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)

The purpose of the present study was to determine the prevalence of thromboembolic events in patients with primary and secondary (ischemic) dilated cardiomyopathy (DC), with regard to basic rhythm, sinus or atrial fibrillation. Retrospectively, over three years, from January 1, 1989 to December 31, 1991, the case histories of 75 inpatients with DC, mean age 56.2 +/- 14.1 years, 41 in sinus rhythm and 34 in atrial fibrillation from Clinic Hospital Split were analyzed and compared to those of 75 controls (heart failure with no DC). The incidence of thrombi, embolisms and mortality in both subgroups was similar, while the prevalence of thromboembolic events was significantly higher in the analyzed than in the control group (decompensated patients with ischemic cardiomyopathy and without cardiomegaly) (9/75:1/75, p < 0.05). Prospectively, between 9 and 22 months, from December 1, 1991 to September 30, 1993 51 consecutive decompensated outpatients with DC, in NYHA class II and III, mean age 54.2 +/- 15 years, were followed-up. Bilirubin, lactic dehydrogenase, prothrombin time and activated partial thromboplastin time were determined. 1-D and 2-D transthoracic echocardiographic exam was performed and clinical status was assessed. There were 24 patients in sinus rhythm and 27 patients in atrial fibrillation. The prevalence of thromboembolic events, thrombi and mortality in both subgroups was similar. The laboratory findings, indicators of possible thrombogenesis or thrombolysis, did not show any significant difference in both subgroups. The incidence of thrombi in both parts of this study was low, amounted to only 9.5% (12/126) with no clear signs of thromboembolism (these patients were anticoagulated!). Altogether 12.6% (16/126) patients suffered thromboembolic events, 9 in retrospective and 7 in prospective part of the trial (more patients were anticoagulated in prospective then in retrospective study, 5 versus 19; p < 0.05). We conclude that thromboembolism in patients with decompensated DC are rare, but appear at significantly higher rate than in decompensated patients with ischemic cardiomyopathy and no cardiomegaly. The beneficial effects of anticoagulant therapy are to be expected in these patients regardless of the basal rhythm. This hypothesis must, however, be assessed in a prospective, multicentric trial.
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PMID:[Occurrence of thromboembolic complications in patients with dilated cardiomyopathy. Retrospective-prospective study]. 937 20

Ischemic hepatitis, a relatively infrequent disorder occurring in 0.16% to 0.50% of patients admitted to medical intensive care units, often follows episodes of hypotension or acute heart failure. Investigating the clinical characteristics of patients with ischemic hepatitis may add to our understanding of the pathogenesis and significance of this syndrome. We therefore conducted a retrospective analysis of 34 patients to examine the possible contribution of the various baseline characteristics to the severity of the hepatic damage. In all patients liver disease was unexpected and in some, liver dysfunction dominated the clinical picture. All patients had high serum glutamic pyruvic transaminase (SGPT) and lactic dehydrogenase (LDH) levels (mean +/- SE, 2073 +/- 255 international units and 6085 +/- 748 international units, respectively). The mean SGPT/LDH ratio was 0.34. Most patients had coagulopathy with a prolonged prothrombin time (mean +/- SE, 5.86 +/- 1.37 international normalized ratio [INR]). The most common diagnosis on admission was respiratory distress secondary to various causes. Before the development of the hepatic dysfunction, respiratory failure and hypoxemia were observed in 68% of the patients, whereas hypotension was observed in only 38%. More than 90% of the patients had three or more associated comorbid conditions. The most frequent of these were left heart failure (88.2%), right heart failure (67.6%), chronic obstructive lung disease (58.8%), and chronic renal failure (55.9%). During the acute episode, more than 90% of the patients had transient deterioration of their renal functions. Hypoglycemia was noted in 11 patients (32.4%), and the glucose level was inversely correlated with the SGPT level (r = -0.43, p = 0.01). Stepwise multiple regression analysis showed that left heart failure, systolic blood pressure lower than 90 mm Hg, and female gender, together, accounted for 34% of the variance of the peak SGPT levels (p = 0.002). Fourteen (41.2%) patients died during the 3-month follow-up period, but none from the hepatic injury. None of the clinical or laboratory parameters measured predicted mortality. Clearly, ischemic hepatitis is associated with a high risk of death. The characteristic patients are those with multiple underlying systemic diseases and conditions, especially those with left heart failure. Liver function test results and levels of liver enzymes should be monitored in these patients, particularly when they are admitted for respiratory deterioration and episodes of hypotension.
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PMID:Ischemic hepatitis: clinical and laboratory observations of 34 patients. 960 Mar 66

