[Side-effects of osmotic diuresis].
Explore the source record for details and available documents.
Diuretics↗
SEARCH · Search PubMed
Results for “DIURESIS AND DIURETICS”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
[Effect of diuretics on thiamine elimination].
Explore the source record for details and available documents.
Animals↗
A synthetic deamino-carba-analogue of oxytocin with a raised natriuretic-diuretic effect in rats.
Explore the source record for details and available documents.
Animals↗
Action of diuretics at the cellular level.
Classification of diuretics is based on their site and mechanism of action in the nephron. The most frequently used substances comprise 1. the mostly proximally acting carbonic anhydrase inhibitors (CAI); 2. the loop diuretics (LD); 3. the early distally acting thiazides (TZ); and 4. the K+ sparing diuretics (KS) acting in the distal tubule. CAI such as acetazolamide inhibit the dehydration of H2CO3 at the luminal membrane, the hydration of CO2 within the proximal tubule cell and the exit of HCO-3 out of the cell. As a result of this proximal reabsorption of HCO-3 is reduced, a slight diuresis and saluresis is induced. The enhanced urinary excretion of HCO-3 will cause a metabolic acidosis. LD inhibit the Na+2Cl-K+ carrier in the thick ascending limb of the loop of Henle (TAL). This produces a marked diuresis and saluresis which is accompanied by enhanced Ca2+, Mg2+, K+ and acid excretion. TZ inhibit the Na+Cl- cotransporter in the early distal tubule. The diuresis is less marked than that induced by LD but the renal losses of K+ are comparable. KS inhibit Na+ channels present in the luminal membrane of the cortical collecting tubule. This leads to a very limited diuresis, but a marked attentuation of renal K+ losses. All diuretics act by inhibiting the admission of Na+ (LD, TZ, KS) or HCO-3 (CAI) into the cell. Their organotropy is merely due to the fact that they are concentrated in tubule fluid by volume reabsorption and by proximal tubule secretion.
Animals↗
The alpha 1-blocker dapiprazole inhibits diuresis but not drinking and feeding induced by U-50,488H.
To further explore the interaction between opiates and catecholamines in the control of water balance, we studied the effects of the alpha 1-adrenoceptor antagonist dapiprazole on the modifications in drinking and diuresis produced by U-50,488H (a selective kappa-opiate agonist), morphine, naloxone, and amphetamine in rats. Because animals were maintained in a free-feeding paradigm and water intake is also controlled by feeding (prandial drinking), food intake was also measured. At doses administered (3-6 mg/kg, IP), dapiprazole had no effect on basal food and water intake or on diuresis. Nor did it modify changes in feeding and drinking produced by U-50,488H, morphine, naloxone, and amphetamine. It did, however, antagonize the diuretic effect of both U-50,488H and amphetamine. In addition, suppression of diuresis was obtained by combining doses of dapiprazole and morphine or naloxone that were devoid of antidiuretic effects when administered independently. A further experiment showed that diuresis produced by water load was also prevented by dapiprazole. alpha 1-Adrenoceptors thus appear to play a role in the regulation of water balance in a condition of free access to water, inhibiting diuresis without affecting drinking.
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
"Well-tempered" diuresis renography: its historical development, physiological and technical pitfalls, and standardized technique protocol.
Differentiating the various causes of hydronephrosis from that of obstruction can be very difficult. Diuretic renography has been adopted as a noninvasive clinical management tool to assist in this differentiation. However, the correlation of the results of diuresis renography, the Whitaker test, and the surgical results has only been between 40% and 85%. This is believed to be due to the many physiological factors and technical pitfalls of the technique. These include variable renal function, variable compliance of the collecting system, the effect of back pressure from a full bladder, the state of hydration, the choice of radiopharmaceutical, and the timing of the diuretic injection. Even the technique of measuring the clearance half-time (T 1/2) is controversial, with at least eight different methods defined. In order to diminish the effect of these variables, a standardized protocol for diuretic renography has been proposed by a consortium of members of the Society for Fetal Urology and the Pediatric Nuclear Medicine Club of the Society of Nuclear Medicine. These include a standardized hydration with a dilute glucose solution, bladder catheterization and measurement of urine output response, uniform radiopharmaceutical choice, and diuretic dose with specific timing of the diuretic injection. The various methods for T 1/2 calculation are illustrated, and various stereotypical renogram and diuresis response curves are offered as aids in the interpretation of the study. Diuresis renography is one of the most complex functional studies in nuclear medicine today. A thorough understanding of the physiological basis for diuresis renography and the pitfalls of the technique is required for its appropriate use in the management of patients suspected of urinary tract obstruction.
