Benefit In Congestive Heart Failure Research Articles

Expatiating the Pharmacological and Nanotechnological Aspects of the Alkaloidal Drug Berberine: Current and Future Trends

Traditionally, herbal compounds have been the focus of scientific interest for the last several centuries, and continuous research into their medicinal potential is underway. Berberine (BBR) is an isoquinoline alkaloid extracted from plants that possess a broad array of medicinal properties, including anti-diarrheal, anti-fibrotic, antidiabetic, anti-inflammatory, anti-obesity, antihyperlipidemic, antihypertensive, antiarrhythmic, antidepressant, and anxiolytic effects, and is frequently utilized as a traditional Chinese medicine. BBR promotes metabolisms of glucose and lipids by activating adenosine monophosphate-activated protein kinase, stimulating glycolysis and inhibiting functions of mitochondria; all of these ameliorate type 2 diabetes mellitus. BBR has also been shown to have benefits in congestive heart failure, hypercholesterolemia, atherosclerosis, non-alcoholic fatty liver disease, Alzheimer’s disease, and polycystic ovary syndrome. BBR has been investigated as an interesting pharmacophore with the potential to contribute significantly to the research and development of novel therapeutic medicines for a variety of disorders. Despite its enormous therapeutic promise, the clinical application of this alkaloid was severely limited because of its unpleasant pharmacokinetic characteristics. Poor bioavailability, limited absorption, and poor water solubility are some of the obstacles that restricted its use. Nanotechnology has been suggested as a possible solution to these problems. The present review aims at recent updates on important therapeutic activities of BBR and different types of nanocarriers used for the delivery of BBR in different diseases.

DITPA (3,5-Diiodothyropropionic Acid), a Thyroid Hormone Analog to Treat Heart Failure

In animal studies and a pilot trial in patients with congestive heart failure, the thyroid hormone analog 3,5 diiodothyropropionic acid (DITPA) had beneficial hemodynamic effects. This was a phase II multicenter, randomized, placebo-controlled, double-blind trial of New York Heart Association class II to IV congestive heart failure patients randomized (2:1) to DITPA or placebo and treated for 6 months. The study enrolled 86 patients (n=57 to DITPA, n=29 to placebo). The primary objective was to assess the effect of DITPA on a composite congestive heart failure end point that classifies patients as improved, worsened, or unchanged based on symptom changes and morbidity/mortality. DITPA was poorly tolerated, which obscured the interpretation of congestive heart failure-specific effects. Fatigue and gastrointestinal complaints, in particular, were more frequent in the DITPA group. DITPA increased cardiac index (by 18%) and decreased systemic vascular resistance (by 11%), serum cholesterol (-20%), low-density lipoprotein cholesterol (-30%), and body weight (-11 lb). Thyroid-stimulating hormone was suppressed in patients given DITPA, which reflects its thyromimetic effect; however, no symptoms or signs of potential hypothyroidism or thyrotoxicosis were seen. DITPA improved some hemodynamic and metabolic parameters, but there was no evidence for symptomatic benefit in congestive heart failure.

Regular thermal therapy may promote insulin sensitivity while boosting expression of endothelial nitric oxide synthase – Effects comparable to those of exercise training

Regular thermal therapy, using saunas or hot baths, has the potential to improve impaired insulin sensitivity and boost endothelial expression of the "constitutive" isoform of nitric oxide synthase--effects, analogous to those of aerobic training that should promote vascular health. Previous clinical reports suggest that hot tubs may be beneficial for diabetic control, and that sauna therapy can decrease blood pressure in essential hypertension and provide symptomatic benefit in congestive heart failure. For those who lack ready access to a sauna or communal hot tub, regular hot baths at home may suffice as practical thermal therapy. Thermal therapy might be viewed as an alternative to exercise training in patients too physically impaired for significant aerobic activity.

Eplerenone: a new selective aldosterone receptor antagonist.

