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

Understanding of the causes of pulmonary oedema must be based on knowledge of the mechanism responsible for fluid exchange between the several compartments of the normal lung. Recent physiological studies have clarified the main features of these mechanisms. However in three areas knowledge is still incomplete--the magnitude of the hydrostatic and oncotic forces responsible for fluid movement within the lung, the means by which protein leaks across the wall of small pulmonary vessels and the routes by which fluid and protein pass between the interstitial tissues of the lung and the alveolar space. Further work is needed in these areas. On the basis of this physiological knowledge the mode of development of hydrostatic oedema, the role of lymphatics in pulmonary oedema, and the several stages of pulmonary oedema development that may culminate in alveolar flooding are now clearly understood. Knowledge is less complete about oedema due to increased vascular permeability. In some experimental models, such as alloxan, leakage is due to irreversible injury to the alveolar wall; in other models, including ANTU, oedema formation has been shown to depend upon minor and reversible changes in pulmonary vascular endothelium similar to those that cause exudate formation in areas of acute inflammation. In no instance is detailed information available of both the rate and magnitude of protein leakage and of the morphological basis of increased vascular permeability. Further work is required in this area. Present knowledge allows an adequate explanation of the changes that occur in many clinically important types of pulmonary oedema, including cardiac failure and neurogenic pulmonary oedema. Other types of oedema, notably that which may complicate traumatic shock or extrapulmonary sepsis and high altitude pulmonary oedema, are more complex and the details of their pathogenesis are still obscure.
 ...
PMID:Current views on the mechanisms of pulmonary oedema. 36 92

The recent discovery of endothelium-derived relaxation factor (EDRF) has altered the traditional classification of vasodilators used in angina pectoris and heart failure. If a vasodilator induces release of EDRF from the epithelium it is classified as endothelium-dependent, if not it is independent. Sodium nitroprusside and SIN-1 (active metabolite of molsidomine) are the main independent vasodilators since the endothelium relaxation factor appears to be principally a nitric oxide radical in these synthetic vasodilators. In contrast, calcium-channel blockers and a good number of endogenous chemical mediators (acetylcholine, bradykinin, serotonin, etc.) are endothelium-dependent. Furthermore, simple increase in blood flow through the large vessels can result in endothelium-dependent vasodilation (flow rate-dependence) the extent of which depends on the drug examined. The fact that the pharmacologic response of a vasodilator can be altered under certain pathologic conditions (atherosclerosis, hypertension, diabetes, etc.) further increases the importance of the role of the vascular endothelium in the action of vasodilators since endothelial modulation may then be completely diverted to secretion of endothelium-derived contracting factors (EDCFS).
 ...
PMID:[Vasodilator agents and the vascular endothelium]. 262 13

Review of histopathological material in nine autopsies and 35 skin biopsy specimens of Kaposi's sarcoma in male homosexuals suggested that aberrant lymphaticovenous connections occur in the earliest stage of the Kaposi lesion. Venular glomeruloid structures in the dermis and their analogous radial venolymphatic channels in medium-sized and larger veins signified coupling of the lymphatic and venous systems, a characteristic previously noted in angiographic studies and considered to be unique in Kaposi's sarcoma. Lymphatic channels penetrated veins selectively rather than arteries, particularly in deep fat, liver, gastrointestinal submucosa and the hilum of lymph nodes. The initiation of the Kaposi lesion thus may be an abnormal recapitulation of the coupling of venous and lymphatic systems which occurs during embryonic growth. A chronological staging scheme is used which proposes lymphaticovenous union as the initial morphological differentiating event. The precise origin of the characteristic spindle cells in the developing lesion remains unclear, although convergent differentiation of lymphatic and blood vascular endothelium may be considered. Alteration of the microcirculation, particularly that distal to the capillary bed, may explain several of the histopathological and haemodynamic features of Kaposi's sarcoma, including lesional thrombosis and infarction, tissue haemorrhage, vascular dilatation, cavernous pseudoangiomas and acute right-sided heart failure.
 ...
PMID:Kaposi's sarcoma. Origin and significance of lymphaticovenous connections. 308 37

