Ruben P. Laguens

Endurance Training in the Spontaneously Hypertensive Rat: Conversion of Pathological into Physiological Cardiac Hypertrophy

The effect of endurance training (swimming 90 min/d for 5 days a week for 60 days) on cardiac hypertrophy was investigated in the spontaneously hypertensive rat (SHR). Sedentary SHRs (SHR-Cs) and normotensive Wistar rats were used as controls. Exercise training enhanced myocardial hypertrophy assessed by left ventricular weight/tibial length (228±7 versus 251±5 mg/cm in SHR-Cs and exercised SHRs [SHR-Es], respectively). Myocyte cross-sectional area increased ≈40%, collagen volume fraction decreased ≈50%, and capillary density increased ≈45% in SHR-Es compared with SHR-Cs. The mRNA abundance of atrial natriuretic factor and myosin light chain 2 was decreased by the swimming routine (100±19% versus 41±10% and 100±8% versus 61±9% for atrial natriuretic factor and myosin light chain 2 in SHR-Cs and SHR-Es, respectively). The expression of sarcoplasmic reticulum Ca2+ pump was significantly augmented, whereas that of Na+/Ca2+ exchanger was unchanged (93±7% versus 167±8% and 158±13% versus 157±7%, sarcoplasmic reticulum Ca2+ pump and Na+/Ca2+ exchanger in SHR-Cs and SHR-Es, respectively; P<0.05). Endurance training inhibited apoptosis, as reflected by a decrease in caspase 3 activation and poly(ADP-ribose) polymerase-1 cleavage, and normalized calcineurin activity without inducing significant changes in the phosphatidylinositol 3-kinase/Akt pathway. The swimming routine improved midventricular shortening determined by echocardiography (32.4±0.9% versus 36.9±1.1% in SHR-Cs and SHR-Es, respectively; P<0.05) and decreased the left ventricular free wall thickness/left ventricular cavity radius toward an eccentric model of cardiac hypertrophy (0.59±0.02 versus 0.53±0.01 in SHR-Cs and SHR-Es, respectively; P<0.05). In conclusion, we present data demonstrating the effectiveness of endurance training to convert pathological into physiological hypertrophy improving cardiac performance. The reduction of myocardial fibrosis and calcineurin activity plus the increase in capillary density represent factors to be considered in determining this beneficial effect.

Satellite cells of skeletal muscle fibers in human progressive muscular dystrophy

In biopsy specimens of five cases of human progressive muscular dystrophy studied with the electron microscope a special kind of cell located between the two layers of the surface membrane complex of the muscle fiber is described. Based on the fact that they hypertrophy when the muscle fiber is damaged, and especially when it is regenerating, it is suggested that they might perform a trophic function, acting as an intermediate cell between the tissue space and the muscle fiber. Auf Grund elektronenmikroskopischer Untersuchungen von Muskelbiopsien von fünf Fällen menschlicher progressiver Muskeldystrophie wird eine besondere Zellart beschrieben, die zwischen den beiden Lagern des oberflächlichen Membrankomplexes der Muskelfasern gelegen ist. Da diese Zellen hypertrophieren, wenn die Muskelfaser geschädigt ist, besonders aber, wenn sie regeneriert, wird angenommen, daß sie eine trophische Funktion besitzen und als celluläre Vermittler zwischen Gewebsraum und Muskelfaser dienen.

Ultrastructural and morphometric study of the human heart muscle cell in acute coronary insufficiency.

In 13 patients with acute coronary insufficiency (intermediate syndrome, postinfarction angina, and progressive angina), samples of the ischemic area of the myocardium were studied with the electron microscope and by morphometric methods in order to describe quantitatively the mitochondrial population. Three indices were measured: the fractional volume of the mitochondrial compartment of the cytoplasm, the number of mitochondria per unit volume of heart tissue, and the average individual mitochondrial volume. As a control, the same study was performed on samples obtained from patients with chronic coronary insufficiency and mitral stenosis. In all the ischemic hearts the most conspicuous ultrastructural modification of the muscle cells consisted in an irregular distribution of the mitochondriranules. Generally, odd shaped mitochondria were found. The modifications were not diffuse, and almost normal heart muscle cells were seen alongside deeply altered ones. In addition a definite decrease in the fractional volume of the mitochondrial compartment was found, which was apparently due to a decrease in the number of mitochondria per unit volume of cytoplasm. The average individual mitochondrial volume was similar in acute coronary insufficiency and in the control cases. On the basis of this evidence it is postulated that in sublethal ischemia definite ultrastructural modifications of the heart muscle cells are associated with a decrease in the number of mitochondria per unit volume of cytoplasm.

Radial artery graft vasospasm.

