Licofelone, a dual cyclooxygenase/5-lipoxygenase inhibitor, reverses endotoxin-induced impaired atrial chronotropic responsiveness to cholinergic stimulation in rats

Evidence show that endotoxemia is linked with tachycardia. The exact mechanism of tachycardia is not well-understood, but it seems that impaired cardiac chronotropic responsiveness to cholinergic stimulation plays a role in this phenomenon. The aim of this experiment was to study the effect of licofelone as a dual cyclooxygenase (COX)/5-lipoxygenase (5-LOX) inhibitor in modulation of atrial chronotropic hyporesponsiveness to cholinergic stimulation in endotoxemic rats, compared with hydrocortisone and indomethacin in in vitro and in vivo studies. Rats were injected by either of lipopolysaccharide (LPS) or saline. The isolated atria were incubated with licofelone, hydrocortisone, or indomethacin in an organ bath set up. In a separate experiment, rats were injected with licofelone, hydrocortisone, or indomethacin prior to isolation of the atria. Then, in both experiments, chronotropic responsiveness to cumulative concentrations of carbacholine in organ bath was recorded. LPS injection decreased the chronotropic responsiveness to cholinergic stimulation in both in vitro and in vivo experiments, significantly (P