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Biomedical subjects

W H Abelmann

Publications and source records attributed to W H Abelmann.

At least 19 recordsLinked to original sources
PubMed1992

Prevalence and etiology of idiopathic dilated cardiomyopathy (summary of a National Heart, Lung, and Blood Institute workshop.

Idiopathic dilated cardiomyopathy (IDC) is the primary indication for cardiac transplantation, with associated costs of approximately $177 million per year. Recognizing the economic implications of IDC, the increasing incidence, and the limited information on pathogenesis and prognosis, the National Heart, Lung, and Blood Institute convened a workshop on the Prevalence and Etiology of Idiopathic Dilated Cardiomyopathy on June 13 to 14, 1991. The difficulties of studying the disease were reviewed, including its relatively low prevalence, its potentially pluricausal nature, and the fact that it is often a diagnosis of exclusion. Still, it presents significant challenges to the cardiovascular scientific community, since the mechanism of myocardial damage and related etiologic and prognostic factors are virtually unknown. The development of more reliable measures of immune-mediated damage and noninvasive measures of impaired cardiac function present new research opportunities in this disorder. Standardized diagnostic criteria for use in observational and interventional trials were developed, and priorities for future research were proposed. Population-based registries and nested case-control studies, where feasible, are appropriate study designs for tracking incidence and prevalence, and for identifying risk factors, respectively. Interventional studies should focus on secondary prevention, through modifying immune-mediated damage in clinically evident dilated cardiomyopathy, and through prevention of sudden death in patients with the disorder. Primary prevention trials must await the identification of modifiable risk factors and of appropriate and effective interventions.

Cardiomyopathy, Dilated↗
PubMed1992

An experimental model of acute and subacute viral myocarditis in the pig.

Twenty-six young pigs were infected with encephalomyocarditis virus, observed clinically, studied at intervals by noninvasive and invasive methods to assess cardiac function and eventually examined pathologically. All infected animals appeared ill, usually manifesting diminished appetite, lethargy and fever. Spontaneous mortality occurred either 1 to 4 or 20 to 21 days after infection. Electrocardiographic abnormalities, seen in the majority of animals, comprised ST-T wave changes, conduction disturbances or ventricular ectopic rhythm. The majority of animals manifested echocardiographic evidence of left ventricular dilation and decreased systolic function, which improved with time in some animals. Hemodynamic studies revealed elevation of biventricular filling pressures in 3 of 10 animals; as a group, infected animals manifested significantly elevated right ventricular filling pressures. In selected animals, the feasibility of gallium scans as well as left ventriculography and coronary angiography was demonstrated. At autopsy, heart weight/body weight ratio was significantly elevated in infected animals. The heart of all but two animals showed active myocarditis associated with fibrosis and focal calcification in the later stages. In general, the cardiovascular manifestations were parallel with those seen in acute and subacute myocarditis in humans. It is concluded that encephalomyocarditis infection in the pig is a large animal model of viral myocarditis suitable for assessing alterations in the structure and function of the cardiovascular system and the effects of interventions.

Animals↗
PubMed1991

Natural evolution of cardiac function, cardiac pathology and antimyosin scan in a murine myocarditis model.

Serial technetium-99m radionuclide ventriculograms, indium-111 antimyosin antibody scans and tissue biodistribution studies were performed in C3H/He mice with experimentally induced viral encephalomyocarditis and the results were compared with pathologic assessments of myocardial necrosis. Postinfection ejection fraction decreased on days 10 (20.7 +/- 5.5%, n = 6), 20 (18.6 +/- 15.2%, n = 5), 30 (18.5 +/- 7.7%, n = 5) and 150 (30.0 +/- 18.7, n = 6) (p less than 0.001) in comparison with that in uninfected control mice (63.3 +/- 3.1%, n = 6). In the same group of animals, indium-111 antimyosin antibody scans showed intense positive myocardial accumulation on day 10 (in six of six mice) and only slight accumulation on day 20 (in one of five mice). In the chronic stage, two of five mice on day 30 and two of six mice on day 150 still showed positive uptake. The antimyosin scan myocardium to lung uptake ratio (expressed as mean count density [mean counts/pixel of the region] ratio) increased greatly on day 10 (p less than 0.001 versus values in uninfected control mice) but not subsequently. Biodistribution studies of the indium-111 antimyosin antibody showed that the heart to blood count ratio was significantly higher on day 10 (p less than 0.001 versus values in control mice) but not on days 20, 30 and 150. Pathologic examination showed active and ongoing severe myocardial necrosis with dilated ventricles on day 10. On day 20, there was less active necrosis and healing had appeared to begin. On days 30 and 150, myocardial fibrosis increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Immunosuppression with high doses of cyclophosphamide reduces the severity of myocarditis but increases the mortality in murine Coxsackievirus B3 myocarditis.

