Intermittent dobutamine hydrochloride infusions in outpatients with chronic congestive heart failure

Patients with severe chronic congestive heart failure were treated with intermittent dobutamine hydrochloride infusions administered on an outpatient basis with a portable infusion device. Eleven patients (eight women and three men), ages 28-71 years, were given initial dobutamine hydrochloride infusions at a rate of 1-2 micrograms/kg/min, and the dose was gradually increased to a maximum dose of 15 micrograms/kg/min. Patients were considered dobutamine responders if their cardiac output increased by at least 30% and pulmonary-capillary wedge pressure did not rise. After a sustained hemodynamic response was demonstrated, the infusion was discontinued to assess the patients' symptoms during drug-free intervals. The patients were instructed and trained in proper catheter care after a venous-access catheter was surgically implanted. Patients were also shown how to use the ambulatory infusion pump. The patients were treated with long-term intermittent dobutamine hydrochloride infusions for 3-24 months. All patients adjusted easily to the routine of catheter and pump care and drug administration. The mean dose of dobutamine hydrochloride resulting in the maximum improvement in cardiac index was 9.4 micrograms/kg/min. All patients observed an improvement in their symptoms of congestive heart failure during the drug infusions and the intervals between the infusions. There was a mean reduction of 1.2 in New York Heart Association functional class. There were 18 congestive heart failure-related hospital readmissions among the 11 patients during 108 cumulative months of long-term dobutamine therapy. The intermittent administration of dobutamine hydrochloride via a portable infusion system appears to have improved the functional capacity of the 11 patients studied. This may be a viable treatment alternative for selected ambulatory patients with severe heart failure who demonstrate hemodynamic improvement with dobutamine.     

Use of beta-adrenergic blocking agents in congestive heart failure

The use of beta-adrenergic blocking agents in patients with congestive heart failure (CHF) is reviewed. The sympathetic nervous system plays an important compensatory role in maintaining inotropic support of the failing heart; therefore, beta blockers have long been considered contraindicated in CHF patients. However, prolonged excessive activation of the sympathetic nervous system may be detrimental. Several clinical trials have shown improved functional status and hemodynamic indices in some patients with dilated cardiomyopathy who received beta blockers. The maximum effect required up to 12 months. Two studies also showed trends toward improved survival. Aspects of study design that appear to be associated with the observation of a favorable response to beta blockade in CHF patients are a low initial dosage, gradual adjustment of the dosage, and a sufficient duration of therapy. Trials with unfavorable results lacked one or more of those design characteristics. Mechanisms proposed to underlie the beneficial effects of beta blockers in CHF patients include up-regulation of beta-receptors, reduction in cardiac energy requirements, protection of the myocardium against norepinephrine toxicity, and anti-arrhythmic effects. Most studies were conducted in patients with idiopathic dilated cardiomyopathy; it is unknown whether beta-blocker therapy is equally beneficial in patients with CHF arising from other causes. Metoprolol is the agent for which there is the most experience; comparative efficacy trials have not been conducted. Beta-adrenergic blockers appear to be beneficial in some patients with CHF. Further trials are needed to identify the patients most likely to respond and the drugs most likely to work.     

硝酸甘油微量注射器持续泵注治疗重症充血性心力衰竭临床观察

目的：观察治疗重症充血性心力衰竭（CHF）的疗效方法。方法：选择50例充血性心力衰竭心功能Ⅲ～Ⅳ级住院患者,均进行病因和对症治疗并按CHF常规处理,包括低盐饮食,在应用洋地黄、利尿剂和血管紧张素转换酶抑制剂（ACEI）的基础上,应用硝酸甘油微量注射器以2～7mg/h持续泵注,连续7d。动态观察血压、临床症状、体征。结果：治疗1周后,总有效率为94%。结论：硝酸甘油注射液可有效治疗重症CHF,能明显改善患者心脏功能,短期应用副作用少、安全性好。     

Effects of prazosin, SGB-1534, dobutamine and isoproterenol on congestive heart failure in dogs

Effects of prazosin, dobutamine, isoproterenol and SGB-1534, a new alpha-blockade, on congestive heart failure (CHF) in dogs were investigated. The model was made by protease injection into the left ventricular free wall, saline loading, and dextran and methoxamine infusions. By this maneuver, left atrial pressure (LAP), systemic vascular resistance (SVR) and left ventricular end-diastolic pressure (LVEDP) were markedly increased, aortic blood flow (AoBF) was decreased, and systemic blood pressure was unchanged. In this model, the intravenous administration of prazosin (0.1 approximately 10.0 micrograms/kg, i.v.) increased AoBF and decreased LAP in a dose-dependent manner. The improvement of the CHF by prazosin was considered to result from its vasodilating action. SGB-1534 (0.1 approximately 10.0 micrograms/kg, i.v.) improved the CHF mainly through its vasodilating and positive inotropic actions, which is because SGB-1534 decreased SVR and increased Vmax. The magnitudes of vasodilation by SGB-1534 was greater than those by prazosin. These data indicate that SGB-1534 is useful in the treatment of CHF. Both dobutamine (5 approximately 100 micrograms/kg, i.v.) and isoproterenol (0.001 approximately 0.1 micrograms/kg, i.v.) improved the CHF through their vasodilating and positive inotropic actions in the canine CHF. The ratio of positive inotropism/vasodilation was greater for dobutamine than isoproterenol. The vasoconstriction by the large dose of dobutamine might participate in this difference between dobutamine and isoproterenol.     

