The Impact Of Remote Ischemic Conditioning On Blood Pressure Variability And Heart Rate Variability In Healthy Adults

Background and Objective:Remote ischemic conditioning(RIC)is an intervention that may exert a protective effect over multiple tissues or organs by neuromodulation,humoral regulation,and immunomodulation,in which one or more cycles of ischemia/reperfusion are applied in distant tissues or organs to make the remote tissues and organs resistant to the subsequent prolonged ischemia insult.As the basic physiological characteristics of humans,blood pressure variability(BPV)and heart rate variability(HRV)are defined as blood pressure and heart rate oscillations in relation to the mean values,and can assess the balance of neuroendocrine regulation.It has been well documented that the association between abnormal BPV and HRV,and many diseases are close.However,whether RIC can regulate BPV and HRV in humans remains unknown.The main objective of this study is to assess the impact of RIC on BPV and HRV and how long its impact will last to further clarify the mechanism of the protective effect of RIC and provide a theoretical basis for the clinical translation of RIC.Materials and Methods:Fifty healthy adult volunteers(age 34.54 ± 12.01 years,22 men [44%],all Asian)were included for this self-controlled interventional study on four consecutive days.In order to avoid any confounding factors caused by the physiological circadian rhythm,serial beat-to-beat monitoring was performed at the same seven time points(7,9,and11 AM;2,5,and 8 PM;and 8 AM on the next day)before and after RIC.The seven time points on the RIC day were defined as baseline,1 hour,3 hours,6 hours,9 hours,12 hours and 24 hours after RIC,respectively.And the values of blood pressure and heart rate were also recorded.The values of BPV included standard deviation(SD),successive variation(SV),average real variability(ARV),and variation independent of mean(VIM).The variables of HRV analyzed in time-domain measures performed as statistical measures,NN intervals,SDNN,SDANN,RMSSD and SDNNindex,and geometric measures,HRV triangular index and TINN.The frequency-domain parameters,total power,the power of very low frequency(VLF;0-0.04 HZ),lowfrequency(LF;0.04–0.15 Hz),high-frequency(HF;0.15–0.40 Hz),normalized LF(LF/ [total power-VLF]),normalized HF(HF/ [total power-VLF])and the ratio of LF to HF(LF/HF)were also calculated.The non-linear parameters were obtained by Poincaré plot(SD1,SD2 and SD1/SD2),entropy-based measures(Samp En),and detrended fluctuation analysis(DFA α1 and DFA α2).Repeated measurement analysis of variance was used to test the differences of observed values at different time points.A mixed linear model for repeated measurements was used to compare the different parameters of BPV and HRV between RIC and different time points.In the mixed linear model,both of the two factors(RIC and time)were included and considered to be factors of repeated measurements.Results:Systolic blood pressure was decreased significantly by approximately 5 mm Hg at6 and 12 hours after RIC(p=0.042,0.044,respectively);diastolic blood pressure was reduced by about 5 mm Hg,7 mm Hg,and 4 mm Hg at 1 hour(p=0.037),6 hours(p<0.001),and 24 hours(p=0.009),respectively;and mean arterial pressure was reduced by approximately 6 mm Hg and 5 mm Hg 6 hours(p=0.002)and 24 hours(p=0.014)after RIC,respectively.One hour after RIC,time domain index of HRV,SDNN(p=0.029)and frequency domain index,total power(p=0.046)were significantly increased;VLF was significantly higher(p=0.032)12 hours after RIC;1hour and 3 hours later,LF was increased(p=0.022,0.040,respectively);non-linear index,SD2 was significantly increased one hour and 12 hours after RIC(p=0.045,0.041,respectively).Among these parameters,LF and SD2 reflected cardiac sympathetic and parasympathetic nervous system activity.In repeated measurement analysis,pulse pressure,heart rate,BPV and other indices of HRV revealed no difference between the control and RIC day.Conclusions:RIC resulted in a drop of blood pressure and an increase in HRV,however,no significant change of beat-to-beat BPV was found.RIC may offer protection in both early and delayed windows by regulating autonomic nervous system activity,however,the balance of the sympathetic and parasympathetic nervous systems was not altered.Since decreased HRV has been identified to be associated with the incidence and poor prognosis of many diseases,as a therapeutic target,RIC may favorably influence the development and progression of different diseases by ameliorating HRV.