Correlation of cardiac troponin T gene mutations to hypertrophic cardiomyopathy in Chinese patients / 南方医科大学学报

<p><b>OBJECTIVE</b>To study cardiac troponin T (TNNT2) gene mutations in Chinese patients with hypertrophic cardiomyopathy (HCM) and analyze the correlation between the genotype and phenotype.</p><p><b>METHODS</b>Ninety-five unrelated Chinese patients with HCM and 120 control individuals were screened for TNNT2 gene mutations. Seven exons (8, 9, 10, 11, 14, 15, and 16) in the functional regions of TNNT2 gene were amplified using PCR and the products were sequenced. The patients with positive results underwent further family screening.</p><p><b>RESULTS AND CONCLUSION</b>This study did not find any HCM-caused mutations in TNNT2 gene, a result different from the reported rates of TNNT2 gene mutation ranging from 10% to 20% in other nations, suggesting that TNNT2 gene is not a susceptible gene for HCM in Chinese population.</p>

Association between myocardial calpain activation and apoptosis in lipopolysaccharide-induced septic mouse model / 中华心血管病杂志

<p><b>OBJECTIVE</b>in septic mice, myocardial calpain was activated and induced caspase-3 activation, the association between calpain activation and apoptosis was explored in this experiment.</p><p><b>METHODS</b>in in vivo model, adult C57 mice were injected with lipopolysaccharide (LPS, 4 mg/kg, i.p.) to induce sepsis. Myocardial calpain and caspase-3 activities, protein levels of calpain-1, calpain-2, calpastatin, Bcl-2 and Bid were detected by Western blot analysis and myocardial apoptosis was detected by TUNEL, myocardiac function was evaluated by Langendorff system. In in vitro model, adult rat cardiomyocytes were incubated with LPS (1 microg/ml) or co-incubated with calpain inhibitor-III (10 micromol/L), calpain activity, caspase-3 activity, protein levels of Bcl-2 and Bid, and cardiomyocyte apoptosis were detected.</p><p><b>RESULTS</b>in septic mice, myocardial calpain and caspase-3 activity were increased up to 2.7- and 1.8-folds, respectively. Both calpain inhibitor-III and PD150606 significantly attenuated the increase of caspase-3 activity. Myocardial protein levels of calpain-1, calpain-2, calpastatin, Bcl-2 and Bid were similar between control and septic mice, and no cleavage of both Bcl-2 and Bid was found in septic mice. Calpain inhibitor-III significantly improved myocardial function in septic mice. In in vitro model, calpain and caspase-3 activities were increased after 4 h LPS treatment, co-treatment with calpain inhibitor-III prevented caspase-3 activity increase, protein Bcl-2 and Bid were similar between normal cardiomyocytes and LPS-treated cardiomyocytes. Cardiomyocyte apoptosis was similar in in vivo and in vitro septic models.</p><p><b>CONCLUSION</b>myocardial calpain activity is increased in LPS induced septic mice, subsequent caspase-3 activation may contribute to myocardial dysfunction in septic mice without aggravating myocardial apoptosis and Bcl-2 and Bid are not involved on calpain induced caspase-3 activation in our model.</p>

Link between cardiac myosin binding protein-C gene mutation of Pro1208fs and Gly507 Arg and hypertrophic cardiomyopathy in Chinese patients / 中华心血管病杂志

<p><b>OBJECTIVE</b>To detect gene mutations associated with hypertrophic cardiomyopathy (HCM) in Chinese patients and possible correlations between genotype and phenotype.</p><p><b>METHODS</b>Twenty-one unrelated patients with hypertrophic cardiomyopathy were studied. The clinical data including symptoms, physical examination, echocardiography and electrocardiography were collected. The full ecoding exons of cardiac myosin-binding protein C gene (cMYBPC3) were amplified with PCR and the products were sequenced.</p><p><b>RESULTS</b>Two mutations were identified in probands from two families. One mutation was frame shift mutation Pro1208fs in the exon 32 of the cMYBPC3 gene. Pro1208fs mutation was identified in a 59 years old female patient with familial hypertrophic cardiomyopathy. Symptom onset was late and a favorable clinical course was evidenced in this patient. Another mutation was missence mutation Gly507Arg in the exon 17 of the MYBPC3 gene identified in a 24 years old male patient. Diffuse thickness of left ventricular wall, impaired diastolic function and enlarged left atria were evidenced in echocardiography. No mutation was identified in the 80 control healthy individuals.</p><p><b>CONCLUSION</b>cMYBPC3 might be the disease-causing genes in Chinese patients with hypertrophic cardiomyopathy.</p>

