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)

Circulating levels of B-type natriuretic peptide (BNP) and NH(2)-terminal-proBNP (NT-proBNP) increase in response to volume overload and help in the differential diagnosis of acute heart failure. Elevated plasma BNP levels are observed also in sepsis and do not always correspond to left ventricular dysfunction. Here, we investigated plasma NT-proBNP fluctuations in response to human bacterial endotoxinemia, an experimental model of systemic infection and inflammation. Escherichia coli endotoxin (LPS) (2 ng/kg) was administered to 10 healthy volunteers in a randomized, placebo-controlled, cross-over design. Plasma NT-proBNP, C-reactive protein (CRP), COOH terminal pro-endothelin-1 (CT-proET-1), and midregional-pro-adrenomedullin (MR-proADM) were measured at hourly intervals for 6 h. LPS administration induced a continuous increase in plasma NT-proBNP that reached peak values after 6 h (40.7 +/- 7.9 vs. 16.1 +/- 3.2 pg/ml in placebo days, mean +/- SE; P = 0.023). The profile of changes in NT-proBNP correlated to changes in body temperature (P < 0.001), heart rate (P = 0.005), CRP (P < 0.001), and CT-proET-1 (P = 0.008), but not to blood pressure values. Our results demonstrate that plasma NT-proBNP increases in a model of systemic infection/inflammation in healthy men with normal heart function. This finding emphasizes the necessity to consider concomitant infections when interpreting elevated circulating NT-proBNP concentrations.
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PMID:Plasma NT-proBNP increases in response to LPS administration in healthy men. 1884 86

This article provides information and a commentary on trials relevant to the pathophysiology, prevention, and treatment of heart failure presented at the Heart Failure Society of America and the American Heart Association meetings in 2008. Unpublished reports should be considered as preliminary, as analyses may change in the final publication. (i) SADHART-CHF showed no difference in outcome for heart failure patients with depression treated with sertraline compared with placebo. (ii) A controlled release carvedilol formulation showed similar LV haemodynamic effects to the standard carvedilol formulation in the COMPARE study. (iii) A post hoc analysis of the MOMENTUM study suggested that patients with less severe heart failure may be more likely to benefit from a continuous aortic flow augmentation device. (iv) A thyroid hormone analogue was poorly tolerated in patients with heart failure. (v) HF-ACTION showed that exercise training is safe and offers modest clinical benefits in patients with heart failure. (vi) Irbesartan failed to improve outcomes in patients with preserved ejection fraction in the I-PRESERVE study. (vii) A phase II study of beta-interferon administration in patients with dilated cardiomyopathy showed encouraging results. (viii) The BACH study showed that mid-regional pro-adrenomedullin was more accurate than BNP or NT-proBNP at predicting outcome at 90 days in patients with acute heart failure. (ix) A secondary analysis from ATHENA showed a reduction in cardiovascular hospitalizations and strokes for patients with atrial fibrillation receiving dronedarone compared with placebo.
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PMID:Clinical trials update from the Heart Failure Society of America and the American Heart Association meetings in 2008: SADHART-CHF, COMPARE, MOMENTUM, thyroid hormone analogue study, HF-ACTION, I-PRESERVE, beta-interferon study, BACH, and ATHENA. 1916 21

Our previous study showed elevation of plasma adrenomedullin (ADM) during static handgrip in patients with heart failure (HF). It is hypothesized that ADM increases with left ventricle dysfunction during handgrip and thus plays a compensatory role. In the present study pre-ejection period (PEP) and left ventricular ejection time (LVET) were used to assess cardiac performance in 24 male HF patients (II/III class NYHA) during two 3-min bouts of handgrip at 30% of maximal voluntary contraction (MVC) performed alternately with each hand without any break between the bouts. Plasma ADM, noradrenaline (NA), adrenaline (A), heart rate (HR), blood pressure (BP) and stroke volume (SV) were determined. During handgrip plasma ADM, NA, A, HR, BP, PEP/LVET increased, PEP was prolonged and LVET shortened. The increases in plasma ADM correlated with changes in: PEP (r = -0.881), LVET (r = 0.713), PEP/LVET (r = -0.769), SV (r = 0.836), diastolic BP (r = 0.700), total peripheral resistance (TPR) (r = 0.718) and noradrenaline (r = 0.756). The study demonstrated that in HF patients changes in plasma ADM during handgrip are related to cardiac performance.
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PMID:Relationships between plasma adrenomedullin concentration and systolic time intervals during static handgrip in patients with heart failure. 1920 15

