Production of cardiac muscle abnormalities in offspring of rats receiving triiodothyroacetic acid (triac) and the effect of beta adrenergic blockade.

As a part of a continuing study on the effects of thyroid hormones on heart muscle, triiodothyroacetic acid (triac), either alone or concurrently with propranolol, has been administered to rats during pregnancy. Control groups received either buffer or propranolol. Offspring, which were given no further treatment, were killed at intervals after birth and their hearts examined histologically, histochemically, and electron microscopically. At 2, 6, and 14 days, offspring of triac-treated rats showed cardiac hypertrophy and, at ultrastructural level, marked disarray of the myofibrils was present. By 28 days, arrangement of the myofibrils had become regular but hypertrophy persisted and was still found in rats examined at 56 days of age, after which time the myocardium was normal. Offspring of rats which had received propranolol at the same time as triac showed a similar pattern of hypertrophy but myofibrillar disarray was not found. Propranolol alone produced no abnormalities. These findings provide further evidence that thyroid hormone analogues can adversely affect heart muscle. When considered in conjunction with previous experiments which showed that thyroxine or triac cause severe hypertrophy but not disarray when given directly to growing rats, they suggest that thyroid hormones can produce a spectrum of abnormalities, thought to depend on the stage of myocardial development at which the stimulus is administered. In the present experiment, the triac-induced myofibrillar disarray but not the hypertrophy was prevented by propranolol, indicating that beta-adrenergic blockade or some other action of propranolol protects the developing myofibrils. Possible mechanisms for the adverse effects of thyroid hormones and the protective action of propranolol are discussed.

Effect of triac and beta-adrenergic blocking agents on the myocardium of developing rats.

Triiodothyroacetic acid, triac, when given to rats during pregnancy, causes hypertrophy and intracellular disarray in the hearts of their offspring and concurrent treatment with dl propranolol can prevent the latter abnormality. Further experiments have been carried out to test the effect of dl oxprenolol and d propranolol on triac-induced myofibrillar disarray. Administration of dl oxprenolol at the same time as triac prevented disarray but a higher dose than that of dl propranolol was required to produce this effect. Disarray was also prevented by d propranolol. Selective consideration of the membrane stabilising, beta blocking and agonist activities of dl oxprenolol and d and dl propranolol leads to the conclusion that although direct or indirect beta stimulation by triac may play a small part in its disruptive effect on the developing myocardium, its main deleterious action can be blocked by membrane stabilisation.

The role of Coxsackie B viruses in the pathogenesis of myocarditis, dilated cardiomyopathy and inflammatory muscle disease.

Coxsackie B viruses are members of the family Picornaviridae which have been associated by retrospective serology with a range of muscle diseases, particularly myocarditis, dilated cardiomyopathy and epidemic pleurodynia (epidemic myalgia or Bornholm disease). It has been proposed that virus-induced myocarditis disposes to the development of idiopathic dilated cardiomyopathy. However, despite many attempts, isolation of infectious virus or immunofluorescent detection of virus-specific antigens in the affected tissue is rare, although virus may be found in faeces early in infection. This discrepancy awaited the development of nucleic acid probes to resolve the problem of whether virus was present consistently in myocardium or other muscle tissues. We report here the synthesis of Coxsackie B virus-specific complementary DNA (cDNA) probes and their use in molecular hybridizations to quantitative slot-blots of RNA prepared from either endomyocardial or skeletal muscle biopsy specimens. Of 50 patients with histologically proven myocarditis or dilated cardiomyopathy, 28 (56%) had an endomyocardial biopsy specimen positive for the presence of Coxsackie B virus-specific RNA. Twenty-two patients with other cardiac diseases of known aetiology, unrelated to virus infection, were all negative. Multiple biopsies were obtained from 20 patients with myocarditis or dilated cardiomyopathy and 15 of these (75%) had at least one biopsy specimen positive, indicating the focal nature of the disease. In analogous investigations, Coxsackie B virus-specific RNA was detected in four out of seven single skeletal muscle biopsy specimens from patients suffering from juvenile dermatomyositis, and one out of two patients with adult polymyositis. Ten muscle controls, either normal or Duchenne muscular dystrophy, were negative for virus RNA.

Results of biventricular endomyocardial biopsy in survivors of cardiac arrest with apparently normal hearts.