Eplerenone is a specific aldosterone receptor antagonist that has been shown to have antihypertensive efficacy and to reduce end-organ manifestations in experimental animal models. Studies in humans have confirmed the blood pressure-lowering efficacy of this agent, as well as providing evidence of benefit in congestive heart failure. The side-effect profile indicates that the specificity of eplerenone for the mineralocorticoid receptor is responsible for the lower incidence of sex hormone- related side-effects than have been seen with other mineralocorticoid receptor blockers. Hyperkalemia is most frequently observed with eplerenone among patients with severe impairment of renal function and in diabetics with microalbuminuria, especially in combination with angiotensin-converting enzyme inhibitors. This agent appears to be a promising and effective new addition for the treatment of hypertension and heart failure with few of the side-effects that have plagued earlier drugs of this class.

Loop Diuretic Absorption

Objectives. The present study was undertaken to determine if direct blockade of angiotensin II receptors by losartan potassium as compared to ACE inhibition might result in greater tolerability in patients with congestive heart failure in whom ACE inhibition resulted in hyperkalemia and azotemia. Background. Blockade of angiotensin II receptors by losartan potassium may produce similar benefits in congestive heart failure as ACE inhibition. However, some observations suggest losartan potassium may have different effects on renal function than ACE inhibition. Methods. Five consecutive patients with severe congestive heart failure were identified in whom treatment with ACE inhibition was complicated by hyperkalemia (K>5.7) and azotemia. In three of these patients losartan potassium was substituted for ACE inhibition while losartan potassium was added to treatment with ACE inhibition in the remaining two. The mean of four serial values of potassium, blood urea nitrogen, and creatinine were compared before and after change in treatment using a two tailed t test. Results. The addition or substitution of losartan potassium resulted in statistically insignificant reductions in blood urea nitrogen and creatinine and a significant reduction in potassium from 5.7±0.1 to 4.9±0.3, p<0.03. Two patients who had required kayexalate were withdrawn. In all patients, hyperkalemia resolved and did not reoccur. Conclusions. There appear to be fundamental differences between the effects of losartan potassium and ACE inhibitors on potassium excretion in congestive heart failure patients with mild to moderate renal insufficiency. Losartan potassium may also be associated with less azotemia in such patients. These differences may have important clinical implications, particularly in the subset of patients in whom ACE inhibition is poorly tolerated as a result of hyperkalemia and azotemia.

Differential effects of direct antagonism of AII compared to ACE inhibitors on serum potassium levels and azotemia in patients with severe congestive heart failure.

OBJECTIVES. The present study was undertaken to determine if direct blockade of angiotensin II receptors by losartan potassium as compared to ACE inhibition might result in greater tolerability in patients with congestive heart failure in whom ACE inhibition resulted in hyperkalemia and azotemia. BACKGROUND. Blockade of angiotensin II receptors by losartan potassium may produce similar benefits in congestive heart failure as ACE inhibition. However, some observations suggest losartan potassium may have different effects on renal function than ACE inhibition. METHODS. Five consecutive patients with severe congestive heart failure were identified in whom treatment with ACE inhibition was complicated by hyperkalemia (K>5.7) and azotemia. In three of these patients losartan potassium was substituted for ACE inhibition while losartan potassium was added to treatment with ACE inhibition in the remaining two. The mean of four serial values of potassium, blood urea nitrogen, and creatinine were compared before and after change in treatment using a two-tailed t test. RESULTS. The addition or substitution of losartan potassium resulted in statistically insignificant reductions in blood urea nitrogen and creatinine and a significant reduction in potassium from 5.7+/-0.1 to 4.9+/-0.3, p<0.03. Two patients who had required kayexalate were withdrawn. In all patients, hyperkalemia resolved and did not reoccur. CONCLUSIONS. There appear to be fundamental differences between the effects of losartan potassium and ACE inhibitors on potassium excretion in congestive heart failure patients with mild to moderate renal insufficiency. Losartan potassium may also be associated with less azotemia in such patients. These differences may have important clinical implications, particularly in the subset of patients in whom ACE inhibition is poorly tolerated as a result of hyperkalemia and azotemia. (c)2000 by CHF, Inc.

Herbs and dietary supplements in the prevention and treatment of cardiovascular disease.

