64
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Myocardial recovery during mechanical circulatory support: cellular, molecular, genomic and organ levels

      brief-report

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Mechanical circulatory support is a life-saving therapy that will become either a bridge-to-transplantation or definitive therapy if heart transplantation is not possible. Failing hearts supported by a ventricular assist device  were often found to recover at molecular and cellular level but translation of these changes into functionally-stable cardiac recovery allowing long-term heart transplantation/ventricular assist device-free outcomes after weaning from ventricular assist device is relatively rare and related to the etiology, severity and duration of myocardial damage. The reason for the discrepancy between high recovery rates on the cellular and molecular levels and the low rate of cardiac recovery allowing ventricular assist device explantation is unknown.

          Related collections

          Most cited references59

          • Record: found
          • Abstract: found
          • Article: not found

          Left ventricular assist device and drug therapy for the reversal of heart failure.

          In patients with severe heart failure, prolonged unloading of the myocardium with the use of a left ventricular assist device has been reported to lead to myocardial recovery in small numbers of patients for varying periods of time. Increasing the frequency and durability of myocardial recovery could reduce or postpone the need for subsequent heart transplantation. We enrolled 15 patients with severe heart failure due to nonischemic cardiomyopathy and with no histologic evidence of active myocarditis. All had markedly reduced cardiac output and were receiving inotropes. The patients underwent implantation of left ventricular assist devices and were treated with lisinopril, carvedilol, spironolactone, and losartan to enhance reverse remodeling. Once regression of left ventricular enlargement had been achieved, the beta2-adrenergic-receptor agonist clenbuterol was administered to prevent myocardial atrophy. Eleven of the 15 patients had sufficient myocardial recovery to undergo explantation of the left ventricular assist device a mean (+/-SD) of 320+/-186 days after implantation of the device. One patient died of intractable arrhythmias 24 hours after explantation; another died of carcinoma of the lung 27 months after explantation. The cumulative rate of freedom from recurrent heart failure among the surviving patients was 100% and 88.9% 1 and 4 years after explantation, respectively. The quality of life as assessed by the Minnesota Living with Heart Failure Questionnaire score at 3 years was nearly normal. Fifty-nine months after explantation, the mean left ventricular ejection fraction was 64+/-12%, the mean left ventricular end-diastolic diameter was 59.4+/-12.1 mm, the mean left ventricular end-systolic diameter was 42.5+/-13.2 mm, and the mean maximal oxygen uptake with exercise was 26.3+/-6.0 ml per kilogram of body weight per minute. In this single-center study, we found that sustained reversal of severe heart failure secondary to nonischemic cardiomyopathy could be achieved in selected patients with the use of a left ventricular assist device and a specific pharmacologic regimen. Copyright 2006 Massachusetts Medical Society.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Tumor necrosis factor-alpha and tumor necrosis factor receptors in the failing human heart.

            Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that produces negative inotropic effects in the heart. Recently, elevated levels of TNF-alpha have been reported in patients with advanced congestive heart failure. Although TNF-alpha is thought to exert its deleterious effects by binding to two cell surface receptors, TNFR1 and TNFR2, the level of expression and regulation of TNF receptors in the heart in cardiac disease states is not known. We examined mRNA and protein levels for TNFR1, TNFR2, and TNF-alpha in explanted hearts from organ donors as well as in patients with end-stage dilated cardiomyopathy (DCM) and ischemic heart disease (IHD). Northern blot analysis revealed that mRNA for TNFR1 and TNFR2 was present in nonfailing, DCM, and IHD hearts. TNFR1 and TNFR2 receptor protein levels, as measured by ELISA, were decreased 60% in DCM and IHD patients compared with nonfailing hearts (P < .005). To determine a potential mechanism for the decrease in TNF receptor expression, we measured levels of circulating soluble TNF receptors (sTNFRs) in DCM and IHD patients. This analysis showed that there was a significant one-and-a-half to threefold increase in sTNFRs in DCM (P < .03) and IHD patients (P < .001). Another important finding was that TNF-alpha mRNA and TNF-alpha protein were present in the explanted hearts from DCM and IHD patients but not in nonfailing hearts. In summary, the results of this study constitute the initial demonstration that TNF receptor proteins are dynamically regulated in patients with advanced congestive heart failure. Moreover, the observation that failing hearts express elevated levels of TNF-alpha suggests that overexpression of this cytokine may be one of several different maladaptive mechanisms responsible for the progressive cardiac decompensation that occurs in advanced heart failure.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Altered expression of beta-adrenergic receptor kinase and beta 1-adrenergic receptors in the failing human heart.

              In chronic heart failure, the positive inotropic effects of beta-adrenergic receptor agonists are greatly reduced, in part as a result of two alterations of the cardiac beta-adrenergic receptors: loss of their function (receptor uncoupling) and reduction of their number (downregulation). In vitro studies have shown that a major mechanism leading to beta-adrenergic receptor uncoupling involves phosphorylation of the receptors by the specific beta-adrenergic receptor kinase (beta ARK). We have therefore investigated expression of beta ARK and beta-adrenergic receptors in samples from the left ventricles of patients with dilated cardiomyopathy or ischemic cardiomyopathy and from nonfailing control ventricles. Contractile responses to beta-receptor stimulation were decreased in the failing hearts compared with control hearts, whereas those to forskolin and calcium remained unchanged. The messenger RNA (mRNA) levels of beta ARK, beta 1- and beta 2-receptors, and of glyceraldehyde phosphate dehydrogenase and beta-actin as controls were measured by quantitative polymerase chain reactions. In addition, beta ARK enzyme activity assays were performed, and the levels of beta 1- and beta 2-receptors were determined by radioligand binding. beta ARK mRNA levels were increased almost threefold in both forms of heart failure, and beta ARK activity was enhanced. beta 1-Receptor mRNA levels and beta 1-receptor numbers were decreased by approximately 50% in both failing groups, whereas these levels were unaltered for beta 2-receptors. There were no differences between dilated and ischemic cardiomyopathy for any of these parameters. In addition to other alterations found in failing hearts, the diminished response to beta-receptor agonists appears to involve the combined effects of enhanced expression of beta ARK and reduced expression of beta 1-receptors.
                Bookmark

                Author and article information

                Journal
                Heart Lung Vessel
                Heart Lung Vessel
                2282-8419
                hlv
                Heart, Lung and Vessels
                EDIMES Edizioni Internazionali Srl
                2282-8419
                2283-3420
                2015
                : 7
                : 2
                : 110-120
                Affiliations
                Deutsches Herzzentrum Berlin, Germany, Department of Cardiothoracic and Vascular Surgery
                DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany
                Author notes
                Michael Dandel MD, PhD Deutsches Herzzentrum Berlin, Augustenburger Platz, 1 13353 Berlin, Germany; E-mail: dandel@ 123456dhzb.de
                Article
                201502110
                4476765
                fabe6e9a-5914-4609-a616-a81aecc37fb0
                Copyright © 2015, Heart, Lung and Vessels

                This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Brief-Report

                heart failure,ventricular assist devices,ventricular function,myocardial recovery,survival,risk factors

                Comments

                Comment on this article