Diuretics↗
Diuretics in cardiovascular therapy: the new clinicopharmacological bases that matter.
Diuretics in current use include early distal tubular (i.e., thiazide-type), loop (i.e., furosemide-type), and potassium-and-hydrogen-retaining substances. Available oral formulations of diuretics differ in terms of their renal excretory potency in man, as formally assessed through the effect of a single dose on 24-hour natriuresis in healthy subjects. The 2.5 mg formulation of the loop diuretic torasemide does not increase mean 24-hour natriuresis, and it is therefore considered a very-low-dose formulation. Amiloride 5 mg and torasemide 5 mg and 10 mg, which increase mean 24-hour natriuresis by less than 40%, are considered low-dose or low-potency diuretic formulations of diuretic substances. Hydrochlorothiazide 25 and 50 mg, furosemide 40 and 80 mg, and torasemide 20 mg, which increase mean 24-hour natriuresis by more than 40%, are considered high-dose or high-potency formulations. A rebound in natriuresis follows the early-after-dosing increase in this variables caused by loop diuretics; hence many oral formulations of loop substances are less potent natriuretics than most oral formulations of thiazide-type diuretics. Hydrochlorothiazide 25 mg and furosemide 80 mg have similar natriuretic potencies. During once-daily administration of diuretic formulations of diuretics to subjects without edema and normal renal function, the increases in 24-hour natriuresis and diuresis that follow the first dose disappear or attenuate markedly. This is due to neuroendocrine reactions to diuretic-induced sodium loss and its attendant hemodynamic shifts. Some of these reactions, e.g. the increase in plasma aldosterone that takes place, account for an elevation in kaliuresis that occurs during once-daily treatment with a high-dose formulation of a thiazide-type diuretic. Common fixed-dose combinations of a thiazide-type or a loop diuretic and a potassium-and-hydrogen-retaining substance generally do not change kaliuresis, but they increase natriuresis strikingly. Thiazide-type and loop diuretics decrease and increase calciuresis respectively; none of these actions wanes during prolonged administration. Plasma renin activity and aldosterone do not rise in response to very-low-dose formulations of loop diuretics taken once daily. Glomerular filtration rate tends to fall in the course of once-daily administration of high-dose formulations of diuretics, but not during prolonged once-daily treatment with very-low-dose formulations of loop diuretics.
Aldosterone↗
Diuretic and uricosuric activity of 6,7-dichloro-2,3-dihydro-5-(2-thienylcarbonyl)benzofuran-2-carboxylic acid and stereoisomers in chimpanzee, dog and rat.
The racemate and the d-isomer of 6,7-dichloro-2,3-dihydro-5-(2-thienylcarbonyl)benzofuran-2-carboxylic acid exhibited diuretic activity in the chimpanzee, dog and rat. In the chimpanzee, the diuresis and natriuresis presumably resulted from a site of action in the thick ascending limb of Henle's loop. The l-isomer was uricosuric but devoid of any diuretic action in the chimpanzee and similarly was not diuretic in the dog and rat. Various proportions of the two isomers were tested in the chimpanzee in an attempt to produce an optimal diuretic and uricosuric profile. It was concluded that the racemic mixture, under these experimental conditions, was responsible for the most effective overall response. This is apparently the first time in which there is a distinct separation of diuretic and uricosuric actions in the enantiomers of a racemic diuretic uricosuric agent.
Animals↗
Acute effects of furosemide on blood pressure in functionally anephric, volume-expanded rats.
