Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In human heart failure the positive inotropic and cAMP-elevating effects of both beta-adrenoceptor agonists and phosphodiesterase inhibitors are diminished. This has been explained at least in part by an increase in the inhibitory signal-transducing G protein (Gi) and unchanged stimulatory G protein (Gs). In the present study we determined the mRNA expression pattern of the alpha subunits of Gi-1, Gi-2, Gi-3, and Gs in myocardial tissue samples of patients undergoing heart transplantation. Northern blot analysis of total RNA extracted from left ventricles with 32P-labeled cDNAs demonstrated expression of Gi alpha-2, Gi alpha-3, and Gs alpha mRNA. In contrast, Gi alpha-1 mRNA was not detectable. To investigate whether the increased ratio of Gi/Gs might be due to altered gene expression, we compared mRNA levels of Gi alpha-2, Gi alpha-3, and Gs alpha in left ventricular myocardium from failing hearts with idiopathic dilated cardiomyopathy (n = 8) and ischemic cardiomyopathy (n = 6) and from nonfailing hearts from transplant donors (n = 8). Compared with nonfailing control hearts, the Gi alpha-2 mRNA was increased by 75 +/- 26% (p less than 0.05) in idiopathic dilated cardiomyopathy hearts and 90 +/- 26% (p less than 0.05) in ischemic cardiomyopathy hearts. Gi alpha-3 and Gs alpha mRNA levels were similar in the three groups. The results suggest that as in other mammalian species, Gi alpha-2 and Gi alpha-3 mRNA are the predominant Gi alpha mRNA subtypes in human ventricular myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased messenger RNA level of the inhibitory G protein alpha subunit Gi alpha-2 in human end-stage heart failure. 155 Nov 95

It has been suggested that chronically reduced myocardial adenosine triphosphate (ATP) content causes contractile dysfunction in dilated cardiomyopathy. Because total adenine nucleotides (ATP, adenosine diphosphate and monophosphate) may reflect chronic changes in energy metabolism better than may ATP alone, myocardial ATP, and adenosine diphosphate and monophosphate were determined in endomyocardial biopsy specimens from 19 patients with dilated cardiomyopathy, and decreased left (30 +/- 2%) and right (34 +/- 3%) ventricular ejection fractions, and from 11 patients with ischemic cardiomyopathy (left ventricular ejection fraction 38 +/- 3%), and compared with those from 28 normal control subjects (ejection fraction greater than 55%) to assess myocardial energy metabolism in heart failure. Myocardial norepinephrine was measured simultaneously in the same biopsy specimens to assess if the myocardium studied for adenine nucleotide content was metabolically altered. Myocardial total adenine nucleotides as well as ATP levels in 19 patients with dilated cardiomyopathy (39 +/- 3 and 23 +/- 3 nmol/mg of noncollagen protein, respectively) were unchanged in comparison with those of control subjects (37 +/- 4 and 23 +/- 3, respectively); patients with ischemic cardiomyopathy were not significantly different (30 +/- 3 and 19 +/- 3, respectively). Myocardial norepinephrine in the same biopsy specimens from patients with dilated (5.8 +/- 1.1 pg/micrograms of noncollagen protein) or ischemic (5.7 +/- 1.3) cardiomyopathy was significantly decreased compared with that of normal control subjects (12 +/- 1.1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myocardial adenine nucleotide concentrations and myocardial norepinephrine content in patients with heart failure secondary to idiopathic dilated or ischemic cardiomyopathy. 159 72

In patients with congestive heart failure, down-regulation of beta-adrenoceptors is present, probably as a result of sympathetic overstimulation. In end-stage dilated cardiomyopathy, beta 1-adrenoceptor density is markedly reduced, while beta 2-adrenoceptor density is normal. This latter finding does not necessarily imply normal sensitivity to beta 2-stimulation, due to possible alterations in the beta-adrenoceptor/adenylate cyclase complex beyond the receptor. In some disease states, such as ischemic cardiomyopathy and mitral valve disease, there seems to be a concomitant reduction of the beta 1- and beta 2-adrenoceptor density. The finding of beta-adrenoceptor down-regulation has stimulated the search for novel therapeutic approaches in heart failure patients. Beta-agonists could even further down-regulate beta receptors, and this perhaps explains why they seem not to be useful in long-term use. Agents that directly stimulate adenylate cyclase activity, such as forskolin, or that increase cyclic adenosine monophosphate degradation, such as the phosphodiesterase inhibitors, are being tested. Beta-adrenoceptor blocking agents were used in treatment of heart failure before beta-adrenoceptor down-regulation was recognized in these patients. It is tempting to speculate that the beneficial clinical and hemodynamic effects seen in these patients treated with metoprolol is indeed due to an antagonism of the beta-adrenoceptor down-regulation. Studies testing whether beta-adrenoceptor blocking agents can improve survival in congestive heart failure patients are on-going.
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PMID:Receptor function in heart failure. 164 66

