6-ketoprostaglandin-f1-alpha and Heart-Failure

The prostaglandin-thromboxane system, platelet hemostasis and central hemodynamics were evaluated in 51 patients with heart failure-complicated acute myocardial infarction during aspirin, roxicam and basic (nitrates + cardiac glycosides + diuretics) therapies. The new non-steroidal antiinflammatory agent roxicam was shown to selectively inhibit thromboxane, without affecting prostacyclin levels. The agent may be regarded as the drug of choice in using antiaggregatory therapy in patients with myocardial infarction concurrent with heart failure.

Topics: 6-Ketoprostaglandin F1 alpha; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cardiac Glycosides; Diuretics; Epoprostenol; Heart Failure; Humans; Myocardial Infarction; Nitrates; Piroxicam; Thromboxane A2; Thromboxane B2; Thromboxanes

In a randomized double-blind cross-over study the effects of rhein (administered as diacetyl-rhein 50 mg b.d. for 5 days) and placebo on renal arachidonic acid metabolism and renal function have been compared in 12 elderly patients (mean age 75.2 years) with congestive heart failure, whose renal function was known to be dependent on the integrity of the renal prostaglandin system. Rhein like placebo, did not induce any change in the urinary excretion of prostaglandin (PG) E2, 6-keto-PGF1 alpha and thromboxane (TX) B2, nor did it affect creatinine clearance, blood urea, urine output, natriuresis, body weight, plasma renin activity or plasma aldosterone concentration. Separate analysis of the results obtained in the 5 patients receiving diuretic treatment did not show any significant effect of rhein as compared with placebo on the parameters investigated. Serum TXB2 concentration during whole blood clotting, as an index of platelet arachidonic acid metabolism, also showed no significant difference when DAR and placebo were compared. It is concluded that in patients with congestive heart failure rhein does not inhibit renal or platelet eicosanoid metabolism, nor does it modify renal function, sodium excretion or the renal response to diuretics.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Aged, 80 and over; Aldosterone; Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acids; Cyclooxygenase Inhibitors; Dinoprostone; Double-Blind Method; Female; Heart Failure; Humans; Kidney; Kidney Function Tests; Renin

The objective of this investigation was to study the effects of the two NSAIDs sulindac and naproxen on renal hemodynamics and excretion of water, salt and the prostacyclin metabolite 6-keto-PGF1 alpha in patients with well controlled congestive heart failure. Ten elderly females with congestive heart failure treated with oral furosemide were given four doses of sulindac and naproxen every twelve hours after a control day in a double-blind cross-over fashion. Naproxen significantly decreased the urinary excretion of water (19%), sodium (26%), chloride (26%), 6-keto-PGF1 alpha (76%) and decreased osmolal clearance by 18%. Sulindac had no significant effect on those parameters. There were no significant changes in glomerular filtration rate, renal blood flow, plasma renin activity, plasma aldosterone, free-water clearance or clearance of furosemide with either treatment. We conclude that renal prostaglandins are involved in the control of sodium excretion and urinary volume in patients with congestive heart failure even if renal hemodynamics are unaffected. Sulindac seems to be a selective inhibitor of extrarenal cyclooxygenase and consequently an appropriate drug for patients who require both diuretics and anti-inflammatory therapy.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Chlorides; Clinical Trials as Topic; Diuresis; Double-Blind Method; Female; Glomerular Filtration Rate; Heart Failure; Humans; Indenes; Kidney; Naproxen; Sodium; Sulindac

The aim of the present work was to analyze coronary endothelial function in the transgenic mouse model of dilated cardiomyopathy (Tgalphaq*44 mice).. Coronary vasodilatation, both NO-dependent (induced by bradykinin) and PGI(2)-dependent (induced by acetylcholine), was assessed in the isolated hearts of Tgalphaq*44 and FVB mice. Cardiac function was analyzed in vivo (MRI).. In Tgalphaq*44 mice at the age of 2-4 months cardiac function was preserved and there were no alterations in endothelial function. By contrast, in Tgalphaq*44 mice at the age of 14-16 months cardiac function was significantly impaired and NO, but not PGI(2)-dependent coronary function was altered. Interestingly, the basal level of PGI(2) in coronary circulation increased fourfold as compared to FVB mice. Cardiac O(2) (-) production increased 1.5-fold and 3-fold in Tgalphaq*44 vs. FVB mice at the age of 2-6 and 14-16 months, respectively, and was inhibited by apocynin. Interestingly, inhibition of NADPH oxidase or NOS-3 normalized augmented PGI(2) production in Tgalphaq*44 mice. There was also an increased expression of gp91phox in Tgalphaq*44 vs. FVB hearts, without evident alterations in the expression of COX-1, COX-2, NOS-3 and PGI(2)-synthase.. In the mouse model of dilated cardiomyopathy, endothelial dysfunction in coronary circulation is present in the late but not the early stage of heart failure pathology and is characterized by a decrease in NO bioavailability and a compensatory increase in PGI(2). Both the decrease in NO activity and the increase in PGI(2) activity may result from excessive O(2) (-) production by cardiac NADPH oxidase in Tgalphaq*44 hearts.