Broad-breasted white turkey poults fed furazolidone developed dilated cardiomyopathy (DCM) characterized by ventricular dilatation, decreased ejection fraction, beta1-receptor density, sarcoplasmic reticulum (SR) Ca2+-ATPase, myofibrillar ATPase activity, and reduced metabolism markers. We investigated the effects of carteolol, a beta-adrenergic blocking agent, by administrating two different dosages (0.01 and 10.0 mg/kg) twice a day for 4 wk to control and DCM turkey poults. At completion of the study there was 59% mortality in the nontreated DCM group, 55% mortality in the group treated with the low dose of carteolol, and 22% mortality in the group treated with the high dose of carteolol. Both treated groups showed a significant decrease in left ventricle size and significant restoration of ejection fraction and left ventricular peak systolic pressure. Carteolol treatment increased beta-adrenergic receptor density, and the high carteolol dose restored SR Ca2+-ATPase and myofibrillar ATPase activities, along with creatine kinase, lactate dehydrogenase, aspartate transaminase, and ATP synthase activities, to normal. These results show that beta-blockade with carteolol improves survival, reverses contractile abnormalities, and induces cellular remodeling in this model of heart failure.
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PMID:Cellular and molecular remodeling in a heart failure model treated with the beta-blocker carteolol. 1033 Feb 54

The use of the potent antitumor antibiotic doxorubicin (DOX) is hampered because of its severe cardiac toxicity that leads to the development of cardiomyopathy and heart failure. In this study, we have developed a cell culture model for DOX-induced myocardial injury using primary adult rat cardiomyocytes that were cultured in serum-free medium and exposed to 1 to 40 microM DOX. DOX caused a dose-dependent release of sarcosolic enzyme lactate dehydrogenase (LDH) from cultured myocytes. The release of LDH was prevented by the cell-permeable superoxide dismutase (SOD) mimetic (MnTBAP), but was unaffected by either cell-impermeable SOD enzyme, or manganese (II) sulfate. Ebselen, a glutathione peroxidase (GPx) mimetic, enhanced the protection of cardiomyocytes afforded by MnTBAP. DOX caused the increased formation of oxidants in cardiomyocytes, and MnTBAP lowered the amount of intracellular oxidants induced by DOX. In addition, DOX selectively inactivated aconitase in cardiomyocytes, and MnTBAP partially reversed this inactivation. Ebselen further amplified the protective effect of MnTBAP on aconitase activity. These results suggest that the SOD mimetic MnTBAP prevents DOX-induced damage to cardiomyocytes and that the GPx mimetic ebselen synergistically enhanced the cardioprotection afforded by MnTBAP. Relevance of these findings to minimizing cardiotoxicity in cancer treatment is discussed.
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PMID:Cell-permeable superoxide dismutase and glutathione peroxidase mimetics afford superior protection against doxorubicin-induced cardiotoxicity: the role of reactive oxygen and nitrogen intermediates. 1044 96

The diagnostic accuracy of KL-6 as an indicator of amiodarone-induced pulmonary toxicity was studied in 14 men (mean age = 62 +/- 12, range 33-76 years) treated with amiodarone. The indications for amiodarone were sustained ventricular tachycardia in 13 patients and atrial fibrillation in 1 patient with refractory heart failure. The KL-6 cut-off level was set at 520 U/mL. Group A consisted of two patients with amiodarone-induced pulmonary toxicity, group B of five patients with other pulmonary disorders, and group C of seven patients without pulmonary disease. KL-6 levels, percent diffusing capacity for carbon monoxide (%DLCO), and other laboratory markers were compared among these three groups. KL-6 levels were significantly higher in group A than in group B and C (2550 +/- 36, 252 +/- 99, 198 +/- 82 U/mL, respectively; P < 0.0001). KL-6 levels in group B were below the cutoff value. %DLCO, C-reactive protein (CRP), and lactic dehydrogenase (LDH) were abnormal in group A. The abnormal rates of CRP and LDH in group B were 80% and 40%, respectively. Of the seven patients with pulmonary disease, three patients (43%) could not undergo %DLCO testing because of poor physical condition. In one patient with amiodarone-induced pulmonary toxicity, the KL-6 level increased from 695 to 2,100 U/mL at a time of progression of interstitial changes. KL-6 may be a useful marker of amiodarone-induced pulmonary toxicity.
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PMID:Diagnostic accuracy of KL-6 as a marker of amiodarone-induced pulmonary toxicity. 1113 80