We report an unusual case of vasospasm of a grafted radial artery complicated with ventricular fibrillation during the postoperative course of coronary artery bypass graft surgery. To our knowledge this is the first documented case of a radial artery graft spasm leading to a severe arrhythmia. The arrhythmia resolved spontaneously. Radial artery graft spasm was demonstrated by angiography and was successfully resolved by intravenous nitroglycerin administration.

Presence of viral particles in the salivary gland of Calomys musculinus infected with Junin virus by a natural route.

Calomys musculinus, a wild cricetid rodent, is one of the main reservoirs of Junin virus. Six of these animals were infected by being placed in close contact with animals that had been experimentally infected with the virus. They were sacrificed at 10, 15 and 20 months after contact, and their salivary glands were studied by ultrastructural, immunohistochemical and virological methods. Two animals developed chronic viremia and low titers of complement-fixing antibodies. These animals were the only ones that had high viral titers in salivary glands and blood and viral antigen and particles in salivary glands. Although some of the other animals had viremia at the beginning of the experiment, it was absent 5 months later. Complement-fixing antibodies developed in all animals. On the basis of these findings, we assumed that the salivary gland is an important site of viral synthesis and excretion. This type of chronic infection, with persistent viremia and virus shedding, is possibly important for virus perpetuation in nature and transmission to man.

Presence of cells producing antiheart autoantibodies in the inflammatory infiltrate of chronic chagasic myocarditis.

Chagasic myocarditis is associated with the appearance of circulating antiheart autoantibodies. In order to find out if there was local synthesis of those antibodies we investigated, by means of a solid immunoenzymatic technique, the presence of cells secreting antibody (ASC) against syngeneic soluble heart antigens in the mononuclear cell (MNC) population isolated from the hearts of mice chronically infected with Trypanosoma cruzi. In seven animals the number of ASC ranged between 300 and 2080 per 10(6) MNC. A similar number of cells was observed when the assay was carried out with T. cruzi-soluble antigens. When the ASC were enumerated in an assay simultaneously with both antigens, their number doubled that found in the single antigen assay, suggesting that there was no cross-reactivity between the heart and the parasite antigens. These results indicate that some of the cells in the inflammatory infiltrate of chronic chagasic myocarditis synthesize IgG autoantibodies against heart antigens, a phenomenon which may lead to a local concentration of antibody large enough to induce tissue damage.

Pathogenicity of an Attenuated Strain (XJCl3) of Junin Virus

Infection of guinea pigs with an attenuated strain of Junin virus (JV) produced 16% mortality between days 17 and 27 postinfection (p.i.). The morphological study showed a marked pancreatitis between days 6 and 23 p.i. and meningoencephalitis between days 17 and 20 p.i. in a large proportion of the animals. These lesions were coincident with the presence of JV antigenic determinants in the pancreatic acinar cells, neurons and blood vessels of the brain. Infectious virus could be isolated from lymph nodes, spleen, bone marrow, lungs, adrenal glands, and brain. The lesions appeared to be reversible, as they were absent in animals studied after day 64 p.i. Meningoencephalitis, present in all animals dying spontaneously, appeared to be the most important cause of death. Our observations indicate that more accurate markers of virulence must be investigated in the search for attenuated strains of JV as potential vaccine candidates for Argentine hemorrhagic fever.

Presence of anti-Trypanosoma cruzi antibodies in the sera of mice with experimental autoimmune myocarditis

The existence of antigens shared in common byT. cruzi and heart muscle cells is suggested by the presence of antibodies binding to the parasite surface in the serum of mice with autoimmune myocarditis induced by immunization with syngeneic heart antigens.

Fine structure of the small bowel in dermatitis herpetiformis

In seven patients with dermatitis herpetiformis, the intestinal structure was studied by means of the electron microscope. In 5 patients the absorptive epithelial cells showed variable modifications consisting of a dilatation of the rough endoplasmic reticulum and an overdevelopment of the smooth endoplasmic reticulum. The striated border microvilli were abnormal and presented edema and fusion with occasional disappearance, leaving clear areas on the intestinal surface. In two patients the ultrastructural study showed no modifications of the epithelial cells. In all the cases examined the only constant finding consisted of a marked lymphocytic infiltration of the epithelium. The lymphocytes traversed through the basement membrane and were located in the intercellular space. The latter was frequently widened. The widening of the intercellular space was interpreted as secondary to the passage of the leukocytes through the epithelium. On the basis of this study it was suggested that the lymphocytic infiltration could impair the absorptive ability of the intestinal epithelium, and that the electron microscopic study supports the opinion that some relationship exists between the intestinal changes in dermatitis herpetiformis and those present in non tropical sprue.

Protective and immunostimulating activity of a low dose of cyclophosphamide in the experimental infection of mice with foot-and-mouth disease virus.

Administration to mice of a low, non-immunosuppressive dose of cyclophosphamide 4 days before infection with foot-and-mouth disease virus decreases viral replication, enhances the immune response against the virus and prevents panceatic damage.