| Intracerebral hemorrhage(ICH)is a disease with high rates of disability and mortality.Cardiac complications are common in patients with ICH and are closely related to patient prognosis,however,the mechanism of their occurrence has not been fully elucidated.Therefore,it is necessary to search for risk factors related to cardiac injury after ICH from the perspective of clinics,and explore the pathogenesis of cardiac injury after ICH based on animal models.Hereby,we conducted this research and represented the results and conclusion as follows:Objective:1.To explore the main risk factors of ECG abnormality and myocardial enzyme elevation through the retrospective analysis of electrocardiogram(ECG)abnormality and myocardial enzyme elevation in patients with ICH.2.To observe the role of splenectomy in secondary heart injury after ICH,so as to understand the role of monocytes and immune-inflammatory mechanism,by means of establishing an animal model of secondary heart injury following ICH.3.To observe the changes of monocytes in spleen and heart and their effects on heart damage after ICH,by using angiotensin converting enzyme inhibitor(ACEI)to reduce the content of angiotensin II(Ang II)in rat peripheral circulation;and to explain the role of Ang II and monocytes by comparing with the effects of splenectomy.Methods:1.In accordance with the inclusion and exclusion criteria,208 patients with ICH were retrospectively analyzed in terms of demographic data,medical history,past history,clinical manifestations,ECG,serum myocardial enzymes,and head CT at admission,in order to find independent risk factors affecting ECG abnormalities and increased myocardial enzymes.2.ICH model and splenectomy model were established in rats,and rats were divided into blank control group,splenectomy group,cerebral hemorrhage group and splenectomy group.Cardiac damage was observed by ECG,echocardiography,myocardial enzyme detection and pathological examination.The changes of monocytes in heart and spleen were observed by immunofluorescence staining.The number of monocytes in the spleen,peripheral circulation and heart were detected by flow cytometry.The contents of monocyte chemoattractant protein 1(MCP-1),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in rat heart tissue were detected by Western-blot.3.Rats with ICH model,splenectomy model and ACEi gavage model were established.Rats were divided into 6 groups: control group,splenectomy group,ICH group,ICH+splenectomy group,ICH+ACEi group,ICH+ACEi+splenectomy group.The changes of peripheral circulation Ang II were detected by Elisa.Transwell cell migration assay was used to detect the induction effect of Ang II on spleen monocyte migration in vitro.The pathological changes of heart and spleen were observed.The changes of monocytes in heart and spleen were observed by immunofluorescence staining.Flow cytometry was used to detect the number of monocytes in heart,spleen and whole blood.The contents of Mc P-1,IL-6 and TNF-α in heart tissue were detected by Western-blot.ECG,echocardiography and myocardial enzyme detection were used to observe myocardial damage.Results:1.145 patients(69.71%)with ICH suffered at least one kind of ECG abnormality;The incidence of several common ECG abnormalities in descending order were: corrected QT prolongation,ST segment depression,T wave inversion.The serum level of at least one myocardial enzyme was elevated in 139 patients(66.83%),and the incidence of myocardial enzyme elevation in descending order was lactate dehydrogenase(LDH),hypersensitive cardiac troponin T(hs-c Tn T),creatine kinase(CK)and creatine kinase isoenzyme(CKMB).Secondary intraventricular hemorrhage and hematoma volume > 30 ml were independent predictors of corrected QT prolongation.Location of hematoma in thalamus,hematoma volume > 30 ml,insular involvement and secondary ventricular hemorrhage were independent predictors of ST segment depression.Insular involvement and hematoma volume >30 ml were independent predictors of creatine kinase elevation.Glasgow coma score≤ 8 and insular involvement were independent predictors of creatine kinase myocardial isoenzyme elevation.Secondary ventricular hemorrhage was an independent predictor of lactate dehydrogenase elevation.Advanced age,hyperglycemia at admission,and history of antiplatelet drug use were independent predictors of hypersensitive cardiac troponin T elevation.2.The ECG of rats with ICH showed the upward shift of J-point,the increase of T-wave amplitude and the increase of PR interval.Echocardiography showed that left ventricular ejection fraction(LVEF)and left ventricular short axis shortening rate(LVFS)decreased.Serum CK,CKMB,LDH and hs-c Tn T increased.The structure of cardiac tissue is disordered,the cardiomyocytes are swollen and arranged disorderly,the gap between cardiomyocytes is reduced,accompanied by extensive cardiomyocyte necrosis and inflammatory cell infiltration.Splenectomy could alleviate the above symptoms of myocardial injury after ICH.Monocytes in spleen decreased significantly after ICH,while monocytes in heart and peripheral blood increased after intracerebral hemorrhage.Splenectomy could reduce monocytes in heart and peripheral blood after ICH.The expression of MCP-1,IL-6 and TNF-αincreased after ICH.Splenectomy could down-regulate the expression of these inflammatory factors.3.The content of Ang II in peripheral circulation increased after ICH,and the content of Ang II decreased with use of ACEi.Ang II could induce the migration of spleen monocytes in vitro.In rats with ICH,spleen monocytes increased after reducing Ang II in blood.Monocytes from the spleen decreased in the heart.The expression of Mc P-1,IL-6 and TNF-α decreased in the heart.ECG,echocardiography,myocardial enzyme,pathology and other cardiac injury indexes of rats improved after use of ACEi.Conclusions:1.The strongest risk factors of ECG and myocardial enzyme abnormalities after ICH were hematoma spread to insular lobe,secondary ventricular hemorrhage and hematoma volume > 30ml;GCS ≤ 8 points,hematoma locates in thalamus,old age,admission hyperglycemia,previous use of antiplatelet aggregation drugs were also related to abnormal ECG and increased myocardial enzymes.2.Injection of 100μ L of arterial blood into the upper insula of healthy SD rats can lead to abnormal ECG,increased myocardial enzymes,decreased cardiac systolic function and pathological changes of the heart.This method can simulate the pathophysiological process of secondary cardiac damage in patients with ICH.3.Splenectomy can reduce the damage of the heart after ICH and improve the function of the heart.4.The directional migration of monocytes from spleen to heart after ICH is involved in the secondary cardiac injury,and Ang II is an important inducer to drive the directional movement of monocytes.The reduction of Ang II can simulate the protective effect of splenectomy on the heart after ICH,which provides a new theoretical fundamental for the treatment of secondary cardiac injury after ICH. |
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