Study On The Correlation Between Serum 25-(OH)H And Cardiac Autonomic Nerve Function

Objective: Vitamin D has a wide range of physiological effects.Vasovagal syncope(VVS)due to cardiac autonomic nerve dysfunction is clinically common.Evidence for an association between vitamin D and cardiac autonomic nerve function is rarely reported.The aim of this study was to investigate the relationship between serum 25-(OH)D concentration and cardiac autonomic nerve function and its predictive value for VVS,and to provide a reference for clinical management strategies.Methods: Design of animal experiments and clinical studies to validate.(1)Thirty male SD rats aged 9-10 weeks with body masses of300-325 g were divided into experimental(vitamin D deficient chow)and control(normal chow)groups according to the random number table method,12 h incandescent light/12 h night.Body mass changes were recorded during the feeding period(10 weeks)and heart rate variability(HRV)at rest and after exercise stimulation were collected at the end of the 10 th week.Immunohistochemistry(IHC)for atrial and ventricular tyrosine hydroxylase(TH),biochemical assays for acetylcholine(Ach)and nitric oxide(NO),enzyme-linked immunosorbent assay(ELISA)for serum 25-(OH)D and atrial and ventricular noradrenaline(NA)concentrations.The m RNA and protein expression levels of the K+ ion channel Kir 3.1,HERG,KVLQT1 and Min K were detected by q RT-PCR and Western blot,respectively.(2)One hundred and thirty-nine Han Chinese children aged 4-17 years with confirmed VVS were included in the experimental group: 34 were cardioinhibitory type vasovagal syncope(VVS-CI),55 were vasoinhibitory type vasovagal syncope(VVS-VI)and 50 were mixed type vasovagal syncope(VVS-M).The control group consisted of 278 Han Chinese children aged 4-17 years old who were matched for health check-ups at the same time.ELISA was used to determine the serum25-(OH)D concentrations in all children tested.The differences in serum25-(OH)D concentrations were compared between the experimental and control groups,VVS-CI,VVS-VI and VVS-M.(3)Intervention was carried out in 40 Han Chinese children aged6-16 years with confirmed VVS.Health education,autonomic nerve function training and vitamin D supplementation(1200 IU/d)were provided and the follow-up was(66.5±8.1)days.Based on the HUTT results,the study participants were divided into a responsive group and a non-responsive group.Baseline serum 25-(OH)D concentrations,post-intervention serum 25-(OH)D concentrations and the magnitude of their changes were compared between the two groups.Results:(1)Body weight,serum 25-(OH)D,blood creatinine,blood triacylglycerol,haemoglobin and calcium and phosphorus concentrations in atrial and ventricular tissue were significantly lower in the experimental group than in the control group(P<0.01).HRV short time frequency domain analysis,the resting state experimental group had reduced low frequency power(LF)(P<0.05),reduced high frequency power(HF)(P<0.01),an increase in very low frequency power(VLF)(P<0.01)and an increase in LF/HF(P<0.01).The motor stimulation state decreased HF(P<0.01),increased VLF(P<0.01)and increased LF/HF in the experimental group compared to the control group(P<0.01).The number of TH-staining positive cells and the levels of Ach,NA and NO in the atrial ventricular tissue were significantly lower in the experimental group compared to the control group: TH left atrium tissue(P<0.01),left ventricle tissue(P<0.01),right atrium tissue(P<0.05),and right ventricle tissue(P<0.01).Ach left atrial tissue(P<0.01),left ventricular tissue(P<0.01),right atrial tissue(P<0.01)and right ventricular tissue(P<0.01).NA(P<0.01),NO(P<0.01).Expression of m RNA and protein of Kir3.1,HERG,KVLQT1 and Min K was inhibited in the experimental group when compared to the same site(atrial or ventricular)tissue assay.(1)Atrial tissue m RNA expression of Kir 3.1(P<0.01),HERG(P<0.01),KVLQT1(P<0.01),Min K(P<0.01).(2)Ventricular tissue m RNA expression of Kir 3.1(P<0.01),HERG(P<0.01),KVLQT1(P<0.01),Min K(P<0.01).(3)Atrial tissue protein expression of Kir 3.1(P<0.01),HERG(P<0.01),KVLQT1(P<0.01),Min K(P<0.01).(4)Ventricular tissue protein expression of Kir 3.1(P<0.01),HERG(P<0.01),KVLQT1(P<0.01),Min K(P<0.01).(2)Serum 25-(OH)D concentration was reduced in the experimental group compared to the control group(P<0.01).The ROC curve AUC for serum 25-(OH)D concentration to predict VVS was 0.876,95% CI(0.839,0.914),and the cut-off value of serum 25-(OH)D concentration of 51.55nmol/L was taken to predict VVS with a sensitivity of 89.9% and specificity of 74.8%.(3)In the responders group,serum 25-(OH)D concentrations increased significantly from baseline in those with baseline serum25-(OH)D <50 nmol/L(P<0.05).Serum 25-(OH)D concentrations did not change significantly from baseline in the non-responsive group after intervention.Conclusions:(1)Vitamin D deficiency affects ANS function in the rat heart.(2)Serum 25-(OH)D concentrations are lower in children with VVS than in healthy children.Serum 25-(OH)D concentrations have diagnostic predictive value for VVS.(3)Serum 25-(OH)D may approach the "appropriate" nutritional criteria for vitamin D(50 nmol/L)as VVS disease improves.