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Endotoxin impairs the human pacemaker current If

Introduction

Lipopolysaccharides (LPSs) trigger the development of sepsis by Gram-negative bacteria and cause a variety of biological effects on host cells including alterations in ionic channels. As heart rate variability is reduced in human sepsis and endotoxemia, we hypothesized that LPS affects the pacemaker current If in the human heart, which might – at least in part – explain this phenomenon.

Methods

Isolated human myocytes from right atrial appendages were incubated for 6–10 hours with LPS (1 μg/ml and 10 μg/ml), and afterwards used to investigate the pacemaker current If. The If was measured with the whole-cell patch-clamp technique (at 37°C).

Results

Incubation of atrial myocytes with 10 μg/ml LPS was found to significantly impair If by suppressing the current at membrane potentials positive to -80 mV and slowing down current activation, but without effecting maximal current conductance. Furthermore, in incubated cells (10 μg/ml) the response of If to β-adrenergic stimulation (1 μM isoproterenol) was significantly larger compared with control cells (the shift of half-maximal activation voltage to more positive potentials amounted to 10 mV and 14 mV in untreated and treated cells, respectively). Simulations using a spontaneously active sinoatrial cell model indicated that LPS-induced If impairment reduced the responsiveness of the model cell to fluctuations of autonomic input.

Conclusion

This study showed a direct impact of LPS on the cardiac pacemaker current If. The LPS-induced If impairment may contribute to the clinically observed reduction in heart rate variability under septic conditions and in cardiac diseases like heart failure where endotoxin could be of pathophysiological relevance.

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Zorn-Pauly, K., Pelzmann, B., Lang, P. et al. Endotoxin impairs the human pacemaker current If. Crit Care 12, P248 (2008). https://doi.org/10.1186/cc6469

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Keywords

  • Heart Rate Variability
  • Isoproterenol
  • Human Heart
  • Atrial Appendage
  • Current Conductance