The vascular endothelium releases vasoactive substances that appear to play an important role in the normal regulation of peripheral vasomotor tone. Nitric oxide, endothelins, prostaglandins, and other endothelium-derived vasodilating and vasoconstricting factors are released by the vascular endothelium in response to a diverse array of hormonal, pharmacologic, chemical, and physical stimuli. Shear stress, produced by pulsatile blood flow at the endothelial cell luminal surface, alters endothelial production of several endothelium-derived vasoactive substances, which may contribute to regional regulation of skeletal muscle blood flow during exercise. Abnormal vascular endothelium function has been shown in both experimental and clinical heart failure. Preliminary data suggest that abnormalities of endothelial function may contribute to increased peripheral vasomotor tone during exercise in patients with congestive heart failure.
 ...
PMID:The role of endothelium-derived vasoactive substances in the pathophysiology of exercise intolerance in patients with congestive heart failure. 763 Oct 19

Over the last years it has become evident that endothelium is one of the most active paracrine organs releasing a number of vasoactive substances. These mediators, by acting on subjacent vascular smooth muscle, play and important role in control of vasomotor tone and of platelets aggregation. The relations between vascular endothelium and cardiovascular risk factors are complex. Functional abnormalities of vascular endothelium are probably segmental and may differ in individual cases. Experimental and clinical study has demonstrated that all cardiac endothelial cells, coronary vascular and endocardial, modulate the performance of underlying myocardium. Modulation of the left ventricular function by endothelial cells constitutes an important autoregulation of muscle-pump performance of the heart by altering the duration of contraction and diastolic function. It is likely that cardiac endothelial cells take part in extrinsic and intrinsic cardiac compensatory mechanisms and, although there is still no direct evidence, they may be closely involved in pathophysiology of heart failure in humans.
 ...
PMID:Paracrine modulation of coronary vasomotor tone and myocardial performance by vascular and endocardial endothelium. 763 15

The basal release of endothelium-derived nitric oxide (EDNO) is considered to play an important role in regulating the vascular tone in normal subjects; however, its role in the presence of acute heart failure is unknown. This study was designed to clarify the role of a basal release of EDNO in the presence of acute heart failure. Acute ischemic left ventricular (LV) dysfunction was produced in 22 dogs by coronary microembolization. After the embolization, only saline solution was intravenously infused for sixty minutes in 10 dogs. In another 12 dogs, NG-monomethyl-L-arginine (L-NMMA), which is known to inhibit the formation of EDNO in the vascular endothelium, was intravenously infused at a rate of 20 micrograms/kg/minute for sixty minutes. Infusion of saline solution did not produce any changes in hemodynamic variables. Infusion of L-NMMA caused increases in mean aortic pressure, systemic vascular resistance, and LV end-diastolic pressure without changes in the LV peak + and - dP/dt (time constant) of LV pressure fall, and these changes were associated with a giant "v" wave in the tracing of left atrial pressure and a decrease in cardiac output. The basal release of EDNO may play an important role in the prevention of afterload elevation, subsequent cardiac output reduction, and afterload mismatch in the presence of acute heart failure.
 ...
PMID:Basal release of endothelium-derived nitric oxide plays an important role in the prevention of afterload mismatch in acute left ventricular dysfunction. 766 79

The effect of vascular endothelium, endocardium, and coronary endothelium on vascular tone and myocardial contraction-relaxation sequence in heart failure is discussed. Vascular endothelium affects underlying vascular smooth muscle through paracrine secretion of relaxing and constricting factors. In heart failure, systemic vasoconstriction results not only from neuroendocrine activation, but also from disturbed local endothelial control of vascular tone because of impaired endothelial-dependent vasodilation and because of increased plasma concentration of endothelin. Experimental evidence obtained in isolated cardiac muscle strips established the influence of endocardial endothelium on the duration of myocardial contraction and on the onset of myocardial relaxation. By analogy to vascular endothelium, both diffusible agents that abbreviate (endothelial-derived relaxation factor-like substance) and those that prolong (endocardin) myocardial contraction have been shown to be released from the endocardium. Similar agents are released from the coronary endothelium and, because of the close proximity of capillaries and myocytes, could exert a major effect on myocardial performance. Endothelial dysfunction and concomitant lack of release of myocardial relaxant factors could explain left ventricular relaxation abnormalities observed in the cardiac allograft or in arterial hypertension. Since endothelial-derived relaxation factor or nitric oxide mediates the coronary reactive hyperemic response, a negative inotropic action of nitric oxide could contribute to left ventricular failure when left ventricular wall stress is elevated, as occurs after myocardial infarction in the noninfarcted zone and during left ventricular volume or pressure overload in the absence of adequate hypertrophy.
 ...
PMID:Endothelial control of vascular and myocardial function in heart failure. 794 59

