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)

Experiments were conducted in anesthetized dogs comparing the effects of PGA1, PGE2, and diazoxide on myocardial contractile force (MC). The three agents were given in successive bolus injections intravenously in equidepressor doses and myocardial contractile force was measured by means of a strain-gauge arch sutured onto the right ventricle. The drugs were administered before and during ganglionic (hexamethonium) and beta-blockade (practolol). Both PGA1, and PGE2 caused a marked rise in MC, 24 and 20 per cent, respectively, before blockade and 10 and 11 per cent during blockade. Diazoxide caused only a minimal rise, 0.9 per cent, before blockade and a marked fall, 27 per cent, during blockade. Diazoxide administration during left ventricular bypass indicates that the decrease in MC is not a direct result of alterations in preload or after load. It is suggested that hypertensive patients treated with autonomic blocking agents may be more susceptible to heart failure in response to diazoxide therapy.
 ...
PMID:Effect of PGA1, PGE2, diazoxide on myocardial contractile force. 0 54

To test the efficacy of exogenous prostaglandins for vasodilator therapy in heart failure, we studied the hemodynamic, hormonal, and renal effects of prostaglandin E2 (1.5-150 ng/kg/min) in six conscious dogs before and after induction of heart failure by right ventricular pacing (250 beats/min, 10 days). In healthy dogs, PGE2 decreased the mean arterial pressure (MAP) by a reduction in total peripheral resistance (TPR), increased cardiac output (CO), stroke volume (SV), and heart rate with no effect on right atrial pressure (RAP). Plasma levels of renin (PRC) and norepinephrine (NE) were increased at the highest dosage. Renal plasma flow (RPF) and sodium excretion (UNaV) were augmented without a change in the glomerular filtration rate (GFR) and urine flow (UF). In dogs with heart failure, PGE2 lowered the MAP and TPR and elevated the CO and SV without an effect on the RAP, PRC, and NE. The RPF and GFR were not changed, but the increase in UNaV was preserved and UF significantly augmented. In experimental heart failure, PGE2 increases the CO due to arteriolar dilation and afterload reduction without inducing further neurohumoral activation and exerts potent natriuretic and diuretic action. Therefore, PGE2 may have beneficial effects in heart failure therapy.
 ...
PMID:Prostaglandin E2 in dogs with heart failure: hemodynamic, hormonal, and renal effects. 128 Jul 9

Exogenous prostaglandin (PG) administration has been proposed as a vasodilator therapy for heart failure patients. The effects of this therapy on renal function have not been well studied in this disorder. Therefore, we investigated the renal effects of the PGI2 analog iloprost in comparison to PGE2 in 12 conscious dogs before and after induction of a low cardiac output state by rapid right ventricular pacing (250 beats/min for 10 days). In healthy dogs, 5 to 150 ng/kg/min iloprost increased renal plasma flow without affecting glomerular filtration rate and decreased urine flow without affecting natriuresis. PGE2 at the same dosages increased renal plasma flow and urinary sodium excretion without changing the glomerular filtration rate or amount of diuresis. In dogs with low cardiac output and lower basal renal plasma flow, iloprost did not change renal plasma flow, but decreased glomerular filtration rate and filtration fraction. In these animals, PGE2 insignificantly increased renal plasma flow, but significantly augmented urine flow and sodium excretion. We therefore conclude that in an experimental low cardiac output state, PGI2 may cause a deterioration of renal function. In contrast, PGE2 induces natriuresis and diuresis despite an attenuated increase in renal plasma flow. Thus, PGE2 promises to exert a more favorable profile of renal effects in heart failure therapy.
 ...
PMID:Prostaglandin I2 versus prostaglandin E2 in dogs with and without low cardiac output. Differential effects on renal function. 157 44

In heart failure, neurohumoral factors are important determinants of left-ventricular function, not only by direct mechanisms on the myocardium, but also by indirect effects through modulation of pre- and afterload. In experimental models of heart failure, as well as in patients with cardiac dysfunction, it has been demonstrated in the early phase of the disease that the sympathetic activity and the secretion of atrial natriuretic peptide are stimulated. This is associated with an increased synthesis of vasodilator prostaglandins in the kidney, predominately prostaglandin E2. Prostaglandin E2 plays an important role by its vasodilator and natriuretic properties in preserving renal blood flow, natriuresis and diuresis. The stimulation of the secretion of atrial natriuretic peptide in relatively moderate heart failure leads to a suppression of the activation of the renin-angiotensin-aldosterone system. In more severe heart failure vasoconstrictor, sodium and water-retaining mechanisms like the renin-angiotensin-aldosterone system are activated with the consequence of an increase of systemic vascular resistance, a reduction of renal blood flow, and an increased fluid retention. The inhibition of cyclooxygenase, leading to a blockade of the synthesis of prostaglandins, leads in early heart failure to a dramatic change in renal blood flow with an increase of renal vascular resistance and a decrease of renal perfusion which causes renal functional impairment.
 ...
PMID:[Renin, aldosterone and prostaglandins in heart failure]. 179 34

