in animals. Histologically, it demonstrated skeletal and cardiac muscle necrosis, with floccular degeneration and proliferation of sarcolemmal nuclei. Recently, it was described as an experimental model of mitochondrial myopathy in hens chronically treated withSenna occidentalis.Currently, skeletal muscles of chicks intoxicated with seeds of the poisonous plantS. occidentaliswere studied by histochemistry and electron microscopy. Since birth, the birds were fed ground dried seeds of this plant with a regular chicken ration at a dose of 4% for 11 days. Microscopic examination revealed, besides muscle-fiber atrophy, lipid storage in most fibers and a moderate amount of cytochrome oxidase-negative fibers. By electron microscopy, enlarged mitochondria with disrupted or excessively branched cristae were seen. This picture was characteristic of mitochondrial myopathy. These findings have hitherto remained unnoticed in skeletal muscle of young birds treated withS. occidentalis.

Sodium- and calcium-de-endent steps in the mechanism of neonatal rat cardiac myocyte killing by lonophores: I. The sodium-carrying lonophore, monensin

Toxicosis by monensin, a Na +-selective ionophore, induces skeletal and cardiac muscle necrosis. Cultured neonatal rat cardiac myocytes were killed by monensin (>0.2 μg/ml) beginning at 30 min and completing by 60–90 min. Other cultured cell types presumably lacking excitable membranes were not killed by monensin under these conditions. Cardiac myocytes were also killed by nigericin and nonactin (monovalent cation-carrying ionophores with low ion selectivity), but not by valinomycin, which has a high selectivity for K +. Monensin-induced killing was associated with formation of blebs in cell membranes and subsequent swelling of the cells during the early phases of killing, whereas surface membranes of cells permeabilized to trypan blue dye contained discrete small holes visible by scanning electron microscopy. Monensin-induced killing occurred at extracellular Na + concentrations ≥10 m m, but not when Li +, K +, Cs +, Rb +, or choline ions replaced Na + at concentrations up to 0.15 m. Killing was prevented at extracellular pH values ≤6.4 and was enhanced by ouabain, an inhibitor of Na + K + - ATPase-mediated Na + transport. Several characteristics of monensin-induced cardiac myocyte killing were similar to those observed during killing induced by the Ca 2+-carrying ionophore, A23187 plus Ca 2+, including a requirement for extracellular Ca 2+ concentrations >0.5 m m, inhibition by Mn 2+ and Ni 2+, and an associated stimulation of arachidonic acid release. The cell killing characteristics are consistent with a monensin-induced Na + influx which admits toxic levels of extracellular Ca 2+ to the cytoplasm of cells with excitable membranes, possibly via Na + Ca 2+ antiporter protein(s).

Dégénérescence sévère du muscle cardiaque provoquée par <em>Clostridium perfringens</em> de type A chez des jeunes dromadaires (<em>Camelus dromedarius</em>)

Clostridium perfringens type A was isolated from different organs and intestines from three to five weeks old camel calves which have died from heart muscle necrosis. No other bacterial pathogens were isolated. Virus isolation on two different cell lines including a fetal camel skin were also negative. Mice which were injected with bacteria free filtrates prepared from intestinal contents of necropsied camel calves died after one to six hours demonstrating the presence of clostridial toxins. Our findings suggest that the cardiac muscle necrosis is caused by Clostridium perfringens type A toxins.

Thrombolytic therapy and acute myocardial infarction

Coronary thrombosis and subsequent time-dependent wavefroat cardiac muscle necrosis ate the pathophysiological hallmarks of an acute myocardial infarction. Early treatment of the thrombus by intravenous thrombolytic therapy results in a major reduction of mortality by salvage of myocardial muscle and preservation of left ventricular function. Although the benefit of streptokinase has been best documented, second generation thrombolytics (APSAC and rt-PA) are probably superior thrombolytic agents. The data on the additive effect of inhibition of platelet aggregation with low dose acetylsalicylic acid as degree of thrombolysis and mortality after a myocardial infarction are convincing. The reduction in mortality brought about by intravenous thrombolytic therapy is highly time-dependent, so that its application in a patient presenting with an acute myocardial infarction must be considered as a race against time. thrombolytic therapy / myocardiel infarction / fibrinogenolysis.

The association of cardiac muscle necrosis and inflammation with the degenerative and persistent myopathy of MDX mice

Two groups of “mdx” mice, totalling 36 animals of both sexes aged between 8 and 30 weeks, have been studied. In the first group of 10 males and 10 females, 8 males (at 8, 12, 20 and 30 weeks) and 4 females (at 12 and 30 weeks) showed severe limb muscle degeneration and inflammation with prominent regeneration and central nucleation of myofibres; fibrosis and fatty infiltration were not a feature. Five males (at 8, 20 and 30 weeks) and 2 females (at 30 weeks) also showed myocardial necrosis and inflammation. In the second group of 8 males and 8 females only 1 mouse, female at 25 weeks, showed similar changes including the myocardial lesion. Three females showed only focal myopathic changes. All the remaining animals in both groups were normal. These findings in terms of the severity and persistence of the myopathy and the myocardial lesion, not hitherto noted in mdx, suggest that it may be of value as an animal model of Duchenne muscular dystrophy (DMD) and/or other human muscle diseases. The variability probably reflects a failure to preserve an homozygous strain.

