Cardiomyopathic Changes Research Articles

Transmural heterogeneity of myocardial integrated backscatter in diabetic patients without overt cardiac disease

It is important to detect early changes in diabetic myocardium, because some diabetic patients suffer from diabetic cardiomyopathy, especially those with poorer glycemic control or hypertension (HT). To clarify whether ultrasonic tissue characterization can noninvasively detect ultrastructural changes in diabetic myocardium, we analyzed the transmural heterogeneity in myocardial integrated backscatter (THIB) in 20 diabetic patients and 16 normal subjects. THIB was defined as the absolute value of difference of integrated backscatter between the endocardial and epicardial half of the myocardium. THIB in diabetic patients was significantly greater than that in normal subjects. In diabetic patients, there was a significant correlation between glycosylated hemoglobin and THIB, and the greater THIB was shown in patients with HT compared with those without HT. Early changes in the myocardium, related to increased interstitial collagen deposition or other occult cardiomyopathic changes, may be detected on the basis of quantitative analysis of THIB in diabetic patients.

Early onset heart failure in transgenic mice with dilated cardiomyopathy.

In children, dilated cardiomyopathy is due to a variety of etiologies and usually carries a grave prognosis. The purpose of the present study was to carefully follow the progression of events leading to cardiac dilatation and congestive heart failure in a dilated cardiomyopathy model in neonatal and juvenile mice. These initial steps are often not well characterized. Furthermore, the loss of gap junctions and reduced electrical coupling of cardiomyocytes frequently found in human cardiomyopathies are also observed in these early stages. By 2 wk of age, molecular markers associated with hypertrophy were already altered. Cardiomyocyte hypertrophy, reduced connexin43 expression, and decreased conduction velocity were apparent by 4 wk, before overt cardiac dysfunction (decreased shortening fraction and chamber remodeling) that was not present until 12 wk of age. Our results show that in this model cardiomyopathic changes are present by 2 wk after birth and progress rapidly during the subsequent 2 postnatal weeks. Combined with the observations of other models of heart disease, we suggest that the first 2 wk of postnatal life are absolutely critical for normal cardiac development, and events that perturb homeostasis during this period determine whether the heart will continue to develop normally. These animals exhibit early symptoms of disease including reduced connexin43 and conduction defects before impaired cardiac function and demonstrate for the first time a temporal association between decreased connexin43 levels and the initiation of a contractility deficit that ends in heart failure.

The conserved phosphoinositide 3-kinase pathway determines heart size in mice.

Phosphoinositide 3-kinase (PI3K) has been shown to regulate cell and organ size in Drosophila, but the role of PI3K in vertebrates in vivo is not well understood. To examine the role of PI3K in intact mammalian tissue, we have created and characterized transgenic mice expressing constitutively active or dominant-negative mutants of PI3K in the heart. Cardiac- specific expression of constitutively active PI3K resulted in mice with larger hearts, while dominant-negative PI3K resulted in mice with smaller hearts. The increase or decrease in heart size was associated with comparable increase or decrease in myocyte size. Cardiomyopathic changes, such as myocyte necrosis, apoptosis, interstitial fibrosis or contractile dysfunction, were not observed in either of the transgenic mice. Thus, the PI3K pathway is necessary and sufficient to promote organ growth in mammals.

Protective effects of carvedilol against doxorubicin-induced cardiomyopathy in rats