ST2 is the receptor for interleukin-33, a cytokine with antihypertrophic and antifibrotic effects on the myocardium. Serum levels of the soluble form of ST2 serve as a biomarker for ventricular biomechanical strain and provide prognostic information in patients who have symptomatic heart failure. Adrenomedullin is a vasoactive peptide whose actions run counter to the physiologic derangements of clinical heart failure. It appears that measurements of serum adrenomedullin levels can be used to identify those patients who have advanced heart failure and who are at increased risk for heart failure-related death.
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PMID:ST2 and adrenomedullin in heart failure. 1963 Nov 76

Synthetic organoselenium compounds can be tailored to achieve greater chemopreventive efficacy with minimal toxic side effects by structural modifications. Two organoselenium compounds (Se I and Se II) were synthesized and evaluated for their antihypertensive and therapeutic properties by adrenomedullin (ADM) levels and tyrosine hydroxylase (TH) activity assays in rat heart tissue. 7,12-Dimethylbenz[a]anthracene (DMBA) is known to generate DNA-reactive species during their metabolism, which may enhance oxidative stress in cells. TH is thought to be a rate-limiting enzyme in the biosynthesis of catecholamines. ADM, a potent endogenous vasodilating and natriuretic peptide, may play an important role in the pathophysiology of chronic heart failure. The effects of Se I and Se II were investigated on TH activity, ADM and total RNA levels in the hearts of albino Wistar rats. TH activity was found to be increased significantly by the effect of DMBA (P<0.05). This increase was restricted in the Se I and Se II treated groups. ADM level was found to be decreased insignificantly by the effect of DMBA (P>0.05). Total RNA level was found to be decreased significantly by the effect of DMBA (P<0.05). This study demonstrates that synthetic organoselenium compounds can regulate DMBA-induced stress related changes in rat heart.
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PMID:Role of selenium compounds on tyrosine hydroxylase activity, adrenomedullin and total RNA levels in hearts of rats. 1970 12

Biomarkers can provide insights into underlying mechanisms and lead to better understanding of complex disease states. This enhanced understanding can then be integrated into disease management, which can lead to better therapies and ultimately to improved patient outcomes. The natriuretic peptides (NPs) are established cost-effective biomarkers in heart failure and have set the standard for how a well-validated biomarker can be useful in the diagnosis/prognosis, monitoring of response to therapy, and management of chronic disease. Newer biomarkers such as midregional pro-adrenomedullin, ST2, and neutrophil gelatinase-associated lipocalin are emerging as adjuncts to NPs in the management of heart failure patients.
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PMID:Biomarkers of heart failure. 2065 7

Heart failure goes beyond mechanical dysfunction and involves an interplay of multiple pathophysiologic mechanisms, including inflammation, tissue remodeling, neurohormonal and endocrine signaling, and interactions with the renal and nervous systems. This article highlights some novel biomarkers that may aid in diagnosis, treatment, and prognosis of acute heart failure, specifically focusing on ST2, endoglin, galectin-3, cystatin C, neutrophil gelatinase-associated lipocalin, midregional pro-adrenomedullin, chromogranin A, adiponectin, resistin, and leptin and their emerging clinical roles.
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PMID:Novel biomarkers in acute heart failure. 2168 44

AM5 (adrenomedullin 5), a newly described member of the CGRP (calcitonin gene-related peptide) family, is reported to play a role in normal cardiovascular physiology. The effects of AM5 in HF (heart failure), however, have not been investigated. In the present study, we intravenously infused two incremental doses of AM5 (10 and 100 ng/min per kg of body weight each for 90 min) into eight sheep with pacing-induced HF. Compared with time-matched vehicle control infusions, AM5 produced progressive and dose-dependent increases in left ventricular dP/dt(max) [LD (low dose), +56 mmHg/s and HD (high dose), +152 mmHg/s] and cardiac output (+0.83 l/min and +1.81 l/min), together with decrements in calculated total peripheral resistance (-9.4 mmHg/min per litre and -14.7 mmHg/min per litre), mean arterial pressure (-2.8 mmHg and -8.4 mmHg) and LAP (left atrial pressure; -2.6 mmHg and -5.6 mmHg) (all P<0.001). HD AM5 significantly raised PRA (plasma renin activity) (3.5-fold increment, P<0.001), whereas plasma aldosterone levels were unchanged over the intra-infusion period and actually fell in the post-infusion period (70% decrement, P<0.01), resulting in a marked decrease in the aldosterone/PRA ratio (P<0.01). Despite falls in LAP, plasma atrial natriuretic peptide and B-type natriuretic peptide concentrations were maintained relative to controls. AM5 infusion also induced significant increases in urine volume (HD 2-fold increment, P<0.05) and urine sodium (2.7-fold increment, P<0.01), potassium (1.7-fold increment, P<0.05) and creatinine (1.4-fold increment, P<0.05) excretion and creatinine clearance (60% increment, P<0.05). In conclusion, AM5 has significant haemodynamic, endocrine and renal actions in experimental HF likely to be protective and compensatory in this setting. These results suggest that AM5 may have potential as a therapeutic agent in human HF.
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PMID:Haemodynamic, endocrine and renal actions of adrenomedullin 5 in an ovine model of heart failure. 2208 8

