Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with chronic congestive heart failure manifest > or = 1 of the following abnormalities: diastolic dysfunction, systolic dysfunction, and arrhythmias. Diastolic dysfunction, one of the first symptoms to occur during hypertensive cardiopathy, depends on both active relaxation of the cardiac muscle and passive ventricular compliance. The ability of the ventricles to relax depends on normal calcium metabolism and adenosine triphosphate concentration. Ability to extrude intracellular calcium is depressed in the hypertrophied, overloaded heart as compared with the normal myocardium. Myocardial fibrosis is the major cause of increased diastolic ventricular stiffness. Left ventricular (LV) hypertrophy and myocardial fibrosis also greatly increase the likelihood of ventricular arrhythmias, in particular by prolonging the QRS interval and facilitating the occurrence of reentry arrhythmias. Findings in animal studies have indicated that such fibrosis, which involves excessive collagen deposition, is independent of LV hypertrophy and that LV hypertrophy does not necessarily result in myocardial fibrosis. Instead, the development of myocardial fibrosis is sensitive to circulating levels of both angiotensin II and aldosterone, and the fibrotic response to each of these substances is independent. The aldosterone antagonist spironolactone prevents myocardial fibrosis in several animal models, thus confirming the importance of aldosterone in the genesis of excessive collagen deposition.
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PMID:Role of mechanical and hormonal factors in cardiac remodeling and the biologic limits of myocardial adaptation. 842 5

A change in muscle length significantly alters the developed tension in mammalian cardiac muscle compared to that in skeletal muscle fibers. The intracellular mechanisms related to the length-dependent change in developed tension have been studied using Ca2+ indicators in intact preparations; a cross-bridge-dependent change in the affinity of troponin-C for Ca2+ is a possible mechanism. This hypothesis is further supported by the measurement of Ca2+ bound to troponin-C in skinned preparations. The molecular mechanism of the cross-bridge-dependent change in the affinity of troponin-C for Ca2+ is not fully understood although the studies which employ the substitution of troponin-C in skinned preparations, transgenic animals and in an animal model with heart disease have been performed. We reviewed the current studies by analyzing the intracellular mechanism responsible for the length-dependent change in tension development in mammalian cardiac muscle.
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PMID:Cross-bridge-dependent changes in the intracellular Ca2+ concentration in mammalian cardiac muscles. 867 41

X-linked dilated cardiomyopathy (XLDC) is a familial heart disease presenting in young males as a rapidly progressive congestive heart failure, without clinical signs of skeletal myopathy. This condition has recently been linked to the dystrophin gene in some families and deletions encompassing the genomic region coding for the first muscle exon have been detected. In order to identify the defect responsible for this disease at the molecular level and to understand the reasons for the selective heart involvement, a family with a severe form of XLDC was studied. In the affected members, no deletions of the dystrophin gene were observed. Analysis of the muscle promoter, first exon and intron regions revealed the presence of a single point mutation at the first exon-intron boundary, inactivating the universally conserved 5' splice site consensus sequence of the first intron. This mutation introduced a new restriction site for MseI, which cosegregates with the disease in the analyzed family. Expression of the major dystrophin mRNA isoforms (from the muscle-, brain- and Purkinje cell-promoters) was completely abolished in the myocardium, while the brain- and Purkinje cell- (but not the muscle-) isoforms were detectable in the skeletal muscle. Immunocytochemical studies with anti-dystrophin antibodies showed that the protein was reduced in quantity but normally distributed in the skeletal muscle, while it was undetectable in the cardiac muscle. These findings indicate that expression of the muscle dystrophin isoform is critical for myocardial function and suggest that selective heart involvement in dystrophin-linked dilated cardiomyopathy is related to the absence, in the heart, of a compensatory expression of dystrophin from alternative promoters.
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PMID:A point mutation in the 5' splice site of the dystrophin gene first intron responsible for X-linked dilated cardiomyopathy. 878 42

