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)

Inhibition of the renin-angiotensin system is being applied with considerable success to the treatment of hypertension and heart failure. Angiotensin-converting enzyme (ACE) inhibitors are the only currently available agents that can achieve this objective. In general, the major therapeutic effects of these agents in the treatment of mild to moderate hypertension or of heart failure are exerted on the vascular tissue through inhibition of the renin-angiotensin system and, secondarily, of the sympathetic nervous system. When cardiovascular functional reserve is diminished and autoregulation of regional and systemic blood flow is strained, however, ACE inhibitors may affect other organ functions (heart, kidneys, and possibly brain), hormones other than the renin system, and local tissue humoral systems. The interrelations between the renin-angiotensin system and several other vasoactive systems--including circulating and locally generated tissue hormones and centrally acting neurohormonal factors--are complex and unclear. A better understanding of these mechanisms and interrelations would allow for a more rational therapeutic use of these agents. Unknown also are the clinical effects of prolonged ACE inhibition. Whether the use of ACE inhibitors can provide primary cardiorenal protection requires proof through definitive clinical trials.
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PMID:Long-range safety and protective benefits of angiotensin-converting enzyme inhibitors for hypertension. Do we need more clinical trials? 846 May 11

Apoptosis, the well-characterized form of active programmed cell death, is a physiologic phenomenon in embryonal and fetal life in developing organs. Severe hypoxia, which occurs in most preterm infants, also leads to cell death, which may be necrotic or apoptotic. The aim of our study was to examine the incidence of apoptosis in various organs (such as lung, kidney, and brain) of preterm infants who suffered from clinically proven respiratory distress causing infantile respiratory distress syndrome (IRDS), cardiac failure, and periventricular leukomalacia (PVL). Twenty-four autopsy cases were studied histologically to detect the apoptotic ratio, which was performed on the basis of hematoxylin and eosin staining and validated by terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) reaction. Elevated apoptotic ratio was found in stages II, III, and IV of bronchopulmonary dysplasia (BPD) among alveolar and bronchiolar cells. The apoptotic activity was very low in stage I of BPD. High apoptotic ratio was detected in hypoxic injuries of the central nervous system (CNS) of preterm infants. Features of apoptosis were present in proximal and excreting tubules of the kidney. Significant elevation of apoptotic activity may play a role in the development of BPD, ischemic brain lesions, and renal failure.
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PMID:Apoptosis in various organs of preterm infants: histopathologic study of lung, kidney, liver, and brain of ventilated infants. 1142 Apr 27

The levels and pathophysiological role of amino terminal C-type natriuretic peptide in heart failure are unknown. The potential of plasma amino-terminal C-type natriuretic peptide (N-CNP) as a marker of cardiac function was investigated in symptomatic patients. In 305 patients with recent-onset dyspnea and/or peripheral edema, presenting to primary care, assay of plasma amino-terminal C-type natriuretic peptide and other plasma vasoactive hormones was conducted together with echocardiography. Heart failure was diagnosed in 77 (of the 305) patients by rigorous application of predefined criteria. Plasma amino-terminal C-type natriuretic peptide concentrations were elevated in patients with heart failure, and by univariate analysis were related to age, renal function, and other hormones. On multivariate analysis, tertile of plasma N-CNP interacted with tertile of plasma amino-terminal B-type natriuretic peptide to predict heart failure independent of age, gender, renal function, or echocardiographic left ventricular fractional shortening. N-CNP showed significant relations to concurrent plasma CNP, atrial natriuretic peptide (ANP), N-ANP, B-type (or brain) natriuretic peptide (BNP), N-BNP, endothelin-1, and adrenomedullin but not to echocardiographic indicators of left ventricular systolic function. Plasma amino-terminal C-type natriuretic peptide is elevated in heart failure and is related to other plasma hormones in heart failure. These findings suggest a possible compensatory response from the peripheral vasculature to heart failure by an endothelium-based vasodilator peptide and mandate further exploration of the role of C-type natriuretic peptide in this condition.
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PMID:Amino-terminal pro-C-type natriuretic peptide in heart failure. 1465 55