Hemodynamics and myocardial metabolism at rest and during exercise were investigated in 21 patients with heart failure. The patients were evaluated before and after long-term treatment (14 +/- 7 months) with the beta-adrenergic blocking agent metoprolol. Clinical improvement with increased functional capacity occurred during treatment. Maximal work load increased by 25% (104 to 130 W; p less than 0.001). Hemodynamic data showed an increased cardiac index (3.8 to 4.6 liters/min per m2; p less than 0.02) during exercise. Pulmonary capillary wedge pressure decreased at rest (20 to 13 mm Hg; p less than 0.01) and during exercise (32 to 28 mm Hg; p = NS). Stroke volume index (30 to 39 g.m/m2; p less than 0.006) and stroke work index (28 to 46 g.m/m2; p less than 0.006) increased during exercise and long-term metoprolol treatment. The arterial norepinephrine concentration decreased at rest (3.72 to 2.19 nmol/liter; p less than 0.02) but not during exercise (13.2 to 11.1 nmol/liter; p = NS). The arterial-coronary sinus norepinephrine difference suggested a decrease in myocardial spillover during metoprolol treatment (-0.28 to -0.13 nmol/liter; p = NS at rest and -1.13 to -0.27 nmol/liter; p less than 0.05 during exercise). Coronary sinus blood flow was unchanged during treatment. Four patients produced myocardial lactate before the study, but none produced lactate after beta-blockade (p less than 0.05). There was no obvious improvement in a subgroup of patients with ischemic cardiomyopathy. In summary, there were signs of increased myocardial work load without higher metabolic costs after treatment with metoprolol.
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PMID:Exercise hemodynamics and myocardial metabolism during long-term beta-adrenergic blockade in severe heart failure. 168 Jan 33

Beta-blockers were initially given to patients with chronic heart failure due to ischemic heart disease and resting tachycardia. The prompt effect on severe backward heart failure was directly associated with an immediate fall in heart rate. This observation led to long-term administration to patients with idiopathic dilated cardiomyopathy and, later, to patients with ischemic cardiomyopathy and secondary cardiomyopathies as well. Due to marked down-regulation of beta receptors, patients with heart failure are extremely sensitive to beta blockade. A test dose of metoprolol 5 mg b.i.d. for 2 days is recommended to select patients for long-term beta-blockade, followed by careful titration with increment in dose over 6 weeks. One important effect of beta-blockade in the early phase of treatment is a reduction in the myocardial energy demand early after the onset of long-term treatment. After 1 month of treatment with beta-blockers, marked improvement of diastolic function is observed. This effect might be attributed to inhibition of calcium overload. After 3 months of treatment, an increase in ejection fraction can be observed, which might be attributed to upregulation of beta receptors. The withdrawal of long-term treatment was followed by a deterioration of heart function in 61% of patients and improvement was seen after reinstitution of beta-blockade. There was an increase in cardiac index and stroke work index at rest as well as during supine exercise. A marked fall in left ventricular filling pressure at rest and unchanged filling pressure during supine exercise was noted, while exercise capacity increased by 25%. A similar pattern was seen in patients with ischemic cardiomyopathies and other secondary cardiomyopathies. However, the increase in ejection fraction in the ischemic cardiomyopathy group was lower (0.06) compared to the groups with dilated cardiomyopathy and other secondary cardiomyopathies (0.18).
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PMID:Beta-adrenergic blockade in dilated cardiomyopathy, ischemic cardiomyopathy, and other secondary cardiomyopathies. 168 23

Two dimensional echocardiographic studies were performed in 70 patients with chronic heart failure. Thirty six had dilated cardiomyopathy and normal coronary arteries and 34 had ischemic cardiomyopathy with severe multivessel coronary disease. All patients had a dilated and hypocontractile left ventricle. Ejection fraction assessed by radionuclide ventriculography was less than 40% in all patients. Regional wall motion abnormalities were detected in 16 (44%) of 36 patients with dilated cardiomyopathy and 22 (65%) of 34 patients with ischemic cardiomyopathy (NS). High echodensity of the regional wall motion abnormality suggesting a myocardial scar were found in 4 (25%) of 16 patients with dilated cardiomyopathy and in 9 (41%) of 22 with ischemic cardiomyopathy (NS). Diffuse wall motion abnormalities were present in 20 (56%) patients with dilated cardiomyopathy and 12 (35%) with ischemic cardiomyopathy (NS). Right ventricular dilatation was found in 21 (58%) and 20 (59%) patients with dilated and ischemic cardiomyopathy, respectively (NS). No differences between groups were found regarding the left ventricular size and function. In conclusion, two dimensional echocardiography cannot be reliably used in patients with chronic heart failure to differentiate dilated cardiomyopathy from ischemic cardiomyopathy.
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PMID:[Differential diagnosis of congestive cardiomyopathy and myocardial ischemia: two-dimensional echocardiography has a limited value]. 184 52

