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Antiarrhythmic effect of interleukin-1 (IL-1) in conjunction with contractile depression

While IL-1 is known to be cardiodepressant via the induction of an inducible nitric oxide synthase (iNOS) and enhanced production of nitric oxide (NO), conflicting results have been reported regarding its potential to induce or suppress arrhythmias. Here we report a potent antiarrhythmic effect of IL-1β in conjunction with an enhanced release of NO.

Methods

Neonatal rat cardiomyocytes (CM) were incubated for 24 h in the absence or presence of lL-lβ (l00 U/ml) in serum-free medium. Thereafter, the production of NO was assessed by a NO-sensitive microelectrode and the Griess reaction. For testing contractile performance, cells were electrically triggered at constant pace and monitored continously.

Results

Il-1β (24 h) resulted in a significant increase in the contents of NO, nitrite and lactate (indicative of altered energy metabolism) in the culture supernatants, which was suppressed by simultaneous administration of dexamethasone (Dex.) (0.1 μM). The cardiodepressant IL-1β effect was documented by a lacking response in pulsation amplitude to the isoproterenol-challenge (control: n = 20, 148% ± 20 versus IL-1β : n = 27, 103% ± 3*, P < 0.05), which was preserved by co-incubation with Dex. (control: n = 21, 131% ± 10 versus IL-1β: n = 27, 130% ± 8). Arrhythmias were regularly elicited in controls upon α -adrenoceptor-stimulation (16/17), even if the duration of the electrical pulse was increased to keep the cells in pace. In contrast, recordings of IL-1β-treated CM (n = 11) did not display beating irregularity. If, however, Dex. was added to the incubation medium, arrhythmias occurred both in the groups without IL-1β (9/11) and with IL-1β (9/10).

Conclusion

A potentially beneficial antiarrhythmic effect of IL-1β may go along with its cardiodepressant action in vivo.

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Schlegel, F., Werdan, K. & Müller-Werdan, U. Antiarrhythmic effect of interleukin-1 (IL-1) in conjunction with contractile depression. Crit Care 3, P109 (2000). https://doi.org/10.1186/cc483

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Keywords

  • Nitric Oxide
  • Nitrite
  • Simultaneous Administration
  • Antiarrhythmic Effect
  • Griess Reaction