The hypotensive effect of loop diuretics is primarily mediated by a decrease in extracellular fluid volume that follows the intense diuresis. In the present study we investigated whether furosemide (1.25 mg/kg i.v.) can acutely lower blood pressure independently of its diuretic action. The experiments were performed in four groups of male Wistar rats: (a) rats in which furosemide was administered after bilateral ligation of renal vessels and saline (0.9% NaCl at a rate of 0.25 ml/min to a final volume of 1% of body weight) infusion; (b) rats in which furosemide was injected after bilateral ligation of ureters and saline infusion; (c) rats pretreated with indomethacin (3 mg/kg i.p. for 4 days) in which furosemide was injected after bilateral ligation of ureters and saline infusion; (d) sham-operated rats with intact kidneys. All the groups were compared with appropriate time controls. After furosemide injection, heart rate and blood pressure were serially recorded for 30 min by plethysmography. Hematocrit, plasma 6-keto-prostaglandin F1 alpha levels and plasma renin activity were measured at baseline and 20 min after furosemide injection. No change in blood pressure followed furosemide administration in rats with ligation of the renal vessels. Conversely, furosemide induced a rapid and significant fall in blood pressure associated with a significant increase in heart rate in rats with ligation of the ureters and rats with intact kidneys. Indomethacin pretreatment prevented the furosemide-induced decrease in blood pressure in rats with ligation of the ureters. Hematocrit and plasma 6-keto-prostaglandin F1 alpha levels were not affected by furosemide in either group.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Atrial natriuretic peptide in children with nephrotic syndrome].
The mechanism causing sodium retention in nephrotic syndrome remains controversial. There is an increasing evidence that sodium retention is directly due to an intrarenal mechanism. Atrial natriuretic peptide (ANP), realized from the heart during hypervolaemia, increases glomerular filtration rate, renal sodium and water elimination in both experimental animals and healthy men. In attempt to clarify the possible role of ANP in the mechanism of sodium retention in nephrotic syndrome we carried out this study. The purpose was: a) to determine plasma concentrations of ANP and values of creatinine clearance (CCr), natriuresis and diuresis both in basal conditions and after remission of the ilness, and b) to analyze the influence of acute hypervolaemia on ANP, Ccr, diuresis and natriuresis. A group of 12 children (aged 2-13 years) was studied during relapse and remission of nephrotic syndrome. In addition, 8 patients were studied during acute hypervolaemia due to intravenous infusion of 12% albumine. Twelve healthy children served as control group. Our results showed that in nephrotic syndrome group ANP was higher than in control group. Creatinine clearance, diuresis and natriuresis were significantly lower during relapse than in remission. The increase in Ccr, diuresis and natriuresis were observed during infusion of albumine, but no correlation was found between increased ANP and other parameters. This study showed that during relapse of nephrotic syndrome plasma concentrations of ANP are moderately elevated, but Ccr, diuresis nad natriuresis are blunted. We speculate that natriuretic and diuretic effects of ANP are impaired in children with nephrotic syndrome.
Adolescent↗
Management of heart failure. I. Pharmacologic treatment.
OBJECTIVE: This review of the pharmacologic treatment of heart failure due to left ventricular systolic dysfunction summarizes the recommendations of the expert panel for the Agency for Health Care Policy and Research Heart Failure Guideline. It provides specific advice to help guide practitioners through clinical decision making. DATA SOURCES: Data were obtained from English-language studies and referenced in MEDLINE or EMBASE between 1966 and 1993. We used the search terms heart failure, congestive; congestive heart failure; heart failure; cardiac failure; and dilated cardiomyopathy in conjunction with terms for the specific treatments. Where data were lacking, we relied on opinions of panel members and peer reviewers. STUDY SELECTION: Only large prospective trials were used to estimate treatment efficacy. Smaller trials, case series, and case reports were reviewed for the incidence of adverse effects. DATA EXTRACTION AND SYNTHESIS: Randomized clinical trials were reviewed for inclusion and exclusion criteria, patient outcomes, adverse effects, and eight categories of study quality using a defined list of study flaws. CONCLUSION: Angiotensin-converting enzyme (ACE) inhibitors should be given to all patients unless specific contraindications exist. Diuretics should be used judiciously early in treatment to prevent excessive diuresis that could prevent titration of ACE inhibitors to target doses. Digoxin has not been shown to affect the natural history of heart failure and should be reserved for patients who remain symptomatic after treatment with ACE inhibitors and diuretics. Isosorbide dinitrate and hydralazine hydrochloride should be tried in patients who cannot tolerate ACE inhibitors or who have refractory symptoms.
Angiotensin-Converting Enzyme Inhibitors↗
An orally active adenosine A1 receptor antagonist, FK838, increases renal excretion and maintains glomerular filtration rate in furosemide-resistant rats.