Carvedilol (CAR) is a vasodilating β-blocker which also has antioxidant properties. CAR produces dose-related reduction in mortality in patients with congestive heart failure. In the present study, we tested the hypothesis that CAR protects against doxorubicin (DOX)-induced cardiomyopathy in rats. Sprague-Dawley rats were treated with DOX, CAR, CAR+DOX, or atenolol (ATN)+DOX. DOX (cumulative dose, 15 mg kg ) was administered intraperitoneally, and CAR (30 mg kg daily) or ATN (150 mg kg daily) was administered orally. Three weeks after the completion of these treatments, cardiac performance and myocardial lipid peroxidation were assessed. Mortality was observed in the DOX (25%) and ATN+DOX (12.5%) groups. Compared with control rats, DOX significantly decreased systolic blood pressure (104 ± 4 vs. 120 ± 4 mmHg, P < 0.05) and left ventricular fractional shortening (38.8 ± 3.1 vs. 55.4 ± 1.3%, P < 0.01), and resulted in a significant accumulation of ascites (14.4 ± 4.9 vs. 0 ml, P < 0.01). CAR significantly prevented the cardiomyopathic changes caused by DOX, while ATN did not. The myocardial thiobarbituric acid reactive substances (TBARS) content was significantly higher in DOX-treated rats than in control rats (80.4 ± 7.1 vs. 51.5 ± 1.2 nmol g heart, p < 0.01). CAR prevented the increase in TBARS content (48.8 ± 3.0 nmol g heart, P < 0.01 vs. DOX group), whereas ATN had no significant effect (74.3 ± 5.2 nmnol g heart). CAR also significantly prevented the increase in both myocardial and plasma cholesterol concentrations caused by DOX. These data indicate that CAR protects against DOX-induced cardiomyopathy and that this effect may be attributed to the antioxidant and lipid-lowering properties of CAR, not to its β-blocking property.

Mechanisms of beneficial effects of probucol in adriamycin cardiomyopathy.

Probucol, a lipid-lowering drug, has been shown to offer protection against adriamycin-induced cardiomyopathy. In order to define the mechanism of this protection, we examined changes in antioxidants and lipid peroxidation in hearts as well as lipids in hearts and plasma from rats treated with either adriamycin or adriamycin and probucol with appropriate controls. Any potential free radical quenching as well as growth inhibitory effects of probucol were also examined using Chinese hamster ovary (CHO) cells in culture. In animal model, adriamycin caused a significant depression in glutathione peroxidase and increased plasma and cardiac lipids as well as lipid peroxidation. Probucol treatment modulated adriamycin-induced cardiomyopathic changes and increased glutathione peroxidase and superoxide dismutase activities. In the presence of adriamycin under hypoxic conditions, formation of adriamycin semiquinone radical was detected by ESR. The cell growth in these cultures was also inhibited by adriamycin in a dose-dependent manner. Probucol had no effect on adriamycin-induced growth inhibition as well as formation of semiquinone radicals. It is proposed that probucol protection against adriamycin cardiomyopathy is mediated by increased antioxidants and lipid-lowering without any effect on free radical production.

Myofibril degeneration caused by tropomodulin overexpression leads to dilated cardiomyopathy in juvenile mice.

Loss of myofibril organization is a common feature of chronic dilated and progressive cardiomyopathy. To study how the heart compensates for myofibril degeneration, transgenic mice were created that undergo progressive loss of myofibrils after birth. Myofibril degeneration was induced by overexpression of tropomodulin, a component of the thin filament complex which determines and maintains sarcomeric actin filament length. The tropomodulin cDNA was placed under control of the alpha-myosin heavy chain gene promoter to overexpress tropomodulin specifically in the myocardium. Offspring with the most severe phenotype showed cardiomyopathic changes between 2 and 4 wk after birth. Hearts from these mice present characteristics consistent with dilated cardiomyopathy and a failed hypertrophic response. Histological analysis showed widespread loss of myofibril organization. Confocal microscopy of isolated cardiomyocytes revealed intense tropomodulin immunoreactivity in transgenic mice together with abnormal coincidence of tropomodulin and alpha-actinin reactivity at Z discs. Contractile function was compromised severely as determined by echocardiographic analyses and isolated Langendorff heart preparations. This novel experimentally induced cardiomyopathy will be useful for understanding dilated cardiomyopathy and the effect of thin filament-based myofibril degeneration upon cardiac structure and function.

