The Experimental And Clinical Research On Cardiac Structure, Function, Neurohormone, Cell, Molucule And Gene Modulation And The Relationship Among Them In Pneumonia Complicated With Heart Failure

Background and objectives:Pneumonia is a common disease in pediatrics.Till now,pneumonia is still one of the common infectious diseases resulting in death. Pneumonia is pulmonary inflammation caused by different pathogen or other factors.The common clinical manifestations of pneumonia are fever, cough,dyspnea and fixed pulmonary moist rales. Pneumonia can cause many complications including heart failure, air exchange insufficiency,toxic encephalopathy, respiratory failure and opportunistic pathogen infection. All of pulmonary disease per se and secondary complication are the important reasons of high mortality. Heart failure is a severe clinical syndrome,which affects the children health and brings heavy burden to both family and society. The mechanisms of pneumonia with heart failure are very complicated . All of diagnostic criterion are clinical symptoms and signs. There are intimate relationships between the respiratory and circulation system functions.It is very difficult to judge whether the manifestations(for example dyspnea and so on) are caused by heart failure or by severe peumonia.There has exsisted violent controversyfor many years on whether pneumonia combined with heart failure. These influence the effect of treatment.We explored the effect of peumonia on heart from orga^ tissue> neurohormone^ celK molecule and geng level by animal and clinical experiments in order to ensure whether severe peumonia could complicate with heart failure .We also study the pathogenesis of heart failure including cardiac structure, function, neurohormone, cell, molucule and gene to supply theory basis for the treatment of peumonia complicating with heart failure. Methods:1. The construction of model rat with staphylococcus aureus peumoniaFifty Wistar rats were be used. Thirty rats were distributed as peumonia group, thenty rats as control group randomly. Staphylococcus aureus was injected to peumonia group and physiological saline to control group by intratracheal injection. After inoculation,we observed the actions,diets,body form and hair color of the rats daily. The rats were examed by transthoracic echocardiography after five days. Then the rats were killed and the serum,heart,lung and liver samples were taken for study. The pathological changes of heart,lung and liver were observed.2. The measurement of the changes of cardiac structure and function by echocardiography in peumonia rat and patientsWe measured the following indexes by echocardiograph model Agilent Sonos5500: heart rate(HR), aortic root diameter(AO),left atrium diameter(LA),right ventricular diameter(RV),interventricular septum(IVS),left ventricular end-diastolic internal diameter(LVDD), left ventricular end-systolic internal diameter(LVSD),left entricular posterior wall thickness(LVPW),main pulmonary artery(MPA),peak flow velocity of aorta(PFVA),flow velocity integral of aorta(Viao),leak flow velocity of pulmonary artery(PFVP),flow velocity integral of pulmonary artery (Vipa).We also calculated left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS) and the rate of left atrium diameter and aortic root diameter(LA/AO).The calculational formulae as follows:LVEF%= (l.VDD3-LVSD3) / LVDD3 X 100 LVFS%= (l.VDD-LVSD) /LVDD X 100 ALL numerical values were mean of five cardiac cycles. 3. The detection of serum brain natriuretic peptide(BNP) The serum level of BNP was detected by ELISA.4.The detection of serum cardiac troponin T(cTnT) in rats with peumonia The serum level of cTnT was detected by ELISA.5.The detection of serum cardiac troponin I(cTnl), creatinine kinase of myocardial isoenzyme(CK-MB) in children with peumonia.(1) The serum level of cTnl was detected by ELISA.The nomal upper limit is 0.15ng/ml.(2) The serum level of CK-MB was detected by complete automatism biochemical analysis instrument model EncoreTH made in USA.6.The detection of the expression of myocardium myosin heary chain(MHC)mRNA in rats with peumoniaThe expression of MHC mRNA was detected by RT-PCR.7. The detection of apoptosis of myocardium cells in rats with peumonia The apoptosis of myocardium cells was detected by TUNEL.8. The detection of the expression of myocardium Bcl-2 and Bax gene in rats with peumoniaThe myocardium Bcl-2 and Bax gene was detected by immunohistochemical method. Results:1. All of the rats with peumonia had pathological changes in the lungs, which indicated that the models were constructed successfully.There were 93.3 percent cases having pathological changes in myocardium,suggesting that peumonia could have effect on myocardium.2. The means of left atrium diameter(LA) ^ left ventricular end-systolic internal diameter(LVSD)> pulmonary artery(PA)> the rate of left atrium diameter and aorticroot diameter( LA/AO)in rats with peumonia were remarkably larger than those of control group(P< 0.01), which indicated that the hearts of rats with peumonia enlarged.3. The means of peak flow velocity of aorta (PFVA) , leak (low velocity of pulmonary artery(PFVP), flow velocity integral of aorta(Viao), flow velocity integral of pulmonary artery (Vipa), left ventricular ejection fraction (LVEF) and left ventricular fractional shortening( LVFS) in rats with peumonia were lower than those of control group significantly(P< 0.01),indicating that the heart function was worse in rats with peumonia than that of control group.4. The EF,FS,PFVA and PFVP in children with heart failure were