Congestive heart failure (CHF) is a major cardiovascular disorder that is increasing in incidence, prevalence, and lethality. The prognostic significance of cardiac troponin levels among symptomatic and asymptomatic CHF has attracted recent interest. We sought to assess the significance of cardiac troponins in heart failure. These cardiac markers are associated with decreased left ventricular ejection fraction and poor prognosis in patients with CHF and are related to the severity of heart failure. The mechanism for the release of these markers seems to be from ventricular remodeling, ongoing myocyte degeneration, the presence of coronary artery disease, and reduced coronary reserve. In addition to B-type (brain) natriuretic peptide (BNP), cardiac troponin levels measured in patients admitted to the hospital could help risk-stratify patients and manage them effectively. BNP and cardiac troponins are easy to measure and can be repeated many times to follow patients, without interobserver variability. Theoretically, BNP is a marker of heart failure status and cardiac troponin is a marker of myocyte injury. The first therapeutic goal could be relief of circulatory congestion and lowering of BNP. The second goal could be attenuation of myocyte injury and lowering of cardiac troponins. Measuring and monitoring the levels of both could be highly effective means to reliably stratify the patients into low-, intermediate-, and high-risk groups for cardiac events and progression of heart failure. Furthermore, large-scale trials are necessary to establish them as noninvasive monitoring markers of heart failure and effectiveness of treatment.
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PMID:Cardiac troponin levels in heart failure. 1466 59

Aldosterone exerts cardiovascular effects by influencing epithelial fluid and electrolyte excretion, and thus blood volume and pressure. Mineralocorticoid receptors (MR) are found in epithelial and non-epithelial tissues (vessel walls, heart, brain), with high affinity for aldosterone and physiological glucocorticoids cortisol and corticosterone. MR blockade by spironolactone or eplerenone favorably affects cardiovascular outcomes. In some situations (primary aldosteronism, experimental mineralocorticoid administration) activation of cardiovascular MR reflects aldosterone levels inappropriate for salt status. In others (heart failure, essential hypertension) aldosterone and Na(+) status are often normal pretreatment; cardiovascular MR may thus be activated by normal glucocorticoid levels after tissue damage and reactive oxygen species generation. Therefore, although unilateral adrenalectomy is preferred therapy for unilateral aldosterone-producing adenoma or hyperplasia, MR blockade may be useful in cardiovascular diseases where aldosterone levels are normal.
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PMID:Aldosterone as a cardiovascular risk factor. 1580 7

Mineralocorticoid receptors (MR) bind both mineralocorticoids and glucocorticoids with high affinity (deoxycorticosterone = corticosterone >/= aldosterone = cortisol), and are found in both Na(+) transporting epithelia (e.g. kidney, colon) and nonepithelial tissues (e.g. heart, brain). MR evolved before aldosterone synthase, consistent with their acting in nonepithelial tissues as high affinity glucocorticoid receptors, essentially always occupied by normal levels of endogenous glucocorticoids. In epithelial tissues the enzyme 11beta hydroxysteroid dehydrogenase Type 2 (11betaHSD2) allows aldosterone to selectively activate MR, by converting cortisol to cortisone and NAD to NADH. 11betaHSD2 debulks intracellular cortisol by 90%, to levels approximately 10-fold those of aldosterone, so that when the enzyme is operating most epithelial MR are occupied but not activated by cortisol. When intracellular redox state is changed-by inhibition of 11beta HSD2, generation of reactive oxygen species, or intracellular introduction of oxidised glutathione (GSSG)-cortisol changes from an MR antagonist to an MR agonist. This bivalent activity of cortisol appears to underlie the therapeutic efficacy of MR blockade in heart failure (RALES, EPHESUS) and in essential hypertension, providing a rationale for MR blockade in cardiovascular disease not characterized by elevated aldosterone levels. Its wider (patho)physiologic implications, particularly for neurobiology, remain to be explored.
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PMID:Mineralocorticoid receptors: distribution and activation. 1594 87

Nesiritide is the recombinant form of human B-type (brain) natriuretic peptide (BNP), and its amino acid sequence is identical to that of endogenous human BNP. Administration of nesiritide results in venous and arterial vasodilation, as well as enhanced diuresis. Given the many limitations of therapies previously available for the treatment of acute decompensated heart failure, the anticipation was that nesiritide would offer a safer and more effective therapeutic option. Recently, two meta-analyses raised the question of safety with nesiritide therapy, specifically an increased risk of renal dysfunction and mortality. Although several studies generated information regarding the potential role of nesiritide in various settings, the questions raised by the meta-analyses are concerning. Our hope is that future clinical trials will address the concerns raised and provide a better understanding of the role of nesiritide in the management of acute decompensated heart failure. Until these data are available, nesiritide use should be limited.
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PMID:Nesiritide: harmful or harmless? 1699 57

