ISSN:0268-4705    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:0268-4705    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

There have been tremendous advances in our understanding of the pathophysiology of congestive heart failure, and this has led to improvements in its treatment. Nonetheless, the prevalence of congestive heart failure and the associated mortality and morbidity continue to increase. Hence, there remains a need for additional therapeutic approaches that will complement current management with diuretics, angiotensin-converting enzyme inhibitors, other vasodilators, and digoxin. This article reviews a number of potential avenues that are currently being evaluated or remain targets for future investigation. Given our current understanding of the mechanisms of progression of left ventricular dysfunction, therapies that limit neurohormonal activation or interfere with its consequences and those that improve the balance between myocardial energy requirements and supply appear to be the most promising. Agents that improve hemodynamics without altering the underlying pathophysiology may produce short-term symptomatic improvement but have limited potential to alter the natural history of congestive heart failure. Positive inotropic therapies probably fall into this category, but most of these also appear to accelerate progression and increase mortality. In the long-term, specific interventions that reverse changes at the cellular and molecular level offer the greatest promise.

ISSN:0268-4705    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

We review recent publications that use molecular and cellular biology to explore the diagnosis and treatment of cardiovascular diseases that have relevance to heart failure. Familial hypertrophic cardiomyopathy has now been shown to be due to mutations not only in the previously described β myosin heavy chain gene, but also in the troponin T and α-tropomyosin genes, thus providing some symmetry to the idea that this is a molecular disease of the sarcomere. The basis for a type of familial dilated cardiomyopathy without substantial skeletal muscle involvement, caused by a mutation in the dystrophin gene, has been explored. However, by-and-large, the disease basis for most patients with dilated cardiomyopathy remains a molecular mystery. The role of a polymorphism in the angiotensin-converting enzyme gene was examined as a risk factor for a number of cardiovascular diseases. In animal models, the hypothesis that the devolution from hypertrophy to heart failure includes alterations in the molecular direction of extracellular matrix production gained some support. The experimental foundation was laid this year for the concept of and approach to cardiomyocytoplasty—the molecular and cellular treatment of heart failure by augmentation, repair, or replacement of cardiac myocytes—by experiments in cardiac gene transfer and transgenic animals. Gene causes and cures for restenosis after angioplasty garnered considerable attention. As we gain greater understanding of the molecular basis for disease, we will also have to increase our wisdom in the application of genetic testing.

ISSN:0268-4705    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Many studies published in 1994 significantly added to our understanding of the pathophysiology of heart failure at the cellular and subcellular level. This field continues to advance using different but complementary approaches. One approach is to study human myocardium, thereby providing data that is directly relevant to clinical disease. Another approach is to study mouse myocardium, taking advantage of transgenic technology to alter gene expression and directly study cause-and-effect relationships. Additionally, other animal models of heart failure (eg, pressure overload, volume overload, and paced tachycardia) continue to provide important information. Abnormalities of calcium cycling, myofilament sensitivity to calcium, cross-bridge kinetics, the myocyte cytoskeleton, and energetics have all been observed in animal models or failing human myocardium. The cellular and molecular basis for these abnormalities is now being explored. This understanding is essential for developing novel treatment strategies that may one day include gene therapy.

ISSN:0268-4705    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

A number of animal models have been developed to study both the pathophysiology of heart failure and new therapeutic approaches to this complex syndrome. The most widely used preparations today are the models of rapid ventricular pacing in the dog and myocardial infarction in the rat. Other common approaches include surgically induced pressure or volume overload and toxic myocardial depression. There is no ideal animal model that both perfectly imitates human heart failure and is technically feasible in the laboratory. Each model has advantages and specific limitations, and extrapolations from experimental to clinical heart failure therefore require critical evaluation. Still, animal models have provided new insights into many aspects of the complex pathophysiology of this syndrome and have helped to investigate the efficacy of new therapeutic interventions.