Cardiac Involvement in Patients with Chronic Fatigue Syndrome as Documented with Holter and Biopsy Data in Birmingham, Michigan, 1991-1993

We report the prevalence of abnormal oscillating T-waves at Holter monitoring in a consecutive case series of 67 chronic fatigue syndrome (CFS) patients from an infectious diseases center in Birmingham, Michigan, in the years 1991-1993 , and compare these abnormal T-waves to similar tests in 78 non-CFS patients matched for age, place, time, and the absence of known other confounding medical diseases. Patients in both groups had normal resting 12-lead electrocardiograms (ECGs), rest/stress myocardial perfusion studies (thallium 201 or TC-99 sestamibi studies and two-dimensional echocardiograms (except for the incidental findings of mitral valve prolapse without significant regurgitation or, an incidental nonsignificant aortic stenosis). The prevalence of labile Twave abnormalities by Holter monitoring was greater in CFS patients than in non-CFS patients (P<.01). Repetitive T-wave flattening was a sensitive indicator of the presence of CFS. The absence of these abnormal T-waves made the diagnosis of CFS unlikely (statistical sensitivity, 0.96). The combination (e.g., the presence of both oscillating Twave flattenings plus T-wave inversions) was an accurate indicator of the possible presence of CFS. Right ventricular endomyocardial biopsies in CFS patients showed a single patient with lymphocytic myocarditis. Light and electron microscopic cardiomyopathic changes were present in the others. Copywrite 1997 Williams & Wilkins

Peptides Derived from Cardiovascular G-protein-coupled Receptors Induce Morphological Cardiomyopathic Changes in Immunized Rabbits

An experimental model of early-stage cardiomyopathy was created by immunizing rabbits for 1 year with synthetic peptides corresponding to the sequence of the second extracellular loop of eitherβ1-adrenoceptors or M2-muscarinic receptors. Thirty male rabbits were used and divided into three groups: a control group (n=10), a group immunized with the peptide corresponding to theβ1-adrenoceptor (β1group) (n=10) and a group immunized with the peptide corresponding to the M2-muscarinic receptor (M2 group) (n=10). In the sera from both groups of immunized rabbits high-titres of anti-peptide antibodies were found throughout the study period but not in the sera from control rabbits or in the preimmune sera of immunized rabbits. No significant cross-reaction with peptides other than those used for immunization was found. The myocardial receptor density of both immunized groups displayed a strong trend toward receptor up-regulation. This was significant in theβ1group but not in the M2 group. Both groups of immunized rabbits displayed significantly enlarged ventricles and thinner walls, as compared with the control group. However, in contrast to theβ1group, which showed enlarged cavities in both left and right ventricles, the M2 group was mainly affected in the right ventricles. Moreover, morphological examinations of the hearts of rabbits from both immunized groups demonstrated focal myofibrillar lysis, loss of myofilament, mitochondrial swelling and condensation, sarcoplasmic vacuolation, deposition of dense granules in the sarcoplasm and the myofibrils. One of the six control rabbit hearts which were examined showed mild degenerative changes in the myocardium and scant mononuclear cell infiltration. However, when all the control rabbit hearts were examined by electron microscopy, no significant alterations were found. These results suggest that immunization by peptides, corresponding to the target sequences for anti-receptor autoantibodies in idiopathic dilated cardiomyopathy induces morphological changes in the heart similar to those found in the human disease.

Involvement of phosphorylation in doxorubicin-mediated myofibril degeneration. An immunofluorescence microscopy analysis.

