Congestive Heart Failure Medical and Health News Headlines

Current status and future prospects for cell transplantation to prevent congestive heart failure.

Semin Thorac Cardiovasc Surg. 2008;20(2):131-7

Authors: Menasché P

Although most cardiac cell therapy trials have focused on patients with acute myocardial infarction, attempts at "regenerating" chronically failing hearts have also been performed. These studies have entailed use of skeletal myoblasts and bone marrow-derived cells. In the case of skeletal myoblasts, the randomized placebo-controlled myoblast autologous grafting in ischemic cardiomyopathy (MAGIC) trial has failed to show that myoblast injections increased ejection fraction beyond that seen in controls but the finding that the highest dose of myoblasts resulted in a significant antiremodeling effect compared with the placebo group provides an encouraging signal. In the case of bone marrow cells, surgical injections of the mononuclear fraction combined with coronary artery bypass surgery have not shown a substantial benefit but positive results have been reported with intraoperative epicardial injections of CD133(+) progenitors. There are three possible reasons for these mixed results. The first is the marked heterogeneity of cell functionality (particularly in the case of bone marrow), which would expectedly translate into variable clinical outcomes. The second reason is the low rate of sustained engraftment. The third possible explanation is a mismatch between the choice of end points and the presumed mechanism of action of the cells. The initial assumption that adult stem cells could effect myocardial tissue regeneration has led to usual focus on ejection fraction as the major surrogate endpoint. It is now increasingly recognized that adult stem cells, in contrast to their embryonic counterparts, have little if any regenerative capacity and that their presumed beneficial effects more likely involve paracrine signaling, in which case infarct size, perfusion, or left ventricular volumes might be more appropriate markers. Altogether, these observations provide a framework for future research, the results of which will then have to be integrated in the protocol design of second-generation clinical trials.

PMID: 18707646 [PubMed - in process]

Intraoperative cell transplantation for congestive heart failure: experience in china.

Semin Thorac Cardiovasc Surg. 2008;20(2):126-30

Authors: Zhang H, Wei YJ, Hu SS

Despite significant improvement in the management of congestive heart failure (CHF), it still is a major worldwide public health problem. Currently, cell-based regenerative medicine has been developed as a promising therapeutic option for patients with CHF. Considering the large and growing population, it is estimated that over 5 million patients in China may need such a cell-based therapy to replace or repair the damaged myocardium. Cardiac surgery has emerged as an important player in heart cell therapy in China in recent years. Here, we summarize our achievements in both preclinical and clinical studies of intraoperative cell transplantation, and present our understanding of future research in this attractive field.

PMID: 18707645 [PubMed - in process]

Paracrine effects of cell transplantation: modifying ventricular remodeling in the failing heart.

Semin Thorac Cardiovasc Surg. 2008;20(2):87-93

Authors: Fedak PW

Structural ventricular remodeling determines the clinical progression of heart failure and has emerged as an important target for the development of novel medical and surgical therapeutic strategies. Cell transplantation is an innovative biologic therapy that may restore myocardial structure and function in failing hearts. With current forms of cell transplant therapy, true myocardial regeneration has been limited. However, cell transplantation can predictably limit maladaptive ventricular remodeling through multiple synergistic paracrine mechanisms. Some of the paracrine factors released by transplanted cells have been defined. These paracrine signals may provide beneficial effects by stimulating angiogenesis, limiting matrix disruption, and preventing apoptosis. In addition, cell transplantation may induce mobilization and homing of endogenous repair cells to injured myocardium through paracrine signals. Paracrine mediators released from transplanted cells work through multiple, diverse, and interrelated molecular pathways resulting in synergistic effects on the remodeling process. Although true myocardial regeneration remains the ultimate goal of cell therapy, the anti-remodeling abilities of cell transplantation can be harnessed to complement our contemporary surgical approaches for patients with myocardial injury at risk of congestive heart failure.

PMID: 18707639 [PubMed - in process]

Chapter 3 natriuretic peptides in vascular physiology and pathology.