Through release of paracrine and autocrine substances, the vascular endothelium exerts a profound influence on the contractile and growth state of underlying vascular smooth muscle. In heart failure, there is now compelling evidence that endothelium-mediated relaxation is attenuated in response to muscarinic stimulation in both the coronary and peripheral circulation of humans. This impaired response is present regardless of the etiology of heart failure. The mechanisms, significance and etiologic importance of this endothelial defect are not yet understood. Possibilities include 1) alterations in endothelial cell surface receptors or abnormalities of postreceptor signal transduction; 2) abnormalities of endothelium-derived relaxing factor production or release; 3) rapid inactivation of endothelium-derived relaxing factor; and 4) an increase in endothelium-derived contracting factor production and activity in heart failure. We currently have little understanding of the mechanisms accounting for this dysfunctional state of the endothelium. Future research efforts should be directed toward an understanding of these mechanisms.
 ...
PMID:The dysfunctional endothelium in heart failure. 839 32

Tumor necrosis factor (TNF) enhances leukocyte adherence to vascular endothelium and increases procoagulant activity in the endothelial cells. Thus it may be implicated in the pathogenesis of acute vascular occlusions. To study the role of TNF in the early stages of acute myocardial infarction (MI), the authors measured circulating TNF levels in the sera of patients with acute MI and unstable angina pectoris. Blood samples were obtained within six hours after onset of chest pain and stored at -70 degrees until tested. A sensitive sandwich enzyme-linked immunosorbent assay (ELISA) test was used for TNF measurement. C-reactive protein (CRP) levels were determined semiquantitatively. Immediate complications such as heart failure, arrhythmia, and shock were also noted. Twenty-four patients with electrocardiographically and biochemically confirmed acute MI and 14 patients with unstable angina pectoris were included in the study. TNF levels were serially assessed at the time of admission and at hours 6, 24, 48, 72, and 96 after onset of chest pain in 2 patients with acute MI. Detectable TNF was found in 13 sera of the acute MI group (range; 10-1510 pg/mL) and 4 sera of the angina pectoris group (range; 15-240 pg/mL). There was no correlation between the serum TNF levels and the occurrence of complications and the extent of myocardial damage. CRP response was unrelated to TNF levels. Contrary to previous reports, serial measurement of TNF revealed that peak values were reached within six hours and disappeared after twenty-four hours.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Serum tumor necrosis factor levels in acute myocardial infarction and unstable angina pectoris. 845 86

Ventricular remodeling is a repair process. It can follow myocardial infarction, mechanical overload (for example, in hypertension or valvular heart disease), and also occurs in inflammation and dilated cardiomyopathy. Remodeling can be an (early) adaptive process followed by a maladaptive (late) phase and involves all cells that are present in the myocardium - the myocyte, the interstitial cells, the vascular endothelium, and the immune cells. Despite the varying etiopathology that these different aspects of heart disease share, a similar sequence of molecular, biochemical and mechanical events that can lead to heart failure, myocyte hypertrophy, extensive extracellular matrix production and fibrosis, even in patients who were previously unaffected by the original disease process (for example, inflammation or infarction). Heart failure can be influenced by treatment of the underlying disease and by modification of the remodeling process, for example, by ACE inhibitors (cardioreparation). In experimental animals it has been clearly demonstrated that ACE inhibitors may even prevent a genetically predetermined left ventricular hypertrophy (cardioprevention).
 ...
PMID:Ventricular remodeling. 868 17


1 2 3 4 5 6 7 8 9 10 Next >>