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Werdan, K; Schmidt, H; Ebelt, H; Zorn-Pauly, K; Koidl, B; Hoke, RS; Heinroth, K; Müller-Werdan, U.
Impaired regulation of cardiac function in sepsis, SIRS, and MODS.
Can J Physiol Pharmacol. 2009; 87(4):266-274 Doi: 10.1139/Y09-012 [Poster]
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Co-Autor*innen der Med Uni Graz
Koidl Bernd
Zorn-Pauly Klaus

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In sepsis, systemic inflammatory response syndrome (SIRS), and multiorgan dysfunction syndrome (MODS), a severe prognostically relevant cardiac autonomic dysfunction exists, as manifested by a strong attenuation of sympathetically and vagally mediated heart rate variability (HRV). 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 If 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, beta-blockers, and angiotensin-converting enzyme inhibitors in patients with MODS.
Find related publications in this database (using NLM MeSH Indexing)
Adrenergic beta-Antagonists - therapeutic use
Angiotensin-Converting Enzyme Inhibitors - therapeutic use
Animals -
Heart - physiopathology
Heart Rate - drug effects
Humans -
Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use
Multiple Organ Failure - drug therapy
Multiple Organ Failure - physiopathology
Prognosis -
Sepsis - drug therapy
Sepsis - physiopathology
Systemic Inflammatory Response Syndrome - drug therapy
Systemic Inflammatory Response Syndrome - physiopathology
Vagus Nerve - physiology

Find related publications in this database (Keywords)
Autonomic dysfunction
heart rate variability (HRV)
HCN channel
cardiac pacemaker current I-f
systemic inflammatory response syndrome (SIRS)
multiorgan dysfunction syndrome (MODS)
angiotensin-converting enzyme inhibitors (ACEI)
multiorgan failure (MOF)
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