Matthieu Soulié1, Leandro Fontana Pires2, Agathe Cambier2, Ixchel Lima-Posada1, Frédéric Jaisser1
¹ Inserm, UMRS 1138, centre de recherche des cordeliers, campus des cordeliers – Sorbonne université, Paris, France
² Physiological monitoring instruments, ETISENSE SAS, Lyon, France
Abstract
Patients with Chronic Kidney Disease (CKD) have increased risk of cardiovascular mortality from arrhythmias and sudden cardiac death. The pathogenesis by which CKD predisposes to sudden cardiac death remains unknown but may involve electrolyte imbalances, atrial/ventricular extracellular matrix remodeling as well as electrophysiological remodeling. Of interest mineralocorticoid receptor (MR) antagonists have been consistently reported by us and others to be beneficial, partly by reducing atrial fibrillation and sudden cardiac death.
The aim of this study was to characterize the electrocardiogram (ECG) remodeling occurring in a rat CKD model before testing the impact of MR antagonists.
ECG were recorded using non-invasive jacket (DECRO, ETISENSE) in a pre-clinical non-diabetic CKD rat model. Twelve weeks after 5/6 nephrectomy, rats were housed in 12 h light/12 h dark phases and was recorded every 30 minutes from 1pm until 10am the following day. Heart rate (HR), ECG interval calculation and wave durations were averaged every hour in all animals and compared between the two groups during the Light/Dark (L/D) phases.
Twenty-two hours cardiac chronobiological characterization by ECG study shows that CKD has a global impact on several electrophysiological parameters (as shown in Table 1 ). In the CKD group compared to the SHAM group, we observed a decreased HR and QRS interval (QRSi) in both phases, a decreased P wave duration (Pdur) during the dark phase and an increased QT interval (QTc) and T-wave duration (Tdur) during light phase. The study of cardiac variability showed the expected difference in LF/HF (reflecting the state of the orthosympathetic/parasympathetic balance) between the light and dark phases in the SHAM group while it is lost in the CKD group.
Electrocardiogram parameters are altered in the 5/6 nephrectomy CKD rats compared to SHAM rats. Loss of L/D variation of P waves, increased duration of T waves and QTc and loss of cardiac variability suggest increased sensibility to arrythmia. Further experiments using pharmacological challenges will be used to test this hypothesis as well as MR antagonism to assess potential benefits on ECG parameters.