The Experimental Study In The Role Of Antibodies Against M₂-muscarinic Receptor In The Pathogenesis Of Chronic Cor Pulmonale

MATERIALS and METHODS: Experimental animals: 72 Wistar healthyrats of either male weighing 200³00g were divided randomly into sixexperimental groups: 1.Hypoxic group: (1) Single hypoxic group in which thetypical model of chronic cor pulmonale was constructed according to the methodof XUE's .(2)Hypoxic and Injected with FeCl₃ group, based on the Hypoxicgroup plus FeCl₃ at the same time .2. Hypoxic and interferential group: (1)Cyclosporin A group, with the same method as the hypoxic group pluscyclosporin A at the same time. (2) Nicardipine group ,on the same condition asthe hypoxic group plus nicardipine interfering at the same time.3.Control groupwas fed in normal condition. 4.Immunized group was immunized byM₂-muscarinic receptor peptide . Observed data include detecting the antibody ofM₂ receptor by SA-ELISA and pulmonary artery pressure by the method ofSUN's, cardiac anatomic measurement, cardiac and pulmonary light microscopy,cardiac transmission electronic microscopy examination and agarose gelelectrophoresis. RESULT: 1.Cardiac anatomic measurement: The ventricles of both hypoxic group andimmunized group were weightier than control group. But hypoxic andinterferential group had no significant changes . 2.Antibody of M₂ receptor: Compared by time and quantity, the P/N ofimmunized group was very high after the first immunity, than higher and higheralong with the immunities. Hypoxic group was very high after two weeks. On thecontrary , hypoxic and interferential group's changes were obviously slowly. 3.Pulmonary artery pressure: The pulmonary artery pressure in both hypoxicgroup and cyclosporin A group was higher than other groups. 4.Light microscopy :In both hypoxic group and immunized group, the heartsdisplayed significant alterations as showed by disorder of cardiac muscle fiberand necrosis of myocardial cells together with the infiltration of inflammatorycells. There was no difference in light microscopic findings in both hypoxic andinterferential group. 5.Cardiac transmission electronic microscopy examination: In bothimmunized group and hypoxic group , the hearts showed significant alterationssuch as focal cardiac muscle fiber lysis ,loss of normal muscle fiber bandingpattern , mitochondrial swelling and condensation ,sarcoplasmic vacuolation anddeposition of dense granules in both the sarcoplasmic and muscle fiber. Thecontour of myocytes was irregular and plasma membranes were discontinuous insome cells. All altered myocytes were fairly widely distributed throughout themyocardium .The interstitim showed edema depodits of flocculent serum proteins,occasional activated fibroblasts and increased amounts of collagen fibers. Noobvious alteration were observed in hypoxic and interferential group. 6.Agarose gel electrophoresis: Both immunized group and hypoxic groupshowed DNA fragmentation that produced a ladder of the internucleosomal DNAbands. No ladder of the internucleosomal DNA bands was seen in bothcyclosporin A group and control group. CONCLUSION: 1.In hypoxic group, the rate of positive antibody and the titers of antibodiesto M2-muscarinic receptor in the sera have been kept with a very high level,which experimentally indicates that there were a great relationship between theantibodies against M₂-muscarinic receptor and the pathogenesis of chronic corpulmonale. 2.The fact that the rate of positive antibody and the titers of antibodies toM2-muscarinic receptor in the sera closely related to the pathological damage inright and left ventricles but to pulmonary hypertension shows the antibodies toM2-muscarinic receptor play a very important role in the development of thepathological alterations in chronic cor pulmonale. 3.The immunosuppression of autoimmunity can effectively prevent chroniccor pulmonale from the development of the pathological alterations.