Liao Yuhua

Effect of anti-cardiac myosin antibody on prognosis of patients with acute myocardial infarction

SummaryTo study whether there was an anti-cardiac myosin antibody (AMA) in serum of patients with myocardial infarction (AMI), relationship between AMA and the prognosis in patients with AMI was investigated. In 67 patients with acute AMI, AMA was assayed by ELISA and left ventricular structure and cardiac function were examined by echocardiography at the end of the first week after infarction and during a 6-month follow-up. The patients with AMI were divided into AMA-positive group and AMA-negative group. The parameters of left ventricular end-diastolic function and prognosis were compared between the two groups. Results showed that the AMA was positive in 18 patients with AMI, with a positive rate of 26.87 %, while it was negative in 20 health donors. The locations of myocardial infarction in the two groups were similar. There were significant differences in Killip class I (22.22 % vs 55.10 %,P < 0.05), decreasing of wall motion and ventricular aneurysm (92.85 % vs 37.5 %,P < 0.01) between the positive group and the negative group. During a 6-month follow-up, the mortality was higher in AMA positive group than in AMA negative group (38.89 % vs 10.20 %,P < 0.05). It is concluded that AMA can be detected in serum of patients with AMI and can serve as an important autoimmune marker. The autoimmune response might take place in AMI. AMA was associated with the left ventricular remodeling and the prognosis of AMI.

HLA-DRB1 gene polymorphism in patients with dilated cardiomyopathy

SummaryTo probe into the genetic background and immunopathogenesis of dilated cardiomyopathy (DCM), HLA-DRBl gene polymorphism in 68 patients with DCM and 175 normal control subjects were analyzed by using the polymerase chain reaction/sequence specific primer (PCR/SSP) techniques. It was found that the frequencies of HLA-DRBl * 15 and HLA-DRBl * 03 alleles were significantly lower in DCM patients than those in normal controls (14.71% vs 29.71% and 4.41% vs 15.43%, respectively), the relative risks (RR) in the DCM patients being 0.41 and 0.25, respectively, allP>0.05. However, the frequencies of HLA-DRBl 11 and HLA-DRB1* 12 alleles were significantly higher in the DCM patients than in controls (29.4% vs 12.00% and 36. 76% vs 12. 57%, respectively) with the RR in the DCM patients being 3.06 and 4.04, respectively, allP>0. 01. These findings further demonstrated that-immunogenetics might play a predominant pathogenetic role in partial DCM patients.

Myosin-induced autoimmune myocarditis in BALB/C mice

SummaryExperimental mice were immunized with cardiac myosin and complete Freund’s adjuvant (CFA) on days 0, 7 and 30 and control mice were immunized with CFA. Sera and myocardium samples were harvested on days 15, 21 and 120 after the first immunization. Pathological findings demonstrated that there were necrosis and inflammatory infiltration in acute stage and fibrosis mainly in chronic stage of experimental group. Anti-myosin antibodies were also found in sera of experimental mice, but not in control group. Our study showed that cardiac myosin served as an autoantigen to provoke autoimmunity and lead to the transformation of VMC into DCM.

Possible association of HLA-DRB1 gene with the autoantibody against myocardial mitochondria ADP/ATP carrier in dilated cardiomyopathy.

SummaryTo probe the genetic background and immunopathogenesis of dilated cardiomyopathy (DCM) 77 patients with DCM, HLA-DRB1 gene polymorphism were analyzed by using the polymerase chain reaction/sequence specific primer (PCR/SSP) technique and autoantibody against myocardial mitochondria ADP/ATP carrier were examined by using the Immunoblot analysis. The frequency of HLA-DRB1*0901 allele was significantly higher in DCM patients in which autoantibody against ADP/ATP carrier of myocardial mitochondria is positive in contrast with those in which the autoantibody is negative (25.46% vs 3.45%,P<0.05), the relative risk (RR) being 9.56. The other frequencies of HLA-DRB1 alleles have no significant difference in the antibody positive group and negative group. It is possible that a subset of DCM patients may exist in which autoimmunity is associated with genetic factors.

