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Eighteen consecutive patients, admitted with a diagnosis of dilated cardiomyopathy (DCM), to the Cardiology Section, Department of Internal Medicine, University Hospital, Uppsala, Sweden were enrolled into the study. All patients suffered signs of cardiac incompensation of variable duration. Patients were defined by conventional clinical investigations including chest X-ray, ultrasound, g-camera, catheterization and endomyocardial biopsy with histological evaluation by a specially trained pathologist. Angiography was performed to exclude ischemic heart disease. Several patients were diagnosed as having a specific reason for the cardiac insufficiency, like pheochromocytoma, SLE, ethylism, ischemic heart disease and hypertrophic cardiomyopathy. In this group all 7/7 had negative serology against Coxsackie B viruses. In the other group of idiopathic CM, no other etiology could be found. Serological analysis in this group showed high IgM titres against Coxsackie viruses in 6/8 patients. EDTA-blood was taken for tissue-typing using DNA probe hybridisation. 6/12 patients had DQB1:4 using the newest nomenclature, vs 17% in the control population. The reversed picture was observed for DQB1:2, occurring in 1/12 patients, vs 19% in the normal population, thus indicating a protective value of this genotype, which to our knowledge has not been described before. The results indicate a dual dependence of (host) genotype and (virus) serotype according to the Doherty-Zinkernagel hypothesis. Thus, it would also be in agreement with the virus-immune hypothesis suggested more than 20 years ago to explain the enigmatic pathogenesis of DCM.

The enteroviruses, especially the Coxsackie B viruses, predominate as causative agents in myopericarditis and may be involved in the pathogenesis of dilated cardiomyopathy. Some studies suggest that these and other viruses might be implicated even in atherosclerosis and myocardial infarction. True incidence data of myopericarditis in the population at large are hardly feasible, since the disease is most often mild or subclinical. The long-term prognosis is favorable even in a majority of hospital-treated patients. A recent histopathological study of unselected autopsy cases employing the "Dallas criteria" for a diagnosis shows a myopericarditis incidence of 1.06 per cent. A link between myopericarditis and dilated cardiomyopathy is supported by findings of enteroviral RNA in biopsies and explanted hearts in the latter condition. A partly new panorama of viral heart disease is emerging in heart transplant recipients and AIDS patients.

The antiviral efficacy of WIN 54954 was demonstrated in vivo in a Coxsackie B 3 virus (Woodruff strain) induced myocarditis mouse model. The model was selected because of the high mortality rate during the first week, which was convenient for antiviral therapy regimen studies. The antiviral component WIN 54954 was found to inhibit the early virus-induced mortality almost completely if treatment was started at the same time as virus was inoculated. However, there was still a late mortality, occurring at 1-2 months after virus inoculation. Non-infected mice which were treated with the drug did not show any such late effects. However, drug treatment in non-infected mice did not cause any mortality. When therapy was delayed for one day, 85% survived for 3 weeks as compared to 100% mortality after just over 3 weeks in the infected control group (p0.05). With a delay of 4 days after viral inoculation, a therapeutic effect was still noted. Thus, mortality was virtually abrogated when the compound was given early, but the effect vanished with time of delay. Different preparations of the WIN 54954 substance were tried, and it was found that a fat emulsion containing several nutrients (Nutrodrip) was superior to other used formulations. We conclude that the use of the antiviral drug WIN 54954 in treatment of enteroviral associated diseases is of great value if therapy is started early. Thus therapy is almost fully effective within 24 hours of infection, but the beneficial effects decline with time. Nutrodrip oil emulsion was found superior as vehicle as compared to other formulations.(ABSTRACT TRUNCATED AT 250 WORDS)