Effect of endotoxemia on heart rate dynamics in rat isolated perfused hearts

Introduction: Beat-to-beat variation in heart rate shows a complex dynamics, and this complexity is changed during systemic inflammatory response syndrome (e.g. sepsis). It is not known whether or not cardiac pacemaker dynamical rhythm is affected by sepsis. The aim of this study was to investigate heart rate dynamics of isolated heart as well as expression of pacemaker channels (HCN) in a rat model of sepsis (endotoxemia) compared with normal rats. Methods: Male rats weighing 250-300 g were used in this study. Bacterial lipopolysaccharide was injected intraperitoneally (1mg/kg) in the endotoxemia group, and sterile saline in the control group. Three hours after injection, cardiac tissues were isolated and studied using Langendorff apparatus. Heart rate dynamics was assessed by calculating the standard deviation of inter-beat intervals as well as detrended fluctuation analysis (DFA). Quantitative RT-PCR was used to assess HCN expression in atria. Results: Hypoxia had a significantly different effect on heart rate variability in endotoxemic rats compared with controls (P<0.05). DFA analysis showed a linear relationship between logarithm of variance and the logarithm of scale in both endotoxemic and control rats. Atrial expression of HCN1 and HCN2 at mRNA level were significantly higher in endotoxemic rats in comparison with controls (P<0.05). Conclusion: Spontaneous beatings of isolated hearts exhibit a fractal-like dynamics which did not change after global hypoxia and/or endotoxemia. Endotoxemia was associated with altered heart rate variability and increased expression of pacemaker channels that might play a role in pathophysiology of cardiac complications of sepsis.