Microvascular optical assessment confirms the presence of peripheral autonomic dysfunction in primary biliary cirrhosis
ABSTRACT Autonomic dysfunction (AD) is a significant problem in primary biliary cirrhosis (PBC) and is equally present in early disease stages. Currently, AD in PBC is considered to be central in origin. The aim of this study was to examine peripheral mechanisms in the pathogenesis of AD in PBC using novel microvascular optical assessments for this patient group.
Twenty-four early stage PBC patients and 24 age-matched controls attended for two microvascular optical-based measurement techniques. Firstly, the regulation of microvascular blood volume to the periphery was assessed using multisite photoplethysmography (PPG) by examining the degree of correlation between the right and left sides of the body, with reduced correlation consistent with peripheral AD. Secondly, the peripheral vasomotor reflex response to standing was dynamically tested using laser Doppler flowmetry to quantify the degree of autonomic tone in peripheral vasoconstriction.
PBC patients had a significantly reduced right to left side blood volume multisite PPG correlation compared with controls when corrected for age, body mass index, heart rate and systolic blood pressure [impaired synchronization between pulse wave amplitude between right and left fingers and right and left ears (both P<0.05)]. The veno-arteriolar reflex on standing in PBC patients was significantly lower than for the controls, consistent with poorer autonomic tone for vasoconstriction in PBC (P<0.01).
This study provides evidence for the presence of peripheral autonomic nervous system involvement in PBC. Prospective studies are now warranted to determine the full clinical potential of microvascular optical assessment in PBC.
- [Show abstract] [Hide abstract]
ABSTRACT: Peripheral pulses have been recorded and analysed to determine the accuracy with which pulse transit times (PTTs) can be measured. Measurements of PTT between the ECG Q-wave and various peripheral sites were made in 10 normal subjects on 10 separate days. Mean values were determined for the ears (174 ms), fingers (245 ms), and toes (361 ms). The technique was sufficiently accurate to detect small changes in PTT due to changes in posture; sitting to lying, 5.2 ms. When comparing simultaneous measurements on bilateral sites only small differences in PTT were discovered, and these were not significant in the study group as a whole. However, these differences were significant in some individuals. When the subjects raised a single arm or leg, significant differences (38 ms and 49 ms respectively) were recorded between sides. The day-to-day repeatability sigma (expressed as the square root of the within-subject mean square variance) of individual PTT measurements on a subject (supine) was for ears, fingers and toes respectively 9.4, 9.2 and 12 ms. For right-left differences the repeatability was 7.2, 5.9 and 14 ms. Hence changes in PTTs, or differences between right and left sides, can be detected from single measurements with 95% confidence if they exceed approximately 20 ms in ears or fingers and 30 ms in toes.Clinical Physics and Physiological Measurement 12/1988; 9(4):319-30. DOI:10.1088/0143-0815/9/4/003
- Liver international: official journal of the International Association for the Study of the Liver 11/2009; 29(10):1451-3. DOI:10.1111/j.1478-3231.2009.02141.x · 4.41 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Cardiovascular system dysregulation in the form of autonomic dysfunction is common at all stages of the disease process in the autoimmune liver disease primary biliary cirrhosis (PBC) and associates with the symptom of fatigue. The mechanisms underpinning autonomic dysfunction in PBC are, however, at present unclear. In this study we set out to explore, for the first time, cardiac structure and function in PBC using impedance cardiography (ICG) and magnetic resonance methodologies. ICG was assessed beat to beat in response to orthostasis (by head-up tilt) in age and sex case-matched high-fatigue and low-fatigue PBC groups (assessed by Fatigue Impact Scale), normal control subjects (n = 15 each group) and a liver disease control cohort (primary sclerosing cholangitis). Cardiac structure and bioenergetics were examined in 15 of the PBC subjects and 8 of the normal control subjects by magnetic resonance spectroscopy and cine imaging. Capacity of the left ventricle to respond to orthostasis [left ventricular ejection time (LVET)] was impaired in PBC compared with matched normal control subjects (P = 0.05). This was a PBC-specific phenomenon unrelated to fatigue status. PBC patients exhibited significantly lower cardiac muscle phosphocreatine-to-ATP ratio (PCr/ATP ratio; measure of cardiac bioenergetic integrity) compared with control subjects (P < 0.01). PCr/ATP <1.6 (indicative of increased risk of death in cardiomyopathy) was present in 6/15 (40%) PBC patients (0/8 control subjects; P < 0.05). Cardiac structure and function were similar in all measures of left ventricular morphology between control subjects and PBC. The close relationship between PCr/ATP and LVET seen in normal subjects (r(2) = 0.6; P < 0.05) was lost in PBC patients, a finding compatible with myocardial dysfunction. Significant correlation was seen between fatigue severity in PBC and fall in cardiac output on orthostasis (r(2) = 0.25; P = 0.005). Our findings suggest the presence of altered myocardial function in PBC. Autonomic "dysfunction" may, rather than being an abnormal process, represent a compensatory mechanism to increase cardiac return to mitigate these effects.AJP Gastrointestinal and Liver Physiology 05/2010; 298(5):G764-73. DOI:10.1152/ajpgi.00501.2009 · 3.74 Impact Factor