缩窄性心包炎收缩功能障碍的机制研究

Our own and other studies have shown that left ventricular systolic dysfunction was present in constrictive pericarditis. Our study also found that left ventricular systolic dysfunction still persisted for a long time after pericardiectomy, indicating that the pericardial adhesions was not the only factor leading to left ventricular systolic dysfunction, there may be other potential factors responsible for the abnormalities of left ventricular systolic function in constrictive pericarditis. Based on our own and other previous studies, we propose the following hypothesis: constrictive pericarditis has myocardial ischemia and fibrosis, which are correlated closely with myocardial dysfunction; myocardial ischemia is related to the impairment of cardiac microvascular endothelial function and the decrease of capillaries density. We will establish the animal model of constrictive pericarditis, and evaluate the coronary microcirculation perfusion and reserve function by using myocardial contrast echocardiography combined with adenosine stress test, and assess cardiac microvascular endothelial function through intravascular injection of vasoactive substances. The results will be compared with serological and histopathological findings. We will explore the relationships between the impairment of cardiac microvascular endothelial function, the decrease of capillaries density, myocardial fibrosis and myocardial perfusion and myocardial systolic function in constrictive pericarditis. Our study will provide experimental evidence for the mechanism research about the impairments of myocardial systolic function and myocardial perfusion, to which no similar research has been reported before. This will be of great value for reversing progression of disease, clinical decision making, evaluating the surgical effect and prognosis prediction of patients with constrictive pericarditis.

我们及其他研究表明缩窄性心包炎存在左室收缩功能受损。我们还发现心包切除术后心肌收缩功能虽有改善，但长期仍持续存在异常，表明病变心包的粘连束缚不是导致收缩功能受损的唯一因素，缩窄性心包炎收缩功能异常可能有潜在其他因素。基于我们和其他研究者以往的研究，我们提出以下假设：缩窄性心包炎存在心肌缺血及纤维化，并与心肌功能障碍密切相关；其心肌缺血与心肌微血管内皮功能受损、毛细血管密度降低有关。我们将建立缩窄性心包炎动物模型，应用心肌造影结合腺苷负荷试验分析冠脉微循环灌注及储备功能，通过向冠脉内注射血管活性物质评估心肌微血管内皮功能，对比血清学及组织病理学结果，探讨缩窄性心包炎心肌微血管内皮功能受损、毛细血管密度降低及心肌纤维化与心肌灌注及心肌功能间的关系，为缩窄性心包炎心肌收缩功能及心肌灌注受损机制提供实验依据，这在国内外无同类报道。这将对逆转疾病进展、临床决策制定、评估手术效果及预后判断有重要意义。

心包切除术是目前缩窄性心包炎的确定治疗方法，我们前期研究发现术后心肌收缩功能虽有改善，但长期仍持续存在异常，表明病变心包的粘连束缚不是导致收缩功能受损的唯一因素，其收缩功能异常可能有潜在其他因素。基于我们以往的研究，本项目通过向兔心包腔缓慢滴注Pandian诱导剂来建立缩窄性心包炎模型，应用心肌声学造影结合腺苷负荷评估心肌微循环灌注、冠脉血流储备功能；应用二维斑点追踪技术评估左室收缩功能；对建模前后二维斑点追踪参数改变量与心肌造影参数改变量进行相关性分析。完成上述超声成像后，对心脏进行取材和病理学分析。. 研究发现，静息时，缩窄性心包炎兔左室整体圆周应变、纵向应变、心肌信号强度增加速率（β）及血流量（A×β）明显小于建模前[圆周应变（-9.82±1.63）% VS（-12.90±1.14）%，P＜0.01；纵向应变（-14.70±1.80）% VS（-16.76±2.04）%，P＜0.05；β（0.83±0.26）s-1 VS（1.64±0.96）s-1，P＜0.05；A×β（6.96±3.32）dB/s VS（13.55±8.31）dB/s，P＜0.05]；腺苷负荷状态，模型兔左室整体圆周应变、纵向应变、β及A×β较静息时明显增加[圆周应变（-12.28±1.95）% VS（-9.82±1.63）%，P＜0.01；纵向应变（-18.22±2.00）% VS （-14.70±1.80）%，P＜0.01；β（1.61±0.70）s-1 VS（0.83±0.26）s-1，P＜0.01；A×β（12.01±6.58）dB/s VS（6.96±3.32）dB/s，P＜0.01]，但仍然低于建模前同一状态（均P＜0.05）。建模前后左室整体圆周及纵向应变的减低与A×β的减低呈正相关（分别是r=0.711，P=0.010；r=0.627，P=0.029）；左室整体圆周应变的减低与β的减低呈正相关（r=0.650，P=0.022）。缩窄性心包炎存在明显心肌间质纤维化，心肌胶原容积分数是（25.32±7.48）%；心肌组织内TGF-β1表达呈阳性。. 本研究证实了缩窄性心包炎存在心肌微循环灌注减低、心肌纤维化，并与左室收缩功能减低密切相关，为缩窄性心包炎收缩功能障碍的机制研究提供实验依据，具有潜在的临床应用价值。