Seventeen young patients (10 males and 7 females, aged 14 to 38 years, mean 26.4) without overt organic heart disease, who had been resuscitated from sudden cardiac arrest and referred to our institution during the period 1984 to 1993 for diagnostic evaluation and electrophysiologic study-guided antiarrhythmic therapy, were studied. Patients underwent noninvasive (electrocardiography, echocardiography [2-dimensional and Doppler], and magnetic resonance imaging) and invasive (left ventricular [LV], right ventricular [RV], and coronary angiography, ergonovine testing, electrophysiologic study, and biventricular endomyocardial biopsy) cardiac studies. Six to 8 biopsy fragments per patient were processed for histology and electron microscopy and read by a pathologist blinded to clinical data. Antiarrhythmic drug testing included amiodarone, propafenone, and metoprolol. A cardioverter-defibrillator was implanted in patients with persistently inducible sustained ventricular tachycardia or ventricular fibrillation. Sequential cardiac biopsy specimens were obtained in patients with active myocarditis undergoing immunosuppressive treatment. Periodic 3-month follow-ups included echocardiography and Holter monitoring. Two groups of patients were distinguished by invasive and noninvasive examinations: group I consisted of 9 patients with entirely normal parameters; group II consisted of 8 patients with structural, nonspecific cardiac abnormalities. In this latter group, mild to moderate dilatation and hypokinesia of the left ventricle were documented in 4 patients, concentric LV hypertrophy was seen in three patients, and RV dysfunction was noted in 1 patient. Histologic examination was abnormal in in all patients and revealed specific lesions in 65% of them; LV biopsy specimens allowed a diagnosis in 3 of 7 myocarditic patients with normal RV histology.(ABSTRACT TRUNCATED AT 250 WORDS)

The production of cardiac hypertrophy by tri-iodothyroacetic acid.

Severe cardiac hypertrophy has been produced experimentally in rats by long-term, low-dose treatment with tri-iodothyroacetic acid. The dose used was insufficient to cause any apparent systemic or metabolic effect. It is suggested that similar iodinated substances in the blood in man, resulting from normal or abnormal thyroid hormone catabolism, may be causally related to some forms of cardiomyopathy.

Echocardiography and pathology of left ventricular "false tendons".

The anatomic incidence of left ventricular false tendons has been determined in 100 hearts obtained from consecutive autopsies on patients who had a wide variety of cardiac conditions. In this series, an anomalous band was found in 34 cases. A retrospective two-dimensional (2D) echocardiographic study was able to identify false tendons in only 18 percent of cases with anatomic evidence of them, indicating 2 mm as the limit of resolution of 2D echocardiography even with appropriate projections. Finally, the histologic examination has shown false tendons to contain conduction tissue and thus it is assumed to be intracavitary radiations of the bundle of His. This last consideration introduces new physical and electrophysiologic implications.

Comparison of the haematoxylin basic fuchsin picric acid method and the fluorescence of haematoxylin and eosin stained sections for the identification of early myocardial infarction.

A retrospective study has been carried out on the necropsy material from 30 patients who have died after a clinically diagnosed myocardial infarction. This study has been undertaken to compare the reliability of the fluorescence of infarcted myocardium when stained by haematoxylin and eosin and an adjacent section stained by the haematoxylin basic fuchsin picric acid (HBFP) method to detect early ischaemia. The results showed that the fluorescence technique is reliable, reproducible and coincides with the findings obtained by HBFP stain.

McLeod syndrome: a distinct form of neuroacanthocytosis. Report of two cases and literature review with emphasis on neuromuscular manifestations.

McLeod syndrome was originally described on the basis of a specific blood group phenotype with weak expression of Kell antigens. This erythrocyte abnormality also causes acanthocytosis. The haematological findings are associated with abnormalities in other organ systems, including neuromuscular manifestations. A 51-year-old patient was followed up for 11 years. He presented with persistent muscle creatine kinase elevation and progressive heart disease and later developed a slowly progressive neuropathy and choreic movements. His younger brother presented with grand mal seizures, involuntary movements and high muscle creatine kinase when aged 43 years. Clinical myopathy was absent in both, yet muscle biopsy showed mild myopathic changes. The presence of a motor axonopathy was supported by electrophysiological findings. One brother also showed sensory axonopathy. The movement disorder suggested accompanying basal ganglia dysfunction. Earlier reports of McLeod syndrome are reviewed with respect to neuromuscular involvement. Absence of the Kx membrane protein seems to be the cause of this multi-system disorder.

Dilated cardiomyopathy and myocarditis in Kenya: an endomyocardial biopsy study.

We have studied, by light and electron microscopy, left ventricular endomyocardial biopsy specimens from 18 African patients (14 men) with idiopathic dilated cardiomyopathy in Nairobi. Nine patients (50%) had evidence of healing myocarditis, that is the presence of a mild inflammatory cell infiltration within the myocardium. Interstitial fibrosis was prominent in five patients (28%) and in all 18 specimens there were hypertrophied muscle fibres. Therefore, half of the patients with idiopathic dilated cardiomyopathy had histological signs of a previous myocarditis. There was no serological evidence of a previous or recent coxsackie infection or any other common viral infections. It seems probable that the myocarditis was due to an inappropriate immunological reaction to myocardial muscle.