Changes of neurohumoral factors including vasodilatory prostaglandins (PGs) were investigated in an experimental model of moderate low-cardiac-output status induced by rapid right ventricular pacing (240 beats/min). After 7 days of pacing, we studied the response of renal, hormonal, and hemodynamic parameters to cyclooxygenase inhibition by indomethacin and the effects of the renin system by converting-enzyme blockade in addition to the inhibition of PG synthesis. Lowering cardiac output increased plasma levels of norepinephrine and atrial natriuretic peptide. Plasma renin concentration was suppressed, despite a fall in cardiac output and blood pressure and a stimulation of sympathetic nerve activity. Urinary excretion of PGE2 was increased (P less than 0.04); plasma levels of PGE2 and 6-keto-PGF1 alpha were unchanged as measured in blood from the renal vein, pulmonary artery, and aorta. During low cardiac output, we found a significant decrease of glomerular filtration rate, whereas renal blood flow and renal and peripheral vascular resistances were unchanged. Administration of indomethacin decreased plasma and urinary PGs significantly, markedly reduced renal blood flow, and increased renal vascular resistance without affecting peripheral vascular resistance. The additional blockade of the renin-angiotensin system by captopril showed mainly a vasodilator effect on peripheral arterial resistance vessels, resulting in an increase of cardiac output. Our results suggest that, in moderate low-cardiac-output status, renal blood flow is maintained by renal vasodilator PGs, which counterbalance vasoconstrictor mechanisms like the activated sympathetic nerve activity. We indirectly showed the importance of angiotensin II in preserving glomerular filtration rate, which declines when renin secretion is suppressed, as it may be the case in moderate heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Circulatory and renal control by prostaglandins and renin in low cardiac output in dogs. 252 99

This review updates some recent advances of a new and exciting developments in basic and clinical cardiology: a) the role, in the congestive heart failure (CHF), of the neurohormonal systems (NHS) which act to maintain circulatory homeostatic equilibrium, and b) the therapeutic implications of such a role. Six NHS, acting in CHF, have presently been identified: three of them induce vasoconstriction and sodium retention (sympathetic nervous systems, renin-angiotensin-aldosterone system and arginine-vasopressine system); the remaining three offset or balance the former ones, acting, therefore as "counterregulators" (prostaglandins--PGE2 and PGI2--, dopaminergic system and atrial natriuretic factor). Each one of these NHS influences the "compensatory" mechanisms of heart failure, acting on the target-organs both by direct effects and by interaction with other NHS; consequently, in heart failure, all the NHS are stimulated with the respective increase in the plasma levels of their agents. In asymptomatic stages of ventricular dysfunction the stimulation of the vasodilator-and-natriuretic systems appears to be predominant and able to maintain circulatory equilibrium. However, as the heart dysfunction increases and becomes symptomatic, the vasoconstrictor and sodium-retaining forces appear to predominate; this phenomenon becomes increasingly apparent as the functional class becomes more advanced. The hyperstimulation of these last systems has an extremely important role in the pathophysiology and clinical manifestations of congestive heart failure, as well as in its prognosis. Therefore, the attempts to correct these neurohormonal imbalance in patients with heart failure has a sound rational basis, not only to improve the symptoms and the exercise capacity but also to increase the survival of these patients. At the present time, amongst the potential pharmacological interventions acting on NHS in CHF, the blockade of the SRA system with ACE-inhibitors is generally accepted as the most feasible, the safer and the most effective therapeutic tool. In fact, its application has broadened from an earlier use in severe CHF to other symptomatic stages of cardiac failure, including the milder forms. In addition, preliminary data strongly suggest its unique usefulness in asymptomatic phases of ventricular dysfunction. Looking back at the medical therapy of heart failure, it can be concluded that we are starting a new era. Throughout 200 years (since the introduction of digitalis) the therapeutic goal in CHF has been the improvement of symptoms. With the developments of the present decade, a new and exciting goal is being offered to these patients, called by Packer "the second frontier", that is, the prolongation of their lives.
 ...
PMID:[Neuro-hormonal mechanisms in heart insufficiency--from physiopathology to treatment]. 257 35

