Differences in quantitative EEG between frontotemporal dementia and Alzheimer's disease as revealed by LORETA.

OBJECTIVE: To determine the electrophysiological characteristics of frontotemporal dementia (FTD) and the distinction with Alzheimer's disease (AD). METHODS: We performed analyses of global field power (GFP) which is a measure of whole brain electric field strength, and EEG neuroimaging analyses with sLORETA (standardized low resolution electromagnetic tomography), in the mild stages of FTD (n = 19; mean age = 68.11 ± 7.77) and AD (n = 19; mean age = 69.42 ± 9.57) patients, and normal control (NC) subjects (n = 22; mean age = 66.13 ± 6.02). RESULTS: In the GFP analysis, significant group effects were observed in the delta (1.5-6.0 Hz), alpha1 (8.5-10.0 Hz), and beta1 (12.5-18.0 Hz) bands. In sLORETA analysis, differences in activity were observed in the alpha1 band (NC > FTD) in the orbital frontal and temporal lobe, in the delta band (AD>NC) in widespread areas including the frontal lobe, and in the beta1 band (FTD > AD) in the parietal lobe and sensorimotor area. CONCLUSIONS: Differential patterns of brain regions and EEG frequency bands were observed between the FTD and AD groups in terms of pathological activity. SIGNIFICANCE: FTD and AD patients in the early stages displayed different patterns in the cortical localization of oscillatory activity across different frequency bands.

Increased digitalis-like immunoreactive substances in neonatal plasma measured using fluorescence polarization immunoassay.

OBJECTIVE: To better define the reported increased digitalis-like immunoreactive substances (DLIS) in neonatal plasma, we studied the relation among plasma DLIS level, blank intensity (BLK-I) value at FPIA measurement and plasma total bilirubin level. METHODS: The DLIS levels were measured in 10 neonates with or without jaundice and 10 infants in good health, using fluorescence polarization immunoassay (FPIA) and microparticle enzyme immunoassay (MEIA). BLK-I value and plasma total bilirubin level were also measured simultaneously. RESULTS: In neonates with jaundice, DLIS using FPIA, BLK-I and total bilirubin level were 0.58 +/-0.13 ng/mL, 2598 +/- 408, and 17.98 +/- 1.13 mg/dL, respectively, before phototherapy, and 0.33 +/-0.06 ng/mL, 1886 +/- 237, and 15.16 +/- 2.07 mg/dL after phototherapy. Corresponding values in neonates without jaundice were (DLIS: 0.34 +/-0.04 ng/mL; BLK-I: 1,764 +/- 278; total bilirubin: 10.37 +/- 4.54 mg/dL); in healthy infants (0.12 +/-0.06 ng/mL, 400.7 +/- 4.6 and 0.42 +/- 0.13 mg/dL, respectively) and in healthy volunteers (0.10 +/-0.07 ng/mL, 403.1 +/- 8.4, and 0.58 +/- 0.30 mg/dL, respectively). Using MEIA, DLIS was not detected in 10 neonates, 10 infants and 20 healthy volunteers. CONCLUSIONS: A fluorescent compound related to bilirubin increased the BLK-I value in the measurement of neonatal plasma using FPIA. The fluorescence was not the result of endogenous digitalis-like factors.

Angiotensin II receptor blockade prevents microangiopathy and preserves diastolic function in the diabetic rat heart.

BACKGROUND: Cardiac microangiopathy may be involved in the development of heart failure in diabetes mellitus. OBJECTIVE: To evaluate the effect of angiotensin II receptor blockade on cardiac function and fine structures in diabetes. METHODS: Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats (n = 30), a model of spontaneously developing diabetes mellitus, and their diabetes resistant counterparts (n = 20) were used. At 30 weeks of age, when the OLETF rats show hyperglycaemic obesity with hyperinsulinaemia, the animals were divided into two groups and given candesartan, an angiotensin II receptor blocker, 0.2 mg/kg/day, or vehicle for six weeks. Capillary density was evaluated in the left ventricular myocardium by electron microscopy, matrix metalloproteinase (MMP) activity by zymography, and cytokines by reverse transcriptase polymerase chain reaction. RESULTS: Compared with the control rats, the OLETF rats at 36 weeks showed decreased peak negative dP/dt (mean (SD): 2350 (250) v 3492 (286) mm Hg/s) and increased cardiomyocyte diameter (24.3 (0.6) v 18.9 (0.6) microm) (both p < 0.05). Thickening of the capillary basement membranes and decreased capillary density were observed. Angiotensin receptor blockade improved almost all the haemodynamic variables, and the histological findings became similar to those of the controls. Angiotensin receptor blockade also activated MMP-2 and prevented an increase of inflammatory cytokines, especially interleukin (IL)-1beta and IL-6, in the diabetic heart. CONCLUSIONS: Angiotensin II receptor blockade preserved left ventricular diastolic function. It was also potent at improving cardiomyocyte diameter and the thickening of the capillary basement membrane, increasing MMP-2 activity, and decreasing inflammatory cytokines. With all these changes, candesartan could contribute to cardioprotection in diabetes mellitus.