Loss of myofilaments has been observed in both adaptive cardiac responses (i.e., hypertrophy) as well as in chemotheraputic use of antineoplastic drugs with cardiotoxic side effects (i.e., doxorubicin). An understanding of the degenerative process is a prerequisite for determining approaches to limit the cardiomyopathic changes associated with chronic heart disease or long-term chemotheraputic treatments. However, little is known about the specific events and molecular changes that initiate the degenerative process. To study this process, neonatal rat cardiomyocytes were treated with doxorubicin, which induced rapid and widespread thin-filament degeneration as observed by fluorescence confocal microscopy. Which demonstrated deterioration of sarcomeric thin-filament structure. Changes in the spontaneous beating of cardiomyocytes corresponding with myofibrillar degeneration were apparent using differential interference contrast video microscopy. After finding induction of kinase activity by doxorubicin in cultured cardiomyocytes, the protective effects of specific inhibitors of kinase activity were assessed for their ability to inhibit doxorubicin-induced myofibrillar break-down. Doxorubicin-induced changes appeared similar to the degeneration observed after treatment with a protein kinase activator (phorbol 12-myristate 13-acetate) or a serine-threonine protein phosphatase inhibitor (okadaic acid). Collectively, these results indicate that activation of protein kinase is an important event in the initiation of myofibrillar degeneration by doxorubicin. Further analyses of myofibrillar proteins with respect to biochemical modifications will be necessary to determine if phosphorylation events transmit signal(s) to initiate degeneration.

Quantitative assessment of myocardial ultrasound tissue characterization through receiver operating characteristic analysis of Bayesian classifiers

Objectives. This work proposes a self-consistent assessment methodology for quantitative evaluation of any combination of diagnostic features, with the immediate goal of quantitatively assessing the discriminating power in diabetic patients of features derived from ultrasound backscatter from myocardium.Background. Four features from analysis of left ventricular myocardial ultrasound backscatter have previously been shown to be sensitive to potentially cardiomyopathic changes in patients with insulin-dependent diabetes mellitus who have no overt heart disease. The measured features were significantly different between such patients and normal control subjects, as well as among groups of such patients with and without systemic complications of the disease. The quantitative discriminating potential of the features was not assessed.Methods. Multivariate classifier functions were constructed and analyzed by using the methodology of the receiver operating characteristic curve, which allows quantitative assessment of the discriminating power of these features, alone or in combination. The area under the receiver operating characteristic curve—the true positive rate averaged over all false positive rates—was used as a summary measure of performance.Results. In distinguishing patients with insulin-dependent diabetes mellitus from normal control subjects, the most discriminating combination of ultrasound features for the detection of such changes in these patients yielded receiver operating characteristic curves with area measures of ∼0.80; for such patients with retinopathy the measure increased to 0.90. This performance is comparable to that of many commonly used diagnostic tests.Conclusions. A self-consistent set of evaluation methodologies has quantitatively demonstrated the sensitivity of four ultrasound backscatter features to otherwise latent changes in myocardial structure that accompany the evolution of insulin-dependent diabetes mellitus. The results are remarkable in themselves and suggest the potential of the features for the general field of cardiac ultrasound tissue characterization.

Probucol protects against adriamycin cardiomyopathy without interfering with its antitumor effect.

The usefulness of adriamycin (ADR), a potent antitumor antibiotic, is limited by the development of life-threatening cardiomyopathy and congestive heart failure. Subcellular changes leading to heart failure are suggested to be mediated by a drug-induced increase in free radicals and lipid peroxidation. In an earlier study, concurrent treatment with probucol (PROB), a lipid-lowering drug with strong antioxidant properties, was shown to offer only partial protection against ADR cardiomyopathy. The present study had two aims: to determine whether this protective effect can be improved further by extended treatment with PROB, and to determine whether PROB affects the antitumor properties of ADR. ADR (cumulative dose, 15 mg/kg body wt) was administered in rats in six equal injections (IP) over a period of 2 weeks. Three weeks after the end treatment, cardiomyopathy and congestive heart failure were characterized by ascites, congested liver, depressed cardiac function, elevated left ventricular end-diastolic pressure, and myocardial cell damage. Myocardial glutathione peroxidase (GSHPx) activity was decreased and lipid peroxidation was increased. Administration of PROB (cumulative dose, 120 mg/kg body wt) in 12 equal injections (IP), before and concurrent with ADR, completely prevented these cardiomyopathic changes, normalized left ventricular function, lowered mortality, and eliminated ascites. Treatment with PROB was also accompanied by an increase in myocardial GSHPx and superoxide dismutase activities with a concomitant decrease in lipid peroxidation. Tumor regression in syngeneic DBA/2 mice inoculated with L5178Y-F9 lymphoma cells in the ADR+PROB group was significant and comparable to the ADR group. These data show for the first time that PROB can provide complete protection against ADR cardiomyopathy without interfering with antitumor properties of the drug. This protective effect of PROB may be related to the maintenance of the antioxidant status of the heart.