By sequestering activator calcium, the sarcoplasmic reticulum (SR) plays the central role in the excitation-contraction (E-C) cycle of cardiac muscle. Hence, functional changes in the SR in diseased myocardium might critically determine its mechanical characteristics. Previously, we demonstrated that both Ca2+ release and uptake were increased in SR isolated from hearts showing compensatory left ventricular (LV) hypertrophy taken from pressure-overloaded rats. However, it has not been elucidated whether such alterations also occur in the volume-overloaded myocardium. Rats in which volume-overloaded hypertrophy had been induced by aortocaval shunt 12 weeks prior to the investigation were compared to sham-operated controls in terms of SR Ca2+ uptake and release, and density of Ca2+ releasing channels (ryanodine receptors, RyR). Isometric tension and intracellular Ca2+ transients were also measured using the bioluminescent Ca2+ indicator, aequorin, in isolated LV papillary muscles. The extent of hypertrophy was verified by measuring the ratio of biventricular weight to body weight. In vivo, the aortocaval shunt rats showed normal LV contractility and slightly depressed LV relaxation, indicating a compensatory (adaptive) stage of LV function. In contrast, Ca2+ release, uptake, and maximal number of [3H]-ryanodine binding sites were all significantly lower in aortocaval shunt rats than in controls. Both the Ca2+ transients and isometric relaxation of the isolated myocardium were significantly prolonged in aortocaval shunt rats, though their amplitudes were similar in the two groups. Thus, the volume-overloaded cardiac hypertrophy, even at its hemodynamically compensatory (adaptive) stage, (i) was accompanied by abnormal Ca2+ handling, as indicated by prolonged intracellular Ca2+ transients and isometric tension traces, (ii) seems to involve subcellular mechanisms related to decreases in SR Ca2+ release and uptake functions, as well as to a decrease in the number of RyR. Therefore, changes in the intracellular processes underlying cardiac E-C coupling, including SR function, precede the development of this type of heart disease.
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PMID:Early changes in the functions of cardiac sarcoplasmic reticulum in volume-overloaded cardiac hypertrophy in rats. 916 Aug 62

Molecular expression cloning techniques revealed that patients with severe chronic Chagas heart disease showed a strong humoral response against the cloned C-terminal portion of the Trypanosoma cruzi ribosomal P2beta protein, previously named JL5. The main linear epitope of this polypeptide was mapped to the 13 C-terminal amino acid sequence EEEDDDMGFGLFD (named R13), which is almost identical to the mammalian ribosomal P consensus sequence EESDDDMGFGLFD (named H13). Enzyme-linked immunosorbent assay measurements demonstrated that sera from patients with chronic Chagas heart disease presented a very specific anti-P humoral response with high anti-R13, but low H13 antibody levels. We attempted to develop an animal model that would reproduce, at least partially, two features of the human infection: (1) the serological pattern of the anti-P response, and (2) specific cardiac symptoms. To this effect, mice were immunized with T. cruzi P2beta recombinant protein. Immunization reproduced the typical anti-P antibody profile defined for chronic infections, but did not induce cardiac inflammatory lesions. However, it altered significantly the electrocardiograms of immunized mice. It is suggested that this assay represents a functional test for assessing the biological activity of antibodies against T. cruzi ribosomal P protein on cardiac muscle.
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PMID:Immunization with recombinant Trypanosoma cruzi ribosomal P2beta protein induces changes in the electrocardiogram of immunized mice. 921 90

Arrhythmogenic right ventricular dysplasia is a disease of the cardiac muscle of unknown etiology. Landmarks of this disease are the presence of muscular atrophy and replacement of ventricular myocardium by adipous and fibroadipous tissue. This disease was originally described by Fontaine et al in 1977 during surgical ablation of drug refractory ventricular tachycardias in patients without evident structural heart disease. During surgery anomalies in contractility of the right ventricle and the presence of adipous tissue were documented. Some years later, Markus et al reported the first clinical series of patients with arrhythmogenic right ventricular dysplasia. Since then, this disease has been widely recognized and must be considered in the differential diagnosis of all patients with ventricular arrhythmias originating in the right ventricle.
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PMID:[Arrhythmogenic dysplasia of the right ventricle]. 934 Jun 94

The first case of chronic cardiac toxicity due to an antimalarial agent was reported in 1971 and since then several cases of heart failure, restrictive cardiomyopathy or atrioventricular block have been ascribed to this family of drugs. We report the case of a 43-year-old woman who developed juvenile chronic arthritis at the age of ten, followed in adulthood by sero-positive rheumatoid arthritis. In 1980 she was put under chloroquine sulfate (hydroxychloroquine was not available) in a dose of 200 mg/d (152.66 mg of chloroquine), with 10 mg/day of prednisone. She developed myalgia and increased skin pigmentation, but disregarded recommendations that these symptoms required discontinuation of chloroquine therapy. She was lost to follow-up, but continued the chloroquine therapy of her own accord. In December 1993, she developed a third-degree atrioventricular block with syncopes requiring implantation of a pacemaker. The rare but well-documented myopathy induced by antimalarial agents can produce early severe lesions of the cardiac muscle, which may have a predilection for the interventricular septum, explaining the risk of atrioventricular block. Although histologic studies were not performed in our patient, the clinical evidence of toxicity, absence of underlying heart disease and fairly young age of the patient pointed to chloroquine toxicity. Periodic cardiac investigations including electrocardiography may be warranted in patients under antimalarial therapy.
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PMID:Third-degree atrioventricular block in a patient under chloroquine therapy. 952 87

