The Effect Of Regulators Of G-protein Signaling-5 On Cardiac Electrophysiology In Myocardial Infarction Mouse

Background G protein signal pathway plays an important role in the regulation of cardiac rhythm and the occurrence of arrhythmia. RGS5 (regulators of G-protein signaling 5) is an important negative regulator of G protein. Studies have pronounced that RGS5 can regulate the blood pressure and vascular regeneration:The deficient of RGS5 reduced systolic blood pressure and diastolic blood pressure by the nitric oxide (NO) signaling pathway. RGS5 also negatively regulate the mature of vascular cells. Therefore, we hypothesized that RGS5 plays an important role in cardiac electrophysiology. In this research we used RGS5-deficient mice to study its effect on cardiac autonomic rhythms and cardiac electrophysiological changes and its mechanism after myocardial infarction, looking for a new target for the regulation of cardiac electrophysiology.Part 1:The effect of RGS5 on heart rate and heart rate variability in miceObjective The purpose of this study was to investigate the changes of heart rate and heart rate variability(HRV) of RGS5-deficient mice.Methods Wild type C57BL/6 mice (WT group) and RGS5-/- knockout mice (RGS5-/- group) ranging in age from 8 to 12 weeks, body weight from 25g to 28g. ECG recordings (48h) were obtained in an unrestrained, temperature-controlled environment with the mice housed in isolated cages far away from the stimulation of other animals and with normal light-dark cycles with telemetry monitor implants. ECG signal processing was performed with the software program Chart 7.0 and HRV analysis with the HRV plug-in for Chart 7.0 (AD Instruments, Germany).Results 1. Heart rate:During the ECG recording, heart rate was higher in RGS5-/-compared with WT mice but that did not reach statistical significance. Significant diurnal variation in heart rate was observed in both RGS5-/- and WT mice. The acrophases of RGS5-/- and WT mice were identified in the dark phase between 11pm and 2am. No significant arrhythmias were detected in both groups during the study.2. Time domain analysis:SDNN reflecting total autonomic variability were higher in RGS5-/- mice. The RMSSD was significantly lower but pNN6 was higher in RGS5-/-mice during day and night time.3. Frequency domain analysis:RGS5-/- mice appeared to confer significant decreases in LF power. The normalized HF (nHF) frequency band, representing mainly the parasympathetic nervous system, was higher in the RGS5-/-mice compared to their littermates. The normalized LF (nLF) frequency band, which is under the influence of both the sympathetic and the parasympathetic systems, was significantly lower in the RGS5-/- mice. The LF/HF, a measure of the sympathovagal balance independent of total power variations, was clearly decreased in the RGS5-/-mice pointing to a parasympathetic preponderance.Conclusion We tested the autonomic nervous system's impact on heart rate regulation in RGS5-/- mice. Our results demonstrate that RGS5-/- mice showed no significant difference with WT mice in heart rate, but decreased in HRV. Taken together, our studies establish that RGS5 plays an important role in regulating sinus rhythm.Part 2:The mechanism and effect of RGS5 on electrophysiology following myocardial infarctionObjective The purpose of this study was to investigate the changes of electroph-ysiological characteristics of RGS5-deficient mice and its relationship between the RGS5 and the occurrence of ventricular arrhythmias (VAs) after myocardial infarction.Methods Wild type C57BL/6 mice (WT group) and RGS5-/- knockout mice (RGS5-'-group) ranging in age from 8 to 12 weeks, body weight from 25g to 28g.1. Employing radiotelemetry transmitter (DSI), ECG of two groups was record for three days, then the interval of PR?the interval of QT and the duration of QRS wave and other characteristics of ECG were analysis by LabChart 7. Meanwhile, observe the occurrence of the spontaneous ventricular arrhythmias (VAs).2. Employing the monophasic action potential (MAP) and programmed electrical stimulation technique from the ventricle of Langendorff-perfused hearts, the monophasic action potential duration (MAPD)?ventricular effective refractory period (VERP)?spontaneous and induced VAs were observed.Results 1. The RGS5-deficient mice had no obvious changes on the function of heart. The QT interval of RGS5-deficient mice was prolonged, and its monophasic action potential is extended. Meanwhile, there was no significant difference in VERP. And occurrence of ventricular arrhythmias was more than control group, but the occurrence of spontaneous arrhythmias in vivo was not obvious increase.2. After 4 weeks of MI, cardiac function was significantly decreased, but the survival rate had no obvious difference. Compared with WT myocardial infarction group, APD90 of RGS5-deficient mice with myocardial infarction group was significantly prolonged and ventricular effective refractory period had no obvious change. But the occurrence of ventricular arrhythmias in RGS5-deficient mice with myocardial infarction was lower. The induced ventricular arrhythmias by Programmed electrical stimulation (PES) or Burst was more than other groups.Conclusion RGS5 absence induced prolonged repolarization and has major influences on ventricular arrhythmic developing.