Topics: 6-Ketoprostaglandin F1 alpha; Age Factors; Animals; Cardiomyopathy, Dilated; Coronary Artery Disease; Cyclooxygenase 1; Cyclooxygenase 2; Cytochrome P-450 Enzyme System; Disease Models, Animal; Endothelium, Vascular; Epoprostenol; Heart Failure; Intramolecular Oxidoreductases; Membrane Proteins; Mice; Mice, Inbred Strains; Mice, Transgenic; Myocardium; NADPH Oxidases; Nitric Oxide; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Superoxides; Vasodilation

Previous studies suggest that the acute haemodynamic effects of loop diuretics are due to a direct dilation of blood vessels and are not related to diuretic properties, but possibly to prostaglandin secretion.. We investigated whether in vitro human endothelial and renal epithelial cells responded to torasemide or furosemide with enhanced secretion of the vasodilator prostaglandin prostacyclin (PGI2). We also investigated the effects of loop diuretics on plasma concentrations of PGI2 and its physiological antagonist thromboxane after 25 min of administration of drugs in 44 patients with congestive heart failure (CHF) and 44 healthy volunteers.. The PGI2 levels were measured after extraction in ethyl acetate by RIA as levels of 6-KetoPGF1alpha, a stable metabolite from a non-enzymatic degradation. TxB2 concentration, the stable hydrolysis product of TxA2, was also measured by RIA.. In human endothelial and renal epithelial cells, both loop diuretics induced an increase of 6-KetoPGF1alpha secretion that reached a peak after about 5 min and remained stable for 30 min of exposure to the drugs. The magnitude of the phenomenon was lesser in epithelial than in endothelial cells. Moreover, in both cell lines, there was a significantly higher secretion of 6-KetoPGF1alpha to torasemide than furosemide (P < 0.05). Concentrations of 6-KetoPGF1alpha at baseline were similar between the groups of CHF patients receiving the two different drugs. After 25 min of both drugs, 6-Keto-PGF1alpha significantly increased (P < 0.01), and this was significantly higher in patients treated with 10 mg of torasemide (P < 0.05 vs furosemide). Levels of PGI2 at baseline were lower in healthy controls than those reached by CHF patients and similar between groups. After 25 min of both drugs, PGI2 plasma levels were significantly increased (P < 0.01). Baseline values of TxB2 were significantly higher in CHF patients compared with controls (P < 0.01 vs respective groups). and, more importantly, furosemide but not torasemide increased TxB2 levels in patients and controls (P < 0.05 vs baseline).. Our study is the first demonstration in human tissue of increased secretion of PGI2 both in vitro and in vivo, after torasemide or furosemide administration. This phenomenon, which may explain in part the vasodilatory effects of these drugs, was more evident with torasemide and was reached at lower concentrations of the drug. Accordingly, we also found that furosemide but not torasemide stimulated the release of the PGI2 physiological antagonist thromboxane in CHF patients and healthy controls.

Topics: 6-Ketoprostaglandin F1 alpha; Diuretics; Endothelium, Vascular; Epithelium; Epoprostenol; Female; Furosemide; Heart Failure; Hemodynamics; Humans; In Vitro Techniques; Kidney; Male; Middle Aged; Sulfonamides; Thromboxane B2; Torsemide; Vasodilator Agents

Hemodynamic and neurohumoral responses to supine bicycle exercise were evaluated in 16 patients with congestive heart failure (New York Heart Association functional class II-III) and in 8 normal controls. We determined cardiac output by the dye-dilution method, and forearm hemodynamics by plethysmography. The patients had lower resting cardiac and stroke indexes (p < 0.05) than the normal controls. During exercise, the increase in the cardiac index due to an increase in heart rate, was less than that in the controls. Resting and exercise systemic vascular resistance indices were higher in the patients (p < 0.05). The patients had lower resting forearm blood flow and higher forearm vascular resistance (p < 0.05), and the increases during exercise were comparable in the 2 groups. However, forearm venous tone and venous pressure increased more in the patients (p < 0.05). Exercise duration was shorter in the patients (p < 0.01). Resting plasma angiotensin II and norepinephrine were similar in the 2 groups, but plasma 6-keto-prostaglandin F1 alpha and atrial natriuretic peptide were higher in the patients. During exercise, all of these neurohumoral parameters rose more in the patients than in the controls (p < 0.05). Thus, the patients exhibited impaired central and peripheral hemodynamics both at rest and during exercise. The excessive exercise responses of all of the neurohumoral factors suggest that both vasoconstrictor and vasodilator systems are activated in heart failure.

