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)

Central to a unifying hypothesis of body fluid regulation is maintenance of arterial circulatory integrity. This may be disturbed by arterial underfilling, either from reduction in cardiac output or by peripheral arterial vasodilation. In cardiac failure (CF), cardiac output falls and the nonosmotic release of arginine vasopressin (AVP) and expression of AVP mRNA in the hypothalamus are stimulated. V2 AVP receptor antagonists correct the impaired water excretion in rats with low-output CF, increase solute free water clearance, correct the hyponatremia in congestive CF patients, and normalize urinary concentrations of the aquaporin-2 (AQP-2) water channels. In conditions associated with peripheral vasodilation, such as cirrhosis, nonosmotic release of AVP also occurs, and AQP-2 gene expression in the rat kidney is up-regulated. In cirrhosis, nitric oxide-mediated vasodilation occurs early prior to water retention. V2 antagonists reverse the latter. In normal pregnancy, plasma AVP is relatively high for the degree of hypoosmolality. Pregnant rats up-regulate AQP-2 in the renal papilla, an effect reversed by V2 receptor antagonists. This supports the hypothesis that AVP is an important mediator of renal water retention in pregnancy. In summary, AVP-mediated water retention through collecting duct AQP-2 water channels is important in both low-output CF and high-output states such as cirrhosis and pregnancy. V2 receptor antagonists reverse the water retention and down-regulate AQP-2 water channels.
 ...
PMID:Pathophysiology of renal fluid retention. 973 67

Hyponatremia is common in advanced heart failure and relates to the severity of the disease. Non-osmotic arginine vasopressin (AVP) release and biosynthesis have been shown to be increased during chronic cardiac failure (CHF) and baroreceptors pathways have been demonstrated to play a major role in this non-osmotic stimulation of AVP. Decreased cardiac output unloads the baroreceptors and activates the sympathetic nervous system, thus stimulating AVP through a separate pathway which overrides the osmotic pathway. Besides sympathetic nervous system activation, neurohumoral peptides, such as angiotensin II, endothelins, natriuretic peptides and prostaglandins, could also participate in the non-osmotic AVP activation. The vasoconstrictor effect of AVP has been supported by the decrease systemic vascular resistance during the administration of V1 receptor AVP antagonist in CHF patients. Administration of V2 receptor AVP antagonists corrects the hyponatremia and has been demonstrated to improve survival in animal models of heart failure. Preliminary data in humans with CHF also demonstrate urinary dilution and correction of hyponatremia with orally active non-peptide V2 receptor antagonists. Finally, upregulation of the AVP-regulated water channels, aquaporin-2 (AQP2), located in the collecting duct cells has been shown in experimental heart failure. This AQP2 upregulation can be entirely suppressed by V2 receptor AVP antagonists paralleling the correction of the hyponatremia. Thus, non-osmotic release of AVP in CHF upregulates AQP2 water channels, enhances water reabsorption and causes hyponatremia. The V1, and perhaps the V2, receptor activation may also diminish cardiac function.
 ...
PMID:Recent advances in the understanding of water metabolism in heart failure. 1002 33

The pituitary-thyroid axis and neurohumoral activation indexes were simultaneously investigated in 16 in-patients hospitalized for cardiac heart failure (CHF), New York Heart Association (NYHA), class II-IV, and Killip clinical scale, class II-III, to evaluate their relationship with CHF morbidity and the relative prognostic value. At entry the patients were divided into two subgroups (A and B), according to the severity of CHF. Patients were further classified into two subgroups, according to the subsequent clinical course (C, poor outcome and D, improved clinical course). Blood samples were obtained every day for the radioimmunoassay measurement of plasma alpha-atrial natriuretic peptide (alphaANP), arginine vasopressin (AVP), and thyroid hormones, and the results were compared with those of 12 control subjects. At admission, alphaANP and 3,3',5'-triiodothyronine (rT3) values were higher, while 3,3',5-triiodothyronine (T3) to rT3 (T3/rT3) ratio was lower in subgroups A and B than in controls (p<0.001), respectively, and in C than in D (p<0.001), respectively, according to the prognosis. Conversely, no differences in other thyroid indexes, nor a significant correlation between alphaANP and either rT3 or T3/rT3 ratio were present in any of the subgroups. AVP plasma levels in subgroup A were not statistically different from those of controls, whereas they were significantly decreased in subgroups B and C (p<0.05) and D (p<0.001). In conclusion, these results indicate that in CHF the pituitary-thyroid axis is not altered, that alphaANP and T3/rT3 ratio are non-invasive and reliable predictors of severity and prognosis, while AVP might be affected by the different pathological processes leading to CHF or by the concomitant use of drugs.
 ...
PMID:AlphaANP, AVP, and pituitary-thyroid axis in patients with congestive heart failure and acute respiratory failure. 1061 26