Sex differences exist in the hypertrophic response, cardiac remodeling, and transition to heart failure of hypertensive patients, and while some of these differences are likely influenced by estrogen, the genetic pathways downstream of estrogen that impact on cardioprotection have yet to be fully elucidated. We have previously shown that the cardioprotective effects of adrenomedullin (AM), an emerging clinical biomarker for cardiovascular disease severity, vary with sex in mouse models. AM signaling during cardiovascular stress is strongly modulated by receptor activity-modifying protein 3 (RAMP3) via its interaction with the G protein-coupled receptor calcitonin receptor-like receptor (CLR). Like AM, RAMP3 expression is potently regulated by estrogen, and so we sought to determine the consequences of genetic Ramp3 loss on cardiac adaptation to chronic hypertension, with a particular focus on characterizing potential sex differences. We generated and bred RAMP3(-/-) mice to RenTgMK mice that consistently display severe angiotensin II-mediated CV disease and compared CV disease progression in RenTgMK to that of RenTgMK:RAMP3(-/-) offspring. As expected, RAMP3 gene expression was higher in cardiovascular tissues of RenTgMK mice and more strongly up-regulated in female RenTgMK mice relative to wildtype controls. RAMP3 loss did not affect the development of hypertension or the presence and severity of perivascular and interstitial fibrosis in the left ventricle (LV). However, echocardiography revealed that while RenTgMK mice developed concentric cardiac hypertrophy with sustained systolic function, male RenTgMK:RAMP3(-/-) mice showed evidence of LV chamber dilatation and depressed systolic function, suggestive of cardiac decompensation. Consistent with these measures of heart failure, male RenTgMK:RAMP3(-/-) mice had increased cardiac apoptosis and elevated activation of Akt. These phenotypes were not present in female RenTgMK:RAMP3(-/-) mice. Collectively, these data demonstrate a sex-dependant, cardioprotective role of RAMP3 in the setting of chronic hypertension.
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PMID:Loss of receptor activity-modifying protein 3 exacerbates cardiac hypertrophy and transition to heart failure in a sex-dependent manner. 2210 Mar 52

Biomarker changes may provide physicians with objective evidence of treatment efficacy in patients with acute decompensated heart failure (ADHF) and facilitate early hospital discharge. The authors hypothesize that mid-regional-pro-adrenomedullin (MR-proADM), C-terminal-pro-endothelin-1 (CT-pro-ET-1), and mid-regional-pro-atrial natriuretic peptide (MR-proANP) change during the first 24 hours of ADHF therapy. Eligible patients had an emergency department diagnosis of ADHF and fulfilled modified Framingham criteria. Clinical data, serum, and plasma values were collected at enrollment, 2 to 4 hours, and 12 to 24 hours after treatment. Changes in biomarker concentrations from baseline to 2 to 4 hours, baseline to 12 to 24 hours, and 2 to 4 to 12 to 24 hours were calculated. Fisher exact and Kruskal-Wallis tests were used for comparisons. Forty-eight patients were included. The median age was 62 years (range 40-88), 54% were men and 50% were white. More patients had changes in MR-pro-ANP levels in the first 2 to 4 hours after ADHF therapy compared with MR-proADM or CT-pro-ET-1 (36% vs 16% and 24%). However, 12 to 24 hours after therapy, similar proportions of patients had changes in MR-proANP, MR-proADM, and CT-proET-1 levels (47%, 41%, and 49%). In this preliminary study, patients with ADHF had measurable changes in MR-proANP, MR-proADM, and CT-pro-ET-1 24 hours after initial therapy. A study of association with clinical course and outcomes to determine the role of these markers in risk-stratification is warranted.
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PMID:Biomarker changes during acute heart failure treatment. 2243 55


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