Topics: 6-Ketoprostaglandin F1 alpha; Angiotensin II; Atrial Natriuretic Factor; Exercise; Exercise Test; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Neurotransmitter Agents; Rest

Before and after oral administration of sustained Ligustrazine, changes of hemorrheology and TXA2/PGI2 were evaluated in 16 patients with advanced chronic pulmonary heart disease. A decrease in whole blood and plasma viscosity, and reductions in hematocrit and fibrinogen were found after one course of treatment with sustained Ligustrazine. The mechanism of these effects may be related to improved modulation of imbalance of TXA2/PGI2 in patients with advanced chronic pulmonary heart disease.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Aged, 80 and over; Blood Viscosity; Female; Fibrinolytic Agents; Heart Failure; Hematocrit; Humans; Male; Middle Aged; Pulmonary Heart Disease; Pyrazines; Thromboxane B2

In 14 patients with severe congestive heart failure, the effects of captopril on the forearm circulation were evaluated with strain gauge plethysmography. Changes in plasma renin activity, angiotensin II, norepinephrine, epinephrine, bradykinin, prostaglandin E2, and 6-keto-prostaglandin F1 alpha concentrations were also measured. To determine whether the prostaglandins contribute to the peripheral hemodynamic response to captopril, the hemodynamic and hormonal measurements were repeated after pretreatment with indomethacin, an inhibitor of prostaglandin synthesis. Ninety minutes after administering a single dose of captopril (25 mg), mean blood pressure and venous pressure decreased (p less than 0.01 and p less than 0.05, respectively), forearm blood flow and maximum venous volume increased (p less than 0.05 for both), and forearm vascular resistance and forearm venous tone decreased (p less than 0.05 for both). Captopril also improved forearm venous distensibility (p less than 0.05). Pretreatment with oral indomethacin (50 mg) significantly blunted all of these captopril-induced hemodynamic changes. The blockage of the renin-angiotensin system by captopril was unaltered by indomethacin pretreatment. Captopril significantly increased plasma bradykinin, prostaglandin E2, and 6-keto-prostaglandin F1 alpha (p less than 0.05 for each). Indomethacin pretreatment did not affect the captopril-induced increase in bradykinin, but it did completely eliminate the increase in the prostaglandins. Plasma catecholamines did not change with captopril. These data suggest that the vasodilator prostaglandins play a significant role in captopril's peripheral vasodilative effects in congestive heart failure.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Bradykinin; Captopril; Dinoprostone; Female; Forearm; Heart Failure; Hemodynamics; Humans; Indomethacin; Male; Middle Aged; Plethysmography; Regional Blood Flow; Renin-Angiotensin System

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)

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Catecholamines; Dinoprostone; Diuretics; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Renin-Angiotensin System; Sulfonamides

There is little, if any, good evidence in the literature to indicate a role for cardiovascular PG in congestive heart failure, either in its pathogenesis or as a consequence of and defense against its manifestations. Usually congestive heart failure is considered to develop as a vicious cycle in which impaired cardiac output, increased peripheral resistance, decreased renal blood flow, increased renin release and further increased peripheral resistance and decreased cardiac output are important constituents. Increased sympathetic activity may promote cardiovascular PG formation through the sympathetic neurotransmitter noradrenaline; such an action has, however, not been documented hitherto. Furthermore, increased plasma renin activity may promote PG formation via increased circulating levels of angiotensin; even such an action remains, however, to be demonstrated. If the heart failure leads to local tissue ischemia the hypoxia as such, or the subsequent increase in adenosine production, may also facilitate cardiovascular PG formation. All these mechanisms, if operative, would counteract the increased peripheral resistance, by promoting the formation of vasodilator PG. On the other hand PGI2 stimulates renal formation of renin, which would act to elevate the peripheral resistance. These contradictory effects of endogenously formed PG focus on the need for more careful studies on their involvement in the hemodynamic consequences of congestive heart failure: until more data are available it is impossible to know whether an activated synthesis of PG should be regarded as advantageous and worth therapeutical support, or negative and subject to inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Dinoprost; Dinoprostone; Epoprostenol; Heart Failure; Humans; Indomethacin; Kidney; Prostaglandin Antagonists; Prostaglandins; Prostaglandins E; Prostaglandins F; Thromboxane A2