Numerical densities of intramembrane particles in the cardiac sarcolemma of normal and myopathic Syrian hamsters

The purpose of this study was to examine the density of intramembrane particles in the cardiac sarcolemma of normal and myopathic Syrian hamsters in a search for a morphological marker of a putative membrane defect. Hereditary cardiomyopathy in hamsters is manifested by progressive multifocal skeletal and cardiac muscle necrosis. Although pharmacological and biochemical data suggest a molecular defect in the cardiac sarcolemma, there has been no morphological observation that would substantiate this suggestion. We quantified numerical densities of intramembrane particles in freeze-fractured sarcolemmal membrane protoplasmic and extracellular faces from the left and right ventricular myocardium of female 25-day-old hamsters of the U.M.-X 7.1 cardiomyopathic line compared with sex- and age-matched randomly bred Syrian hamsters. Intramembrane particle numerical densities significantly increased above control values in cardiomyopathic hamsters for protoplasmic face (from 2188 ± 61 to 2454 ± 89 μm −2 in left ventricle ( P < 0.025) and from 2255 ± 83 to 2574 ± 56 μm −2 in right ventricle ( P < 0.001)). There was no significant difference between intramembrane particle densities of normal and cardiomyopathic hamsters for extracellular face (707 ± 45 and 687 ± 49 μm −2 in the left ventricle and 742 ± 41 and 746 ± 28 μm −2 in the right ventricle). These results implicate an increase of protoplasmic face-associated integral proteins in the sarcolemmal membrane of cardiomyopathic hamster. The significance of this finding is not known. It may represent an adaptive change related to a molecular defect in the sarcolemmal membrane of cardiomyopathic hamster.

Method for determining the volume of cardiac muscle necrosis in patients with myocardial infarction

A method is proposed for determining the volume of cardiac muscle necrosis in patients with transmural, subendocardial and subepicardial myocardial infarctions using the ECG method. To facilitate calculations, a table of the volume of myocardial necrosis has been compiled. The technique was tested on 160 patients.

Prevention by hypothermia of paradoxical calcium necrosis in cardiac muscle

Isolated rat hearts were perfused with calcium-free medium at either 37° or 4°C, and electrical and mechanical phenomena recorded. The calcium-free perfusion of the isolated rat heart at 37°C for periods in excess of 3 min, caused quick cessation of contractile activity with electro-mechanical dissociation. When calcium was restored to the perfusate at 37°C irreversible electro-mechanical dissociation and myocytolysis occurred, accompanied by a massive efflux of intracellular constituents into the perfusate. When the isolated rat heart was perfused with calcium-free medium at 4°C, both the electrocardiogram and contractility disappeared within 15–20 s. The restoration of calcium to these hearts perfused with calcium-free medium at 4°C, permitted rapid recovery of cardiac function upon warming to 37°C. Electron microscopy of hearts perfused with calcium after calcium-free perfusion at 37°C and 4°C showed that at 37°C extensive alteration and lysis of the cardiac organelles occurred, whereas at 4° they were well protected. Uptake of 45Ca 2+ by the myocardium subsequent to calcium-free perfusion at 37°C was approximately 20 times greater than that observed in hearts subjected to calcium deprivation at 4°C. These findings lend support to the view that the paradoxical calcium necrosis of cardiac muscle at 37°C is due to the massive influx of calcium into the cardiac muscle cells following damage to the sarcolemma. It is suggested that the damage to the sarcolemma observed at 37° consists of loss of membrane-bound proteins responsible for the physiologic “calcium channel”. At 4°C their escape from the bilayer appears to beretarded by a more sluggish shift in conformation from the calcium-bound to the calcium-free state, and a more crystalline membrane.

Cardiac tissue response to endotoxin.

Administration of catechol amines together with endotoxin to normal rabbits results in a greater degree of inflammation and necrosis of cardiac muscle than is produced by either agent alone. The damage is prevented or markedly reduced by pretreatment with dibenamine. It can be produced by endotoxin in shocked animals without the catechol amines, presumably because the amines are already present in high concentration. Although the data obtained do not demonstrate that a specific cardiac lesion attributable to endotoxin is a key factor in development of irreversibility to transfusion in hemorrhagic shock, they are not inconsistent with such a hypothesis.

STUDIES OF TOCOPHEROL DEFICIENCY IN INFANTS AND CHILDREN

VITAMIN E was recognized some 35 years ago as a fat-soluble substance necessary for reproduction in the rat. Its potency is measured by assay for fertility and its synonym, tocopherol, comes from Greek words which mean "to bear offspring." Review of the original studies of Mason and his co-workers and of his interpretive writings provides a good stimulus for pediatric interest in the subject. It is proposed to review some literature on the pathologic lesions produced in animals and on the tocopherol content of foods, and then summarize data collected at the Colorado General, Sinai and Johns Hopkins Hospitals on tocopherol deficiency in infants and children. Most of the latter data and detailed references to the literature have been published elsewhere. PATHOLOGIC FINDINGS IN EXPERIMENTAL ANIMALS Although vitamin E has been dubbed the anti-sterility vitamin, its absence from the diet has produced a variety of pathologic states, differing from one species to another, and at different ages in the same species. Some of the conditions found are: Fetal resorption; testicular degeneration; encephalomalacia; "exudative diathesis"; generalized edema; brownish discoloration of smooth muscle, adipose tissue and liver; acute hemorrhagic necrosis of the liver; degeneration of renal tubules; focal necrosis of cardiac muscle; and nutritional muscular dystrophy. Provocative findings in E-deficient animals that call to mind clinical problems in premature infants are: Hemorrhagic manifestations in rat fetuses and chick embryos; hemorrhages in the lungs, visceral and cranial cavities in puppies; subcutaneous, pulmonary and cerebral edema in young chickens, anemia in monkeys; and hemolysis after administration of large doses of vitamin K to rats.