1. Loop and thiazide diuretics are common therapeutic agents for the treatment of sodium retention and oedema. However, resistance to diuretics and decreases in renal function can develop during diuretic therapy. Adenosine causes renal vasoconstriction, sodium reabsorption, and participates in the tubuloglomerular feedback mechanism for the regulation of glomerular filtration rate. 2. We tested the hypothesis that the selective adenosine A(1) receptor antagonist FK838 is orally active and causes diuresis and natriuresis, but maintains glomerular filtration rate in normal rats or in rats with furosemide resistance. 3. In normal male Sprague - Dawley rats, FK838 dose-dependently increased urine flow and sodium and chloride excretion while sparing potassium. In combination with furosemide, FK838 enhanced the diuretic and natriuretic actions of furosemide to the same extent as hydrochlorothiazide and did not increase the potassium loss in normal rats. In furosemide-resistant rats, FK838 increased urine flow and electrolyte excretion to a greater extent than hydrochlorothiazide. In addition, hydrochlorothiazide significantly decreased glomerular filtration rate, whereas FK838 maintained glomerular filtration rate in furosemide-resistant rats. 4. This study shows that the adenosine A(1) receptor antagonist FK838 is orally active and causes potent diuresis and natriuresis and maintains glomerular filtration rate in normal or furosemide-resistant rats. Adenosine A(1) receptor antagonists may be novel therapeutics for the treatment of oedema in normal or otherwise diuretic-resistant patients.
Adenosine A1 Receptor Antagonists↗
Continuous infusion versus bolus injection of loop diuretics in congestive heart failure.
BACKGROUND: Loop diuretics, when given as intermittent bolus injections in acutely decompensated heart failure, may cause fluctuations in intravascular volume, increased toxicity and development of tolerance. Continuous infusion has been proposed to avoid these complications and result in greater diuresis, hopefully leading to faster symptom resolution, decrease in morbidity and possibly, mortality. OBJECTIVES: To compare the effects and adverse effects of continuous intravenous infusion of loop diuretics with those of bolus intravenous administration among patients with congestive heart failure Class III-IV. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003) and the HERDIN database. We also contacted pharmaceutical companies. SELECTION CRITERIA: Randomized controlled trials comparing the efficacy of continuous intravenous infusion versus bolus intravenous administration of loop diuretics in congestive heart failure were included DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed study eligibility, methodological quality and did data extraction. Included studies were assessed for validity. Authors were contacted when feasible. Adverse effects information was collected from the trials. MAIN RESULTS: Eight trials involving 254 patients were included. In seven studies which reported on urine output, the output (as measured in cc/24 hours) was noted to be greater in patients given continuous infusion with a weighted mean difference (WMD) of 271 cc/24 hour (95%CI 93.1 to 449; p<0.01). Electrolyte disturbances (hypokalemia, hypomagnesemia) were not significantly different in the two treatment groups with a relative risk (RR) of 1.47 (95%CI 0.52 to 4.15; p=0.5). Less adverse effects (tinnitus and hearing loss) were noted when continuous infusion was given, RR 0.06 (95%CI 0.01 to 0.44; p=0.005). Based on a single study, the duration of hospital stay was significantly shortened by 3.1days with continuous infusion WMD -3.1 (95%CI -4.06 to -2.20; p<0.0001) while cardiac mortality was not significantly different in the two treatment groups, RR 0.47 (95% CI 0.33 to 0.69; p<0.0001). Based on two studies, all cause mortality was not significantly different in the two treatment groups, RR 0.52 (95%CI 0.38 to 0.71; p<0.0001). REVIEWER'S CONCLUSIONS: Currently available data are insufficient to confidently assess the merits of the two methods of giving intravenous diuretics. Based on small and relatively heterogenous studies, this review showed greater diuresis and a better safety profile when loop diuretics were given as continuous infusion. The existing data still does not allow definitive recommendations for clinical practice and larger studies should be done to more adequately settle this issue.
Diuretics↗
Continuous infusion versus bolus injection of loop diuretics in congestive heart failure.
