Cyuan-Cin Liu

Multiscale cross-approximate entropy analysis as a measure of complexity among the aged and diabetic.

Complex fluctuations within physiological signals can be used to evaluate the health of the human body. This study recruited four groups of subjects: young healthy subjects (Group 1, n = 32), healthy upper middle-aged subjects (Group 2, n = 36), subjects with well-controlled type 2 diabetes (Group 3, n = 31), and subjects with poorly controlled type 2 diabetes (Group 4, n = 24). Data acquisition for each participant lasted 30 minutes. We obtained data related to consecutive time series with R-R interval (RRI) and pulse transit time (PTT). Using multiscale cross-approximate entropy (MCE), we quantified the complexity between the two series and thereby differentiated the influence of age and diabetes on the complexity of physiological signals. This study used MCE in the quantification of complexity between RRI and PTT time series. We observed changes in the influences of age and disease on the coupling effects between the heart and blood vessels in the cardiovascular system, which reduced the complexity between RRI and PTT series.

Novel application of parameters in waveform contour analysis for assessing arterial stiffness in aged and atherosclerotic subjects

OBJECTIVE Although contour analysis of pulse waves has been proposed as a non-invasive means in assessing arterial stiffness in atherosclerosis, accurate determination of the conventional parameters is usually precluded by distorted waveforms in the aged and atherosclerotic objects. We aimed at testing reliable indices in these patient populations. METHODS Digital volume pulse (DVP) curve was obtained from 428 subjects recruited from a health screening program at a single medical center from January 2007 to July 2008. Demographic data, blood pressure, and conventional parameters for contour analysis including pulse wave velocity (PWV), crest time (CT), stiffness index (SI), and reflection index (RI) were recorded. Two indices including normalized crest time (NCT) and crest time ratio (CTR) were also analysed and compared with the known parameters. RESULTS Though ambiguity of dicrotic notch precluded an accurate determination of the two key conventional parameters for assessing arterial stiffness (i.e. SI and RI), NCT and CTR were unaffected because the sum of CT and T(DVP) (i.e. the duration between the systolic and diastolic peak) tended to remain constant. NCT and CTR also correlated significantly with age, systolic and diastolic blood pressure, PWV, SI and RI (all P<0.01). CONCLUSION NCT and CTR not only showed significant positive correlations with the conventional parameters for assessment of atherosclerosis (i.e. SI, RI, and PWV), but they also are of particular value in assessing degree of arterial stiffness in subjects with indiscernible peak of diastolic wave that precludes the use of conventional parameters in waveform contour analysis.

Multiscale Cross-Approximate Entropy Analysis as a Measurement of Complexity between ECG R-R Interval and PPG Pulse Amplitude Series among the Normal and Diabetic Subjects

Physiological signals often show complex fluctuation (CF) under the dual influence of temporal and spatial scales, and CF can be used to assess the health of physiologic systems in the human body. This study applied multiscale cross-approximate entropy (MC-ApEn) to quantify the complex fluctuation between R-R intervals series and photoplethysmography amplitude series. All subjects were then divided into the following two groups: healthy upper middle-aged subjects (Group 1, age range: 41–80 years, n = 27) and upper middle-aged subjects with type 2 diabetes (Group 2, age range: 41–80 years, n = 24). There are significant differences of heart rate variability, LHR, between Groups 1 and 2 (1.94 ± 1.21 versus 1.32 ± 1.00, P = 0.031). Results demonstrated differences in sum of large scale MC-ApEn (MC-ApEnLS) (5.32 ± 0.50 versus 4.74 ± 0.78, P = 0.003). This parameter has a good agreement with pulse-pulse interval and pulse amplitude ratio (PAR), a simplified assessment for baroreflex activity. In conclusion, this study employed the MC-ApEn method, integrating multiple temporal and spatial scales, to quantify the complex interaction between the two physical signals. The MC-ApEnLS parameter could accurately reflect disease process in diabetics and might be another way for assessing the autonomic nerve function.

Early Administration of Carvedilol Protected against Doxorubicin-Induced Cardiomyopathy.