To test the therapeutic efficacy of immunosuppression with cyclophosphamide (CYP) on coxsackievirus B3 (CB3) myocarditis, 2-week-old DBA/2 mice were inoculated with 3 X 10(2) plaque-forming units of CB3 virus. CYP (100 mg/kg/day s.c.) was administered daily on days 0-8 (experiment 1; group 2), days 8-21 (experiment 2; group 4), and days 21-34 (experiment 3; group 6). Groups 1, 3, and 5 were infected control groups for each experiment. Spleen, thymus, and body weights were measured. In experiment 1, survival rate in group 2 on day 8 was low compared with group 1 (nine of 51 versus eight of 28; p = NS), and myocardial virus titers in group 2 on day 8 were higher (p less than 0.05) compared with group 1; however, cellular infiltration and myocardial necrosis in group 2 were less severe (p less than 0.05), and serum neutralizing antibody titers were decreased (p less than 0.01). In experiment 2, survival rate in group 4 on day 21 was significantly lower (six of 24 versus 12 of 16; p less than 0.01), but cellular infiltration, myocardial necrosis, and calcification in group 4 were significantly less severe, and serum neutralizing antibody titers were decreased (p less than 0.01). In experiment 3, survival rate, cardiac histopathology, and serum neutralizing antibody titers did not differ between groups 5 and 6. In experiments 1, 2, and 3, the treated groups were characterized by lower spleen-to-body-weight and thymus-to-body-weight ratios and by marked cellular depletion in spleen and thymus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

In vivo significance of T cells in the development of Coxsackievirus B3 myocarditis in mice. Immature but antigen-specific T cells aggravate cardiac injury.

Acute myocardial damage similar to that seen in human myocarditis occurs in BALB/c mice after infection with coxsackievirus B3 (CB3) or encephalomyocarditis virus (EMC). To investigate the role of antigen-specific T cells in the pathogenesis of this disorder, we compared CB3 disease expression in T cell-deficient, athymic nude (nu/nu) mice, in heterozygote (nu/+) mice with normal T cell function, and in nu/nu mice reconstituted with spleen cells from CB3- or EMC-infected nu/+ mice. Acute myocarditis occurred in both nu/nu and nu/+ mice. Severe myocarditis, however, developed only in nu/+ and nu/nu mice reconstituted with CB3-sensitized T cells, but not in those reconstituted with EMC-sensitized T cells. Myocardial virus titer and serum anti-CB3 antibody production were similar in nu/+ and nu/nu groups. Additionally, the presence of Thy 1.2 (pan T), Ly 1 (precursor of other T cell subsets), and Ly 2 (suppressor/cytotoxic T) positive cells was demonstrated in the myocardium in nu/+ and nu/nu mice reconstituted with CB3-sensitized T cells, but not with T cells sensitized by another virus, EMC. These results indicate that immature but antigen-specific T cells play a role in the pathogenesis of ongoing myocarditis.

Animals↗
PubMed1989

Characteristics of lymphocytes cultured from murine viral myocarditis specimens: a preliminary and technical report.

Long-term culture of lymphocytes from myocardial biopsy specimens has been reported. To test the usefulness of this technique in experimental models of murine myocarditis, the culture and characterization of lymphocytes from mice infected with encephalomyocarditis virus or coxsackievirus B3 were studied. Lymphocytes were successfully cultured from three hearts of encephalomyocarditis virus-infected mice in interleukin 2-containing culture. After approximately 10 days, lymphocytes migrated out of myocardium in the chronic stage of myocarditis and gradually increased in numbers. More than half of the exuding cells were Thy 1.2-positive. None of the myocardial samples from coxsackievirus B3-infected mice grew out lymphocytes. Pathologic examination of all specimens showed myocardial necrosis with lymphoid infiltration. Although further studies are needed, this preliminary study suggests that the technique of lymphocyte culture may promote new insights into the pathogenesis of experimental myocarditis.

