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)

Endothelin-1, a member of a novel family of regulatory peptides, is the most potent vasoconstrictor and pressor substance known. Endothelin-1 is a 21-amino-acid endothelium-derived peptide causing uniquely sustained vasoconstriction. In addition, endothelin-1 has pronounced effects on the coronary, renal and cerebral circulations, enhances responses to other vasoconstrictors, and is comitogenic. Recent studies have shown that the endothelins are essential for normal fetal development, and that endothelin-1 plays an important physiological role in the regulation of basal vascular tone and blood pressure in healthy humans. There is now also a wealth of evidence suggesting that endothelin-1 is a key mediator in a range of cardiovascular diseases associated with sustained vasoconstriction, such as chronic heart failure, and with vasospasm, such as subarachnoid haemorrhage. In addition, endothelin-1 appears to act in opposition to nitric oxide to promote the atherosclerotic process. There are a large number of oral and intravenously active endothelin antagonists entering clinical development and a number of clinical studies, particularly with endothelin receptor antagonists, are now under way. Such studies are beginning to define the role of the endothelins in cardiovascular disease and to confirm the potential of the endothelin system as an important new therapeutic target.
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PMID:The endothelin system in cardiovascular physiology and pathophysiology. 954 47

Endothelin-1, discovered in 1988, is a 21-amino-acid peptide and currently the most potent vasoconstrictor and pressor substance known. Generated by vascular endothelial cells in response to a variety of chemical and mechanical signals, endothelin-1 is known to potentiate the actions of other vasoconstrictor substances and act as a comitogen in addition to directly causing vasoconstriction. There is evidence that endothelin-1 may contribute to the pathophysiology of conditions associated with sustained vasoconstriction, such as hypertension and heart failure, vasospastic conditions, such as subarachnoid hemorrhage, and atherogenesis. Studies using endothelin receptor antagonists show that endothelin-1 plays an important role in the maintenance of vascular tone and blood pressure in healthy humans, predominantly via an effect on the vascular smooth muscle ETA receptors. The endothelin receptor antagonist bosentan also effectively lowers blood pressure in hypertensive subjects and produces sustained and favorable effects on systemic and pulmonary hemodynamics in patients with chronic heart failure. A good side-effect profile, together with a potential for inhibition of atherogenesis, makes the endothelin receptor antagonists a potentially interesting class of novel agents for the treatment of cardiovascular disease.
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PMID:Clinical experience with endothelin antagonists. 960 70

Endothelin receptor antagonists have been proposed for the treatment of a variety of disorders in which the endothelins may act as pathogenic mediators, such as congestive heart failure, systemic and pulmonary hypertension, and cerebral vasospasm. Bosentan (Ro 47-0203) is a nonpeptide competitive antagonist, which can be a good tool for studying the endothelin system because it may be administered either acutely or chronically. It is specific for the endothelin system and blocks the actions of endothelin at both mammalian receptors (A and B). In experimental models of heart failure bosentan acts as a vasodilator and neurohormonal blocker that improves overall left ventricular performance and reduces renal dysfunction. Furthermore, in chronic studies, bosentan attenuates cardiac remodeling and significantly improves survival. In patients with chronic heart failure bosentan produces pulmonary and systemic vasodilation and may enhance conventional treatment with angiotensin-converting enzyme inhibitors. Long-term studies are being conducted to characterize the full therapeutic potential of bosentan in chronic heart failure. In experimental models bosentan reverses established pulmonary hypertension. Preclinical efficacy has also been demonstrated in essential hypertension, where bosentan can reduce blood pressure and end-organ damage. Clinical trials in hypertensive patients indicate that bosentan reduces blood pressure without heart rate increase or neurohumoral stimulation. Finally, bosentan is being considered for the treatment of cerebral vasospasm following subarachnoid hemorrhage. Bosentan reverses experimentally induced vasospasm of the basilar artery, and preliminary trials indicate that it can increase cerebral blood flow after aneurysmal subarachnoid hemorrhage.
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PMID:Endothelin antagonism with bosentan: a review of potential applications. 1035 41