Herbs and dietary supplements can have significant physiological effects. Garlic (Allium sativum) has shown beneficial lipid effects in a majority of trials; dried garlic preparations are superior to oil preparations. There is preliminary evidence that indicates that hawthorn (Crataegus species) may provide benefits in congestive heart failure. Coenzyme Q also may be of benefit in congestive heart failure. Although observational studies indicate a protective effect of dietary or supplemental vitamin E, controlled trails have not shown a beneficial effect on angina and have been mixed on whether supplementation decreases major cardiac events. Although several observational studies have noted that fish intake protects against cardiovascular disease, prospective studies are less impressive. Fish oil supplementation may have a mild beneficial effect on hypertension, but there is no effect on total cholesterol levels. Trials are inconsistent on whether fish oil reduces restenosis rates following coronary angioplasty. Carnitine appears to have beneficial effects on congestive heart failure and angina; there is also preliminary evidence that arginine may benefit patients with congestive heart failure or angina. Herbs and supplements have been associated with adverse effects and interactions; for example, garlic inhibits platelet aggregation and can cause significant anticoagulation, and the Chinese herb danshen (Salvia miltiorrhiza) appears to potentiate warfarin. Several herbs and supplements hold promise as adjuncts in the prevention and treatment of cardiovascular disease. There is a need for definitive research on the potential risks and benefits of these compounds, including appropriate dosages and formulations, and delineation of adverse events and interactions. (c)2000 by CHF, Inc.

More Evidence of Beta-Blockers' Benefit in CHF

Although clinical trials have shown that beta-blockers reduce mortality in patients with congestive heart failure (CHF), acceptance has been slow,

Angiotensin-converting enzyme inhibition as antiatherosclerotic therapy: no answer yet

Angiotensin-converting enzyme inhibitors have proven to be of clinical benefit in congestive heart failure. Whether they also provide benefit to patients with coronary artery disease in the absence of congestive heart failure via an antiatherosclerotic mechanism is a question the QUinapril Ischemic Event Trial quantitative coronary angiography (QCA) study attempted to answer: 1,750 patients with normal left ventricular function who were undergoing coronary angiography and angioplasty were randomized to 20 mg/day of quinapril versus placebo and followed for 3 years for cardiac end points. A randomly selected subgroup of the total cohort underwent follow-up angiography. The primary QCA end point was the categorical designation of progression versus nonprogression, defined either by QCA or by a cardiac event in patients selected for the QCA trial who had no usable follow-up x-ray film. Secondary end points in patients with 2 angiograms were: new stenosis development, change in minimum lumen diameter index, and change in percent diameter stenosis index. There were 119 progressors among 243 placebo-treated patients (49%) and 111 progressors among 234 quinapril-treated patients (47%) (p = NS). There were 44 patients with new stenosis developement in the placebo group (19%) and 50 (22%) in the quinapril group (p = NS). Change in minimum lumen diameter index was −0.21 ± 0.03 mm in the placebo group and −0.18 ± 0.03 mm in the quinapril group (p = NS). Finally, change in percent diameter stenosis index was +5.1 ± 1.0 in the placebo group and +3.5 ± 1.0 in the quinapril group (p = NS). Potential confounders of this trial are presented and discussed.

What is the role of angiotensin-converting enzyme inhibitors in congestive heart failure and after myocardial infarction?

To discuss the controversies surrounding the choice of angiotensin-converting enzyme (ACE) inhibitor, and the timing, dosage, and duration of ACE inhibitor therapy for congestive heart failure (CHF) and after myocardial infarction (MI). The beneficial effects of ACE inhibition in patients with CHF and after MI are reviewed. Human clinical trials are reviewed and their clinical implications are discussed. MEDLINE searches (1985-1995) identified human clinical trials and review articles. Landmark human clinical trials with morbidity and mortality end points were included. The validity of the study data were assessed on the basis of study methods, population characteristics, and statistical power. ACE inhibitors exert beneficial effects in patients with CHF by hemodynamic and neurohormonal mechanisms. The attenuation of ventricular remodeling that occurs with ACE inhibition does not fully explain the results of clinical trials in patients after MI. Routine determination of ejection fraction to guide ACE inhibitor therapy is not as important as the patient's clinical status. Clinicians should titrate the chosen ACE inhibitor on the basis of hemodynamic response to target doses used in major clinical trials. Because the beneficial effects of ACE inhibitors appear to be a class effect, choice of an agent should include cost considerations and the results of clinical trials. ACE inhibitor reduce morbidity and mortality in selected CHF and post-MI patients. Patients with symptomatic CHF benefit most from ACE inhibitor therapy, and it should be continued indefinitely. Treatment effects in asymptomatic patients are delayed. The role of ACE inhibitor therapy in preventing morbidity and morality in asymptomatic patients with preserved ventricular function requires further study.

