Shih-Chien Sun

Coxsackie B viral myocarditis and valvulitis identified in routine autopsy specimens by immunofluorescent techniques

Abstract From a survey of 55 routinely autopsied hearts, studied by means of the immunofluorescent antibody techniques, Coxsackie B group virus antigens were found in the myocardium in 17 cases (30.90 per cent) and in both the myocardium and mitral valve in 3 cases (5.45 per cent). A chronic focal, interstitial myocarditis was noted in all 17 cases upon routine histologic study. A high percentage of positive viral antigen was found in hearts of children (75 per cent) and infants (35.71 per cent). The criteria for positive immunofluorescent identification of antigen consisted of intracytoplasmic localization of the fluorescence in the affected myofibers and in fibrocytes of the mitral valves. Chronic Coxsackie virus valvulitis is shown to be present in man in certain types of unexplained chronic valvular heart disease. It is postulated that some instances of chronic valvular disease previously thought to be post rheumatic in origin may represent chronic viral valvulitis. These studies also suggest a possible role of the Coxsackie virus as a cause of some congenital cardiac defects and stillbirths.

Changes in ultrastructure and respiratory control in mitochondria of rat heart hypertrophied by exercise

Abstract The electron-microscopic morphology, mitochondrial respiratory rates and respiratory control ratios, and the histochemical distribution of mitochondrial enzymes were studied in the ventricular myocardium of young female rats during the time-course of repeated exercise by swimming. Following swimming between a total of 140 and 180 hours (at the rate of 6 hours a day, 6 days a week) there was a large increase in mitochondrial mass. The respiratory rate of these mitochondria showed no change with α-ketoglutarate, succinate, or pyruvate, and slight increase with glutamate. With only the latter substrate, however, a considerable increase of the mitochondrial respiratory control ratio was observed. Already at this stage of exercising, which represented an optimum physical condition of the animals, some scattered degenerative foci in the myocardium were noted showing fusion, swelling, clumping and reduction of mitochondrial cristae, and disoriented indistinct myofilaments in which the sarcomere bands could not be seen. These foci showed decrease of histochemically detectable succinic dehydrogenase and β-hydroxybutyric dehydrogenase. In advanced stages of exercising (for 361–490 hours of swimming) the animals showed physical exhaustion and were unable to maintain the same rate of exercising. The distribution and extent of the above focal degenerative changes in the myocardium of these animals were considerably more pronounced, and this was paralleled by a return of the mitochondrial respiratory control ratio (with glutamate) to the base level; there was no change in the respiratory rates with any of the substrates, however. There was no change in the Ca ++ - and Mg ++ -activated, histochemically demonstrable, ATPase levels in the myocardium during the entire time-course of exercising. The findings suggest that the increase of mitochondrial mass is a compensatory response to exercise and this increase brings about focal regions of hypoxia during over-exercise, responsible for the degenerative changes. The respiratory control increase with glutamate, at the stage of optimum exercise, possibly represents a regulatory mechanism limiting amino acid catabolism via the tricarboxylic acid cycle during high overall anabolic activity.

Coxsackie B4 Viral Nephritis in Mice and Its Autoimmune-Like Phenomena.∗

Summary Coxsackie B4 virus may be highly nephrotropic. It may produce a viral nephritis and provoke an autoimmune-like reaction in the affected renal tissue of the experimentally infected mice. In this study, by means of immunonuorescent technique, both the specific viral antigen and immuno-globulin deposit were demonstrated in the glomeruli of infected mice within 5 to 8 weeks after inoculation with Coxsackie B4 virus. It is suggested that the virus may play a significant etiologic role in the pathogenesis of acute and chronic renal disease in man, of which disease the etiologic source is often unknown.

Diphtheritic myocarditis: A histochemical and electron microscopic study☆

Abstract Electron microscopic, histochemical and histologic studies of diphtheritic myocarditis in a 3 year old child who died of cardiac failure are presented. A correlation between biochemical lesions and morphologic alterations of the myocardium is described. The most striking cytopathologic change was mitochondrial damage associated with depletion of glycogen and accumulation of lipid droplets in the damaged myofibers. The changes appeared to progress throughout the myocardial cells. The localization of the diphtheria toxin was demonstrated in situ in the myocardium by immunofluorescent antibodies. The toxin was patchy in distribution and of varying concentration throughout the myocardium. The toxin was found most frequently and in greatest concentration in the large mononuclear cells which had an eosinophilic cytoplasm in hematoxylineosin stained sections. Since the pathologic lesions of the myocardium in diphtheria vary and are inconsistent, histochemical and immunofluorescent antibody technics are valuable means for detailed study of the pathology of diphtheritic myocarditis and are of considerable aid in the diagnosis of undetermined cases.

Immunofluorescent study of B4 Coxsackievirus valvulitis in mice.

Summary An experimental model of both acute and chronic viral valvulitis was studied by direct immunofluorescent antibody technique with parallel histopathologic observation. Coxsackie B4 virus antigen was visualized in the affected valves and mural endocardium of acute infections and remained in situ even after the tissue developed scarring. The antigen was restricted to the stroma of the infected valves in the early stages and became more discretely localized in the endo-thelial cells at a later period. The intense, specific fluorescent reaction at the base of the affected valves provided evidence of valvular involvement by direct extension from adjacent myocardial lesions. Involvement of valves and mural endocardium of right side of the hearts was more frequent, especially in the early stages of infection. The studies show that the coxsackievirus B4 can produce valvulitis in mice as well as pericarditis, myocarditis and endocarditis.