Subarachnoid hemorrhage (SAH) due to aneurysmal rupture is frequently complicated by cardiopulmonary episodes, including sudden death. We investigated the pathogenesis of cardiopulmonary complications from clinical observation of 715 cases with SAH. There was transient left ventricular asynergy in 9.4% (67/715) of the cases, which consisted of mechanical heart failure and myocardial necrosis. Plasma catecholamine concentration was higher in these patients compared with those without left ventricular asynergy. Transient left ventricular asynergy was considered to result from myocardial derangement: "a panic myocardium," due to a sudden burst of catecholamine. Concerning arrhythmia in SAH, cases with life-threatening arrhythmia, such as ventricular tachycardia or ventricular fibrillation, had higher concentrations not only of plasma catecholamine but also of serum CK-MB, myosin light chain and troponin T, compared with patients who had no ventricular arrhythmia. This implies that life-threatening arrhythmia in SAH would result from myocardial damage due to catecholamine. We devised a novel animal model of SAH in order to clarify the relation between sympathetic nervous activity and myocardial damage immediately after the onset of SAH. The animal experiments showed that sympathetic nervous activity as well as cardiac contractility were transiently elevated, but cardiac function subsequently declined. Serum CK-MB was increased from the onset of SAH and a high value was maintained throughout the entire experimental period. In conclusion, extraordinary transient enhancement of sympathetic nervous activity induces myocardial damage resulting from what is characterized by "a panic myocardium."
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PMID:Subarachnoid hemorrhage and myocardial damage clinical and experimental studies. 1073 53

Several authors described elevated natriuretic peptides, atrial natriuretic peptide(ANP) and brain natriuretic peptide (BNP), in patients with subarachnoid hemorrhage(SAH), which were account for inappropriate antidiuretic hormone(SIADH) or cerebral salt wasting syndrome(CSW). Although the secretion of natriuretic peptide depends on the total blood volume, central venous pressure, and cardiac output volume, the volume of fluid intake in patients with SAH had not been taken in consideration in previous report. We here examined the relationship between fluid intake and the natriuretic peptides in two cases without cardiac failure. ANP elevated 2 or 3 days after SAH and remained in normal range for 2 weeks. BNP elevated when the volume of fluid intake was increased, and BNP did not elevate during the periods with lower fluid intake. Several authors proposed the possibility of iatrogenic factor in natriuresis after SAH and these results supported this opinion.
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PMID:[Relationship between cardiac natriuretic peptide (ANP/BNP) and fluid intake in patients with subarachnoid hemorrhage]. 1121 65

Intra-aortic balloon pump counterpulsation (IABP) was used to treat two patients with symptomatic vasospasm after subarachnoid hemorrhage. One could not tolerate triple H therapy (hypertensive hypervolemic hemodilution) because of poor cardiac function and another suffered acute myocardial infarction after aneurysm surgery followed by cardiac failure. IABP increased cerebral blood flow and prevented cerebral infarction in the former case but this could not reverse cerebral ischemia in the latter. IABP may be one choice for patients with vasospasm after subarachnoid hemorrhage.
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PMID:[Two patients treated with intra-aortic balloon pump counterpulsation after subarachnoid hemorrhage]. 1155 17

Cardiac injury and pulmonary oedema occurring after acute neurological injury have been recognised for more than a century. Catecholamines, released in massive quantities due to hypothalamic stress from subarachnoid haemorrhage (SAH), result in specific myocardial lesions and hydrostatic pressure injury to the pulmonary capillaries causing neurogenic pulmonary oedema (NPO). The acute, reversible cardiac injury ranges from hypokinesis with a normal cardiac index, to low output cardiac failure. Some patients exhibit both catastrophic cardiac failure and NPO, while others exhibit signs of either one or other, or have subclinical evidence of the same. Hypoxia and hypotension are two of the most important insults which influence outcome after acute brain injury. However, despite this, little attention has hitherto been devoted to prevention and reversal of these potentially catastrophic medical complications which occur in patients with SAH. It is not clear which patients with SAH will develop important cardiac and respiratory complications. An active approach to investigation and organ support could provide a window of opportunity to intervene before significant hypoxia and hypotension develop, potentially reducing adverse consequences for the long-term neurological status of the patient. Indeed, there is an argument for all SAH patients to have echocardiography and continuous monitoring of respiratory rate, pulse oximetry, blood pressure and electrocardiogram. In the event of cardio-respiratory compromise developing i.e. cardiogenic shock and/or NPO, full investigation, attentive monitoring and appropriate intervention are required immediately to optimise cardiorespiratory function and allow subsequent definitive management of the SAH.
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PMID:Pulmonary and cardiac sequelae of subarachnoid haemorrhage: time for active management? 1218 19