Ischemic cardiomyopathy refers to a significant impairment of left ventricular function, a condition resulting from atherosclerotic coronary artery disease. The left ventricular ejection fraction is usually 35% or less, and electron microscopy shows an increased deposition of collagen in the space between the capillaries and the myocytes. The present study shows the alteration in collagen concentration and phenotypes in ischemic cardiomyopathy, and the effect captopril treatment has on these parameters. In patients with ischemic cardiomyopathy, collagen concentration estimated from hydroxyproline increased from 7.96 +/- 1.24 mg/g to 13.9 +/- 1.30 mg/g, P less than 0.05. Ischemic cardiomyopathic patients given captopril therapy had a significantly lower collagen concentration of 10.03 +/- 1.46 mg/g, P less than 0.05. The collagen type I:III ratio decreased from 1.93 +/- 0.52 to 1.23 +/- 0.27 in patients with ischemic cardiomyopathy. Of these patients, those receiving captopril had a collagen type I:III ratio of 1.49 +/- 0.38, which did not differ significantly from the ratio of individuals with normal myocardium. There was no significant difference in type I collagen concentration in the myocardium of normal individuals, patients with ischemic cardiomyopathy, and patients with ischemic cardiomyopathy receiving captopril therapy. The type III collagen concentration increased significantly from 2.56 +/- 0.21 mg/g in normal myocardium to 6.10 +/- 0.58 mg/g in ischemic cardiomyopathic myocardium. Patients receiving captopril had a myocardial collagen type III concentration of 4.87 +/- 0.64 mg/g, which was significantly lower than that found in patients with ischemic cardiomyopathy. An increased deposition of type III collagen may be partly responsible for altering the compliance of the myocardium, resulting in dilatation of the heart and possibly leading to eventual heart failure.
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PMID:Alteration of collagen phenotypes in ischemic cardiomyopathy. 191 69

In the present study, the Ca2(+)-sensitivity and myosin light chain patterns of skinned fibers of right atrium and left papillary muscles of 27 patients suffering from mitral valve disease (MVD, moderate heart failure), ischemic cardiomyopathy (ICM, severe heart failure), dilated cardiomyopathy (DCM, severe heart failure), and coronary heart disease (CHD, no heart failure, no atrial hypertrophy) were investigated. Myosin light chains of both chemically skinned and intact samples were studied by two-dimensional gel electrophoresis (2D-PAGE). Ca2(+)-sensitivity of ventricular fibers was about 0.14 pCa-units higher than that of atrial fibers in all groups except dilated cardiomyopathy where this difference was markedly diminished (only 0.06 pCa-units). Generally, Ca2(+)-sensitivity of skinned ventricular fibers was the same among the different heart diseases. Skinned atrial fibers from patients with dilated cardiomyopathy, however, were significantly (about 0.08 pCa-units) more sensitive for Ca2+ than those of the other groups (coronary heart disease, mitral valve disease or ischemic cardiomyopathy) which showed similar Ca2(+)-tension relationships. Ventricle-specific P-light chain forms could be observed in atrial samples from patients of all groups, whereas no atrium-specific light chain forms were detectable in any ventricular sample. It is concluded that there is no difference in Ca2(+)-sensitivity of the ventricular contractile elements of the human heart in different heart diseases. In atrial myocardium, there is an increased Ca2(+)-sensitivity of skinned fibers from hearts with dilated cardiomyopathy which is probably related to an elevation of right atrial pressure.
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PMID:Calcium sensitivity and myosin light chain pattern of atrial and ventricular skinned cardiac fibers from patients with various kinds of cardiac disease. 208 58

Cardiac failure, which used to be rare in coronary heart disease, is now its most common complication. Coronary heart disease can cause or appear as cardiac failure through one or more of 12 mechanisms: acute myocardial infarction, acute reversible ischemia, right ventricular dysfunction, cardiogenic shock, acute mitral regurgitation, ventricular septal perforation, cardiac free wall rupture, ischemic cardiomyopathy, ventricular aneurysm, coexisting diseases, iatrogenesis, and pseudoheart failure. An understanding of the responsible mechanism or mechanisms is essential not only for appropriate treatment but also for prognostication. Various therapeutic modalities, both medical and surgical, should be able to improve not only symptoms but also survival. Current efforts in the management of patients with cardiac failure as a result of coronary heart disease should be aimed at prevention, both primary and secondary.
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PMID:Cardiac failure in coronary heart disease. 220 Feb 54

We studied 11 patients affected by mild essential hypertension during chronic therapy with enalapril (E). After a pharmacological wash-out the patients were treated with E once a day (10-20 mg) for 4 weeks. Before and after the treatment period the patients were studied by means of the isotonic exercise stress test on the cycloergometer with increments of 25 W every 2 min and by means of the Sustained Handgrip test (SHG) at 70% of maximal capacity for 1 min. During the study period E reduced the blood pressure at rest in all patients without untoward effects. During the isotonic test and particularly during SHG, E reduced systolic and diastolic blood pressure (BP) and the product systolic BP x heart rate. The treatment did not influence the time length of the isotonic exercise stress test. Our results suggest that E does not increase the MVO2 at rest and during different types of exercise: this can be very important because many patients affected by hypertension suffer from ischemic heart disease. E is utilized also in patients with heart failure, some of whom have an hypertensive or ischemic cardiomyopathy.
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PMID:[Influence of chronically-administered enalapril on isotonic and isometric exercise in patients with moderate grade hypertension]. 255 75


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