Vasoactive neurohormonal systems (eg, sympathetic nervous system SNS, renin-angiotensin-aldosterone system, and arginine vasopressin AVP) are defense mechanisms designed to preserve arterial volume ...and circulatory homeostasis during periods of low cardiac output. Neurohormonal systems, which are normally stimulated under conditions of acute volume depletion, are activated by the low cardiac output and arterial pressure. However, sustained and chronic activation of these systems, as occurs in congestive heart failure (CHF), can cause progressive ventricular remodeling and worsening heart failure. Vasoconstriction, water retention, and increased blood volume are results of the activation of the SNS, the renin-angiotensin pathway, and AVP secretion. These effects can accelerate progression of CHF, contributing to increased morbidity and mortality. AVP regulates vascular tone and free-water reabsorption, respectively, through the vasopressin V
1a and V
2 receptor subtypes and therefore is a potential neurohormonal target in the treatment of CHF.
Established doxorubicin cardiomyopathy is a lethal disease. When congestive heart failure develops, mortality is approximately 50%. Extensive research has been done to understand the mechanism and ...pathophysiology of doxorubicin cardiomyopathy, and considerable knowledge and experience has been gained. Unfortunately, no effective treatment for established doxorubicin cardiomyopathy is presently available. Extensive research has been done and is being done to discover preventive treatments. However an effective and clinically applicable preventive treatment is yet to be discovered.
The Swan-Ganz balloon flotation catheter was introduced in 1970. It can be placed at the bedside within a few minutes even in critically ill patients. Although placement of these catheters is not ...difficult, some training and experience are required to avoid complications and for proper interpretation of the hemodynamic data that can be obtained by pulmonary artery catheterization. Because of the many advantages of balloon flotation catheters compared with conventional catheters, they have been used without a proper indication and frequently overused in critical care units, resulting in many complications, including mortality. The prospective randomized trials have reported that in the majority of clinical circumstances, the routine use of balloon flotation catheters is not indicated. These results are not surprising because balloon flotation catheters are diagnostic and not therapeutic tools. That we have learned a great deal about hemodynamics in critically ill patients with the use of balloon flotation catheters should not be ignored or forgotten. Furthermore, our clinical knowledge of hemodynamics has been made possible because of extensive experience gained from directly determined hemodynamics with the use of balloon flotation catheters. It should also be realized that despite the introduction and refinement of newer noninvasive imaging modalities, a number of clinical circumstances exist in which determination of hemodynamics with the use of a balloon flotation catheter is necessary and should be considered, but only by experienced physicians. With the proper use of Swan-Ganz catheters, our knowledge of hemodynamics has been enhanced considerably. Its abuse, particularly by relatively inexperienced operators, has resulted in serious complications, including death. Prospective randomized clinical trials have demonstrated that the routine use of Swan-Ganz catheters does not provide any benefit. However, use of the Swan-Ganz catheter is still indicated in many situations.
Abstract Background Diastolic heart failure (DHF) and systolic heart failure (SHF) are 2 clinical subsets of the syndrome of chronic heart failure that are most commonly encountered in clinical ...practice. Methods and Results The clinically overt DHF and SHF appear to be 2 separate syndromes with distinctive morphologic and functional changes although signs, symptoms, and prognosis are very similar. In DHF, the left ventricle is not dilated and the ejection fraction is preserved. In contrast in SHF, it is dilated and the ejection fraction is reduced. The neurohormonal abnormalities in DHF and SHF appear to be similar. The stimuli and the signals that ultimately produce these 2 different phenotypes of chronic heart failure remain, presently, largely unknown. Conclusions Although there has been considerable progress in the management of SHF, the management of DHF remains mostly empirical because of lack of knowledge of the molecular and biochemical mechanisms which produce myocardial structural and functional changes in this syndrome. Further research and investigations are urgently required.
Although the prognosis of systolic heart failure, also called heart failure with reduced ejection fraction, has improved with advances in therapy, the prognosis remains poor in patients who become ...refractory to such therapies. That cardiac transplantation improves the quality of life and survival of such patients has been established, but it is available to a very small number of patients. Thus, newer pharmacologic and nonpharmacologic therapies for patients with refractory systolic heart failure are being explored. Because chronic ischemic heart disease is the most common cause of systolic heart failure, potential exists for revascularization therapy. Although revascularization can be performed with low procedural mortality, improvement in left ventricular function, relief of symptoms, and long-term prognosis appear to be related to the presence and extent of viable ischemic hibernating myocardium. In conclusion, the detection of hibernating myocardium is highly desirable before revascularization treatment is undertaken.
Sphingosine 1-phosphate (S1P) is a biologically active lysophospholipid that serves as a key regulator of cellular differentiation and survival. Immune stimuli increase S1P synthesis and secretion by ...mast cells and platelets, implicating this molecule in tissue responses to injury and inflammation. Binding of S1P to G(i) protein-coupled receptors activates phosphatidylinositol 3-kinase and Akt in a variety of tissues. To elucidate the mechanisms by which S1P enhances adult cardiac myocyte survival during hypoxia, we used a mouse cell culture system in which S1P(1) receptors were observed to transduce signals from exogenous S1P, an S1P(1) receptor antibody with agonist properties, and the pharmacological agents FTY720 and SEW2871. S1P(1) receptor mRNA and protein were abundantly expressed by adult mouse cardiac myocytes. S1P-S1P(1) receptor axis enhancement of myocyte survival during hypoxia was abolished by phosphatidylinositol 3-kinase inhibition. S1P(1) receptor function was closely associated with activation of Akt, inactivation of GSK-3beta, and reduction of cytochrome c release from heart mitochondria. These observations highlight the importance of S1P(1) receptors on ventricular myocytes as mediators of inducible resistance against cellular injury during severe hypoxic stress.
Systolic and diastolic heart failure are the 2 most common clinical subsets of chronic heart failure. Left ventricular "Starling" function is depressed in patients with systolic heart failure. In ...systolic heart failure, left ventricular mass is increased, which can be measured by transthoracic echocardiography. Cardiac magnetic resonance imaging is a more precise technique to measure left ventricular mass. Neurohormonal activation is a major pathophysiologic mechanism for ventricular remodeling and progression of heart failure in systolic heart failure.
Long-term ventricular resynchronization therapy improves symptom status. Changes in left ventricular remodeling have not been adequately evaluated.
Fifty-three patients with systolic heart failure ...and bundle-branch block underwent implantation of biventricular stimulation (BVS) devices as part of a randomized trial. Echocardiograms were acquired at randomization and at 6-week intervals until completion of 12 weeks of continuous BVS. There were no changes in heart rate or QRS duration after 12 weeks of BVS. Serum norepinephrine values did not change with BVS. After 12 weeks of BVS, left atrial volume decreased. Left ventricular end-systolic and end-diastolic dimensions and left ventricular end-systolic volume also decreased after 12 weeks of BVS. Sphericity index did not change. Measures of systolic function, including left ventricular outflow tract and aortic velocity time integral and myocardial performance index, improved.
Long-term resynchronization therapy results in atrial and ventricular reverse remodeling and improved hemodynamics.
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