Institute of Cellular Medicine, Newcastle Univ., UK.
Am J Physiol Gastrointest Liver Physiol. 2010 May;298(5):G764-73. doi: 10.1152/ajpgi.00501.2009. Epub 2010 Feb 4.
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.
心血管系统失调以自主功能障碍的形式在自身免疫性肝病原发性胆汁性肝硬化（PBC）的疾病进程的所有阶段都很常见，并且与疲劳症状有关。然而，目前尚不清楚 PBC 自主功能障碍的机制。在这项研究中，我们首次使用阻抗心动描记术（ICG）和磁共振方法探索 PBC 的心脏结构和功能。我们通过头部倾斜的体位变化来逐拍评估 ICG，将年龄和性别匹配的高疲劳和低疲劳 PBC 组（疲劳影响量表评估）、正常对照组（每组 15 例）和肝病对照组（原发性硬化性胆管炎）进行分组。我们使用磁共振波谱和电影成像检查了 15 例 PBC 患者和 8 例正常对照组的心脏结构和生物能量学。与匹配的正常对照组相比，PBC 患者的左心室对体位变化的反应能力[左心室射血时间（LVET）]受损（P=0.05）。这是一种与疲劳状态无关的 PBC 特异性现象。与对照组相比，PBC 患者的心肌磷酸肌酸与 ATP 比值（PCr/ATP 比值；心脏生物能量完整性的衡量标准）显著降低（P < 0.01）。6/15（40%）PBC 患者的 PCr/ATP <1.6（提示心肌病死亡风险增加）（0/8 对照组；P < 0.05）。在对照组和 PBC 患者中，所有左心室形态测量的心脏结构和功能均相似。在正常对照组中，PCr/ATP 和 LVET 之间存在密切关系（r(2) = 0.6；P < 0.05），而在 PBC 患者中这种关系丢失，提示存在心肌功能障碍。在 PBC 中，疲劳严重程度与体位变化时心输出量下降之间存在显著相关性（r(2) = 0.25；P = 0.005）。我们的研究结果表明，PBC 中存在心肌功能改变。自主“功能障碍”可能不是一种异常过程，而是一种代偿机制，旨在增加心脏回流以减轻这些影响。