We have recently shown that mitochondrial function and energy metabolism are altered in the myocardium as well as in slow and fast locomotor muscles of rats subjected to prolonged congestive heart failure (CHF) suggesting a generalized metabolic myopathy in heart failure. Here, we investigate whether the diaphragm of CHF animals, which experiences both increased work and the general systemic influence of heart failure, will also be susceptible to altered energy metabolism. Biopsies were obtained from the costal diaphragm of failing rats 8 months after aortic banding. A marked increase in type I and type IIa myosin heavy chains at the expense of types IIx and IIb, suggests an adaptation towards a slower phenotype. Glycolytic enzymes decreased in CHF diaphragm with an increase in the H:M lactate dehydrogenase isoenzyme ratio. These results suggest a reorientation of the diaphragm muscle towards a slow, fatigue-resistant phenotype. However, maximal oxidative capacity assessed in saponin-permeabilized fibers in the presence of ADP was considerably reduced in CHF diaphragm (7.7+/-0.4 v 11.8+/-0.7 micromol O2/min/g dry weight in sham P<0.001), suggesting an alteration in oxidative phosphorylation. Furthermore, ADP sensitivity of CHF mitochondria was significantly increased (apparent Km for ADP 308+/-21 v 945+/-106 microM in sham P<0.001), whereas sensitivity to ADP in the presence of creatine was comparable (Km 79+/-12 v 90+/-11 microM in sham). In heart failure, therefore, the diaphragm muscle seems to adapt towards a more slow and economical contraction as a result of increased workload, but this adaptation is limited by the disease-induced altered mitochondrial function.
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PMID:Dual influence of disease and increased load on diaphragm muscle in heart failure. 1127 23

We previously reported that cardiomyocytes produce endothelin (ET)-1 and that the tissue level of ET-1 markedly increased in failing hearts in rats with chronic heart failure. Because the level of plasma ET-1 also increased progressively in patients with breast cancer who received doxorubicin (Dox; Adriamycin), which possesses cardiotoxicity, we hypothesized that ET-1 plays a role in the pathophysiology of cardiomyocytes injured by Dox. In this study, we investigated the effect of ET-1 on the cytotoxicity of Dox in primary cultured neonatal rat cardiomyocytes. The results showed that ET-1 effectively attenuated Dox-induced acute cardiomyocyte cytotoxicity (24-h incubation with Dox) evaluated by in vitro cell toxicity assay [3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay and lactate dehydrogenase release]. The cytoprotective effect of ET-1 was mediated via ET(A) receptors, because pretreatment with the ET(A)-receptor antagonist BQ123 completely suppressed the cytoprotective effect of ET-1, whereas the ET(B)-receptor antagonist BQ788 did not. The cytoprotective effect of ET-1 was abolished by pretreatment with cycloheximide or staurosporine. These results suggest that a protein molecule(s), which is synthesized de novo by the stimulation of protein kinase pathway, is involved in the cytoprotective effect of ET-1. ET-1 increased the expression of an endogenous antioxidant, manganese superoxide dismutase (Mn-SOD), in the cardiomyocytes, as demonstrated by a Western blotting analysis. Pretreatment with an antisense oligodeoxyribonucleotide of Mn-SOD markedly attenuated the cytoprotective effect of ET-1 on the Dox-induced cytotoxicity. However, under conditions of prolonged incubation with Dox (48 h), ET-1 did not affect Dox-induced cardiomyocyte cytotoxicity in culture. These results suggest that ET-1 prevents the early phase of Dox-induced cytotoxicity via the upregulation of the antioxidant Mn-SOD through ET(A) receptors in cultured cardiomyocytes.
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PMID:A novel pharmacological action of ET-1 to prevent the cytotoxicity of doxorubicin in cardiomyocytes. 1129 60

Recently, we have demonstrated that heart failure in rats is associated with a myopathy altering energy metabolism in different muscles, but the origin of this myopathy is still unknown. Here, we studied the possible involvement of increased angiotensin II (Ang II) by treatment with perindopril, an inhibitor of angiotensin-converting enzyme (ACE). The beneficial effects of ACE inhibition could result either from vasodilatation-induced cardiac unloading or from inhibition of the direct angiotensin action on the muscle cells. The model of aortic banding with persisting left ventricular (LV) overload where the cardiac unloading does not occur allows to distinguish between the two effects of ACE inhibition. Four months after aortic clipping (just before the treatment), echocardiographic study showed an impairment of the systolic function (decrease of the LV shortening by 30% and ejection fraction by 21%). Ten-week treatment with perindopril dramatically decreased Ang II plasma level but did not reduce LV hypertrophy though a significant decrease in right ventricular (RV) hypertrophy occurred. Perindopril did not improve alterations in activities of energy metabolism enzymes (creatine kinase, citrate synthase, cytochrome c oxidase, lactate dehydrogenase) either in ventricular or in skeletal (gastrocnemius) muscle. Similarly, ACE inhibition did not improve the main parameters of mitochondrial respiration in permeabilized muscle fibers. These data suggest that the generalized metabolic myopathy induced by the hemodynamic abnormalities conditioned by the continuous LV overload (aorta clipping) does not result from the increase in Ang II level per se. Correction of hemodynamic parameters and LV unloading seem to be the prerequisite for the improvement of muscle energy metabolism abnormalities.
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PMID:Does angiotensin-converting enzyme inhibition improve the energetic status of cardiac and skeletal muscles in heart failure induced by aortic stenosis in rats? 1268 19

