The Animal Experiment And Clinical Study Of Neurohomoral Activation And Myosin Expression In Congestive Heart Failure

Objectives:The purpose of this study are : (1) To study the rabbit myocardial model injured by epinephrine and norepinephrine, and pathogenesis of catecholamine cardiomyopathy. (2) To study the significance of neuroendocrine and sympathetic nervous system in congestive heart failure. (3) To observe the change of quality and quantity of myocardial beta-receptor in congestive heart failure with different heart function grades (NYHA). (4) To study how the congestive heart failure to develop from compensation to decompensation, including the disorder of myocardial construction protein and the Gene expression besides the myocardial quantity. (5) Screening the patients with high risk dysfunction. (6) To instruct the clinicians how to take the medication reasonably, especially the application of beta-adrenergic blocking drugs. The p-blocker may decrease the mortality rate of heart failure and improve heart function. Methods:This experiment includes basic study and clinical study.Basic study: (1) 30 New Zealand rabbits were divided into three groups: control, norepinephrine (NE), epinephrine (AD). Control group, NE group and AD group were intravenausly administered saline (50ml), norepinephrine (Img/kg), and epinephrine (Img/kg) in 90 minutes, respectively. Blood sample were taken 48 hr after NE, AD treatment, and the serum level of NE, AD was assayed. The myocardial tissue samples were fixed in 10% formalin for light microscopy test stained with HE or fixed in 4% formaldehydum polymerisatum for electronic micrograph. Semi-quantitative histological scoring system level was adopted to estimate the extent of myocardial damage.And the remains of myocardial tissue samples were snap-frozen in liquid nitrogen and stored in -70C refrigerator for examining cAMP and apoptosis gene P53 mRNA, Caspase 3 mRNA by RT-PCR. (2) To observe the effect of a-adrenoceptor and b-adrenoceptor on pathogenesis of norepinephrine-induced cardiomyopathy. (3) To study the level of myocardial myosin heavy chain (MHC) expression in rabbit myocardial model injured by norepinephrine and epinephrine.Clinical study: (1) To study the change of neuroendocrine in congestive heart failure, and to assay the inflammation cytokine (TNF-a and IL-6). (2) To evaluate the extent of myocardial damage and the prognosis biochemical marker in congestive heart failure. (3) The quantity of myocardial beta-receptor and isoproterenol sensitivity test was determined. It is that isoproterenol hydrochloride was given as a rapid injection of lower doses. The peak heart rate was calculated by using the three shortest R-R intervals of the electrocardiogram. Isoproterenol sensitivity test was measured from dose/response curves to rapid intravenous injection as the dose required to increase the heart rate by 25 beats per minute (chronotropic dose25 or CD25). The serum concentration of catecholamine was determined by HPLC-ED system. Serum cardiac troponin T (cTNT), a specific marker reflecting myocardial injury was detected by immunoassay. (4) The level of myocardial myosin expression (heavy chain and light chain) was detected in congestive heart failure. The relation of myosin light chain with cardiac function was analysis. Results:Basic study: (1) Epinephrine and norepinephrine were founded to cause signinicant myocardial injuries, including myocardial degeneration, necrosis with leucocytic infilitration, thrombus formation, etc. (2) The electric microscope showed the myocardial mitochondrion swelling, breakage, lysis, abolition in group of epinephrine and norepinephrine. On the other hand, the epinephrine and norepinephrine can cause the myocardial cell apoptosis. (3)Myocardial enzyme patterns, blood cAMP/cGMP were recorded. The epinephrine and norepinephrine can increase the CK-MB and cAMP/cGMP. The influence of a-antagonist (regitine) and b-antagonist (esmolol) on NE-induced myocardial injury was also investigated with respect to the mechanism of NE and AD injury. (4) Apoptosis Gene (P53 and Caspase3) expression increases in the group of NE and AD. (5) C...