Eight patients with chronic heart failure classified as NYHA class II to III (group 1) and nine patients with acute decompensated heart failure classified as NYHA class IV (group 2) were treated with piretanide at a dosage of 12 mg administered intravenously. In both groups the level of prostaglandine PGE2 as well as plasma renine activity significantly increased prior to the onset of diuresis. The percentage increase was more pronounced in group 1 which had lower baseline values. With a time-lag, the norepinephrine plasma level also increased significantly. During the first 30 minutes there was only little effect on blood pressure, pulmonary artery pressure and cardiac output in patients with chronic heart failure (group 1). Only after 60 minutes there was a significant decrease in mean pulmonary artery pressure (from 39 +/- 17 to 33 +/- 18 mm Hg; p less than 0.05). In patients with acute decompensated heart failure (group 2) piretanide led to a significant reduction in mean pulmonary artery pressure (from 42 +/- 13 to 37 +/- 12 mm Hg; p less than 0.05) within 15 minutes after administration, i.e. even prior to the onset of diuresis. Thus, the administration of piretanide had a positive effect on hemodynamics in patients with chronic as well as in patients with acute decompensated heart failure. Significant improvement prior to diuresis onset, however, was only found in patients with acute decompensated heart failure. These effects may be explained by a stimulation of prostaglandines which promote vasodilation. They are increased by the diuresis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Piretanide in chronic and acute decompensated heart failure. Effect on hemodynamics and vasoactive hormones]. 275 12

Vasoconstrictors and vasodilators are both activated in patients with severe heart failure. Vasodilatory prostaglandins are increased in parallel with the degree of activation of neurohumoral vasoconstrictor systems, and may serve to offset the circulatory effects of systemic and regional vasoconstriction. Enhanced vasoconstrictive and vasodilatory activities appear to be especially important in patients with hyponatraemia. These patients may be particularly susceptible to clinical deterioration when given drugs that inhibit prostaglandin synthesis (e.g. indomethacin) and may be more likely to improve when treated with agents that enhance the production of endogenous prostaglandin (e.g. angiotensin converting enzyme inhibitor). Exogenous PGE2 reduces afterload and may be a useful therapeutic agent. Research on vascular and renal prostaglandins should further our knowledge of the pathophysiology and therapy of congestive heart failure.
 ...
PMID:Vascular and renal prostaglandins as counter-regulatory systems in heart failure. 304 94

The effects of polyunsaturated fatty acids (phosphatidylcholine) on renal function in healthy subjects and in patients with chronic renal failure, with liver cirrhosis, and with heart failure were studied. The drug was administered at 3.5 mg/kg i.v. (Linoleic acid 1.24 mg/kg). In all cases, the administration of the drug caused an increased excretion of sodium and especially of water with a reduction in basal urinary hypertonicity. The polyuria was caused by the higher glomerular filtration rate not being counterbalanced by an increase in tubular water reabsorption. The water reabsorption was mostly anisosmotic. The presence of urinary hypertonicity excluded an inhibition of ADH secretion by this drug. The sodium excretion was probably caused by an increase of the glomerular filtration rate whereas no significant changes in the tubular reabsorption of sodium were seen. We found a significant (p 0.05) increase in PGE2 urinary excretion after phosphatidylcholine administration. Lysine - acetylsalicylate injection after phosphatidylcholine, in other trials in the same patients, prevented the effects previously reported. Therefore we suggest that the effects of this drug are mediated by an increased availability of renal prostaglandins.
 ...
PMID:Effects of polyunsaturated fatty acids and prostaglandin synthesis on renal function. 308 1

Congestive heart failure is a complex clinical syndrome characterized by a number of neuroendocrine responses. These responses are probably an evolutionary vestige of mechanisms designed to defend volume and maintain circulatory homeostasis. Activation of the sympathetic nervous system and renin-angiotensin-aldosterone system and the release of vasopressin have been clearly documented in patients with heart failure. Unlike the normal ventricle, the failing ventricle responds to peripheral vasoconstriction and sodium retention with further hemodynamic embarrassment and circulatory congestion. Certain vasorelaxant natriuretic substances are also released during heart failure, perhaps in an attempt to offset excessive peripheral constriction and sodium retention. Prostaglandin E2, atrial natriuretic peptide (or atrial natriuretic factor) and plasma dopamine are found to be increased in some patients with heart failure. However, peripheral constriction and sodium retention appear to be dominant, particularly in the advanced stages of heart failure. An understanding of these neuroendocrine responses has led to new developments in therapy. Angiotensin-converting enzyme inhibitors have emerged as distinctly useful drugs in the treatment of heart failure. Agents designed to block excessive sympathetic drive and inhibit vasopressin are under investigation. Infusion of atrial natriuretic factors and the use of selective dopamine agonists are also undergoing clinical trials in patients with heart failure. Increased knowledge of the neuroendocrine responses will likely result in even newer and more imaginative therapy.
 ...
PMID:Neuroendocrine manifestations of congestive heart failure. 329 96


1 2 3 Next >>