We hypothesized that performance of exercise during heart failure (HF) would lead to hypoperfusion of active skeletal muscles, causing sympathoactivation at lower workloads and alteration of the normal hemodynamic and hormonal responses. We measured cardiac output, mean aortic and right atrial pressures, hindlimb and renal blood flow (RBF), arterial plasma norepinephrine (NE), plasma renin activity (PRA), and plasma arginine vasopressin (AVP) in seven dogs during graded treadmill exercises and at rest. In control experiments, sympathetic activation at the higher workloads resulted in increased cardiac performance that matched the increased muscle vascular conductance. There were also increases in NE, PRA, and AVP. Renal vascular conductance decreased during exercise, such that RBF remained at resting levels. After control experiments, HF was induced by rapid ventricular pacing, and the exercise protocols were repeated. At rest in HF, cardiac performance was significantly depressed and caused lower mean arterial pressure, despite increased HR. Neurohumoral activation was evidenced by renal and hindlimb vasoconstriction and by elevated NE, PRA, and AVP levels, but it did not increase at the mildest workload. Beyond mild exercise, sympathoactivation increased, accompanied by progressive renal vasoconstriction, a fall in RBF, and very large increases of NE, PRA, and AVP. As exercise intensity increased, peripheral vasoconstriction increased, causing arterial pressure to rise to near normal levels, despite depressed cardiac output. However, combined with redirection of RBF, this did not correct the perfusion deficit to the hindlimbs. We conclude that, in dogs with HF, the elevated sympathetic activity observed at rest is not exacerbated by mild exercise. However, with heavier workloads, sympathoactivation begins at lower workloads and becomes progressively exaggerated at higher workloads, thus altering distribution of blood flow.
 ...
PMID:Alteration of humoral and peripheral vascular responses during graded exercise in heart failure. 1113 93

In heart failure, reduced cardiac contractility is accompanied by blunted cAMP responses to beta-adrenergic stimulation. Parathyroid hormone (PTH)-related peptide and arginine vasopressin are released from the myocardium in response to increased wall stress but do not stimulate contractility or adenylyl cyclase at physiological concentrations. To bypass the defective beta-adrenergic signaling cascade, recombinant P1 PTH/PTH-related peptide receptors (rPTH1-Rs) and V(2) vasopressin receptors (rV(2)-Rs), which are normally not expressed in the myocardium and which are both strongly coupled to adenylyl cyclase, and recombinant beta(2)-adrenergic receptors (rbeta(2)-ARs) were overexpressed in cardiomyocytes by viral gene transfer. The capacity of endogenous hormones to increase contractility via the heterologous, recombinant receptors was compared. Whereas V(2)-Rs are uniquely coupled to Gs, PTH1-Rs and beta(2)-ARs are also coupled to other G proteins. Gene transfer of rPTH1-Rs or rbeta(2)-ARs to adult cardiomyocytes resulted in maximally increased basal contractility, which could not be further stimulated by adding receptor agonists. Agonists at rPTH1-Rs induced increased cAMP formation and phospholipase C activity. In contrast, healthy or failing rV(2)-R-expressing cardiomyocytes showed unaltered basal contractility. Their contractility and cAMP formation increased only at agonist exposure, which did not activate phospholipase C. In summary, we found that gene transfer of PTH1-Rs to cardiomyocytes results in constitutive activity of the transgene, as does that of beta(2)-ARS: In the absence of receptor agonists, rPTH1-Rs and rbeta(2)-ARs increase basal contractility, coupling to 2 G proteins simultaneously. In contrast, rV(2)-Rs are uniquely coupled to Gs and are not constitutively active, retaining their property to be activated exclusively on agonist stimulation. Therefore, gene transfer of V(2)-Rs might be more suited to test the effects of cAMP-stimulating receptors in heart failure than that of PTH1-Rs or beta(2)-ARS:
 ...
PMID:Gene transfer of heterologous G protein-coupled receptors to cardiomyocytes: differential effects on contractility. 1130 83