Acetylcholinesterase (AChE, EC 3.1.1.7) is an important enzyme for cholinergic nerve transmission. The action of toxic organophosphates such as nerve agents is based on AChE inhibition. The death following acute nerve agent poisoning is due to central or peripheral respiratory/cardiac failure. Therefore, the changes in AChE activity following nerve agents acting predominantly on the central (sarin, soman) or peripheral (VX) level were studied. It is known that AChE activity in different structures exists in relative excess. Female Wistar rats intoxicated with sarin, soman, and VX in different doses (0.5-2.0 x LD(50)) were divided into groups of survived and died animals. AChE activities in diaphragm, brain parts (pontomedullar area, frontal cortex, basal ganglia, in some cases other parts of the brain) were determined and the rest of activity (in %) was correlated with survival/death of animals. More precise elucidation of action of nerve agents and the assessment of minimal AChE activity in different organs compatible with the survival of organism poisoned with nerve agents were the aims of this study.
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PMID:An attempt to assess functionally minimal acetylcholinesterase activity necessary for survival of rats intoxicated with nerve agents. 1857 26

Traumatic brain injury (TBI) is the leading cause of death and disability among young adults. Numerous safety improvements in the workplace, the addition of airbags to vehicles, and the enforcement of speed limits have all helped to reduce the incidence and severity of head trauma. While improvements in emergency response times and acute care have increased TBI survivability, this has heightened the necessity for developing reliable methods to identify patients at risk of developing secondary pathologies. At present, the primary clinical indicators for the presence of brain injury are the Glasgow Coma Scale (GCS), pupil reactivity, and head computed tomography (CT). While these indices have proven useful for stratifying the magnitude and extent of brain damage, they have limited utility for predicting adverse secondary events or detecting subtle damage. Biomarkers, reflecting a biological response to injury or disease, have proven useful for the diagnosis of many pathological conditions including cancer, heart failure, infection, and genetic disorders. For TBI, several proteins synthesized in astroglial cells or neurons have been proposed as potential biomarkers. These proteins include the BB isozyme of creatine kinase (CK-BB, predominant in brain), glial fibrilary acidic protein (GFAP), myelin basic protein (MBP), neuron-specific enolase (NSE), and S100B.The presence of these biomarkers in the cerebrospinal fluid and serum of patients with moderate-to-severe TBI, and their correlation with outcome, suggest that they may have utility as surrogate markers in clinical trials. In addition, many of these markers have been found to be sensitive indicators of injury, and therefore may have the potential to diagnose persons with mild TBI. In addition to biomarkers that correlate with long-term outcome, a few studies have identified prognostic biomarkers for secondary injury that may be useful in individualizing patient management.
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PMID:Biomarkers in the clinical diagnosis and management of traumatic brain injury. 1903 22

B-type (brain) natriuretic peptide (BNP) is a cardiac hormone whose measurement can be helpful in a variety of clinical settings, but has been most extensively studied in patients with heart failure and acute coronary syndrome (ACS). The value of both BNP and its N-terminal fragment, NT-proBNP, as independent prognostic biomarkers in ACS is supported by data from a number of clinical trials. BNP/NT-proBNP levels can predict death and subsequent development of heart failure, but not recurrent ischemic events. BNP may also be helpful as an aid in establishing the diagnosis of ACS in patients presenting with chest pain. The role of BNP in determining treatment has not yet been defined, though patients with high levels may derive more benefit from invasive management and from treatment with ranolazine. The National Academy of Clinical Biochemists (NACB) guidelines state that measurement of BNP/NT-proBNP may be useful in prognosis for ACS patients, but do not yet recommend its routine use, naming a number of other issues that need to be resolved in the use of this marker. Age- and gender-related decision limits should be determined, and cutoff levels of BNP/NT-proBNP corresponding to low, intermediate, and high risk patients should be ascertained. Additional evidence regarding the impact of BNP/NT-proBNP levels on treatment strategy in ACS patients will be helpful in further defining the role of B-type natriuretic peptide testing in the acute coronary syndromes.
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PMID:The role of B-type natriuretic peptide testing in patients with acute coronary syndromes. 2249 66


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