Bumetanide in congestive heart failure

Summary

Bumetanide, a new diuretic exerting its major effect on the ascending limb of the loop of Henle, was evaluated in 20 patients with congestive heart failure. Dosage ranged from 1 mg to 3 mg daily depending on the patient's condition. The results after 3 and 8 days' treatment showed that bumetanide caused a significant diuresis, an increased excretion of sodium, potassium and chloride, and a comparable fall in the serum levels of these electrolytes. Changes in electrolyte levels were directly related to the dose of the drug. The resultant hypochloraemia was accompanied by a slight metabolic alkalosis.

A comparative crossover study between placebo, bumetanide and frusemide using equipotent doses was performed in 10 patients. Both drugs had a similar effect upon water excretion and the serum and urinary electrolytes.     

beta-Blockers in congestive heart failure

Recent advances in the understanding of the basic mechanisms underlying congestive heart failure (CHF) have focused on the role of neurohormonal activation. Chronic adrenergic overstimulation is directly toxic to myocardial cells, impairs function, causes peripheral vasoconstriction and may induce programmed cell death via apoptosis. beta-Adrenergic blockade can interrupt this pathological process. Accumulating evidence now points to a clear role for beta-blocking agents in the management of heart failure, reducing both the morbidity and mortality associated with CHF. This report will review the recent clinical trials supporting the use of beta-blockers in CHF, briefly highlight some practical considerations in the use of these drugs in patients with CHF and discuss several areas of controversy in which further study is needed.     

Pharmacotherapy of congestive heart failure

A survey is given of the currently used therapeutics in the treatment ot chronic congestive heart failure. Symptomatic treatment is usually performed along the following lines: rest, sodium and fluid restriction to unload the decompensating heart, loop diuretics, angiotensin-converting enzyme inhibitors or other vasodilators; inotropic agenls to improve the heart's mechanical performance; attempts to counteract the neuro-endocrine compensatory mechanisms, that is the activated sympathetic nervous and renin-angiotensin aldosterone systems, as well as the rise in vasopressine levels. New insights have been obtained in the effects of cardiac glycosides, which are probably rather based on counteracting the elevated sympathetic neuronal activity than on their weak and uncertain inotropic action. Angiotensin-converling enzyme inhibitors are probably more effective than classical vasodilators owing to their additional interaction with the neuro-endocrinc compensatory mechanisms. Ibopamine, a prodrug of epinine, appears to be rather a vasodilator and antagonist of the neuro-endocrine compensatory mechanisms than an inotropic agent. The most important clinical trials addressing the efficacy and adverse reactions to the various aforementioned therapeutics are discussed. New, experimental approaches in the drug treatment of chronic congestive heart failure include -blockers, calcium antagonists, vasopressin antagonists and inhibitors of atrial natriuretic peptide degradation.     

Treatment of congestive heart failure

Abstract: The past decade has improved our understanding of the pathophysiological mechanisms underlying the congestive heart failure syndrome. The same decade has seen a considerable expansion in modes of therapy for this syndrome. A review of the present forms of treatment is given.     

多巴酚丁胺与硝酸甘油联用治疗妊娠合并心衰临床观察

目的观察多巴酚丁胺和硝酸甘油联合应用治疗妊娠合并心衰的疗效。方法将60例妊娠合并心衰患者分为对照组和治疗组。对照组常规给予强心、利尿等综合处理；治疗组在此治疗基础上加用多巴酚丁胺60mg和硝酸甘油5～10mg，加入5％葡萄糖液250ml，静脉滴注，滴速为15滴／分，疗程3～7d。观察血流动力学指标及临床症状的变化情况。结果治疗组各项观察指标(CD、EF、AD、E／A)及临床症状有明显改变。结论常规抗心衰药物治疗基础上加用多巴酚丁胺和硝酸甘油可明显改善患者的心功能及临床症状，能较安全地行剖宫产术。     

Magnesium deficiency in congestive heart failure

Abstract: In congestive heart failure several compensatory mechanisms are operating, and may cause severe disturbances of both the internal and external electrolyte balance. The medical treatment prescribed in congestive heart failure also leads to changes in the handling of electrolytes. These combined effects may prove critical to the patient, especially with regard to the emergence of cardiac arrhythmias.     

