| Objective: Right ventricular dysfunction is one of the most important physiopathologic change following pulmonary embolism (PE) and a strong predictor of poor clinical outcome. Echocardiogram is a useful instrument to evaluate heart function, which could show the signs of pulmoanry hypertension, right ventricular overload and pneumocardial disease. According to the sighs aforementioned, sub-massive pulmonary embolism is subdivided. It is still uncertain that the biomarkers detect myocardial injury earlier. N-terminal pro-brain natriuretic peptide (NT-proBNP) and heart-type fatty acid binding protein (H-FABP) are sensitive biomarkers for heart failure and myocardial ischemic injury, which are advocated recently. There are several foreign clinical studies on biomarkers and risk stratification of PE but few of them monitor the serumal concentrations consecutively. In this model of PE, we detect the content of NT-proBNP and H-FABP in serum consecutively, to describe the release kinetics of them, which may be useful for optimization of biomarkers.Meanwhile, revealing the mechanisms of myocardial injury rely on histopathologic and ultramicrostructure changes of myocardium. Method: twenty-four New Zealand rabbits of either gender and weighing 2.5~3.5kg were studied, which the left lower lung artery were obstructed by inflating gas of 5F Berman sacculus catheter to set up rabbit pulmonary embolism model. The animals were randomly divided into four groups: (1)sham operation group(n=6), (2)embolism 0.5h group (n=6), (3)embolism 1h group (n=6), (4)embolism 2h group (n=6). Pulmonary arterial systolic pressure(PASP), pulmonary arterial diastolic pressure(PADP), and pulmonary arterial mean pressure(PAMP) were monitored, and the pulmonary pressure at pre-embolization, embolization instantly, embolization 0.5h, 1h, 2h were recorded. Drawing venous blood of all group rabbits at the corresponding time, centrifuged, then extracted the supernatant. All the serum were preserved in the -20℃refrigerator before the contents of NT-proBNP,H-FABP were measured by sandwich enzyme-linked immunosorbent assay. The rabbits were killed at the end of experiments, and the ventricular myocardium tissue specimen was fixed by 4% polyformaldehyde and 4% glutaraldehyde respectively, then histopathologic and ultramicrostructure changes of myocardium were studied by light microscope and electron micrograph.Results: (1)The change of pulmonary pressure: except for the sham operation group, PASP, PADP, and PAMP were rapidly increased at the moment of embolization, and were higher significantly than pre-embolization(P<0.05,respectively). PASP, PADP, and PAMP were decreased gradually at embolization 0.5h, 1h, but still higher significantly than pre-embolization(P<0.05,respectively), and then decreased to the level of pre-embolization. (2)The change of serum NT-proBNP: except for the sham operation group, the content of NT-proBNP were higher significantly at embolization 0.5h, 1h, and 2h than pre-embolization(P<0.05,respectively), and gradually increased accompanied the prolongation of embolization. When contrasting to the value of corresponding time in different groups, only the content of embolization 1h and 2h were higher significantly than the sham operation group (P <0.05,respectively). (3)The change of serum H-FABP: The content of serum H-FABP were higher significantly at embolization 0.5h, 1h, and 2h than pre-embolization and the sham operation group(P<0.05,respectively). At embolization 2h, there was still not sign of decrease. (4)Histopathologic change of ventricular myocardium: in both sham group and embolism groups, there were not signs of myocardium focal necrosis and bleeding with hematoxylin-eosin staining (H-E staining) under light microscope examination. But in embolism group, myocardial cell nucleus stained darker, even karyopycnosis,and myocardium edema was seen. Transmission electron microscope showed mitochondria swelling, cristae structure derangement, partial cristae disaggregation, vacuolization, even the whole mitochondrion rupture,partial sarcomere disruption in the experimental group.Conclusion: (1)Histopathologic and ultramicrostructure changes of myocardium show the myocardial ischemic injury in PE. (2)Pulmonary vascular resistance, pulmonary arterial pressure and cardiac output interact, to form the base of physiopathologic change of cardiovascular system in PE.(3)NT-proBNP,H-FABP may be the earlier biomarker of myocardial injury, monitoring the contents in serum together is helpful for risk stratification and therapy in PE. |
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