Heterologous antigenicity induced in human aortic homografts during preservation.

A series of rabbit experiments has been carried out to investigate the potential antigenicity of the heat-treated foetal calf serum which is commonly used to enhance viability of preserved aortic homograft valves. In all presensitised animals, the calf serum content of the nutrient medium which infiltrated the aortic wall during preservation provoked a heavy second-set reaction. It is concluded that heat-treated foetal calf serum is a potent heterologous antigen and should not be used for preserving human tissue selected for transplantation.

Injury to the cornea due to fish bile.

A retrospective study of 207 patients with chemical eye injuries in northern Norway revealed that fish bile was the causal agent in 14%. Fish bile caused superficial corneal erosions in 28 of 29 cases. All but one of the patients were professional fishermen or fish industry workers. In one case delayed medical care led to serious corneal opacity. Provided that there was immediate and abundant rinsing of the affected eye and good medical care, the prognosis of fish bile injuries was fairly good. The mechanisms for corneal damage due to fish bile are not clear.

Age-associated changes in the number of neurons in the right atrium.

1. It has been demonstrated that chronotropic responses differ in healthy elderly subjects compared to those in younger normal adults. To evaluate the involvement of the autonomic nervous system, we determined the number of neurons in right atrial strips from six elderly individuals (aged 77 +/- 3.4 years) five of whom had died as the result of extracardiac causes, and from younger adult controls (aged 44.0 +/- 6.0 years) who had died in traffic accidents. 2. There was a significant reduction in the number of neurons of the group of hearts from the elderly (3587 +/- 445, mean +/- SEM) compared with the control group (6412 +/- 377) of five hearts from younger adults (P less than 0.001). 3. It is suggested that this decrease in the number of neurons contributes to the reduced chronotropic responses in the aged. The mechanisms responsible for the neuronal depopulation was not determined.

Nigerian 'heart muscle disease': the late stages of untreated hypertensive heart failure?

Evidence for the hypertensive origin of Nigerian 'heart muscle disease' is presented. Epidemiologically, clinically and pathologically it is similar to hypertensive failure and it is associated with hypertension. It is more severe than hypertensive failure as judged by its prognosis and the myocardial damage at necropsy. The radiographic aortic width and renal histology, but not the retinal arteries have evidence of chronic hypertension in some. Using renal histology and scores on a discriminant analysis it was estimated that 34/62 cases in the necropsy series had been hypertensive . Up to 28 cases had not suffered from chronic hypertension but this figure (3%) of cardiac necropsies does not justify the identification of a highly prevalent myocardial disease in Nigeria. The arguments could apply to South African cryptogenic 'heart disease' and 'Jamaican cardiomyopathy'. The study presents data on the natural history of hypertensive failure.

The behaviour of tympanic membrane perforations in tissue culture: a scanning electron microscopic study.

The effects of keeping rat tympanic membranes with an artificially made pars tensa perforation in tissue culture were observed under a scanning electron microscope. After one day and onwards, spreading and thickening of the keratinizing, outer squamous epithelium (OE) was noted. In addition, ballooning of the innermost cells of the outer epithelium apposing the inner tympanic epithelium (IE) was seen. No appreciable reaction was noted in the connective tissue layer of the drum. The inner tympanic epithelium appeared to be swollen, containing spherical structures in the cytoplasm, especially close to the area of contact with the outer meatal epithelium. No complete cover of the drum defect was seen after 14 days of tissue culture. Hyperplasia and spreading of the keratinizing, outer squamous epithelium of the drum is not sufficient to achieve covering of a drum perforation and complete healing cannot take place unless supported by granulation tissue formation.

Pars flaccida perforation in tissue culture: morphological study.

Subtotal pars flaccida perforation was effected in vitro in rat tympanic membranes. The drums were subsequently kept in tissue culture and after various intervals studied by means of light and scanning electron microscopy. No complete covering of the perforation was seen, though a marked thickening and hyperplasia of the outer, keratinizing, squamous epithelium (OE) was evident. The inner, tympanal epithelium (IE) appeared swollen, containing rounded structures in the cytoplasm especially close to the contact area with the OE. Ingrowth of OE onto the tympanal side of the drum was seen particularly in the areas where the IE was sparse and completely lacking. Complete covering of a drum perforation seems to be dependent on the formation of supporting granulation tissue, probably resulting from an inflammatory reaction in the healing area.