Animals↗
PubMed1989

The challenge of cardiomyopathy.

The combined clinical and pathophysiologic characteristics and diagnostic features as well as current concepts of pathogenesis, therapy and prevention of the principal forms of cardiomyopathy are reviewed. These include hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy and specific cardiac muscle disease. Emphasis is placed on recent developments and unresolved questions requiring application of newer techniques of molecular biology and genetics and adult myocyte culturing.

Cardiomyopathy, Dilated↗
PubMed1989

Monoclonal antibody therapy for prevention of acute coxsackievirus B3 myocarditis in mice.

The efficacy of monoclonal antibodies against T cell subsets in the therapy of experimental myocarditis caused by coxsackievirus B3 (CB3) was investigated. Two-week-old male C3H/He mice were inoculated with CB3 virus. Treatment was begun in the viremic stage (starting on the day of inoculation) in experiment 1 and in the later aviremic stage (starting on day 10) in experiment 2. Rat anti-mouse monoclonal antibodies, Lyt 1 (helper/inducer T) at 1 microgram/mouse (group 2 in experiment 1; group 6 in experiment 2), Lyt 2 (suppressor/cytotoxic T) at 1 microgram/mouse (group 3 in experiment 1; group 7 in experiment 2), and Lyt 1 at 1 microgram plus Lyt 2 at 1 microgram/mouse (group 4 in experiment 1; group 8 in experiment 2), were administered subcutaneously daily for 2 weeks. The treatment groups were compared with infected controls (group 1 in experiment 1; group 5 in experiment 2). In experiment 1, the survival rate in group 4 was higher (p less than 0.01) than in group 1. In experiment 2, mice treated with Lyt 1 plus Lyt 2 (group 8) survived significantly longer (p less than 0.05) than did controls (group 5). In experiment 1, myocardial virus titers on days 5 and 6 did not show any significant differences among the four groups. Serum-neutralizing antibody titers between group 1 and group 4 in experiment 1 or between group 5 and group 8 in experiment 2 did not differ significantly. Histologic examination showed extensive myocardial necrosis and cellular infiltration in untreated groups: there was less infiltration in group 4 and in group 8 and less severe necrosis in group 8.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Absence of effects of cyclosporine on myocardial lymphocyte subsets in Coxsackievirus B3 myocarditis in the aviremic stage.

To test the therapeutic efficacy of immunosuppression with cyclosporine upon the aviremic stage of coxsackievirus B3 (CB3) myocarditis, 2-week-old BALB/c mice were inoculated with 3 x 10(2) plaque-forming units of CB3, and the effects of cyclosporine on peripheral, splenic, and myocardial lymphocyte subsets were investigated. Cyclosporine, 25 mg/kg/day, was administered subcutaneously daily on days 10-31 (experiment 1) and days 30-51 (experiment 2). Treated groups were compared with infected controls for each experiment. In experiment 1, the survival rate of the cyclosporine-treated group was low (17/25 vs. 24/25, p less than 0.05). The severity of myocardial lesions and the distribution of lymphocyte subsets in myocardium and spleen on days 15-18 did not differ between treated and control groups; on the other hand, the percentages of peripheral Thy 1.2+ (pan T) and L3T4+ (activated helper T) cells on days 15-18 were decreased in the treated group, and those of B, Lyt 1+ (helper/inducer T), and Lyt 2+ (suppressor/cytotoxic T) subsets did not differ significantly. Notably, myocardial interleukin-2 receptor (IL-2R) positive cells, through which cyclosporine is considered to act, were scarce in both groups. In experiment 2, survival rates of two groups did not differ (treated, 32/34; untreated, 34/34; p = NS). The severity of myocardial lesions and the distribution of splenic lymphocyte subsets on days 35-38 also were not different between two groups. The percentages of peripheral lymphocyte subsets (Thy 1.2+ and L3T4+) were decreased in the treated group; those of B, Lyt 1+, and Lyt 2+ subsets did not differ significantly. In experiments 1 and 2, the thymus/body weight ratio in the treated groups was smaller than in the untreated group, but the spleen/body weight ratio in the treated group did not differ from the untreated group; histologically, medullary cellular depletion was evident in the thymus, not in the spleen, of the treated groups. We conclude that cyclosporine failed to change the distribution of lymphocyte subsets in the spleen as well as in the myocardium in CB3 myocarditis although it had effects on the peripheral blood and thymus, which may account for the higher mortality in the treated groups. The absence of beneficial effects of cyclosporine upon the CB3-infected myocardium may be related to the paucity of cyclosporine-sensitive cells (IL-2R, L3T4, and Lyt 2 positive cells) in the myocardium.