Autophagic degeneration as a possible mechanism of myocardial cell death in dilated cardiomyopathy.

In failing hearts, cardiomyocytes degenerate and interstitial fibrosis, which indicates cardiomyocyte loss, becomes more prominent in the myocardium. However, the precise mechanism of cardiomyocyte degeneration that leads to cell death is still unclear, although it is presumed that lysosomal function and autophagy play an important role because lysosomal activity increases under stress such as hypoxia. Myocardium that had been resected during partial left ventriculectomy performed in patients with dilated cardiomyopathy (DCM) was examined. Under light microscopy, some cardiomyocytes had a marked scarcity of myofibrils and had prominent cytoplasmic vacuolization. Atrophic and degenerated cardiomyocytes were often observed adjacent to replacement fibrotic tissue. Immunohistochemistry showed positivity for lysosome-associated membrane protein and a lysosomal catheptic enzyme in vacuoles of various sizes in the cardiomyocytes and these lysosomal markers were markedly increased in atrophic and degenerated cardiomyocytes. Electron microscopy revealed that degenerated cardiomyocytes had many vacuoles containing intracellular organelles, such as mitochondria, and were considered to be autophagic vacuoles. In DCM hearts, autophagy appeared to be associated not only with degradation of damaged intracellular organelles but also with progressive destruction of cardiomyocytes. It is possible that autophagic degeneration is one of the mechanisms of myocardial cell death.

Enterovirus RNA replication in cases of dilated cardiomyopathy: light microscopic in situ hybridization and virological analyses of myocardial specimens obtained at partial left ventriculectomy.

OBJECTIVE: Recently, attention has been focused on enteroviral infection of the heart in the genesis of dilated cardiomyopathy (DCM). To determine the location of enteroviral RNA in the myocardium, we performed light microscopic in situ hybridization (ISH) and virological analyses of myocardial specimens obtained at partial left ventriculectomy (PLV). METHODS: Posterolateral walls of the left ventricle from 26 DCM patients were examined. Myocardial specimens were tested for the presence of enteroviral genomes by polymerase chain reaction (PCR). We selected two age-matched groups (10 patients each) in which enteroviruses were either present (EV-plus group) or not (EV-minus group). For both groups, we examined in situ localization of enteroviral RNA in the myocardium by ISH. RESULTS: In PCR studies, both sense and antisense enteroviral RNA were detected in the myocardium of seven patients in the EV-plus group. The presence of this RNA indicates active viral replication in the myocardium. Five of seven patients who exhibited both sense and antisense enteroviral RNA died early after surgery. On ISH, three patients had evidence of active replication of enteroviral genomes. Viral genomes were present in myocardial lesions, especially in endocardial sites. Viral signals were found in degenerating myocardial cells, interstitial inflammatory cells, and endothelial cells of small vessels. These positive signals were not detected in the myocardium of the EV-negative group. CONCLUSIONS: We detected both sense and antisense enteroviral RNA in various myocardial lesions. This suggests that active enteroviral replication plays a role in the development of myocardial lesions in DCM patients. Active viral replication appears to be a prognostic factor for DCM after PLV. Further study of active viral replication in myocardial lesions will provide information useful for evaluating different therapeutic strategies for DCM.

Role of transesophageal echocardiography in the prediction of thromboembolism in patients with chronic nonvalvular atrial fibrillation.

