Endotoxin impairs the human pacemaker current If

Zorn-Pauly, Klaus; Pelzmann, Brigitte; Lang, Petra; Mächler, Heinrich; Schmidt, Hendrik; Ebelt, Henning; Werdan, Karl; Koidl, K; Mueller-Werdan, Ursula

doi:10.1186/cc6469

Cited by 14 publications

(24 citation statements)

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“…As shown above, LPS reduced the beating‐rate of CM. Previous work from heterologous expression systems indicated a direct interaction of LPS with HCN‐channels, without requirement for classical LPS‐mediated signaling pathways, such as NF‐kB or MAP‐kinases . Therefore, we tested the hypothesis that LPS affects the beating frequency via its interaction with HCN‐channels, using the HCN‐channel blocker ivabradine.…”

Section: Resultsmentioning

confidence: 99%

“…In addition to these well‐known inflammatory reactions, we and other laboratories have shown previously that LPS can directly interfere with the electrophysiological properties of HCN‐channels . This may explain (at least in part) the disturbance of HR regulation found in severe sepsis mentioned above.…”

Section: Introductionmentioning

confidence: 83%

“…This may explain (at least in part) the disturbance of HR regulation found in severe sepsis mentioned above. However, so far all data regarding the interaction of LPS with HCN‐channels have been derived either from heterologous expression systems (HEK293‐cells) or from adult human atrial cardiomyocytes with no spontaneous depolarization . Therefore, the experiments presented here aimed to analyze, on the one hand, the effects of LPS at the cellular level in spontaneously beating cardiomyocytes, without interference of the autonomic system.…”

Section: Introductionmentioning

confidence: 99%

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Direct inhibition, but indirect sensitization of pacemaker activity to sympathetic tone by the interaction of endotoxin with HCN‐channels

Ebelt

Geißler

Ruccius

et al. 2015

Clin Exp Pharma Physio

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In critically ill patients regulation of heart-rate is often severely disturbed. Interaction of bacterial endotoxin (lipopolysaccharide, LPS) with hyperpolarization-activated cyclic nucleotide-gated cation-(HCN)-channels may interfere with heart-rate regulation. This study analyzes the effect of LPS, the HCN-channel blocker ivabradine or Ca(2+) -channel blockers (nifedipine, verapamil) on pacemaking in spontaneously beating neonatal rat cardiomyocytes (CM) in vitro. In vivo, the effect of LPS on the heart-rate of adult CD1-mice with and without autonomic blockade is analyzed telemetrically. LPS (100 ng/mL) and ivabradine (5 μg/mL) reduced the beating-rate of CM by 20.1% and 24.6%, respectively. Coincubation of CM with both, LPS and ivabradine, did not further reduce the beating-rate, indicating interaction of both compounds with HCN-channels, while coincubation with Ca(2+) -channel blockers and LPS caused additive beating-rate reduction. In CD1-mice (containing an active autonomic-nervous-system), injection of LPS (0.4 mg/kg) expectedly resulted in increased heart-rate. However, if the autonomic nervous system was blocked by propranolol and atropine, in line with the in vitro data, LPS induced a significant reduction of heart-rate, which was not additive to ivabradine. The in vivo and in vitro results indicate that LPS interacts with HCN-channels of cardiomyocytes. Thus, LPS indirectly sensitizes HCN-channels for sympathetic activation (tachycardic-effect), and in parallel directly inhibits channel activity (bradycardic-effect). Both effects may contribute to the detrimental effects of septic cardiomyopathy and septic autonomic dysfunction.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

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Direct inhibition, but indirect sensitization of pacemaker activity to sympathetic tone by the interaction of endotoxin with HCN‐channels

Ebelt

Geißler

Ruccius

et al. 2015

Clin Exp Pharma Physio

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“…However, in this case, neither diarrhea nor vomiting was observed. Septic shock is also an established trigger of cardiac events [24,25]. The results of the septic screen were unremarkable: C-reactive protein of 7 mg/L, white cells count of 4.7 9 10 9 /L, and neutrophils of 3.2 9 10 9 /L.…”

Section: Discussionmentioning

confidence: 99%

Gitelman syndrome: a rare life‐threatening case of hypokalemic paralysis mimicking Guillain–Barré syndrome during pregnancy and review of the literature

Elkoundi

Kartite

Bensghir

et al. 2017

Clinical Case Reports

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“…As we do not have a pure measure of SNS activity, we cannot make statements on whether the circadian system is influencing both PNS and SNS regulation, or only the PNS distribution. Endotoxin sensitizes cardiac hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels to SNS signals . This complicates the interpretation of HRV changes seen during endotoxaemia since the HR is not purely controlled by ANS but also by the effects of LPS endotoxin.…”

Section: Discussionmentioning

confidence: 99%

Day–night variation in heart rate variability changes induced by endotoxaemia in healthy volunteers

Alamili

Rosenberg

Gögenur

2015

Acta Anaesthesiol Scand

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Endotoxin impairs the human pacemaker current If

Cited by 14 publications

References 0 publications

Direct inhibition, but indirect sensitization of pacemaker activity to sympathetic tone by the interaction of endotoxin with HCN‐channels

Direct inhibition, but indirect sensitization of pacemaker activity to sympathetic tone by the interaction of endotoxin with HCN‐channels

Gitelman syndrome: a rare life‐threatening case of hypokalemic paralysis mimicking Guillain–Barré syndrome during pregnancy and review of the literature

Day–night variation in heart rate variability changes induced by endotoxaemia in healthy volunteers

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