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 antiodarone, 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 3 patients, and RV dysfunction was noted in 1 patient. Histologic examination was abnormal 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. An active lymphocytic myocarditis was observed in 7 patients, hypertrophic cardiomyopathy in 3 patients, RV dysplasia in 1 patient, and nonspecific cardiomyopathic changes in 6 patients. At 38-month follow-up, the mortality rate was 29% (all deaths were sudden). Biventricular endomyocardial biopsy may identify diagnostic lesions in young survivors of cardiac arrest with apparently normal hearts. In some patients LV biopsies revealed myocarditis when RV biopsies were normal.

Synthesis and distribution of atrial natriuretic peptide (ANP) in hearts from normal dogs and those with cardiac abnormalities

The cardiac distribution of immunoreactive atrial natriuretic peptide (IR-ANP) and ANP-specific mRNA was studied in 35 normal dogs and 44 dogs with primary and secondary heart abnormalities. According to clinical and pathological findings the dogs were assigned to seven groups: Group 1, normal young dogs (< 12 months); Group 2, normal adult dogs (> 12 months); Group 3, low to moderate hypertrophy; Group 4, severe hypertrophy; Group 5, dilated cardiomyopathy; Group 6, renal failure with secondary left ventricular hypertrophy; and Group 7, other heart abnormalities. In comparison with hearts of normal dogs, the amount of IR-ANP and ANP-specific mRNA was reduced in the atria and increased in the ventricles of dogs with hypertrophy and cardiomyopathy. The immunoreactivity in normal canine atria was far lower than in control rats and hamsters. The pattern of ventricular immunoreactivity was faint and patchy. Only in a few ventricular localizations of three dogs of Group 5 and one dog of Group 6 was there a granular pattern suggesting the presence of secretory granules. A state of intense secretory stimulation in cardiomyopathy was indicated by electron microscopy. Due to its low concentration and localized pattern, however, IR-ANP does not seem to be a reliable marker for the presence of hypertrophic or cardiomyopathic changes in dogs.

Abnormal myocardial acoustic properties in diabetic patients and their correlation with the severity of disease

Although patients with diabetes mellitus may be afflicted by cardiomyopathy, its prevalence and nature are controversial. Studies have shown that fibrosis alters the acoustic properties of the heart in animals and humans and that the changes are detectable by cardiac tissue characterization with ultrasound. The present study was performed to characterize myocardial acoustic properties in patients with insulin-dependent diabetes to determine whether ultrasound tissue characterization could detect changes potentially indicative of occult cardiomyopathy.The magnitude of cyclic variation of myocardial ultrasound integrated backscatter and its phase delay with respect to the onset of the cardiac cycle in the septum and posterior wall of the left ventricle were measured in 54 patients with diabetes who had no overt cardiac disease. Conventional echocardiography documented normal ventricular systolic function in 96%. As compared with results in age-matched patients without diabetes studied previously, cyclic variation of integrated backscatter was reduced (4.6 ± 0.8 vs. 3.6 ± 1.4 dB; p < 0.001). In addition, delay was significantly increased (0.86 ± 0.09 vs. 0.99 ± 0.15).The primary analysis of the data focused on differences among the diabetic patients. Reduction of cyclic variation of backscatter was greatest in patients with diabetes who had neuropathy (3.2 ±1.0 dB; p < 0.001) as was the increase in delay (1.04 ± 0.16, p < 0.001 vs. values in patients without neuropathy). Retinopathy and nephropathy were associated with abnormal myocardial acoustic properties as well.Thus, abnormalities that may reflect fibrosis or other occult cardiomyopathic changes in diabetic patients without overt heart disease are readily detectable by myocardial tissue characterization with ultrasound and parallel the severity of noncardiac diabetic complications.