The purpose of this study was to determine whether parameters derived from transesophageal echocardiography (TEE) could predict thromboembolism in patients with chronic nonvalvular atrial fibrillation (AF). Eighty-nine patients, mean age 66+/-9 years, who underwent TEE in 1996 to 1999 were studied. The clinical endpoint was a thromboembolic event, including transient ischemic attack (TIA). Sixty-seven patients (75%) were anticoagulated with warfarin after TEE. After a follow-up period of 29+/-10 months, 1 patient died suddenly, 4 had a thromboembolism, and 3 had a TIA; the annual embolic event rate was 3.3%. Left atrial appendage (LAA) thrombus (86% vs 17%, p<0.001), LAA dysfunction (LAA velocity <20 cm/s; 71% vs 25%, p=0.009), and severe LA spontaneous echo contrast (29% vs 2%, p=0.002) were more prevalent in patients with an embolic event than in those without. In patients with LAA thrombus, the annual event rate was 11% as compared with 1.2% in those without (p=0.004). On the Cox proportional hazards model analysis, LAA thrombus (chi-square 7.0, p=0.008), severe LA spontaneous echo contrast (chi-square 7.0, p=0.008), and LAA dysfunction (chi-square 5.9, p=0.015) were significantly related to thromboembolism. Multivariate analysis revealed that LAA thrombus (chi-square 5.5, p=0.019) and LAA dysfunction (chi-square 4.0, p=0.045) were the independent predictors. In conclusion, TEE parameters, particularly the presence of LAA thrombus, can be used to assess thromboembolic potential in patients with chronic nonvalvular AF.

Myocardial inflammatory cell infiltrates in cases of dilated cardiomyopathy as a determinant of outcome following partial left ventriculectomy.

Partial left ventriculectomy (PLV) can be used to treat refractory congestive heart failure caused by dilated cardiomyopathy (DCM). In order to understand the relationship between the underlying myocardial injury and early clinical outcomes after PLV, histopathologic, immunohistochemical and virologic studies of the resected myocardium were performed. The posterolateral left ventricular walls from 27 patients with idiopathic DCM were examined. Cardiomyocyte diameter, degree of myocardial fibrosis, degree of cardiomyocyte degeneration, and degree of inflammatory cell infiltration were compared with mortality rates. Polymerase chain reaction was performed to detect enterovirus genome in the myocardium. Some patients had inflammatory cell infiltrates with focal accumulations of lymphocytes and macrophages, including both cytotoxic/suppressor T-cells and helper/inducer T-cells. The number of inflammatory cells (activated lymphocytes plus macrophages/mm2) was significantly greater in patients who died of cardiac insufficiency after surgery (27.8 +/- 5.7; n = 7) than in the survivors (11.1 +/- 2.5; n = 15). There was no significant difference in the degree of myocardial fibrosis, cardiomyocyte diameter or degree of cardiomyocyte degeneration between the 2 groups. Enterovirus genome was detected in the myocardium of 9 (38%) of 24 patients examined and 5 of these enterovirus-positive hearts had severe inflammatory cell infiltrates (37.9 +/- 2.5/mm2). Early survival in patients undergoing PLV for DCM is significantly affected by the degree of myocardial inflammation, so patients with more severe or ongoing inflammation may have poor clinical outcomes. Chronic myocarditis may play an important role in the etiology and pathophysiology of idiopathic DCM.

Quantification of left atrial appendage spontaneous echo contrast in patients with chronic nonalvular atrial fibrillation.