This study examined the early neurohumoral events in the progression of congestive heart failure (CHF) after myocardial infarction (MI) in rats. Immediately after MI was induced by coronary artery ligation, rats had severely depressed left ventricular systolic function and increased left ventricular end-diastolic volume (LVEDV). Both left ventricular function and the neurohumoral indicators of CHF underwent dynamic changes over the next 6 wk. LVEDV increased continuously over the study interval, whereas left ventricular stroke volume increased but reached a plateau at 4 wk. Plasma renin activity (PRA), arginine vasopressin, and atrial natriuretic factor all increased, but with differing time courses. PRA declined to a lower steady-state level by 4 wk. Six to 8 wk after MI, CHF rats had enhanced renal sympathetic nerve activity and blunted baroreflex regulation. These findings demonstrate that the early course of heart failure is characterized not by a simple "switching on" of neurohumoral drive, but rather by dynamic fluctuations in neurohumoral regulation that are linked to the process of left ventricular remodeling.
 ...
PMID:Progression of heart failure after myocardial infarction in the rat. 1164 Nov 47

Heart failure is a leading cause of morbidity and mortality. In the United States, there are more than 5 million patients with heart failure and over 500,000 newly diagnosed cases each year. Numerous advances have been made in our understanding of the pathophysiologic mechanisms contributing to sodium and water retention in this condition. Important alterations in the sympathetic nervous system and the renin-angiotensin-aldosterone system have been described in heart failure, allowing the use of mechanism-specific treatments such as beta-adrenergic receptor antagonism and angiotensin-converting enzyme inhibition. As our understanding of the roles of the natriuretic peptides and the arginine vasopressin-aquaporin-2 system in the pathophysiology of heart failure evolves, treatments directed toward the alterations in these systems in heart failure can be further developed.
 ...
PMID:Pathophysiology of sodium and water retention in heart failure. 1180 79

As cardiac surgery centers appreciate that ventricular assist devices (VAD) can dramatically impact patient survival as a bridge to transplant or recovery, and possibly permanent therapy, increasing numbers will desire to establish mechanical support programs. A number of vital elements must be put in place in order to operate a successful mechanical support program. Of utmost importance is the assembly of a dedicated team focused on comprehensive care of critically ill patients in need of circulatory support. An ongoing commitment from anesthesiologists, cardiologists, nephrologists, and other support staff is essential. Selection of complementary assist devices should be made to cover the spectrum of required support scenarios, both short- and long-term. Outpatient therapy has become increasingly important in mechanical cardiac assistance and establishment of an office where "LVAD coordinators" see outpatients facilitates this aspect of the program. Critically ill patients in need of cardiac assistance may benefit from specialized medical therapies such as: (1) intravenous arginine vasopressin for vasodilatory hypotension; (2) inhaled nitric oxide for right heart failure; (3) aprotinin to reduce hemorrhage; and (4) early enteral feeding in an effort to reduce infectious complications and improve rehabilitation following VAD implantation. A regional network with spoke hospitals centered around a hub hospital with long-term VAD and heart transplant programs can improve survival of patients with postcardiotomy cardiogenic shock via early transfer to the hub hospital. In this article, we describe the components of our mechanical support program that have allowed us to successfully support patients with heart failure in need of circulatory support.
 ...
PMID:Developing a comprehensive mechanical support program. 1182 65