Animals↗
PubMed1989

Echocardiographic assessment of cardiac chamber size and functional performance in swine.

Ninety nonanesthetized 7- to 16-week-old pigs were studied, using 2-dimensional echocardiography that permits orientation of a targeted M-mode beam perpendicular to structures being studied and allows serial studies of the same cardiac regions. Normative data were obtained and included body weight and measurements of left atrial diameter, mitral valve excursion, aortic root diameter, left ventricular end-diastolic and end-systolic diameters, and left ventricular fractional shortening. A positive correlation was found between body weight and measurements of left atrial diameter, mitral valve excursion, aortic root diameter, left ventricular end-diastolic and end-systolic diameters, and fractional shortening. A correlation was found between body weight and age. Best-fit analysis resulted in all measurements fitting either a first- or second-degree polynomial.

Age Factors↗
PubMed1988

Myocarditis presenting as acute myocardial infarction.

Ten patients with acute myocarditis, who were initially seen with clinical signs of acute myocardial infarction, will be discussed. All had symptoms and seven had laboratory evidence of an acute viral infection. Acute cardiac findings consisted of chest pain in nine patients, compatible ECGs and elevated creatine kinase levels in 10, positive MB fractions in eight, and regional wall motion abnormalities in eight. Acutely, the left ventricular ejection fraction was less than 55% in six patients; ventricular ectopy occurred in five patients, bundle branch block in four, transient junctional escape rhythm in three, and congestive heart failure in three. Among the nine patients followed-up for 1 to 14 months there was one death, five patients had normal results of exercise tests, and three had normal coronary angiograms. Wall motion abnormalities persisted in four patients; ejection fraction improved in five and was less than 55% in three. These findings suggest that focal myocardial damage may occur during acute viral myocarditis and mimic acute myocardial infarction resulting from atherosclerotic coronary artery disease.

Adult↗
PubMed1988

Ribavirin treatment of murine coxsackievirus B3 myocarditis with analyses of lymphocyte subsets.

The efficacy of the synthetic nucleoside ribavirin in the therapy of experimental myocarditis caused by coxsackievirus B3 and its effects on peripheral and splenic lymphocyte subsets were investigated. Two week old male C3H/He mice were inoculated with coxsackievirus B3. Ribavirin was administered subcutaneously on days 0 to 15 (experiment I) and on days 4 to 15 (experiment II) in a dose of 200 (experiment I: Group 2, n = 10; experiment II: Group 5, n = 10) or 400 mg/kg per day (experiment I: Group 3, n = 10; experiment II: Group 6, n = 10). Control mice (experiment I: Group 1, n = 15; experiment II: Group 4, n = 14) received an injection of saline solution. In experiment I, mice treated with ribavirin survived significantly longer than did control mice (p = 0.005, Group 1 versus Group 2; p = 0.001, Group 1 versus Group 3). In experiment II, the survival rate on day 15 in ribavirin-treated mice was high compared with that in control mice (Group 4 = 14.3%, Group 5 = 20%, Group 6 = 50%). Myocardial viral titers on days 5 to 8 were significantly lower in ribavirin-treated mice of both experiments than in control mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Prevention of murine coxsackie B3 viral myocarditis and associated lymphoid organ atrophy with recombinant human leucocyte interferon alpha A/D.

