Assessment of Fetal Autonomic Nervous System Activity by Fetal Magnetocardiography

Aim To clarify the significance of heart rate variability for the evaluation of an autonomic nervous system (ANS) in the normal fetus using fetal magnetocardiography (FMCG). Methods Subjects consisted of normal pregnancy (n = 35) at 28-39 weeks gestation. FMCG was recorded using 64-channel magnetocardiography (MCG) in a magnetically shielded room. The QRS interval was derived from signal-averaged MCG. The R-R interval variability induced by an R-wave trigger was eventually adopted to calculate for time-domain and frequency domain analysis. The power spectrum in the frequency domain was derived from frequency-field components using the maximum entropy method of fetal heart rate variability. Based on frequency analysis, the ranges of the LF and HF domains were defined as 0.01-0.15 and 0.15-0.4 Hz, respectively. We defined a coefficient of variance (CV RR ) as an index of parasympathetic activity, and defined a low frequency/high frequency (LF/HF) ratio as a sympathetic activity. Results The value of CV RR in the normal pregnancy group displayed a slight increasing trend with gestational age (y = 1.77 + 0.10x; r = 0.32). In contrast, the LF/HF ratio in the normal pregnancy group clearly increased over the gestational period (one-way ANOVA: P = 0.003). Conclusions Analyses based on the time and frequency domains of heart rate variability using FMCG enable an evaluation of fetal ANS activity. Sympathetic nervous activity increased with gestational age in the normal pregnancy group

Screening the Single Nucleotide Polymorphisms in Patients with Internal Carotid Artery Stenosis by Oligonucleotide-Based Custom DNA Array

Early screening of individuals considered to be at risk for severe internal carotid artery (ICA) stenosis is an important strategy for preventing ischemic cerebral stroke. The purpose of this study is to screening candidate single nucleotide polymorphisms (SNPs) associated with severe ICA stenosis using a newly developed oligonucleotide-based custom DNA array. The subjects consisted of 47 controls and 46 patients with severe ICA stenosis (≥70%) who underwent carotid endarterectomy (CEA). Subjects gave informed consent and we obtained samples of blood and genomic DNA. We studied 8 candidate genes: renin-angiotensin system [angiotensinogen (AGT), angiotensin II receptor type 1 (AGTR1), nitric oxide synthase 3 (NOS3)]; growth factor [hepatocyte growth factor (HGF)]; transgelin (SM22); cytokine [chemokine receptor 2 (CCR2)]; coagulation-fibrinolysis system [5,10-methylenetetrahydrofolate reductase (MTHFR)]; and plasminogen activator inhibitor 1 (PAI-1). Genotyping of candidate SNPs was done with a line probe assay (LiPA) based on an oligonucleotide-based DNA array. Results: The allele frequency of PAI-1 -1965 delG (odds ratio (OR), 0.3; 95% confidence interval (CI), 0.2–0.6) and MTHFR (OR 1.3, 95% CI, 1.0–1.5) were significantly different between controls and cases with ICA stenosis by Fisher's exact test. Multiple logistic analysis revealed that diabetes mellitus (DM), SNPs in PAI-1 -1965 delG and MTHFR were an independent risk for ICA stenosis. In conclusion, genetic factors of coagulation-fibrinolysis as well as diabetes mellitus (DM) were relevant in ICA stenosis