Clinical Effect And Central Mechanism Of Acupuncture In The Treatment Of Stable Angina Pectoris With Borderline Coronary Lesions

Objective:This clinical study is aimed to evaluate the clinical effect of acupuncture Neiguan and Ximen points in the treatment of stable angina pectoris with moderate coronary artery disease,and explore the regulating effect on cardiac autonomic modulation,and to provide evidience for clinical application.Taking healthy patients and patients with stable angina pectoris with moderate coronary artery disease as the research vector,and using fMRI as the technical approache to abserve the differences of brain functional activities in different body states and the changes in brain network connections before and after treatment,which can explore the central response characteristics of acupuncture in the treatment of stable angina pectoris with moderate coronary artery disease.The characteristics provide a theoretical basis for the central mechanism of acupuncture treatment the disease.Methods:1.Clinical efficacy studyUsing a single-blind,randomized,and controlled method,a total of 65 patients with stable angina pectoris with moderate coronary artery disease were randomly divided into two groups according to 1:1 ratio,electroacupuncture group and sham-electroacupuncture group.On the basis of base treatment,both groups were acupunctured at bilateral Neiguan and Ximen points,once a day,30 min per treatment,6 days a week for 2 weeks,1 day rest in a week.The Seattle Angina Pectoris Scale(SAQ),Self-rating Depression Scale(SDS),Self-rating Anxiety Scale(SAS),and 24-hour Holter electrocardiagram monitor before and after treatment were used to evaluate the clinical symptoms,mood state,and heart rate variability(HRV),the quality of life,which is assessed to evaluate the clinical efficacy of acupuncture at Neiguan and Ximen in the treatment of stable angina pectoris with moderate coronary lesions and the effect on cardiac autonomic function.2.Central mechanism researchAccording to the inclusion and exclusion criteria,8 healthy persons and 22 patients with stable angina pectoris with moderate coronary artery lesions(Electroacupuncture group 12 and Sham-electroacupuncture group 10)were randomly selected,and to take a brain fMRI scans.All groups were age-matched and gender-matched.The differences of brain functional activity in different body states(healthy and patients)were analyzed using regional homogeneity(ReHo)method.Brain fMRI scans were performed in electroacupuncture group and sham-electroacupuncture group at baseline and after treatment in the order of BOLD-fMRI,3D-T1W1,30-min treatment,BOLD-fMRI.According to the methods of regional homogeneity(ReHo)and seed-based functional connectivity analysis,the immediate and long-term effects of acupuncture Neiguan and Ximen in the treatment of stable angina pectoris with moderate coronary artery disease were observed.The central mechanism of acupuncture for stable angina pectoris with moderate coronary lesions was explored by comparing the changes in brain function activities and brain network connections before and after treatment.Results:Clinical research1.Baseline:There was no significant difference in demographic information(gender,age,height,et al),the total score and five-dimensions score of Seattle angina scale(SAQ),self-rating depression scale(SDS)score,self-rating anxiety scale(SAS)score and heart rate variability(SDNN、SDANN、rMSSD、PNN50),(P>0.05).2.Results of electroacupuncture group:The scores of five-dimensions and the total score of SAQ were improved after treatment in electroacupuncture group.There were significant differences in physical activity limitation,angina pectoris stability and angina pectoris attack(P<0.05).There was no statistical significance in treatment satisfaction and disease awareness(P>0.05).After treatment,scale scores improved significantly,the difference was statistically significant(P<0.05).There was significant improvement in heart rate variability(SDNN、SDANN、rMSSD、PNN50)compared with before(P<0.05).3.Results of sham-electroacupuncture group:The scores of five-dimensions and the total score of SAQ were improved,which there were significant differences in physical activity limitation,angina pectoris stability,angina pectoris attack and treatment satisfaction(P<0.05).There was no statistical significance in disease awareness(P>0.05).There was significant improvement in SDS、SAS scale after treatment(P<0.05).The heart rate variability was significantly improved in SDNN、SDANN、rMSSD compared with before(P<0.05).Although the difference in PNN50 was not statistically significant(P>0.05),there was a trend of increase.4.Comparison between two groups:There was significant difference in the stable state of angina pectoris between the two groups(P=0.048,P<0.05),and the electroacupuncture group is better than sham-electroacupuncture group.There was no significant difference between electro-acupuncture group and sham-electroacupuncture group in SAQ total score,physical activity limitation,angina pectoris attack,treatment satisfaction,disease awareness(P>0.05).After treatment,there was no significant difference in time-domain heart rate variability between the two groups(P>0.05)Mechanism studies1.Baseline:Patients with stable angina pectoris with borderline coronary lesions have higher ReHo signals than healthy individuals in ascending parietal convolution,right supramarginal gyrus,left medial superior frontal gyrus,,left inferior temporal gyrus,Left inferior parietal angle,right supplementary exercise area,right hypothalamus,Left medial and lateral buckles,left topside,Right dorsal lateral