The risks and benefits of epinephrine given during cardiopulmonary resuscitation (CPR) are controversially discussed. Animal experiments revealed beta-receptor-mediated adverse effects of epinephrine such as increased myocardial oxygen consumption, ventricular arrhythmia, ventilation-perfusion defects, and cardiac failure in the postresuscitation phase. In clinical studies, high-dose vs. standard-dose epinephrine was unable to improve resuscitation success. During CPR in patients, endogenous arginine vasopressin (AVP) levels were increased and surviving vs. non-surviving patients had significantly higher AVP levels. This may indicate that the human body discharges AVP during life-threatening situations as an additional vasopressor to catecholamines in order to maintain cardiocirculatory homeostasis. In different experimental CPR models, AVP compared with epinephrine given during CPR significantly improved vital organ blood flow, coronary perfusion pressure, resuscitability, and long-term survival. During prolonged CPR with repeated drug administration, AVP but not epinephrine maintained coronary perfusion pressure on a level that ensured return of spontaneous circulation. Also, AVP can be administered successfully in the intravenous dose into the endobronchial tree, and also intraosseously. When given during CPR, AVP induces a transient splanchnic hypoperfusion, and an increase in systemic vascular resistance, both of which normalized spontaneously; furthermore, an oligo-anuric state was not observed. In two clinical studies, AVP vs. epinephrine improved 24-h survival during out-of-hospital CPR, and comparable CPR outcome during in-hospital CPR. The new CPR guidelines of both the American Heart Association and the European Resuscitation Council assign a given CPR intervention into classes of recommendation [class 1 (definitely recommended), class 2 A (intervention of choice), class 2B (alternative intervention), class X (neutral), or class 3 (not recommended)]. For CPR of adults with shock-refractory ventricular fibrillation, 40 units AVP or 1 mg epinephrine is recommended (class 2B); patients with asystole or pulseless electrical activity should be resuscitated with epinephrine. AVP is not recommended for adult cardiac arrest patients with asystole or pulseless electrical activity; or pediatric cardiac arrest patients due to a lack of clinical data. Until definitive data about AVP vs. epinephrine effects during CPR are available, the present state of knowledge should be interpreted that two vasopressors are available for use instead of one.
 ...
PMID:[The use of arginine vasopressin during cardiopulmonary resuscitation. An analysis of experimental and clinical experience and a view of the future]. 1199 81

Previous studies showed that aquaporin 2 (AQP2) is elevated in the kidney of the heart failure rat suggesting that an increased amount of AQP2 contributes to water retention in heart failure. We performed the present study to determine whether angiotensin II play a role in causing an increase in the expression of arginine vasopressin (AVP) V2 and AQP2 mRNA in the kidney of the cardiomyopathic hamster. The expression of AVP V2 and AQP2 mRNA in the inner medullary collecting duct (IMCD) was measured by competitive reverse transcriptase-polymerase chain reaction (RT-PCR) before and after treatment with an angiotensin-converting enzyme inhibitor, enalapril. Our results showed that the expression of AVP V2 (0.53 +/- 0.05 v 1.03 +/- 0.15 amol/microg of total RNA, P <.01) and AQP2 mRNA (0.027 +/- 0.002 v 0.036 +/- 0.002 amol/microg of total RNA, P <.05) in the IMCD of the cardiomyopathic hamster is upregulated. Treating the cardiomyopathic hamster with enalapril for 7 days negated the changes. In situ hybridization experiments confirmed the intensity of the signals for both AVP V2 and AQP2 mRNA was more intense in the IMCD of the cardiomyopathic hamster. Enalapril treatment reduced the signal intensity to a level comparable to the normal hamster. These results suggested that the increases in the expression of AVP V2 and AQP2 mRNA are mediated by angiotensin II.
 ...
PMID:Upregulation of vasopressin V2 and aquaporin 2 in the inner medullary collecting duct of cardiomyopathic hamsters is attenuated by enalapril treatment. 1214 68


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