Value of quantitative analysis of serum cTnT in diagnosis of cardiac disease and myocardial injury.

SummarySerum cTnT, CK-MB and LD1 were measured in 30 patients with AMI, 76 patients with VMC, 12 patients who had undergone operation without cardioplegia, 16 patients who had received open heart operation, 15 patients who had undergone thoracotomy for non-heart surgery and 55 healthy people. Concentration of serum cTnT was 0.057±0. 056 μg/L in healthy people, 0. 069 ± 0. 032 μg/L in patients who underwent thoracotomy for non-heart surgery, 0.328±0.472 μg/L in patients with VMC, 0.388±0.279 μg/L in patients with DCM, 4.259±4. 619 μg/L in patients with AMI, 8.55±6. 78 μg/L in patients who had undergone operation without cardioplegia and 16.03±6. 01 μg/L in heart operation patients. In patients with VCM and DCM, serum cTnT was more specific and sensitive than CK-MB and LD1 for diagnosing myocardial injury. In patients with AMI and heart operation patients, the increasing multiple of serum cTnT was obviously higher than that of CK-MB and LD1. 72 h after heart operation, cTnT was still higher than normal, while CK-MB had returned to normal level. Serum cTnT had higher specificity and sensitivity and longer diagnostic period in diagnosing myocardial injury. Moreover, cTnT assay could indicate the degree of myocardial injury. So, quantitative analysis of cTnT can be used as a routine examination in the diagnosis of myocardial injury.

Mechanism of anti-β-adrenoceptor antibody mediated myocardial damage in dilated cardiomyopathy

SummaryAntibodies against β1-adrenoceptor can be detected in serum of patients with dilated cardiomyopathy (DCM), which have β-agonist-like activity, and induce a positive chronotropic effect on cardiac myocytes by its persistence at full strength. Effects of the antibodies against β-adrenoceptor from sera of patients with DCM on myocardial cytotoxicity and cytoplasmic free Ca2+-concentration ([Ca2+]i) were observed in the cultured single layer SD rat ventricular cells by using the cytotoxicity assay and fluorescent Ca2+- indicator fura-2/AM. The positive sera of the anti-β-adrenoceptor antibodies from patients with DCM markedly enhanced myocardial [Ca2+]i. Betaloc, a βi-receptor blocker, might inhibit the increase of the antibody-mediated myocardial [Ca2+]i, and the sera from healthy donors had no effect on myocardial [Ca2+]i. Our results suggest that the anti-β-adrenoceptor antibody might increase myocardial [Ca2+]i and result in myocardial damage. The antibodies might activate receptor-gating [Ca2+]-channel, thereby causing myocardial [Ca2+]i rise and calcium overload. Early use of betaloc is recommended in the treatment of dilated cardiomyopathy.Antibodies against beta(1)-adrenoceptor can be detected in serum of patients with dilated cardiomyopathy (DCM), which have beta-agonist-like activity, and induce a positive chronotropic effect on cardiac myocytes by its persistence at full strength. Effects of the antibodies against beta-adrenoceptor from sera of patients with DCM on myocardial cytotoxicity and cytoplasmic free Ca(2+)-concentration ([Ca2+]i) were observed in the cultured single layer SD rat ventricular cells by using the cytotoxicity assay and fluorescent Ca(2+)-indicator fura-2/AM. The positive sera of the anti-beta-adrenoceptor antibodies from patients with DCM markedly enhanced myocardial [Ca2+]i. Betaloc, a beta(1)-receptor blocker, might inhibit the increase of the antibody-mediated myocardial [Ca2+]i, and the sera from healthy donors had no effect on myocardial [Ca2+]i. Our results suggest that the anti-beta-adrenoceptor antibody might increase myocardial [Ca2+]i and result in myocardial damage. The antibodies might activate receptor-gating Ca(2+)-channel, thereby causing myocardial [Ca2+]i rise and calcium overload. Early use of betaloc is recommended in the treatment of dilated cardiomyopathy.