OBJECTIVES: The left atrial (LA) appendage is the most common site of thrombus formation in patients with atrial fibrillation, and integrated backscatter allows the quantiative assessment of LA spontaneous echo contrast (SEC). Integrated backscatter was used to examine the significance of measuring appendage SEC, specifically in relation to echocardiographic variables implying thromboembolism, in patients with chronic nonvalvular atrial fibrillation. METHODS: Fifty-two patients with chronic nonvalvular atrial fibrillation and no prior anticoagulant therapy (35 men, 17 women, mean age 66 +/- 7 years) underwent transesophageal echocardiography with integrated backscatter analysis. The LA and LA appendage integrated backscatter intensity were measured with the regions of interest placed in the LA cavity and the appendage, respectively. The integrated backscatter intensity values for these two chambers (corrected "LA" and "LA appendage" integrated backscatter intensity, respectively) were corrected using values from the left ventricular cavity. RESULTS: The LA appendage integrated backscatter intensity values were available in 44 patients (85%). Overall, the corrected LA appendage integrated backscatter intensity was significantly increased compared with the corrected LA integrated backscatter intensity (2.8 +/- 2.2 vs 2.0 +/- 1.8 dB, p < 0.001). The corrected LA appendage integrated backscatter intensity was inversely correlated with the LA appendage velocity (r = -0.37, p < 0.05), but not with the LA dimension, appendage size, or left ventricular function. The corrected appendage integrated backscatter intensity (4.5 +/- 2.3 vs 2.4 +/- 1.9 dB, p < 0.01) and LA integrated backscatter intensity (3.2 +/- 2.1 vs 1.7 +/- 1.7 dB, p < 0.05) were higher in patients who had LA appendage thrombus (n = 8) than those who did not. With the corrected appendage integrated backscatter intensity set at > or = 2.5 dB, the sensitivity for the presence of appendage thrombus was 88% and the specificity was 64%. CONCLUSIONS: Patients with chronic nonvalvular atrial fibrillation had a denser SEC in the LA appendage compared with SEC in the main LA cavity. The severity of the appendage SEC was influenced by the LA appendage function rather than its size. Quantification of SEC in the appendage, rather than main LA cavity, was more valuable for assessing embolic potential.

Development of a simple whole blood panel test for detection of human heart-type fatty acid-binding protein.

OBJECTIVE: For the diagnosis of acute myocardial infarction (AMI), we have developed a rapid and simple whole blood panel test for the detection of human heart-type fatty acid-binding protein (H-FABP) using one-step immunochromatography. METHODS AND RESULTS: We have developed a whole blood panel test for rapid detection of human H-FABP using a one-step immunochromatography technique. The result of this panel test was not affected by the other contents of the blood such as bilirubin, hemoglobin and others. Furthermore, no cross-reactivity of the antibodies was found with other cardiac markers or other tissue-type FABPs. The result of this panel test was similar to the diagnostic cut-off value, 6.2 ng of H-FABP per mL of serum which was evaluated by the enzyme-linked immunosorbent assay (ELISA). CONCLUSION: We have developed a simple one-step immunochromatography technique to detect H-FABP in whole blood sample. Further studies are required to identify the value of this point-of-care testing (POCT) as a diagnostic marker for AMI.

A case of cardiomyopathy showing progression from the hypertrophic to the dilated form: association of Mt8348A-->G mutation in the mitochondrial tRNA(Lys) gene with severe ultrastructural alterations of mitochondria in cardiomyocytes.

This report describes a case of cardiomyopathy with a novel point mutation of mitochondrial DNA coding lysine tRNA in association with severe ultrastructural alterations of the mitochondria in the cardiomyocytes. Abnormalities of energy production and/or abnormal protein synthesis because of the mutation of mitochondrial DNA may have played an important role in the pathogenesis of this case, which showed severe cardiomyocyte degeneration and deterioration from hypertrophic cardiomyopathy to severe dilated cardiomyopathy.

Peflin and ALG-2, members of the penta-EF-hand protein family, form a heterodimer that dissociates in a Ca2+-dependent manner.

Peflin, a newly identified 30-kDa Ca(2+)-binding protein, belongs to the penta-EF-hand (PEF) protein family, which includes the calpain small subunit, sorcin, grancalcin, and ALG-2 (apoptosis-linked gene 2). We prepared a monoclonal antibody against human peflin. The antibody immunoprecipitated a 22-kDa protein as well as the 30-kDa protein from the lysate of Jurkat cells. Western blotting of the immunoprecipitates revealed that the 22-kDa protein corresponds to ALG-2. This was confirmed by Western blotting of the immunoprecipitates of epitope-tagged peflin or ALG-2 whose cDNA expression constructs were transfected to human embryonic kidney (HEK) 293 cells. Gel filtration of the cytosolic fraction of Jurkat cells revealed co-elution of peflin and ALG-2 in fractions eluting earlier than recombinant ALG-2, further supporting the notion of heterodimerization of the two PEF proteins. Surprisingly, peflin dissociated from ALG-2 in the presence of Ca(2+). Peflin and ALG-2 co-localized in the cytoplasm, but ALG-2 was also detected in the nuclei as revealed by immunofluorescent staining and subcellular fractionation. Peflin was recovered in the cytosolic fraction in the absence of Ca(2+) but in the membrane/cytoskeletal fraction in the presence of Ca(2+). These results suggest that peflin has features common to those of other PEF proteins (dimerization and translocation to membranes) and may modulate the function of ALG-2 in Ca(2+) signaling.