Fish oil and other nutritional adjuvants for treatment of congestive heart failure

Published clinical research, as well as various theoretical considerations, suggest that supplemental intakes of the ‘metavitamins’ taurine, coenzyme Q 10, and L-carnitine, as well as of the minerals magnesium, potassium, and chromium, may be of therapeutic benefit in congestive heart failure. High intakes of fish oil may likewise be beneficial in this syndrome. Fish oil may decrease cardiac afterload by an antivasopressor action and by reducing blood viscosity, may reduce arrhythmic risk despite supporting the heart's beta-adrenergic responsiveness, may decrease fibrotic cardiac remodeling by impeding the action of angiotensin II and, in patients with coronary disease, may reduce the risk of atherothrombotic ischemic complications. Since the measures recommended here are nutritional and carry little if any toxic risk, there is no reason why their joint application should not be studied as a comprehensive nutritional therapy for congestive heart failure.

Newer concepts in the medical management of patients with congestive heart failure

Congestive heart failure (CHF) remains a major cause of morbidity and mortality in the United States, especially among the elderly. Although an underlying disturbance in cardiac function can be identified in most patients, manifestations of the disease are greatly influenced by other factors, particularly neurohumoral and peripheral adaptive responses which occur secondary to impaired cardiac function. The renin-angiotensin system (RAS) is integrally involved in the pathophysiology of CHF. Originally considered a humoral system, the RAS is now known to exist and operate within cardiac and vascular tissues. The importance of tissue-specific renin-angiotensin systems in CHF is presently under investigation. Most patients with symptomatic CHF benefit from the administration of an ACE inhibitor. Certain asymptomatic patients, such as those with severe left ventricular (LV) dysfunction and those who are at high risk for LV remodeling after anterior wall myocardial infarction, may also benefit from ACE inhibitor therapy. Diuretics and nitrates improve symptoms and often cardiac output in many patients with CHF. Although many new inotropic agents have been tested in CHF patients, none appear clinically superior to digitalis glycosides. The efficacy of digitalis glycosides in CHF may in part result from sympathoinhibitory properties such as the activation of baroreceptor mechanisms. Despite the fact that many CHF patients die from arrhythmias, treatment of asymptomatic ventricular arrhythmias in these patients is not recommended. Patients with symptomatic or sustained ventricular arrhythmias are best treated by a physician experienced in cardiac electrophysiology. Therapy with beta-blocking drugs for CHF patients is controversial. Anticoagulants are recommended for selected patients with CHF. Finally, exercise therapy may improve functional capacity in some patients with CHF through its effects on peripheral blood vessels and skeletal muscle tissues.

Interaction Between Hydralazine and Nitrovasodilators in Vascular Smooth Muscle

The combination of hydralazine and nitrates has been shown to provide long-term benefit in congestive heart failure, despite a nitrate dosage that should induce tolerance. To assess the interactions between hydralazine and nitroglycerin, aortic rings were isolated from male Wistar rats. In rings precontracted with phenylephrine, hydralazine incubation (10 microM and 0.1 mM) potentiated the responses to nitroglycerin (p < 0.05) but not to sin-1 (a direct activator of guanylate cyclase), 8-bromocyclic guanylate monophosphate, and forskolin (an adenylate cyclase activator). In similar conditions, the incubation of isoniazid (0.1 mM, used as a pyridoxal-sequestering agent without direct vasoactive properties) also potentiated the dose-response curve to nitroglycerin (p < 0.05). In aortas isolated from rats rendered nitrate tolerant in vivo (50 mg/kg subcutaneously twice daily during 4 days), hydralazine partially attenuated tolerance (p < 0.05). Our results suggest that the observed interaction between hydralazine and nitroglycerin may involve an inhibition of pyridoxal-dependent reactions, such as the catabolism of methionine and cysteine. This may enhance the availability of sulfhydryl-containing compounds, and therefore potentiate the responses to nitroglycerin.

