慢性间歇性低氧新西兰兔右心结构和功能的改变

目的建立慢性间歇性低氧（CIH）新西兰兔模型，应用超声心动图观察CIH早期（0~8周）新西兰兔右心结构、功能及血流动力学的动态变化。 方法健康雄性新西兰兔24只置于8%~21%氧浓度的CIH舱内，每天持续6 h，6 d/周，共8周。于CIH第0、1、2、4、6、8周超声心动图观察新西兰兔右心室结构和功能，同时随机处死1只，观察右心室心肌和肺组织的病理变化。采用混合效应模型分析比较制模后0、1、2、4、6、8周右心结构及功能参数。 结果右心结构参数与CIH 0周比较，右心室前后径、长径、基底部横径、中部横径、右心室前壁厚度、右心室流出道内径、肺动脉内径、左肺动脉内径、右肺动脉内径、右心房前后径及右心房上下径8周时增大，但差异均无统计学意义（P均>0.05）。右心室收缩功能参数：与CIH 0周相比，右心室心肌做功指数（RVMPI）于4周减小（F=3.46，P<0.05），三尖瓣环平面收缩位移（TAPSE）于4、6、8周增大（F=3.11、3.41、3.86，P均<0.05），右心室面积变化率（RVFAC）于8周增大（F=3.45，P<0.05），心率校正的等容收缩时间（ICTc）于2、4周时缩短（F=3.13、3.33，P均<0.05），8周时恢复至基础状态，肺动脉血流频谱射血时间（ET）于1、2周缩短（F=3.01、3.15，P均<0.05），加速时间（AT）于1、2、4周缩短（F=3.13、3.15、3.32，P均<0.05）。右心室舒张功能参数：与CIH 0周相比，心率（HR）于1周、2周、4周加快（F=3.06、3.12、3.30，P均<0.05），心率矫正的等容舒张时间（IRTc）于1、2、4周缩短（F=3.15、3.31、3.17，P均<0.05），三尖瓣口舒张早期峰值流速/组织多普勒右心室侧壁三尖瓣环舒张早期峰值速度（E/E′）于1、2周时减小（F=3.13、3.44，P均<0.05），三尖瓣口舒张早期峰值流速/三尖瓣口舒张晚期峰值流速（E/A）于4、6、8周时增大（F=4.01、3.82、3.37，P均<0.05），组织多普勒右心室侧壁三尖瓣环舒张早期峰值速度/组织多普勒右心室侧壁三尖瓣舒张晚期峰值速度（E′/A′）于8周时增大（F=3.81，P<0.05）。病理学检查：右心室心肌细胞CIH 4周心肌结构正常，心肌细胞细长；CIH 8周少部分出现细胞核肥大，染色加深，部分胞质疏松淡染。肺组织CIH 4周肺组织结构正常，肺泡腔无渗出；CIH 8周少部分出现炎性细胞浸润，毛细血管扩张充血，肺小动脉血管壁轻度增厚。 结论CIH早期新西兰兔右心室功能代偿性增强，且早于结构异常；右心室舒张功能代偿早于收缩功能，IRT和ICT是右心舒张及收缩功能代偿的敏感性指标。

Right ventricle structure and function of New Zealand rabbits with chronic intermittent hypoxia by echocardiography

ObjectiveTo observe right ventricle (RV) structure and function of New Zealand rabbits with chronic intermittent hypoxia (CIH) for short-term (0-8 weeks) by echocardiography. MethodsTwenty-four healthy male New Zealand rabbits were set up CIH animal model for 8 weeks. RV structure′s systolic and diastolic function were measured by conventional and tissue Doppler echocardiography at 0, 1, 2, 4, 6 and 8 week and one rabbit was sacrificed randomly for RV myocytes and pulmonary tissue pathology examination. RV structure and function parameters at 0, 1, 2, 4, 6 and 8 week were analyzed by mixed effects model analysis. ResultsRV structure variables: RV, RA at 8 week increased compared with those at 0 week, but had no significant difference (P>0.05); RV systolic function variables: RVFAC at 8 week increased compared with those at 0 week (F=3.45, P<0.05), TAPSE at 4, 6, 8 week increased compared with that at 0 week (F=3.11, 3.41 and 3.86, all P<0.05), RVMPI at 4 week decreased compared with that at 0 week (F=3.46, P<0.05), recovered to baseline at 6, 8 week. Isovolumetric relaxation time (IRTc) corrected by heart rate at 1, 2, 4 week decreased compared with that at 0 week (F=3.15, 3.31 and 3.17, all P<0.05), recovered to baseline at 8 week, ET of PA at 1, 2 week decreased compared with that at 0 week (F=3.01 and 3.15, both P<0.05), recovered to baseline at 4, 6, 8 week, AT of PA at 1, 2, 4 week decreased compared with that at 0 week (F=3.13, 3.15 and 3.32, all P<0.05), recovered to baseline at 6, 8 week. RV diastolic function variables: isovolumetric contraction time (ICTc) corrected by heart rate at 2, 4 week decreased compared with that at 0 week (F=3.13 and 3.33, both P<0.05), E/E′ at 1, 2 week decreased compared with that at 0 week (F=3.13 and 3.44, both P<0.05), recovered to baseline at 4, 6, 8 week, E/A at 4, 6, 8 week increased compared with that at 0 week (F=4.01, 3.82 and 3.37, all P<0.05), E′/A′ at 8 week increased compared with that at 0 week (F=3.81, P<0.05). The myocardial pathology showed that RV myocardial cell structure was normal at 4 week. Nuclei enlarged, stain darkened and some cytoplasms loosed when exposed to CIH for 8 weeks. The structure of lung tissues was normal when exposed to CIH for 4 weeks. Inflammatory cell infiltrated, capillary engorged as well as the wall of pulmonary arterioles thickened slightly at 8 week. ConclusionsRV diastolic and systolic function showed compensatory and structure was normal in early CIH (0-8 week). RV diastolic function compensated earlier than systolic function. IRT and ICT were sensitive indicators of RV systolic and diastolic function compensation.