The purpose of this study was to determine the efficacy of resistance exercise in reversing skeletal muscle myopathy in heart transplant recipients. Myopathy, engendered by both heart failure and immunosuppression with glucocorticoids, is a post-transplant complication. The sequelae of myopathic disease includes fiber-type shifts and deficits in aerobic metabolic capability. We randomly assigned patients to either 6 months of resistance exercise (training group; n = 8) or a control (control group; n = 7) group. Exercise was initiated at 2 months after transplant. Biopsy of the right vastus lateralis was performed before and after the 6-month intervention. Myosin heavy chain (MHC) composition was assessed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Biochemical assays were performed to determine citrate synthase, 3-hydroxyacyl-CoA-dehydrogenase, and lactate dehydrogenase activity. There were no group differences (p >or=0.05) in MHC composition and enzymatic reserve at baseline. Improvements in the training group for citrate cynthase (+40%), 3-hydroxyacyl-CoA-dehydrogenase (+10%), and lactate dehydrogenase activity (+48%) were significantly greater (p <or=0.05) than in the control group (+10%, -15%, and +20%, respectively). Oxidative type 1 MHC isoform concentration increased significantly in the training group (+73%, p <or=0.05) but decreased in the control group (-28%; p <or=0.05). Glycolytic type 2x MHC isoform increased significantly (17%; p <or=0.05) in the control group but decreased (-33%; p <or=0.05) in the training group. This is the first study to demonstrate that resistance training elicits myofibrillar shifts from less oxidative type II fibers to more oxidative fatigue-resistant type I fibers in heart transplant recipients. Resistance exercise initiated early in the post-transplant period is efficacious in changing skeletal muscle phenotype through increases in enzymatic reserve and shifts in fiber morphology.
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PMID:Effect of resistance exercise on skeletal muscle myopathy in heart transplant recipients. 1587 92

Chronic cardiac hepatopathy is a common entity in patients evaluated for heart transplantation (HTX). Hepatic injury is caused by severe heart failure resulting from prolonged recurrent congestion and/or impaired arterial perfusion. No data are available on the reversibility of cardiac hepatopathy in patients undergoing HTX. Data of 56 consecutive adult patients undergoing HTX during 2000-02 at the University Hospital of Innsbruck were analysed retrospectively. The following parameters were evaluated at the time of listing and 3, 6 and 12 months after HTX. Plasma levels of gamma-glutamyl transferase (gamma-GT), alkaline phosphatase (AP), bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and total plasma protein. When listed for HTX, only 12% of all patients analysed had physiological values throughout the seven laboratory parameters assessed. Elevated levels of gamma-GT, AP, bilirubin, AST, ALT, LDH and total plasma protein were detected in 66.6%, 29%, 50%, 16.7%, 10%, 40% and 18% of all patients respectively. Accordingly, median plasma levels of gamma-GT, bilirubin and LDH were elevated, whereas the mean plasma level of AP was at the upper normal range. In contrast, median plasma level of AST and mean plasma levels of ALT and total plasma protein were within the normal range: gamma-GT (median, 109.0; range, 634.0 U/l; n = 36), AP (mean, 120.2 +/- 78.9 U/l; n = 29), bilirubin (median, 1.3; range, 16.1 mg/dl; n = 32), LDH (median, 226.0; range, 2355.0 U/l; n = 33), AST (median, 29.0; range, 145.0 U/l; n = 36), ALT (mean, 28.3 +/- 20.8 U/l; n = 36) and total plasma protein (mean, 7.2 +/- 1.1 g/dl; n = 25). Within 3 months after HTX, elevated parameters except LDH significantly ameliorated: gamma-GT (median, 59.0; range, 1160.0 U/l; P = 0.011), AP (92.2 +/- 75.2 U/l; P = 0.016), bilirubin (median, 0.9; range, 8.1 mg/dl; P = 0.004), LDH slightly increased (median, 281.0; range, 543.0 U/l; P = 0.039), but there was a delayed improvement of this parameter after 6 and 12 months post-HTX. End-stage heart failure is characterized by a cholestatic liver enzyme profile with elevated plasma levels of gamma-GT and bilirubin. These parameters significantly improve within 3 months after HTX. Therefore, chronic cardiac hepatopathy seems to be a benign, potentially reversible disease.
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PMID:Cardiac hepatopathy before and after heart transplantation. 1591 Feb 96


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