BACKGROUND: Loop diuretics, when given as intermittent bolus injections in acutely decompensated heart failure, may cause fluctuations in intravascular volume, increased toxicity and development of tolerance. Continuous infusion has been proposed to avoid these complications and result in greater diuresis, hopefully leading to faster symptom resolution, decrease in morbidity and possibly, mortality. OBJECTIVES: To compare the effects and adverse effects of continuous intravenous infusion of loop diuretics with those of bolus intravenous administration among patients with congestive heart failure Class III-IV. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003) and the HERDIN database. We also contacted pharmaceutical companies . SELECTION CRITERIA: Randomized controlled trials comparing the efficacy of continuous intravenous infusion versus bolus intravenous administration of loop diuretics in congestive heart failure were included DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed study eligibility, methodological quality and did data extraction. Included studies were assessed for validity. Authors were contacted when feasible. Adverse effects information was collected from the trials. MAIN RESULTS: Eight trials involving 254 patients were included. In seven studies which reported on urine output, the output (as measured in cc/24 hours) was noted to be greater in patients given continuous infusion with a weighted mean difference (WMD) of 271 cc/24 hour (95%CI 93.1 to 449; p<0.01). Electrolyte disturbances (hypokalemia, hypomagnesemia) were not significantly different in the two treatment groups with a relative risk (RR) of 1.47 (95%CI 0.52 to 4.15; p=0.5). Less adverse effects (tinnitus and hearing loss) were noted when continuous infusion was given, RR 0.06 (95%CI 0.01 to 0.44; p=0.005). Based on a single study, the duration of hospital stay was significantly shortened by 3.1days with continuous infusion WMD -3.1 (95%CI -4.06 to -2.20; p<0.0001) while cardiac mortality was significantly different in the two treatment groups, RR 0.47 (95% CI 0.33 to 0.69; p<0.0001). Based on two studies, all cause mortality was significantly different in the two treatment groups, RR 0.52 (95%CI 0.38 to 0.71; p<0.0001). AUTHORS' CONCLUSIONS: Currently available data are insufficient to confidently assess the merits of the two methods of giving intravenous diuretics. Based on small and relatively heterogenous studies, this review showed greater diuresis and a better safety profile when loop diuretics were given as continuous infusion. The existing data still does not allow definitive recommendations for clinical practice and larger studies should be done to more adequately settle this issue.
Heart Failure↗
ICI 181,037: a novel eukalemic diuretic with antiarrhythmic activity.
ICI 181,037, the most active compound from a series of 1,1-diarylcarbin-1-ol-2 amines, was evaluated for diuretic and cardiovascular activity. In saline-loaded rats, the magnitude of water diuresis and saluresis produced by ICI 181,037 (10 mg/kg, p.o.) was equal to that of hydrochlorothiazide. Water diuresis and saluresis produced by ICI 181,037 were enhanced with SKF 525A, ampicillin or neomycin plus lincomycin, suggesting that ICI 181,037 is an active diuretic. In conscious dogs, the saluretic activity of ICI d-181,037 (5 mg/kg, p.o.) was about 80% of the corresponding hydrochlorothiazide value, whereas the l-isomer demonstrated only minimum saluretic activity. In both rats and dogs, the concurrent kaliuresis after ICI 181,037 or its enantiomers was minimal as compared to hydrochlorothiazide. Following chronic dosing with diuretic doses, the basal levels of plasma potassium in dogs were not altered. In amphibian in vitro models for mimicking mammalian nephron, ICI 181,037 and its enantiomers demonstrated antinatriferic and antichloriferic activities, suggesting multiple renal sites of action for this agent. Racemic ICI 181,037 and its isomers reversed ouabain-induced arrhythmia in dogs and/or reduced the ouabain-induced mortality in mice after intravenous administration. It is concluded that ICI 181,037, particularly its d-isomer, is a novel eukalemic diuretic and possesses antiarrhythmic activity.
Acetamides↗
Neuropeptide Y-enhanced diuresis and natriuresis in anaesthetized rats is independent of renal blood flow reduction.