Int Rev Cell Mol Biol. 2008;268:59-93

Authors: Woodard GE, Rosado JA

Four major natriuretic peptides have been isolated: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and Dendroaspis-type natriuretic peptide (DNP). Natriuretic peptides play an important role in the regulation of cardiovascular homeostasis maintaining blood pressure and extracellular fluid volume. The classical endocrine effects of natriuretic peptides to modulate fluid and electrolyte balance and vascular smooth muscle tone are complemented by autocrine and paracrine actions that include regulation of coronary blood flow and, therefore, myocardial perfusion; modulation of proliferative responses during myocardial and vascular remodeling; and cytoprotective anti-ischemic effects. The actions of natriuretic peptides are mediated by the specific binding of these peptides to three cell surface receptors: type A natriuretic peptide receptor (NPR-A), type B natriuretic peptide receptor (NPR-B), and type C natriuretic peptide receptor (NPR-C). NPR-A and NPR-B are guanylyl cyclase receptors that increase intracellular cGMP concentration and activate cGMP-dependent protein kinases. NPR-C has been presented as a clearance receptor and its activation also results in inhibition of adenylyl cyclase activity. The wide range of effects of natriuretic peptides might be the base for the development of new therapeutic strategies of great benefit in patients with cardiovascular problems including coronary artery disease or heart failure. This review summarizes current literature concerning natriuretic peptides, their receptors and their effects on fluid/electrolyte balance, and vascular and cardiac physiology and pathology, including primary hypertension and myocardial infarction. In addition, we will attempt to provide an update on important issues regarding natriuretic peptides in congestive heart failure.

PMID: 18703404 [PubMed - in process]

Semicarbazide-sensitive amine oxidase/vascular adhesion protein 1: recent developments concerning substrates and inhibitors of a promising therapeutic target.

Curr Med Chem. 2008;15(18):1827-39

Authors: Dunkel P, Gelain A, Barlocco D, Haider N, Gyires K, Sperlágh B, Magyar K, Maccioni E, Fadda A, Mátyus P

SSAO/VAP-1 is not only involved in the metabolism of biogenic and xenobiotic primary amines and in the production of metabolites with cytotoxic effects or certain physiological actions, but also plays a role, for example, as an adhesion molecule, in leukocyte trafficking, in regulating glucose uptake and in adipocyte homeostasis. Interest in the enzyme has been stimulated by the findings that the activities of the SSAOs are altered (mostly increased) in various human disorders, including diabetes, congestive heart failure, liver cirrhosis, Alzheimer's disease and several inflammatory diseases, although the underlying causes are often unknown. On the basis of their insulin-mimicking effect, SSAO substrates are possibly capable of ameliorating metabolic changes in diabetes, while SSAO inhibitors (somewhat of a contradiction) are of potential benefit in preventing diabetes complications, atherosclerosis and oxidative stress contributing to several disorders or modulating inflammation, and hence may be of substantial therapeutic value. Great efforts have been made to develop novel compounds which may lead to future drugs useful in therapy, based on their effects on SSAO/VAP-1, and some of the results relating to novel substrates and inhibitors are surveyed in the present review.

PMID: 18691041 [PubMed - in process]

The role of correction of anaemia in patients with congestive heart failure: A short review.

Eur J Heart Fail. 2008 Aug 12;

Authors: Silverberg DS, Wexler D, Iaina A, Schwartz D

Many patients with Congestive Heart Failure (CHF) are anaemic. This anaemia is associated with more severe CHF and a higher incidence of mortality, hospitalisation and morbidity. The only way to prove that the anaemia is causing this worsening of CHF is to correct it. We review here some of the published papers about correction of anaemia. Many studies show a positive effect of Erythropoietin (EPO) or its' derivatives when administered in combination with oral or IV iron, with improvements in left and right ventricular systolic and diastolic function, dilation and hypertrophy and renal function. In addition, a reduction in hospitalisations, diuretic dose, pulmonary artery pressure, plasma volume, heart rate, serum Brain Natriuretic Peptide levels, the inflammatory marker Interleukin 6, soluble Fas ligand - a mediator of apoptosis, and improvements in New York Heart Association class, exercise capacity, oxygen utilization, caloric intake, Quality of Life and the activity of Endothelial Progenitor Cells, have been observed. Iron deficiency may also play an important role in this anaemia, since improvements in CHF have also been reported following treatment with IV iron alone. However, until the ongoing large placebo-controlled studies of the EPO derivative darbepoetin or IV iron are completed, we will not know whether these treatments really influence CHF outcome.

PMID: 18703380 [PubMed - as supplied by publisher]