Coxsackie B virus infection in idiopathic dilated cardiomyopathy: clinical and pharmacological implications.

Idiopathic dilated cardiomyopathy (IDC) is a myocardial disease characterised by ventricular dilatation, impaired contractility, and the symptoms of congestive heart failure. Although the causes of IDC remain uncertain, much interest has been focused on the enteroviral infection in the myocardium in the pathogenesis of this disease. Enteroviral RNA has been demonstrated in the myocardium at all stages of IDC. Recent studies using sequence analysis of enteroviral polymerase chain reaction (PCR) products have shown that the viruses detected in hearts of patients with IDC are coxsackie B. In addition, active coxsackieviral RNA replication in the myocardium has been demonstrated by strand-specific detection of viral RNA. Viral antigen has also been found in hearts with IDC by immunohistochemical techniques. In tissue culture experiments and transgenic mice, it has been shown that restricted coxsackieviral RNA replication, and not infectious virus progeny, in the myocardium can impair cardiac contractile function and lead to dilated cardiomyopathy. Coxsackieviral RNA in the myocardium can be a marker of a poor clinical outcome after partial left ventriculectomy, and might influence prognosis after heart transplantation. Therefore, there is a therapeutic need to detect replicating coxsackieviral RNA in the myocardium, and a specific therapy for coxsackie B viruses is indicated in the management of patients with virus-positive IDC.

Evaluation of viral infection in the myocardium of patients with idiopathic dilated cardiomyopathy.

OBJECTIVES: The aim of this study was to evaluate the viral etiology of idiopathic dilated cardiomyopathy (DCM). BACKGROUND: The demonstration of enteroviral genome in hearts with DCM has reinforced the importance of enteroviruses in the pathogenesis of DCM. However, there is uncertainty about the character and activity of enteroviruses detected in the myocardium. Recently, the association of hepatitis C virus or adenovirus with DCM has been reported. METHODS: Myocardial specimens from 26 patients with idiopathic DCM, which were obtained at partial left ventriculectomy (PLV), were examined virologically. Strand-specific detection of enteroviral RNA was performed to differentiate active viral replication from latent persistence. Polymerase chain reaction was used to detect genomic sequences of hepatitis C virus, adenovirus, cytomegalovirus, influenza viruses, mumps virus, herpes simplex viruses, varicella-zoster virus and Epstein-Barr virus. RESULTS: Plus-strand enteroviral RNA was detected in 9 (35%) of the 26 patients. Minus-strand enteroviral RNA was determined in seven (78%) of these nine plus-strand RNA-positive patients. Sequence analysis revealed that the enteroviruses detected were coxsackie B viruses, such as coxsackievirus B3 and B4. However, genetic material from other viruses was not detected. Six (86%) of seven minus-strand enteroviral RNA-positive patients died of cardiac insufficiency within the first six months after PLV. CONCLUSIONS: Coxsackie B viruses were seen in hearts with idiopathic DCM. Active viral RNA replication appeared to be present in a significant proportion of these cases. Minus-strand coxsackieviral RNA in the myocardium can be a marker for poor clinical outcome after PLV. There was no evidence of persistent infection by other viruses in hearts with DCM.

Integrated backscatter assessment of left atrial spontaneous echo contrast in chronic nonvalvular atrial fibrillation: relation with clinical and echocardiographic parameters.