frontal gyrus,Right angular gyrus and left praecuneus.These brain regions are associated with pain,mood,and directed networks2.ReHo after treatment:2.1 Electroacupuncture group:In the resting state,compared with pre-treatment,the ReHo signals in the right middle temporal gyrus,left medial and lateral cingulate gyrus,and left medial superior frontal gyrus decreased in the electroacupuncture group.Elevated ReHo signals appeared in the right occipital gyrus,right topside gyrus and right corner gyrus.2.2 Sham-electroacupuncture group:In the resting state,,compared with pre-treatment,ReHo signals decreased in the left medial and lateral cingulate gyrus and right inferior temporal gyrus.Elevated ReHo signals were observed in the right topside gyrus,the left superior occipital gyrus and the right superior occipital gyrus.2.3 Comparison between two groups:the ReHo signal of the electroacupuncture group was higher than that of the sham-electroacupuncture group in the right angle gyrus,the left topside gyrus and the right postcentral gyrus.Electroacupuncture group had lower ReHo signal than sham-electroacupuncture group in the left medial superior frontal gyrus and left meditemporal gyrus.3.Functional network connectivity after 2 weeks treatment3.1 Cerebral functional network connection after electroacupuncture treatment for 2 weeks:After 2 weeks of treatment,the electroacupuncture group FC in the left supramarginal gyrus and left inferior parietal angle gyrus increased,FC in right central anterior gyrus and left supplementary sports area increased.FC in right supramarginal gyrus and right middle frontal gyrus increased.3.2 Cerebral functional network connection after sham-electroacupuncture treatment for 2 weeks:After 2 weeks of treatment,FC in the left dorsolateral superior frontal gyrus and the left medial superior frontal gyrus increased.FC in left superior occipital gyrus increased.3.3 The difference of brain functional network connection between electroacupuncture group and sham-electroacupuncture group:FC in right orbital superior frontal gyrus,right middle temporal gyrus,Left medial and lateral cingulate gyrus increased.FC in the right medial and lateral cingulate gyrus,left medial frontal gyrus,right inferior temporal gyrus,Left medial and lateral cingulate gyrus,left angular gyrus,right postcentral gyrus increased.4.The immediate effect FC immediate effect FC after acupuncture Neiguan and Xinmen4.1 The immediate effect FC in electroacupuncture group:FC in right inferior temporal gyrus,left middle occipital gyrus,right thalamus,right trigonal inferior frontal gyrus,left lingual gyrus,right parietal cortex increased.FC in left orbital inferior frontal gyrus,right dorsolateral superior frontal gyrus,left dorsolateral superior frontal gyrus,left posterior central gyrus decreased.FC in Left lingual gyrus,right middle occipital gyrus,right anterior cingulate lobe,left medial superior frontal gyrus,left anterior cingulate and lateral cingulate gyrus,right superior occipital gyrus,left medial superior frontal gyrus increased.FC in right paracentral gyrus and left middle frontal gyrus decreased.FC in meditemporal gyrus increased.4.2 The immediate effect FC in sham-electroacupuncture group:FC in left medial frontal gyrus,left lateral posterior superior frontal gyrus,left supplementary motor region,left medial and lateral cingulate gyrus and left medial frontal gyrus decreased.FC in right supramaginal gyrus,right middle frontal gyrus,right superior occipital gyrus,left central posterior gyrus decreased.FC in left fusiform gyrus increased.FC in the dorsolateral superior frontal gyrus decreased.Conclusions:1.On the basis of basic medicine treatment,acupuncture at Neiguan and Ximen points can improve the clinical symptoms,improve the quality of life,adjust the emotional state of patients and improve the function of cardiac autonomic nervous system.And the effects of electroacupuncture treatment is better than sham-electroacupuncture treatment.2.Compared with healthy people,patients with stable angina pectoris with moderate coronary artery disease have abnormal local in multiple brain regions related to pain,emotional regulation and directional network interrelated region.3.The target of acupuncture Neiguan and Ximen points in the treatment of stable angina pectoris with moderate coronary artery disease may be located in the medial superior frontal gyrus and cingulate gyrus of the "pain matrix",which can achieve analgesic effect by affecting the medial pain system and blocking the descending pain pathways.The negative emotion of patients was improved by regulating the cingulate gyrus,superior frontal gyrus,middle temporal gyrus and inferior temporal gyrus.4.The effect of acupuncture at Neiguan and Qiemen in treating stable angina pectoris with moderate coronary artery disease is not regulated by single brain region,but a complex network interaction and integration of multiple functionally brain regions.Acupuncture at Neiguan and Ximen points not only strengthens the connectivity between the default network and the pain and emotion related brain regions,but also strengthens the connectivity between the sensorimotor network and the pain related brain regions.The brain function connection intensity of electroacupuncture treatment is higher than that of sham-electroacupuncture therapy5.Patients with stable angina pectoris with moderate coronary artery disease have abnormal cardiac autonomic nerve function.Targeted regulation of cingulate gyrus and prefrontal cortical areas may be an important mechanism for the regulation of cardiac autonomic nerve function by acupuncture Neiguan and Ximen.