The effects of 15AU81, a chemically stable prostacyclin analog, on the cardiovascular and renin-angiotensis systems of anesthetized dogs

15AU81 is a chemically stable tricyclic benzindene analog of prostacyclin. Prostaglandins, PGI 2 and PGE 2, and their analogs have demonstrated acute hemodynamic benefit in congestive heart failure. The purpose of this study was to evaluate the cardiovascular effects of 15AU81 in anesthetized dogs in order to assess this agent's potential for clinical study in the treatment of congestive heart failure. Four hour intravenous infusions of 15AU81 at 0.1, 0.3, 1.0, or 3.0 μg/kg/min produced dose-dependent decreases in mean arterial blood pressure of 10%, 43%, 55% and 68% respectively with associated decreases in total peripheral resistance of 20%, 32%, 56% and 73%, respectively. 15AU81 dilated the pulmonary circulation; however, the effects of 15AU81 on the pulmonary vascular bed were not dose dependent and not stable over time. Maximal decreases in mean pulmonary artery blood pressure achieved were 9%, 23%, 22% and 18% with an associated decrease in pulmonary vascular resistance of 9%, 33%, 30% and 23%, at doses of 15AU81 of 0.1, 0.3, 1.0 and 3.0 μg/kg/min respectively. The onset of vasodilator effects were rapid, reaching a maximum within 5–10 min with an equally rapid recovery when the infusion was discontinued. Cardiac and hormonal effects associated with 15AU81 treatment included decreases in inotropy, and lusitropy and increases in heart rate and plasma angiotensin II concentration. The increase in plasma angiotensin II concentrated correlated significantly with the decrease mean arterial blood pressure. These effects are interpreted to be generally secondary to the potent and profound vasodilator activity of 15AU81 and not likely due to direct cardiac or neurohumoral effects. The hemodynamic profile of 15AU81 suggests that, through its rapid onset and ability to reduce loading conditions of the right and left ventricles and its chemical stability over natural prostacyclin, this prostacyclin analog may have utility in the management of chronic congestive heart failure.

β-Blockade Treatment in Heart Failure

The efficacy of treatment with diuretics and vasodilators in heart failure has shown that compensatory mechanisms may induce vicious circles that can precipitate the deterioration of congestive heart failure (CHF). By counteracting sympathetic stimulation of cardiac β-receptors, β-blocing drugs could provide some benefit in CHF. Indeed, the sympathetic stimulation ehances metabolic costs and could lead to a further deterioration of myocardial fiber function. This could be counteracted by β-block-ade. On the contrary, the loss of adrenergic reponsiveness due to β-adrenergic downregulation and depletion of norepinephrine stores from sympathetic nerves could be responsible for the progressive deterioration of cardiac function

Felodipine in severe chronic congestive heart failure: Acute effects on central hemodynamics and regional blood flow distribution

In order to assess the effect of felodipine, a new calcium antagonist with vascular selectivity, on regional blood flow distribution at rest in chronic congestive heart failure, ten patients were studied during an acute test. Right heart catheterization allowed the evaluation of hemodynamic parameters; renal blood flow was calculated using paraamino-hippuric acid clearance; hepatic blood flow measurement was based on indocyanine green clearance; and limb blood flow was assessed with venous occlusion plethysmography. Blood samples were collected for the analysis of plasma catecholamines, renin, and aldosterone. All parameters were recorded in duplicate under basal conditions and after felodipine infusion. The infusion of felodipine induced a significant increase in cardiac index, stroke work index, and limb blood flow. Systemic and pulmonary arterial blood pressure, pulmonary wedge pressure, and systemic resistance underwent a significant decrease. The heart rate, pulmonary resistance, renal blood flow, and hepatic blood flow were not changed. In conclusion, felodipine was of benefit in congestive heart failure at rest in an acute test, acting through a marked decrease in vascular resistance and a consequent improvement in cardiac output and limb blood flow. No changes in renal and hepatic blood flow were observed.

Indoramin Shows Acute Benefit in Congestive Heart Failure

Indoramin Shows Acute Benefit in Congestive Heart Failure