1. Neuropeptide Y (NPY) has been reported to enhance diuresis and natriuresis in anaesthetized rats although it is a potent renal vasoconstrictor in vitro in vivo in several species. Therefore, we have investigated anaesthetized rats to see whether reduction in renal blood flow (RBF) and enhancement of diuresis and natriuresis can occur concomitantly, and how diuresis and natriuresis might be enhanced despite reduced RBF. 2. Systemic or intrarenal NPY infusion (0.03-3 micrograms kg-1 min-1) had only a small effect on mean arterial pressure (maximal increase 15-20 mmHg) and heart rate (maximal decrease 30 beats min-1) but dose-dependently reduced RBF (maximal peak reduction 3 ml min-1) Endogenous creatinine clearance was not significantly altered. 3. In anaesthetized rats systemic infusion of 1 or 3 micrograms kg-1 min-1 NPY enhanced urine formation and sodium and calcium excretion by a maximum of 110, 110 and 45%, respectively, but did not alter potassium excretion. Enhancement of diuresis was also detectable in conscious rats. 4. The diuretic and natriuretic effects of systemically infused NPY were at least partly maintained in rats with decapsulated kidneys and in rats where NPY-induced increase of renal perfusion pressure was excluded mechanically by an adjustable clamp placed on the abdominal aorta. 5. Intrarenal infusion of 0.3 or 1 microgram kg-1 min-1 NPY reduced RBF to a greater extent than systemic infusion (maximal peak reduction 4 ml min-1) but caused a smaller enhancement or even a reduction of urine formation and sodium excretion. 6. We conclude that systemic infusion of NPY reduces RBF by a direct effect on the renal vasculature. Systemic NPY infusion enhances urine formation and sodium and calcium excretion. This occurs independently (at least in part) of pressure natriuresis by formation and/or release of an extrarenal factor which might act on distal tubules and/or collecting ducts.
Anesthesia, General↗
Diabetes and diuretic-induced alterations in function of rat urinary bladder.
Studies were done to characterize the bladder dysfunction associated with diabetes mellitus and to distinguish between changes occurring from increased diuresis and autonomic neuropathy. Four experimental conditions were compared: control, 4-wk-streptozocin-induced diabetes, sucrose feeding (diuretic), and galactose feeding (diuretic and sugar alcohol). A 10-fold increase in urine output and 25-50% increases in bladder weight, protein content, and DNA content were observed in all noncontrol treatment groups. Compliance properties were studied by measuring the intravesicular pressure as the bladder was infused with buffer in vitro. All treated bladders exhibited a reduction in plateau pressure and an increase in fluid capacity. Thus, diuresis results in an increased bladder size, which correlates with an alteration of compliance properties. Nervous system control in anesthetized rats was examined by monitoring contractions as the bladder was infused with buffer. Three distinct patterns of response were observed: normal, diabetic, and diuretic (galactose and sucrose treatments). The difference between responses in diuretic and diabetic animals suggests the presence of a diabetes-induced alteration in nerve regulation of the bladder. Reserpine pretreatment of control or diuretic models produced marked changes in the pattern of contractions, whereas pretreatment of diabetic rats had only modest effects. This suggests that diabetic bladders were lacking sympathetic control before the drug treatment. When rats treated for 4 wk with galactose were removed from this diet for 4 wk before testing, the bladders responded similarly to controls. This observation, coupled with the fact that galactose did not produce the same response as diabetes in the in vivo experiment, suggests that the galactose model does not produce irreversible functional neuropathies.
Animals↗
Changing strategies in the management of heart failure.
Forty years ago therapy for congestive heart failure was limited largely to the mercurial diuretics and a variety of cardiac glycoside preparations; these were often ineffective, and the common practice of "pushing" digitalis caused serious, sometimes lethal side effects. Today, a more complete understanding of the regulation of cardiac work and pathophysiology of heart failure is having a profound impact on therapeutic strategy for this common condition. Despite more powerful means to augment myocardial contractility and much more effective diuretics, therapy that relies only on inotropic stimulation and diuresis is no longer optimal for the majority of patients with heart failure. Thus, strategies for the therapy of heart failure must take into account new understanding of mechanisms that initiate, perpetuate and exacerbate the hemodynamic and myocardial abnormalities in these patients. Recognition of the detrimental effects of excessive afterload and the importance of relaxation (lusitropic) as well as contraction (inotropic) abnormalities has led to widespread acceptance of vasodilator therapy, which has dramatically improved our ability to alleviate the symptoms of heart failure. Changes that result from altered gene expression in the hypertrophied myocardium of patients with congestive heart failure can give rise to a cardiomyopathy of overload that, although initially compensatory, may hasten death. These and other advances in our understanding of the pathophysiology, biochemistry and molecular biology of heart failure provide a basis for new therapeutic strategies that can slow the progressive myocardial damage that causes many of these patients to die, while at the same time improving well-being in patients with congestive heart failure.
Cardiotonic Agents↗