Harry L. Colcolough

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.

The effect of ingestion of ethyl alcohol, wine and beer on the myocardium of mice.

Abstract Histologic and ultrastructural changes in the myocardium of mice consuming various concentrations of pure ethanol, beer and wine as their sole liquid intake for 4 to 10 weeks are described. Ultrastructural alterations were seen in the sarcoplasmic reticulum, myofilaments and intercalated discs. The changes were minor but discernible. The pathogenesis of these changes is discussed in terms of a possible direct toxic effect of alcohol on the myocardium.

Pathogenesis of “rheumatic” heart disease: Critique and theory

Abstract Intense clinical and experimental investigation over many years has not clarified the role of the streptococcus in the pathogenesis of “rheumatic heart disease”. This failure may have been due to an inadequate definition of the problem and repeated experimental attempts to prove that the streptococcus is the sole agent responsible for the development of “rheumatic heart disease”. To stimulate another approach to this important problem, the possible role of viruses in the pathogenesis of “rheumatic heart disease” is introduced. There is much evidence to indicate an active role of viruses in the production of heart disease, resembling “rheumatic heart disease”, in man and animals. Also, there is considerable data, both experimental and clinical, to support a viral-streptococcal relationship in the production of disease. Thus, the concept of the streptococcus acting as a conditioning factor for viruses in the production of heart disease in man is suggested. This concept is discussed in relation to some aspects of “rheumatic heart disease”, which, in the past, have been hard to explain. Finally, it is suggested that an earnest attempt be made to provide facilities for viral isolation on a more routine basis in hospitals and medical centers so that progress in this area can be accelerated.

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.

Mural and valvular endocarditis of mice infected with encephalomyocarditis (EMC) virus

Abstract The encephalomyocarditis (EMC) virus is shown to infect readily the heart of mice and to produce myocarditis and valvular endocarditis. In these experiments 1–2 day old newborn mice were found to have extensive mural and valvular endocardial damage, whereas the adult mice had only minor lesions. The pathologic changes include degeneration and necrosis of lining endothelial and stromal cells and inflammatory changes of the valves. The finding of EMC viral crystals in the valves and myocardium of these animals proves the direct entry of virus into the valvular tissue and muscles of the heart. EMC virus can cause both mural and valvular endocarditis in newborn mice. These experiments, with the fact that the EMC virus forms readily detectable crystals, establish a good model for studying viral endocarditis and the natural history of the disease in animals and lend further support to the probable role of viruses in the production of valvulitis in man.

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.