Document Detail


Thrombopoietin modulates cardiac contractility in vitro and contributes to myocardial depressing activity of septic shock serum.
MedLine Citation:
PMID:  20467749     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Thrombopoietin (TPO) is a humoral growth factor that has been shown to increase platelet activation in response to several agonists. Patients with sepsis have increased circulating TPO levels, which may enhance platelet activation, potentially participating to the pathogenesis of multi-organ failure. Aim of this study was to investigate whether TPO affects myocardial contractility and participates to depress cardiac function during sepsis. We showed the expression of the TPO receptor c-Mpl on myocardial cells and tissue by RT-PCR, immunofluorescence and western blotting. We then evaluated the effect of TPO on the contractile function of rat papillary muscle and isolated heart. TPO did not change myocardial contractility in basal conditions, but, when followed by epinephrine (EPI) stimulation, it blunted the enhancement of contractile force induced by EPI both in papillary muscle and isolated heart. An inhibitor of TPO prevented TPO effect on cardiac inotropy. Treatment of papillary muscle with pharmacological inhibitors of phosphatidylinositol 3-kinase, NO synthase, and guanilyl cyclase abolished TPO effect, indicating NO as the final mediator. We finally studied the role of TPO in the negative inotropic effect exerted by human septic shock (HSS) serum and TPO cooperation with TNF-alpha and IL-1beta. Pre-treatment with the TPO inhibitor prevented the decrease in contractile force induced by HSS serum. Moreover, TPO significantly amplified the negative inotropic effect induced by TNF-alpha and IL-1beta in papillary muscle. In conclusion, TPO negatively modulates cardiac inotropy in vitro and contributes to the myocardial depressing activity of septic shock serum.
Authors:
Enrico Lupia; Tiziana Spatola; Alessandra Cuccurullo; Ornella Bosco; Filippo Mariano; Angela Pucci; Roberta Ramella; Giuseppe Alloatti; Giuseppe Montrucchio
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-14
Journal Detail:
Title:  Basic research in cardiology     Volume:  105     ISSN:  1435-1803     ISO Abbreviation:  Basic Res. Cardiol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-05     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0360342     Medline TA:  Basic Res Cardiol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  609-20     Citation Subset:  IM    
Affiliation:
Department of Clinical Pathophysiology, University of Turin, Italy.
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