remarkably lower than those in common peumonia group and control group. Congenital heart disease and pneumonia complicated with heart failure group compared with severe pneumonia complicated with heart failure group, general pneumonia group compared with normal control group , there were no significant differences in EF,FS,PFVA,PFVP.These indicated that severe peumonia could complicate with heart failure.5. The serum level of BNP in rats with pneumonia whose EF were lower was very significantly higher than in rats with pneumonia whose EF were normal and in control group (P<0.01) .6. The serum level of BNP in the rats with peumonia had positive correlation with LA,LVSD,RV and myocardial histopathologic score and had negative correlation with LVEF,LVFS. These indicated that severe peumonia could complicate with heart failure ulteriorly.7. The serum level of BNP is very significantly higher in patients with heart failure compared with general pneumonia group and normal control group. But congenital heart disease and pneumonia complicated with heart failure group compared with severe pneumonia complicated with heart failure group, general pneumonia group compared with normal control group ,there were no significant differences . These indicated that severe peumonia could complicate with heartfailure ulteriorly.8. The serum level of BNP in patients had linear negative correlation with EF, FS, PFVA, PFVP.The correlation between BNP and EF was best. These indicated that the serum level of BNP in patients had significant correlation with cardiac function. The cardiac function may be reflected by the serum level of BNP.9. The serum level of cTnT was significantly higher in rats with pneumonia whose EF were lower than in rats with pneumonia whose EF were normal and in control group (P<0.01 ).The serum level of cTnT in rats with pneumonia had negative correlation with EF,FS and had positive correlation with myocardial histopathologic score(P<0.05). These comfirmed that severe pneumonia could complicated with myocardial damage, which influenced cardiac function.10. The levels of cTnl were higher and EF, FS,PFVA,PFVP were lower in patients with heart failure group than in general pneumonia group and normal control group. But congenital heart disease and pneumonia complicated with heart failure group compared with severe pneumonia complicated with heart failure group, general pneumonia group compared with normal control group ,there were no significant differences . The cTnl and EF, FS,PFVA,PFVP were significantly linear negative correlated. The correlation between cTnl and EF was best. The serum level of cTnl in patients had significantly positive correlation with CK-MB. These comfirmed that severe pneumonia could cause myocardial damage and complicated with heart failure.11. The expression of a — MHCmRNA were lower in the rats with peumonia than that in the control group,while the expression of P —MHCmRNA in the cases with peumonia increased significantly. The relative contents of a —MHCmRNA had negative correlation with myocardial histopathologic score and had positive correlation with EF ,FS. The relative contents of P —MHCmRNA had positive correlation with myocardial histopathologic score and had negative correlation with EF ,FS.These proved that severe pneumonia could complicated with heart failure from gene level.12. The myocardium apoptosis, Bcl-2 gene and Bax gene could be expressed in rats with pneumonia. The positive expression index was significantly higher in pneumonia group than that of control group (P<0.01). While only Bax was expressed slightly in control group. The myocardium apoptosis, Bcl-2 gene and Bax gene in rats with pneumonia had positive correlation with myocardial histopathologic score .The correlation between Bax and myocardial histopathologic score was best. These proved that severe pneumonia could complicate with heart failure from cell and gene level. Conclusions:1. The patients with severe peumonia could have myocardium damage, pulmonary hypertention and cardiac structure changes,leading to heart failure.2. The serum BNP plays an important role in the development of heart failure in the patient with peumonia.EF could be evaluated by the BNP level.BNP could be a biochemistry index used to diagnose cardiac dysfunction. We can realize the degree of heart failure,prevent and treat heart failure by the serum level of BNP. These indicated that severe peumonia could complicate with heart failure ulteriorly from neurohormone level.3. The serum levels of cardiac troponin were elevated in the severe peumonia complicated with heart failure.The serum level of cardiac troponin I was correlated with heart function negatively. Detection of the concentration of cardiac troponin I in serum could forcast heart function. These comfirmed that severe pneumonia could cause myocardial damage and complicated with heart failure from molecule level.4. The cases with severe peumonia had abnormal expression of MHC,with the transformation of a — MHC to 3 — MHC. These proved that severe pneumonia could complicated with heart failure from gene level.5. The cases with severe peumonia had cell apoptosis and abnormal expression of Bcl-2 and Bax gene.The cell apoptosis was not be initiated by the low expression of Bcl-2 ,but induced by the high expression of Bax. These proved that severepneumonia could complicated with heart failure from cell and gene level. .6. It was proved that severe pneumonia could complicate with heart failure from organ ? tissue > neurohormone , cell -. molecule and gene level by animal and clinical experiments.