The effects of recombinant human leucocyte interferon alpha A/D on experimental myocarditis due to coxsackie virus B3 were investigated. Specific plaque reduction assays showed that 50% of in vitro plaque formation in VERO (kidney of African green monkey) cells was inhibited by interferon alpha A/D 48 U.ml-1 when administered 24 h before infection with coxsackie virus B3. Three week old male C3H/He mice were inoculated intraperitoneally with 3 x 10(2) plaque-forming units (pfu) of coxsackie virus B3. Controls (group 1) were injected with saline. Interferon alpha A/D 10(4) (group 2) or 10(3) (group 3) U.g-1.day-1, was administered subcutaneously daily, starting 1 d before the infection. Interferon alpha A/D 10(4) U.g-1.day-1 (group 4) was also given, starting the same day. Each group consisted of ten mice. Animals were sacrificed on d 5 for evaluation. Myocardial virus titres were significantly lower in groups 2, 3, and 4 (p less than 0.05) compared with controls. Histological examination showed extensive myocardial necrosis and cellular infiltration in all untreated mice but less severe necrosis and cellular infiltration in treated groups. Thymus and spleen weights in treated groups were greater than in the untreated group, and cellular depletion was less. Thus interferon alpha A/D effectively inhibited myocardial replication of coxsackie virus B3, reduced the myocardial inflammatory response, and prevented the disease associated lymphoid organ atrophy in this animal model.

Animals↗
PubMed1988

Serial immunologic identification of lymphocyte subsets in murine coxsackievirus B3 myocarditis: different kinetics and significance of lymphocyte subsets in the heart and in peripheral blood.

To elucidate possible immune mechanisms in the pathogenesis of myocarditis, we examined, by immunofluorescence techniques, the serial changes in lymphocyte subsets in the heart, spleen, and peripheral blood of C3H/He mice inoculated coxsackievirus B3 (experiment I). B cells were identified by staining with fluorescein isothiocyanate-labeled rabbit antimouse immunoglobulin. T cell subsets were demonstrated with rat anti-Thy 1.2, anti-Lyt 1, anti-Lyt 2, and anti-L3T4 monoclonal antibodies, respectively, plus fluorescein isothiocyanate-labeled antimouse immunoglobin. The percent of Thy 1.2+, Lyt 1+, and L3T4+ cells was decreased in the peripheral blood on days 3, 7, and 14. B cells were increased on day 3. In contrast, Thy 1.2+ (pan T) or Lyt 1+ cells appeared to occupy the major portion of the myocardium on days 7 and 14, when myocarditis was most severe, while B cells were sparse. For confirmation, serial immunohistologic studies (immunoperoxidase staining) of the hearts of C3H/He mice with coxsackievirus B3 myocarditis were performed (experiment II). Most of the stained cells in the heart were Thy 1.2, Lyt 1, and Lyt 2 positive on days 7 and 14. Thus, independent methods demonstrate that specific antigenic markers on lymphocytes at the site of inflammation in the acute stage of viral myocarditis differ from those on corresponding peripheral lymphocytes, and suggest the possible involvement of Thy 1.2+ (pan T) cells, mainly the Lyt 1+ and Lyt 2+ subsets (immature T cells), in the development of myocarditis in this preparation.

Animals↗
PubMed1988

The dilated cardiomyopathies: experimental aspects.

Dilated cardiomyopathy is characterized by the primacy of systolic dysfunction. Experimental animal models have contributed greatly to our current knowledge and promise to continue to expand our understanding, especially as methods of cellular and molecular biology are increasingly applied. Although specific etiologies dominate in some forms of dilated cardiomyopathy, the cause is generally multifactorial--that is, the full expression results from the interplay of a number of etiologic and enhancing factors. Recognition of these factors paves the way for therapy as well as primary and secondary prevention. This article has focused chiefly on experimental models of dilated cardiomyopathy associated with congestive heart failure and on interventions producing or aggravating heart failure. Many factors associated with the production or aggravation of experimental myocardial necroses have not been considered here. Even so, this overview reaffirms the concept that dilated cardiomyopathies are pluricausal. In Table 3, the major processes identifies as pathogenetic in experimental dilated cardiomyopathy are listed. Table 4 presents a list of major categories of enhancing factors. The evidence offered in this article indicates that in most models many pathogenetic mechanisms and enhancing factors may be operative, and this is also believed to be the case in human dilated cardiomyopathy Recognition of the multifactorial etiologies of the dilated cardiomyopathies is an important first step in therapeutic and preventive interventions. Experimental work in human dilated cardiomyopathy has not been included in this article, but some recent studies provide challenging insights.

Animals↗