Integrated backscatter (IB) provides the quantitative assessment of left atrial spontaneous echo contrast (SEC). The IB intensity of the left atrial cavity relative to the left ventricular cavity is related to atrial thrombus in patients with atrial fibrillation (AF) or sinus rhythm. However, little is known about the relation between the quantitative SEC value of the left atrial cavity and variables implying thromboembolism in nonvalvular AF. To examine this relation, we performed transesophageal echo-cardiography with IB analysis in 65 patients with chronic nonvalvular AF. The quantitative SEC value of the left atrial cavity was defined as the difference between atrial IB intensity and ventricular IB intensity (corrected IB intensity). The corrected IB intensity was correlated with the left atrial dimension (r = 0.25, P =.049), the left atrial appendage velocity (r = -0.41, P <.001), and the duration of AF (r = 0.23, P =. 023). The corrected IB intensity was higher in patients who had a history of hypertension (3.2 +/- 2.2 dB versus 2.0 +/- 1.6 dB, P =. 018), SEC (3.9 +/- 1.9 dB versus 1.4 +/- 1.1 dB, P =.002), and left atrial thrombus (4.5 +/- 2.7 dB versus 2.2 +/- 1.7 dB, P <.001) when compared with those who did not have these abnormalities. The corrected IB intensity was significantly lower in patients with significant mitral regurgitation than in those without it (1.1 +/- 1. 2 dB versus 2.7 +/- 2.0 dB, P =.036). When the cutoff value of the corrected IB intensity was set at >/=2.0 dB, the sensitivity for left atrial thrombus was 78% and the specificity was 55%. In patients with chronic nonvalvular AF, the quantitative SEC value of the left atrial cavity depends on the duration of AF as well as the left atrial dimension and appendage velocity. Although IB may be capable of identifying patients with higher risk of cardiogenic embolism, a large-scale prospective study is needed to actually establish this.

Backscattered electron imaging: A new method for the study of cardiomyocyte architecture using scanning electron microscopy.

Scanning electron microscopy (SEM) with secondary electron emissions is useful for the study of cardiomyocyte architecture, however, the information is limited from the cell surface. Whereas backscattered electron (BSE) emission can give a high-resolution image of the specimen's intracellular structure after heavy metal staining. In this study, we applied BSE imaging analysis to the study of the arrangement of cardiomyocytes in the myocardium. The tissue specimens from a normal fresh monkey heart, normal human heart obtained at autopsy, and surgically resected tissue from a patient with old myocardial infarction in the left ventricular aneurysmectomy were used. The tissue specimens were fixed in neutral formalin, treated with NaOH and then stained with Gomori's silver methenamine reagent followed by tannic acid and osmium tetroxide. After dehydration and drying, the specimens were coated with carbon and examined by SEM with a BSE detector. In the tissue preparations, the A bands of sarcomeres were selectively stained with silver so that the arrangements of subsarcolemmal myofibrils and the intercalated discs were clearly seen in the BSE images. In the left ventricular aneurysmal walls of old myocardial infarction, atrophied cardiomyocytes with disarray of subsarcolemmal myofibrils were observed. The results strongly suggest that BSE images are further applicable to the study of the architecture of cardiac myocytes and their branches, and the arrangement of intracellular myofibrils in various diseased myocardium.

Increased digitalis-like immunoreactive substances in patients with hypertrophic cardiomyopathy.

AIMS: Although increased digitalis-like immunoreactive substances have been found in cases of hypertension and heart failure, no information is available about digitalis-like immunoreactive substances in patients with hypertrophic cardiomyopathy. We investigated digitalis-like immunoreactive substances in the plasma and biopsied specimens of patients with hypertrophic cardiomyopathy. METHODS AND RESULTS: In 40 patients with hypertrophic cardiomyopathy (27 with the non-obstructive type and 13 with the obstructive type), the plasma concentration of digitalis-like immunoreactive substances was studied by fluorescence polarization immunoassay. Right ventricular endomyocardial biopsy specimens were analysed immunohistochemically, using a monoclonal antibody against digoxin. An increase in digitalis-like immunoreactive substances of more than 0.2 ng. ml(-1)in plasma was found in six of 27 patients with non-obstructive hypertrophic cardiomyopathy (22.2%) and five of 13 with obstructive hypertrophic cardiomyopathy (38.4%). Under light microscopy, positive staining against the antibody was observed heterogeneously on some cardiocytes. In non-obstructive hypertrophic cardiomyopathy, digitalis-like immunoreactive substances in the plasma correlated with the left atrial dimension and inversely with the cardiac index. In obstructive hypertrophic cardiomyopathy, plasma and myocardial digitalis-like immunoreactive substances were positively correlated; they also correlated with left ventricular end-diastolic pressures. Under electron microscopy, digitalis-like immunoreactive substances were detected at the sarcolemma in the free wall, T-tubules, intercalated discs and Z-bands of cardiocytes. CONCLUSIONS: Increased digitalis-like immunoreactive substances in plasma and cardiocytes, which may have been caused by pressure and/or volume overload, were found in patients with hypertrophic cardiomyopathy. Digitalis-like immunoreactive substances may act on the sarcolemma of cardiocytes and be transported into the cytoplasm.