Chloramphenicol toxicity associated with severe cardiac dysfunction

A 9-month-old infant experienced severe chloramphenicol toxicity associated with high serum levels (313 micrograms/ml). Cardiovascular collapse with cardiomyopathic changes and impaired left ventricular function was documented by echocardiography. Serial echocardiographic evaluation showed resolution of the cardiomyopathic findings as the chloramphenicol levels were spontaneously cleared. Clinical course was complicated by the development of liver disease and coagulopathy compatible with disseminated intravascular consumption. Patient's recovery was complete and uneventful, nevertheless, chloramphenicol toxicity in childhood is associated with a significant mortality rate of 40%. The related impaired cardiac function, although reversible, appears to play a major role in the pathogenesis and eventual outcome in this syndrome.

Myocardial function and energy substrate metabolism in the insulin-resistant JCR:LA corpulent rat

Alterations in myocardial energy substrate utilization contribute to the development of cardiomyopathic changes in insulin-dependent and non-insulin-dependent diabetic rats. Energy substrate utilization and contractile function, however, have not been characterized in insulin-resistant diabetes. In this study, we studied these parameters in the insulin-resistant obese JCR:LA-cp rat homozygous for the corpulent gene (cp/cp). Homozygous (+/+) or heterozygous (+/cp) lean non-insulin-resistant rats were used as controls. Isolated working hearts from cp/cp and lean control rats were perfused with Krebs-Henseleit buffer containing either 11 mM [U-14C]glucose and 0.4 mM palmitate or 11 mM glucose and 0.4 mM [1-14C]palmitate. Unlike control hearts, hearts from cp/cp rats were found to require high doses of insulin and Ca2+ concentrations of less than or equal to 1.75 mM to maintain mechanical function. In the presence of 2,000 microU/ml insulin, contractile function from cp/cp rat hearts was not depressed in the presence of either 1.25 or 1.75 mM Ca2+. Steady-state glucose oxidation rates in hearts perfused with 1.25 mM Ca2+ and 2,000 microU/ml insulin were 811 +/- 86 (SE) and 612 +/- 51 nmol.min-1.g dry wt-1 in cp/cp and control rats, respectively. Palmitate oxidation was 307 +/- 47 and 307 +/- 47 nmol.min-1.g dry wt-1 in cp/cp and lean control hearts, respectively. Under these perfusion conditions, 40% of myocardial ATP production was derived from glucose, whereas 60% was derived from palmitate in both cp/cp and control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Biopsy in Patients with “Primary” Atrial Fibrillation: Histologic Evidence of Occult Myocardial Diseases