ISSN:0268-4705    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The field of congestive heart failure continues to be vigorously investigated at both the basic science level and in the clinic. As we move from the “hemodynamic” to the “neurohormonal” model of heart failure, more emphasis is being placed on interruption of neurohormone activity as a therapeutic strategy. A number of important clinical trials have been reported in the past year that underscore the potential of using drugs to inhibit neuroendocrine activity. The ultimate neuroendocrine inhibitors are perhaps the P-adrenergic blocking drugs. They have yet to be adequately studied in a statistically powerful, randomized, placebo-controlled multicenter trial. Such a trial is about to begin in North America. In the meantime, numerous studies continue to confirm manifestations of neurohormone imbalance in clinical heart failure. Reduced heart rate variation has been under intensive investigation. A great variety of animal models of heart failure are also currently being studied. Perhaps more important advances have been made in the treatment of patients with heart failure than in any other field in internal medicine in recent years. However, improved patient survival tends to further increase the overall cost of patient care. Perhaps we are simply shifting the patient population, extending survival by 9 to 18 months. More advanced heart failure is more expensive to care for. It is only through understanding the basic biology and pathophysiology of heart failure that fresh new ideas will emerge leading to earlier therapy and, ultimately, prevention of this important disorder.

ISSN:0268-4705    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Chronic heart failure is associated with neurohumoral activation and alterations of the peripheral circulation and skeletal muscle. Several mechanisms are involved in the impaired peripheral perfusion, including increased sympathetic tone and increased vascular stiffness. Recently, data have suggested an important role of the endothelium for perfusion of skeletal muscle in heart failure. Endothelium-dependent dilation of resistance vessels is blunted in patients with severe chronic heart failure. Conceivably, this abnormality may be involved in the impaired reactive hyperemia seen in patients with chronic heart failure. In conductance vessels, flow-dependent dilation is attenuated in patients with chronic heart failure as compared with normal subjects, indicating endothelial dysfunction of large conduit vessels. Dysfunctional endothelium may contribute to impaired tissue perfusion in heart failure. Beyond an impairment of perfusion, skeletal muscle itself is altered in chronic heart failure. The metabolic abnormalities of skeletal muscle in patients with heart failure do not result from inadequate O2 delivery, but from inadequate O2 utilization by mitochondria, consistent with previous findings that the oxidative capacity of mitochondria in skeletal muscle is reduced. It appears that the impaired muscular endurance in heart failure is related to an enhanced glycolytic metabolism secondary to the reduced oxidative capacity of skeletal muscle. The observed low muscular strength appears to be due to a smaller muscle cross-sectional area. Despite successful heart transplantation, only partial improvement of bioenergetic abnormalities was noted in patients 15 months after heart transplantation.

ISSN:0268-4705    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Ventricular arrhythmias are a common problem in patients with heart failure and are an important cause of sudden death. Sustained ventricular arrhythmias are due either to reentry in an old infarct scar, bundle branch reentry, or the electrophysiologic abnormalities that accompany heart failure and hypertrophy. In animal models, ventricular hypertrophy that accompanies heart failure increases susceptibility to polymorphic ventricular tachycardias. Patients resuscitated from a sustained ventricular arrhythmia have a high risk of recurrence. Antiarrhythmic drug toxicity and inefficacy are increased in heart failure. Amiodarone or an implantable defibrillator are the first-line options, and have not been directly compared. Amiodarone appears to be the safest antiarrhythmic drug for treatment of nonsustained arrhythmias and atrial fibrillation. In one randomized trial, amiodarone improved survival in patients with advanced heart failure.

ISSN:0268-4705    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The appreciation that congestive heart failure is not merely a disorder of myocardium has led to a substantial alteration in the treatment of this disease. The use of angiotensin-converting enzyme inhibitors is increasing as their well-demonstrated mortality and symptomatic benefits become better publicized and known. Although diuretics and digoxin continue to remain standard additions to angiotensin-converting enzyme inhibitors for the therapy of congestive heart failure, investigations of these and other agents continue. For example, acceptance of p-blockade as a potentially beneficial therapeutic intervention increased in the past year with the publication of the Cardiac Insufficiency Bisoprolol Study (CIBIS), the largest controlled trial to date. Similarly, survival studies of vasodilators and positive inotropic agents such as vesnarinone are ongoing. Even the effects of exercise in severely ill patients (who were previously advised to be sedentary) are being studied. With the understanding that heart failure is a systemic disease and that controlled trials are needed because many of our assumptions prove to be incorrect, we can expect continued improvement in the management of heart failure.

ISSN:0268-4705    

出版商:OVID    

年代:1995

数据来源: OVID