Anthracyclines, potent cytotoxic agents used to treat a broad spectrum of malignancies, are limited in their use by an attendant risk of cardiotoxicity. Malignancies affect all age ranges, and anthracyclines are used in all age ranges, thereby exposing a broad population of patients to the development of heart disease. For some treated patients, anthracyclines affect cardiac muscle, resulting in cardiomyopathy. The type and degree of cardiomyopathy, as well as when during or after treatment the condition occurs, are dependent on what risk factors are present. Age is a major risk factor. Children and adults may develop restrictive and dilated cardiomyopathy. The length of subsequent survival and amount of subsequent somatic growth may influence late anthracycline-associated cardiac outcome. Early cardiotoxicity, occurring during or within 1 year of completion of treatment, is the largest risk factor for the development of late cardiotoxicity, which occurs beyond a year of completion of treatment. Risk factors, which appear to be specific for early cardiotoxicity in children, include black race, trisomy 21, and the use of amsacrine therapy after anthracycline therapy. More cardiotoxic effects are seen in survivors of childhood cancer, the longer from completion of treatment a patient is followed. Cumulative as well as peak anthracycline doses affect adults and children alike, and cardiotoxicity occurs early and late. In adults, left ventricular contractility is affected by anthracyclines. Children may manifest impairment of left ventricular contractility and increased afterload due to thinning of left ventricular walls. Patients with an early presentation of depressed left ventricular contractility are likely to show progression of cardiac disease with time. In addition, female gender appears to affect early and late cardiotoxicity in both adults and children, although this risk factor has been described predominantly in the survivors of childhood cancer. Thus, although anthracycline chemotherapy has improved overall survivorship of patients with cancer, there is a significant risk of cardiotoxicity associated with this class of drugs.
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PMID:Epidemiology of anthracycline cardiotoxicity in children and adults. 976 28

Transmyocardial laser revascularization (TMR) is used for improving the blood supply to damaged myocardium due to advanced heart disease. We hypothesize that focused ultrasound can be used to generate channels through the cardiac muscle by vaporizing the tissue at the focal spot. The purpose of this study was to evaluate the effects of varying the ultrasound exposure parameters (frequency, amplitude, pulse period, duty cycle, focal depth and exposure time) on the vaporized tissue size and to determine the feasibility of using ultrasound for creating cavities and/or channels in the left ventricular wall for transmyocardial revascularization. Based on in vitro experiments using bovine myocardium, the experiments indicate that a 1 mm diameter channel could be created by using, for example, a focused transducer with a diameter of 10 cm and a radius of curvature of 8 cm operating at a frequency of 2.52 MHz. The required spatial peak intensity during the 0.5-s sonications was found to be 2300 W/cm2 with a pulse repetition period of 40 ms and a 50% duty cycle. These parameters have been used to create cavities during in vivo tests using canine myocardium. The results demonstrated that ultrasound could be used to create small channels through myocardium. The most important potential for ultrasound is its ability to generate these channels completely noninvasively.
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PMID:The feasibility of using focused ultrasound for transmyocardial revascularization. 980 38

The micropathology of chronic Chagas' myocarditis reveals foci of myocardial cell loss associated with an inflammatory infiltrate composed predominantly of lymphomononuclear cells and interstitial fibrosis. The loss of myocardial cells, a devastating phenomenon in this cardiopathy, has been classically attributed to necrosis. In the present study we examined whether the loss of myocardial cells in human chronic Chagas' heart disease could result from cell death by apoptosis. A total of 11 cases of chronic chagasic myocarditis were studied: four hearts were obtained at autopsy within 8 h after death and seven endomyocardial biopsies were taken from chagasic patients with an arrhythmogenic form of the disease. The coronary arteries of all chagasic cases showed no obstructive lesions. The diagnosis of Chagas' disease was based on previously established criteria. Five cases were selected as controls: three hearts were obtained at autopsy within 8 h after death and two endomyocardial biopsies were taken from nonchagasic patients with normal myocardium morphology. As positive controls we used cardiac muscles of myocardial infarction and rat mammary glands on the fourth day after weaning. The TUNEL method was used to identify apoptotic cells in the myocardium. The expression of p53 protein, which directly or indirectly triggers apoptosis, was evaluated using immunohistochemical technique. A few apoptotic cells were stained in chronic chagasic hearts, both biopsy and autopsy cases. However, the stained nuclei were restricted to the mononuclear infiltrate accounting for about 0.5% of the mononuclear cells in the infiltrate. In contrast, the nuclei of cardiomyocytes in both regions bordering on and distant from the microfoci of myocardial cell loss were not stained by the TUNEL method. Moreover, the expression of the protein p53 in cardiomyocytes in chagasic hearts was absent. The results of the present study demonstrating negative in situ labeling of fragmented DNA associated with absence of expression of p53 provide support to the hypothesis that apoptosis is not the mechanism of cell death in chronic chagasic myocarditis. This reinforces the general opinion that the loss of cardiac muscle fibers in chagasic cardiopathy is produced by necrosis. On the other hand, the present results give support to the concept that apoptosis probably play a role in the clearing of lymphomononuclear cells in the inflammatory infiltrate in chronic chagasic myocarditis.
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PMID:Is apoptosis a mechanism of cell death of cardiomyocytes in chronic chagasic myocarditis? 1021 85


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