Fourteen patients (ten men and four women; mean age, 37 years) with lone atrial fibrillation (AF) (1 to 18 months' duration) were evaluated by thyroid function tests, two-dimensional echocardiography, hemodynamics, coronary angiography, and left ventricular endomyocardial biopsy, because of unresponsiveness to the usual antiarrhythmic therapy. The results of the T3, T4, TSH, and TRH tests were normal in all patients; cardiac valves and ventricular and atrial sizes (left atrium less than 40 mm) were within the normal limits; also normal were LVEDP (less than or equal to 10 mm Hg) and EF (greater than 0.50). Histologic findings were abnormal in all cases, with three patients showing cardiomyopathic changes, three other patients showing active myocarditis (lymphocytic in two and eosinophilic in one), and eight patients with nonspecific necrosis or fibrosis or both. Steroids (prednisone; 50 mg/m2 of body surface area daily) used in addition to antiarrhythmic therapy in patients with eosinophilic and lymphocytic active myocarditis were able to cause reversion to sinus rhythm, while the other patients continued to have AF. This study documents that occult myocardial diseases (myocarditis, cardiomyopathy, and nonspecific necrosis or fibrosis) can underlie "primary" AF. The addition of steroids to antiarrhythmic therapy in patients with refractory AF and histologic evidence of active myocarditis seems to be useful in controlling the arrhythmia.

Unexpected myocardial disease in patients with life threatening arrhythmias.

It is not unusual for an individual without recognisable clinical heart disease to have a life threatening arrhythmia. This report describes the results of endomyocardial biopsy in twelve patients who presented with life threatening arrhythmias and normal or near normal cardiac function. The eight men and four women (mean age 35) presented with ventricular tachycardia or fibrillation (nine cases), high grade heart block with inadequate ventricular escape (two cases), and dangerous ventricular extrasystoles (Lown grade 4, one case). In ten of the twelve patients symptoms had been present for less than or equal to 6 months at presentation. No patient had a normal electrocardiogram. Electrophysiological testing confirmed the clinical arrhythmia in all but three patients. Endomyocardial biopsy demonstrated lymphocytic myocarditis in two patients, granulomatous myocarditis in two patients, small vessel vasculitis in one patient, and cardiomyopathic changes in six patients. In one patient the biopsy specimen was normal. Endomyocardial biopsy is a valuable diagnostic tool in patients with unexplained life threatening arrhythmias. In this study half the patients had a treatable form of heart muscle disease.

Myocardial injury following endogenous catecholamine release in rabbits

Catecholamines (CAT) given in large doses produce cardiomyopathic changes in several animal species. This study was designed to determine if endogenous release can also induce cardiac injury. Rabbits were infused with doses of tyramine (TYR), ranging from 200 to 500 micrograms/min/kg, i.v. for 90 min. Arterial pressure and heart rate were measured, as were total CAT concentrations, blood gases, pH and glucose. Two days later the animals were killed and cardiac injury assessed using a histological scoring system. All data were compared with controls given saline. Initial CAT averaged 452 pg/ml, rose to 2890 pg/ml after starting TYR, 500 micrograms/min/kg, and remained elevated for the duration of infusion. Circulating CAT levels were a function of TYR dose, and bore a linear relationship to the histological score (P less than 0.001). Development of lesions was unaltered by beta 1 blockade with practolol, but sharply reduced by alpha blockade with phentolamine (P less than 0.01). Pretreatment with insulin also reduced lesion formation, but diabetic (alloxan) rabbits showed no greater CAT injury. It is concluded that endogenous release of CAT induces myocardial injury in the rabbit in a dose-dependent manner. This is unrelated to myocardial O2 demand, and microvascular pathology was absent. Activation of alpha adrenergic pathways is likely the dominant or exclusive mechanism.

Focal cardiomyopathy and ectopic atrial tachycardia in Beckwith syndrome

The Beckwith syndrome was expanded in 1969 from Weidemann's report by Beckwith 1 to include the presence of macroglossia, omphalocele, adrenal cytomegaly, gigantism and hyperplastic visceromegaly. Increased growth at a cellular and organ level is characteristic of the syndrome, as is increased oncogenic potential. 2 Most neoplasms reported in the syndrome are intraabdominal; cardiac involvement is usually cardiomegaly. 3 The child described herein is unique in 2 aspects: He has a focal cardiomyopathy that contains giant myocar dial cells in the absence of inflammatory changes, and the cardiomyopathic changes are located in regions of ectopic atrial tachycardia.