Aldosterone antagonists in congestive heart failure

The role of aldosterone in the pathophysiology of congestive heart failure (CHF) has long been recognized. The recent RALES (Randomized Aldactone Evaluation Study) trial demonstrated early reduction in morbidity and mortality using spironolactone, an aldosterone receptor antagonist, in combination with angiotensin converting enzyme (ACE) inhibitor and loop diuretic, in patients with heart failure. This effect of spironolactone highlighted the importance of understanding the contributions of the renin-angiotensin-aldosterone system (RAAS) in the progression of CHF, and increased interest in the use of aldosterone antagonists. While ACE inhibitors have had the largest impact on adverse events in CHF, numerous studies have shown that these drugs fail to completely suppress aldosterone. Blocking the effects of residual aldosterone has now been demonstrated to affect prognosis in these patients. This review will discuss the role of aldosterone in the pathophysiology of CHF, with an emphasis on both known and potential therapeutic benefits of aldosterone antagonism.     

Intravenous captopril in congestive heart failure

Hemodynamic and neurohumoral effects of intravenous captopril were studied in ten patients with severe chronic congestive heart failure (NYHA Functional Class III and IV). Incremental bolus doses of captopril, titrated to a maximum cumulative dose of 15 mg, were given at 10-minute intervals. Systemic arterial pressure, mean pulmonary capillary wedge pressure, systemic vascular resistance, mean pulmonary artery pressure, and heart rate decreased (P less than .05). Cardiac index and stroke volume index increased (P less than .05). Maximum hemodynamic effects occurred after cumulative doses of 7 mg and were seen within 30 minutes after initiation of therapy; responses persisted for 30-90 minutes after the last dose. Plasma renin activity increased, and plasma atrial natriuretic factor concentration decreased. No adverse effects were observed with the use of intravenous captopril. Thus, intravenous captopril produces rapid and favorable hemodynamic improvement in advanced heart failure patients.     

左旋多巴治疗充血性心力衰竭

左旋多巴０．２５－０．７５ｇ，ｐｏ，ｔｉｄ治疗４２例（男性２５例，女性１７例，年龄５４±ｓ１３ａ）充血性心力衰竭病人，４ｗｋ为一个疗程。结果，临床显效率为６２％，总有效率为９０％。二维超声心动图测定心功能（ＣＯ、Ｃｌ、ＥＦ）改善，心脏Ｘ线正位片心胸比率缩小，与治疗前比较均有显著性差异（Ｐ＜０．０５），不良反应小。     

Perindopril: in congestive heart failure

Perindopril is a long-acting ACE inhibitor, acting through its only active metabolite perindoprilat. It inhibits the renin-angiotensin system by preventing both the conversion of angiotensin I to angiotensin II and the degradation of bradykinin, thereby reducing the vasoconstriction and left ventricular remodelling characteristic of heart failure. Perindopril 4mg significantly improved a range of haemodynamic parameters in single-dose and long-term (8 weeks and 3 months) studies involving patients with congestive heart failure (CHF), with little or no effect on blood pressure or heart rate. In randomised, double-blind, placebo-controlled clinical trials conducted over 3 months and a large noncomparative study (up to 30 months), perindopril 4mg once daily significantly increased exercise tolerance and reduced symptoms of heart failure in patients with mild to moderate CHF. Perindopril 4mg once daily is generally well tolerated in patients with mild to moderate CHF. In a large noncomparative study the most commonly reported adverse clinical event was cough, which led to 2.8% of patients discontinuing treatment. In short-term comparative trials there was a significantly lower incidence of first-dose hypotension following the recommended starting dose of perindopril 2mg than after the equivalent starting doses of captopril, enalapril and lisinopril.     

Hemodynamic effects of a constant intravenous infusion of piroximone in patients with severe congestive heart failure

The hemodynamic effects and serum levels of piroximone (MDL 19,205), a new inotropic agent with vasodilating properties, were measured in 10 patients with chronic severe congestive failure during a constant 48-h infusion. The initial five patients (group A) received piroximone at 10 micrograms/kg/min; however, because a sustained increase in heart rate greater than or equal to 25% from baseline developed in two patients and an episode of paroxysmal supraventricular tachycardia developed in another, the last 5 patients (group B) received an 8 micrograms/kg/min infusion. Because the steady-state hemodynamic alterations of group A prior to the onset of tachyarrhythmias were similar to those of group B, these results were combined. A significant increase in cardiac output from 3.65 +/- 0.31 (SE) to 5.20 +/- 0.49 L/min and decrease in pulmonary capillary wedge pressure (27 +/- 2 to 20 +/- 2 mm Hg), right atrial pressure (18 +/- 2 to 11 +/- 2 mm Hg), and systemic vascular resistance (1811 +/- 172 to 1293 +/- 80 dynes.s.cm-5) occurred (all p less than 0.05) without a significant change in mean arterial pressure. The peak plasma piroximone level was lower in the eight patients who did not develop a sustained increase in heart rate greater than or equal to 25% above baseline (2.1 +/- 0.5 micrograms/ml; range 1.6-2.9 micrograms/ml) than in the two who did (5.0 and 5.8 micrograms/ml). The latter two patients had the highest serum creatinine levels in the study population.(ABSTRACT TRUNCATED AT 250 WORDS)