This study tested for the benefits of early administration of carvedilol as protection against doxorubicin (DOX)-induced cardiomyopathy. Thirty male, adult B6 mice were categorized into group 1 (untreated control), group 2 [DOX treatment (15 mg/every other day for 2 weeks, i.p.], and group 3 [carvedilol (15 mg/kg/d, from day 7 after DOX treatment for 28 days)], and euthanized by day 35 after DOX treatment. By day 35, the left ventricular ejection fraction (LVEF) was significantly lower in group 2 than in groups 1 and 3, and significantly lower in group 3 than in group 1, whereas the left ventricular (LV) end-diastolic and LV end-systolic dimensions showed an opposite pattern to the LVEF among the three groups. The protein expressions of fibrotic (Smad3, TGF-β), apoptotic (BAX, cleaved caspase 3, PARP), DNA damage (γ-H2AX), oxidative stress (oxidized protein), mitochondrial damage (cytosolic cytochrome-C), heart failure (brain natriuretic peptide), and hypertrophic (β-MHC) biomarkers of the LV myocardium showed an opposite pattern to the LVEF among the three groups. The protein expressions of antifibrotic (BMP-2, Smad1/5), α-MHC, and phosphorylated-Akt showed an identical pattern to the LVEF among the three groups. The microscopic findings of fibrotic and collagen-deposition areas and the numbers of γ-H2AX+ and 53BP1+ cells in the LV myocardium exhibited an opposite pattern, whereas the numbers of endothelial cell (CD31+, vWF+) markers showed an identical pattern to the LVEF among the three groups. Cardiac stem cell markers (C-kit+ and Sca-1+ cells) were significantly and progressively increased from group 1 to group 3. Additionally, the in vitro study showed carvedilol treatment significantly inhibited DOX-induced cardiomyoblast DNA (CD90/XRCC1+, CD90/53BP1+, and r-H2AX+ cells) damage. Early carvedilol therapy protected against DOX-induced DNA damage and cardiomyopathy.

Assessment of autonomic dysfunction in patients with type 2 diabetes using reactive hyperemia

It is known that aging and type 2 diabetes mellitus contribute to atherosclerosis and autonomic dysfunction. By using the air pressure sensing system (APSS), peak-peak intervals (PPIs) of wrist arterial waveforms from baseline and reactive hyperemia (RH) were obtained. Through frequency domain analysis of heart rate variability (HRV) and nonlinear Poincaré method, the HRV of healthy young individuals (Group 1, n=25), healthy upper middle-aged individuals (Group 2, n=22), and patients with type 2 diabetes (Group 3, n=28) were assessed. By using the standard deviation (SD) of the instantaneous PPI variability (SD1)/the SD of the long PPI variability (SD2) ratio (SSR), PPIs of the same individuals before and after RH induction were compared. Reduced SSR₁₋₁₀ was noted only in patients with diabetes. Moreover, a significient correlation between SSR₁₋₁₀ and endothelial function was observed in all subjects (r=0.290, p=0.033) after RH. However, no correlation with low-frequency to high-frequency power ratio (LHR) was noted before and after RH. In conclusion, according to our results, campared to the baseline, there were more significant changes of SSR₁₋₁₀ after RH in patients with diabetes; and, a significient correlation between SSR₁₋₁₀ and endothelial function at the moment of RH was noted.

Digital Pulse Volume Based Endothelial Function Detector for Early Stage Formation of Atherosclerosis

In this paper, we discuss the development of an easy-to-use non-intrusive endothelial function assessment instrument. The instrument records the digital pulse volume (DPV) from the fingers. We studied 42 subjects (28 men and 14 women, 22 to 64 years of age) and showed the good performance of self-developed system for monitoring endothelial function. The system is capable to apply both area under the curve of DPV and traditional amplitude methods for endothelial function assessment. Both methods are highly correlated as well as able to reflect the changes of blood flow volume in reactive hyperemia. At home, only a few minutes are needed for conducting a self endothelial function assessment. Therefore, early self-monitoring of cardiovascular dysfunction and arterial stiffness can be easily and effectively achieved.

Simultaneous assessment of autonomic nervous and vascular endothelial functions in a rat model.

Abstract Despite the importance of translational medicine in cardiovascular research, rat vascular endothelial function and sympathetic activity assessment remains challenging. This study consisted of two parts: part A examined the consistency of reactive hyperemia-elicited dilatation index (DI) before (DIOriginal) and after (DIEEMD) ensemble empirical mode decomposition (EEMD) using Wistar-Kyoto (WKY) rats (n=7). Part B compared the endothelial function and heart rate variability of normal WKY rats (group 1, n=9) with those of spontaneously hypertensive rats (group 2, n=9) at two time points of development. The SD1/SD2 ratio (SSR) was obtained from Poincaré plot analysis to evaluate sympathetic activities. Using a Bland-Altman plot, part A of the study demonstrated a lower agreement of DIOriginal than that of DIEEMD. In part B, despite no significant difference in DIEEMD between the two groups at age 10 weeks, DIEEMD was higher in group 1 (2.25±0.63 vs. 1.43±0.41 for groups 1 and 2, respectively, p=0.004) at 20 weeks. Although no notable change in SSR existed in group 1 between the two time points, a significant difference existed in group 2 (p<0.001). In conclusion, using algorithms of Poincaré plot analysis and EEMD, the impact of age and hypertension on rat vascular endothelial function and heart rate variability can be reliably assessed.

