Diana Zhang Ye

Post: Full-time Ph.D

Origin: Mainland China, Beijing

Enrolled: 1997 - 2001

First Degree:  Bachelor of Medicine

Supervisor:  Prof. Lester Critchley, Prof. Julian Critchley*
[* Department of Clinical Pharmacology]

Title of Thesis:

Noninvasive investigation of the postural circulatory homeostatic mechanisms and autonomic neuropathy

Outline of the Thesis:

The metabolic syndrome, the constellation of hypertension, dyslipidaemia, and diabetes, has become one of the top killers in modern society. The major reasons for this morbidity and mortality can be ascribed to cardiovascular and renal complications in these patients. As the key regulatory mechanisms for maintaining circulatory homoeostasis, the autonomic nervous system and feedback reflexes, such as the baroreflex, play an important role. Consequently, the final measurable outcome of this regulation, the cardiac time series, heart rate (HR), blood pressure (BP) and stroke volume (SV), inevitably become the focus of research. However, integrated study of this series in a continuous manner, has have seldom been reported mainly because of the difficulties in acquiring reliable data for SV in routine clinical settings. This thesis focuses on the responses of the cardiovascular system to head-up tilting (HUT), which was used to invoke a reproducible challenge to homoeostatic mechanisms in patients with components of the metabolic syndrome.

A non-invasive impedance device, the RheoCardioMonitor, was used to estimate SV. The device was evaluated against an established device, the BoMed, using a series of graded HUT in healthy subjects. A statistical method based on the model fitting of time series analysis using the precision error and cumulative sum was developed. A standard test of the postural circulatory reflexes consisting of three consecutive 3-minute 55-degree HUT was then validated in healthy volunteers. This test design was supplemented by another 10-minute supine-tilt session, which was used to collect HR from a heart rate variability (HRV) monitor, SV from the RheoCardioMonitor and BP from the Portapres, a finger plethysmograph providing continuous BP non-invasively. The subjects were six groups of patients with hypertension, dyslipidaemia and diabetics with worsening degrees of albuminuria and explicit clinical evidence of autonomic neuropathy. Response curves to HUT were then constructed for each haemodynamic variable. Data were analyzed to assess autonomic function through spectral analysis of blood pressure variability (BPV) and HRV. Based on the two series with good coherency, an index of baroreflex sensitivity (BRS) was acquired.

The RheoCardioMonitor showed lower SV than BoMed ( P < 0.001), lower precision error ( P < 0.001), and similar trending ability ( P = 0.083). The response to tilting was an initial (dip) in both systolic and diastolic BP followed by a restoration back to the resting value with a similar dip on return to the supine position in age and sex matched healthy subjects. HR traces showed an increase whereas SV a decrease of 30%. In diabetic patients with autonomic neuropathy, BP restoration was lost, HR increase blunted and there was often a paradoxical increase in SV. Their HRV, low frequency (LF) of BPV and BRS were decreased in both the supine and the tilt position ( P < 0.001), whereas high frequency (HF) of BPV increased ( P < 0.001). Hypertensives showed normal response to HUT for SV, HR and BP but with blunted magnitude. Their BRS ( P < 0.001) and HF of HRV decreased ( P = 0.048) and LF of BPV increased ( P = 0.025). The HUT and beat-by-beat analysis of haemodynamic variables provides a useful marker of the integrity of the postural circulatory reflexes and merits further refinement. They were particularly useful when investigating autonomic dysfunction in diabetic and hypertensive patients.

Current Employment: 

Works for Japanese Pharmaceutical Company based in Beijing

Publications arising from her thesis:

(A) Scientific Papers:

  1. Critchley LAH, Zhang Y, Critchley JAJH, Chung RCK. A comparison of two impedance cardiographs using head-up tilting and trend analysis. Journal of Clinical Monitoring and Computing 2002; 17: 153-160.

  2. Zhang Y, Critchley LAH, Critchley JAJH. Averaging improves the quality of impedance stroke volume measurements during the head up tilt test. Journal of Clinical Monitoring and Computing 2002: 17: 187-193.

  3. Y Zhang, LAH Critchley, YH Tam, B Tomlinson. Impaired postural reflexes in the diabetic patients: An assessment using finger plethysmography and impedance cardiography. Diabetologia 2004; 47: 304-311.

(B) Conference Abstracts:

  1. 2000. Proceedings of the IEEE-EMBS Asia-Pacific Conf. Biomed. Eng., HangZhou, China, p350-351. Zhang Y, Critchley LAH, Critchley JAJH. A simulated model of titing for analysis of continuous haemodynamic data series.

  2. 2001. 12th Int. Symp. Autonomic Nervous System. (Am. Autonomic Soc.) Plam Springs, CA, USA. Zhang Y, Critchley LAH, Critchley JAJH, Tam YH, Chung CK, Chan WB, Tomlinson B, Cockram CS, Chan JCN.. The assessment of autonomic dysfunction using RR interval spectral analysis in diabetic patients with increased urinary albunim excretion rates.

  3. 2001. 3rd HK Diabetes & Cardiovascular Risk Factors, East meets West Symposium. Zhang Y, Critchley LAH, Critchley JAJH, Tam YH, Chung CK, Chan WB, Tomlinson B, Cockram CS, Chan JCN. Blood pressure variability of diabetes with and without albuminuria during head up tilt.

  4. 2001. The 1st WHF Global Conference on Cardiovascular Clinical Trials: Hong Kong. Zhang Y, Critchley LAH, Critchley JAJH, Tam YH, Chung CK, Chan WB, Tomlinson B, Cockram CS, Chan JCN. Autonomic nervous system and baroreflex sensitivity impairment in patients with mild hypertension: assessment by spectral analysis.