Brain natriuretic peptide (BNP) is predominantly a cardiac ventricular hormone that promotes natriuresis and diuresis, inhibits the renin-angiotensin-aldosterone axis, and is a vasodilator. Plasma BNP levels are raised in essential hypertension, and more so in left ventricular (LV) hypertrophy and heart failure. Plasma BNP levels are also elevated in ischemic heart disease. Attempts have been made to use plasma BNP levels as a marker of LV dysfunction, but these have shown that plasma BNP levels are probably not sensitive enough to replace echocardiography in the diagnosis of LV dysfunction. Pericardial BNP or N-BNP may be more suitable markers of LV dysfunction. Plasma BNP levels are also elevated in right ventricular dysfunction, pregnancy-induced hypertension, aortic stenosis, age, subarachnoid hemorrhage, cardiac allograft rejection and cavopulmonary connection, and BNP may have an important pathophysiological role in some or all of these conditions. Clinical trials have demonstrated the natriuretic, diuretic and vasodilator effects, as well as inhibitory effects on renin and aldosterone of infused synthetic human BNP (nesiritide) in healthy humans. BNP infusion improves LV function in patients with congestive heart failure via a vasodilating and a prominent natriuretic effect. BNP infusion is useful for the treatment of decompensated congestive heart failure requiring hospitalization. The clinical potential of BNP is limited as it is a peptide and requires infusion. Drugs that modify the effects of BNP are furthering our understanding of the pathophysiological role and clinical potential of BNP. Increasing the effects of BNP may be a useful therapeutic approach in heart failure involving LV dysfunction. The levels of plasma BNP are increased by beta-blockers, cardiac glycosides and vasopeptidase inhibitors, and this may contribute to the usefulness of these agents in heart failure. (c) 2001 Prous Science. All rights reserved.
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PMID:Brain natriuretic peptide: Disease marker or more in cardiovascular medicine? 1275 Jul 64

Cardiac complications are well known after aneurysmal subarachnoid hemorrhage. Electrocardiographic changes occur in 50% to 100% of such cases. Arrhythmias, left ventricular dysfunction, and frank myocardial infarction are infrequently observed. Myocardial infarction must be differentiated from neurogenic stunned myocardium, which is a reversible condition. From 1996 to 2001, 105 patients with aneurysmal subarachnoid hemorrhage underwent endovascular treatment at the University of Michigan. Of these, four patients with no history of cardiac disease experienced cardiac failure related to neurogenic stunned myocardium. All had signs of left ventricular dysfunction, electrocardiographic changes, and elevated cardiac enzymes. Three had pulmonary edema at presentation. All were diagnosed with myocardial infarction. One underwent coronary angiography, which was normal. All were considered poor surgical candidates and underwent endovascular treatment of the aneurysms. Three of four patients developed symptomatic vasospasm, and two required balloon angioplasty. Three patients achieved good outcomes. The eldest died from severe vasospasm that was unresponsive to angioplasty. Reversible cardiac failure associated with subarachnoid hemorrhage may be due the neurogenic stunned myocardium. Frequent symptomatic vasospasm occurs, possibly related to poor cardiac output and the inability to optimize hyperdynamic hypervolemic therapy, particularly with compromised volume status. These patients can be treated with endovascular therapy of the aneurysms and balloon angioplasty as needed. With aggressive management, patients can recover from these reversible cardiac complications.
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PMID:Management of patients with stunned myocardium associated with subarachnoid hemorrhage. 1472 41

A 66-year-old woman presented with subarachnoid hemorrhage(SAH) caused by a ruptured aneurysm of the left middle cerebral artery. Electrocardiography (ECG) disclosed abnormalities resembling acute myocardial infarction. She underwent neck clipping of the aneurysm uneventfully. Sixteen days after admission, ECG again disclosed abnormalities resembling acute myocardial infarction, and echocardiography suggested heart failure. Coronary angiography showed no abnormalities, but left ventriculography showed severe hypokinesia in the apex of the heart consistent with so-called ampulla (takotsubo) cardiomyopathy. The heart failure was treated with catecholamines and her heart function gradually recovered. Ampulla (takotsubo) cardiomyopathy associated with SAH requires careful management of heart function.
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PMID:Ampulla (takotsubo) cardiomyopathy associated with subarachnoid hemorrhage worsening in the late phase of vasospasm--case report. 1501 27


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