Effects of First-Time Overnight CPAP Therapy for Increasing the Complexity of the Patient’s Physiological System

Studies regarding the effects of short-term continuous positive airway pressure (CPAP) therapy are not sufficient. A total of 35 patients with moderate to severe untreated OSA were divided into 2 groups. Group 1 comprised 22 patients who underwent polysomnography (PSG) for one night, and Group 2 comprised 13 patients who received PSG combined with CPAP therapy. To evaluate the influence of receiving CPAP therapy for one night, we measured 5 min wrist pulse signals before and after the experiment to assess heart rate variability, as well as novel short time multiscale entropy (sMSE) indicator that examines complexity in physiological signals. The results show that the participants in Group 1 exhibited significant changes in normalized low-frequency power/normalized high-frequency power (nLF/nHF) (0.72 ± 0.09 versus 1.11 ± 0.11, P = 0.006) values before and after the PSG study. By contrast, the participants in Group 2 showed no significant changes in the 3 indicators. Regarding the sMSE indicator, Group 2 patients exhibited significant increases in the sMSE. CPAP therapy administered for one night can reduce the sympathovagal imbalance in patients with moderate to severe untreated OSA and increase the complexity of the patients physiological system, thereby reflecting their overall improved health.

The factors influence compatibility of pulse-pulse intervals with R-R intervals

Cardiac autonomic dysfunction assessed by power spectral analysis of electrocardigographic (ECG) R-R intervals (RRI) is a useful method in clinical research. The compatibility of pulse-pulse intervals (PPI) acquired by photoplethysmography (PPG) with RRI is equivocal. In this study, we would like to investigate factors influence the compatibility. We recruited 25 young and health subjects divided into two groups: normal subjects (Group1, BMI <; 24, n=15) and overweight subjects (Group2, BMI ≥ 24, n=10). ECG and PPG were measured for 5 minutes. Used cross-approximate entropy (CAE) and Fast Fourier transform (FFT) to obtained compatibility between RRI and PPI. The CAE value in Group1 were significantly lower than in Group2 (1.71 ± 0.12 vs. 1.83 ± 0.11, P = 0.011). A positive linear relationship between CAE value and risk factors of metabolic syndrome. No significantly difference between LFP/HFP ratio of RRI (LHRRRI) and LFP/HFP ratio of PPI (LHRPPI) in Group1 (1.42 ± 0.19 vs. 1.38 ± 0.17, P = 0.064), LHRRRI significantly higher than LHRPPI in Group2 (2.18 ± 0.37 vs. 1.93 ± 0.30, P = 0.005). It should be careful that using PPI to assess autonomic function in the obese subjects or the patients with metabolic syndrome.

In vivo assessment of endothelial function in small animals using an infrared pulse detector

Objective: Endothelial dysfunction is the earliest change in atherosclerosis. Flow-mediated dilatation (FMD) is used to assess endothelial function in humans. However, this assessment is not easy in small animals. This study demonstrated the reliability and reproducibility of a proposed instrument for in vivo assessment of FMD in a rodent model using infrared pulse sensors. Materials and Methods: We used 24 adult male Wistar Kyoto rats randomly divided into three groups. FMD was measured under continuous infusion of normal saline followed by intra-arterial infusion of acetylcholine (Ach; n = 8), sodium nitroprusside (SNP; n = 8), or N∞-nitro-L-arginine methyl ester (L-NAME; n = 8). Results: The dilatation indices (DIs) of all three groups were similar before application of the vasoactive agents (1.82 ± 0.46, 1.81 ± 0.44, and 1.93 ± 0.40, P = 0.877, by one-way analysis of variance). The DI was significantly increased during infusion of Ach (2.97 ± 1.03 vs. 1.82 ± 0.46, P = 0.015), unchanged during infusion of SNP (1.81 ± 0.44 vs. 1.98 ± 0.40, P = 0.574), and attenuated during infusion of L-NAME (1.91 ± 0.40 vs. 1.42 ± 0.35; P = 0.028). Conclusion: The results of this study correlated well with those of human studies, suggesting that this method can be used for in vivo evaluation of endothelial function in small animals.