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The mechanisms underlying this attenuation are not limited to the nervous system. They also include alterations of the cardiac pacemaker cells on a cellular level. As shown in human atrial cardiomyocytes, endotoxin interacts with cardiac hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels, which mediate the pacemaker current I<jats:sub>f<\/jats:sub>and play an important role in transmitting sympathetic and vagal signals on heart rate and HRV. Moreover, endotoxin sensitizes cardiac HCN channels to sympathetic signals. These findings identify endotoxin as a pertinent modulator of the autonomic nervous regulation of heart function. In MODS, the vagal pathway of the autonomic nervous system is particularly compromised, leading to an attenuation of the cholinergic antiinflammatory reflex. An amelioration of the blunted vagal activity appears to be a promising novel therapeutic target to achieve a suppression of the inflammatory state and thereby an improvement of prognosis in MODS patients. Preliminary data revealed therapeutic benefits (increased survival rates and improvements of the depressed vagal activity) of the administration of statins, \u03b2-blockers, and angiotensin-converting enzyme inhibitors in patients with MODS.<\/jats:p>","DOI":"10.1139\/y09-012","type":"journal-article","created":{"date-parts":[[2009,4,14]],"date-time":"2009-04-14T15:14:58Z","timestamp":1239722098000},"page":"266-274","source":"Crossref","is-referenced-by-count":111,"title":["Impaired regulation of cardiac function in sepsis, SIRS, and MODSThis article is one of a selection of papers from the NATO Advanced Research Workshop on Translational Knowledge for Heart Health (published in part 2 of a 2-part Special Issue)."],"prefix":"10.1139","volume":"87","author":[{"given":"Karl","family":"Werdan","sequence":"first","affiliation":[{"name":"Department of Medicine\u00a0III, Martin Luther University Halle-Wittenberg, Ernst-Grube Str. 40, D-06097 Halle (Saale), Germany"},{"name":"Institute of Biophysics, Department of Physiological Medicine, Medical University of Graz, Graz, Austria"}]},{"given":"Hendrik","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Medicine\u00a0III, Martin Luther University Halle-Wittenberg, Ernst-Grube Str. 40, D-06097 Halle (Saale), Germany"},{"name":"Institute of Biophysics, Department of Physiological Medicine, Medical University of Graz, Graz, Austria"}]},{"given":"Henning","family":"Ebelt","sequence":"additional","affiliation":[{"name":"Department of Medicine\u00a0III, Martin Luther University Halle-Wittenberg, Ernst-Grube Str. 40, D-06097 Halle (Saale), Germany"},{"name":"Institute of Biophysics, Department of Physiological Medicine, Medical University of Graz, Graz, Austria"}]},{"given":"Klaus","family":"Zorn-Pauly","sequence":"additional","affiliation":[{"name":"Department of Medicine\u00a0III, Martin Luther University Halle-Wittenberg, Ernst-Grube Str. 40, D-06097 Halle (Saale), Germany"},{"name":"Institute of Biophysics, Department of Physiological Medicine, Medical University of Graz, Graz, Austria"}]},{"given":"Bernd","family":"Koidl","sequence":"additional","affiliation":[{"name":"Department of Medicine\u00a0III, Martin Luther University Halle-Wittenberg, Ernst-Grube Str. 40, D-06097 Halle (Saale), Germany"},{"name":"Institute of Biophysics, Department of Physiological Medicine, Medical University of Graz, Graz, Austria"}]},{"given":"Robert Sebastian","family":"Hoke","sequence":"additional","affiliation":[{"name":"Department of Medicine\u00a0III, Martin Luther University Halle-Wittenberg, Ernst-Grube Str. 40, D-06097 Halle (Saale), Germany"},{"name":"Institute of Biophysics, Department of Physiological Medicine, Medical University of Graz, Graz, Austria"}]},{"given":"Konstantin","family":"Heinroth","sequence":"additional","affiliation":[{"name":"Department of Medicine\u00a0III, Martin Luther University Halle-Wittenberg, Ernst-Grube Str. 40, D-06097 Halle (Saale), Germany"},{"name":"Institute of Biophysics, Department of Physiological Medicine, Medical University of Graz, Graz, Austria"}]},{"given":"Ursula","family":"M\u00fcller-Werdan","sequence":"additional","affiliation":[{"name":"Department of Medicine\u00a0III, Martin Luther University Halle-Wittenberg, Ernst-Grube Str. 40, D-06097 Halle (Saale), Germany"},{"name":"Institute of Biophysics, Department of Physiological Medicine, Medical University of Graz, Graz, Austria"}]}],"member":"155","reference":[{"key":"rg1\/ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejheart.2006.02.001"},{"key":"rg2\/ref2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000138932.17956.F1"},{"key":"rg3\/ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2005.01.005"},{"key":"rg4\/ref4","doi-asserted-by":"publisher","DOI":"10.1016\/S1050-1738(02)00162-7"},{"key":"rg5\/ref5","doi-asserted-by":"publisher","DOI":"10.1038\/35013070"},{"key":"rg6\/ref6","doi-asserted-by":"publisher","DOI":"10.1378\/chest.80.5.579"},{"issue":"23","key":"rg40\/ref40","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1056\/NEJM198706043162301","volume":"316","author":"CONSENSUS Trial Study Group","year":"1987","journal-title":"N. 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