Determination of optimal left ventricular pacing site for cardiac resynchronization therapy by tissue Doppler imaging / 上海第二医科大学学报

Objective To investigate whether the left ventricular delayed contraction site determined by tissue Doppler imaging might be an optimal left ventricular lead position for improved outcomes of cardiac resynchronization therapy (CRT) in patients with non-ischemic cardiomyopathy. Methods Thirty-three patients subjected to CRT were selected, and all were performed conventional ultrasound cardiography and tissue Doppler examinations before operation. The left ventricular delayed contraction site was determined according to the interval between the onset of QRS and the peak systolic velocity. Retrograde coronary venography was performed during operation, and the left ventricular lead site was selected according to the left ventricular delayed contraction site determined by tissue Doppler examination before operation. The coronary sinus lead site was determined under the guidance of X ray of dorsaventral, lateral, right anterior oblique and left anterior oblique positions. Patients were divided into group A(n=20, the left ventricular lead site was in line with the delayed contraction site) and group B (n=13, the left ventricular lead site was not in line with the delayed contraction site). Results There was no significant difference in age, NYHA grading, left ventricular end-systolic volume(LVESV), left ventricular ejection fraction(LVEF), pulmonary arterial systolic pressure, QRS width and Ts-SD between the two groups before operation(P> 0.05). Six months after CRT, there was no significant difference in NYHA grading, LVESV and mitral regurgitation(MR) grading between the two groups(P>0.05), while the increase in LVEF and decrease in LVESV of group A were more significant than those of group B (P<0.01). Conclusion In patients with non-ischemic cardiomyopathy, CRT significantly improves left ventricular performance, and the more favourable outcomes are achieved in those pace at the delayed contraction site. Tissue Doppler imaging may help to guide the implant of left ventricular lead.

Endothelin-1 overexpression inhibits rat pulmonary arterial microvascular smooth muscle cell apoptosis via Akt/PKB pathway / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effects of endothelin-1 (ET-1) overexpression on apoptosis of the rat pulmonary arterial microvascular smooth muscle cells (RPMC) in vitro.</p><p><b>METHODS</b>Primary RPMC obtained from the pulmonary artery and lung microvasculature were identified by immunofluorescence staining and electron microscope technique. The RPMC was transient transfected with the pMEXneo-ET1 and pCDNA5-FRT-TO-ET1-3'UTR plasmids as well as the empty vector respectively via lipofectamine. Flow cytometry was used to assess the cell cycle and apoptosis of RPMC. Akt and Caspase-3 expressions were detected by Western blot and real time RT-PCR.</p><p><b>RESULTS</b>The mRNA of ET(A) expression was significantly higher than that of ET(B) receptor in primary RPMC. Flow cytometry analysis revealed significantly reduced apoptosis in ET-1 transfected RPMC compared to that in vehicle transfected RPMC. Overexpression of ET-1 in RPMC also significantly increased the phosphorylation of Akt and reduced the cleaved Caspase-3 expression.</p><p><b>CONCLUSIONS</b>Overexpression of the ET-1 inhibited RPMC apoptosis and activated Akt/PKB-Caspase-3 signaling pathway, which might be responsible for ET-1 induced the pulmonary microvascular arteries remodeling.</p>

Real-time myocardial contrast echocardiography can predict functional recovery and left ventricular remodeling after revascularization in patients with ischemic heart disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Previous studies showed that preservation of microvascular integrity after myocardial ischemia was associated with myocardial viability. Real-time myocardial contrast echocardiography (RT-MCE) is a promising modality for non-invasive evaluation of microcirculation perfusion. Thus, it provides a unique tool to detect myocardial viability. We sought in this study to investigate the role of RT-MCE in predicting left ventricular (LV) functional recovery and remodeling after revascularization in patients with ischemic heart disease.</p><p><b>METHODS</b>Thirty-one patients with ischemic heart disease and resting regional LV dysfunction were included. LV volume, global and regional function were evaluated by echocardiography before and 6 - 9 months after revascularization. RT-MCE was performed before revascularization using low mechanical index power modulation imaging. Myocardial contrast opacification of dysfunctional segments was scored on a 3-point scale and mean contrast score in dysfunctional segments was calculated. Patients were divided into 2 groups according to mean contrast score in dysfunctional segments: group A, patients with mean contrast score = 0.5 (n = 19); group B, patients with mean contrast score < 0.5 (n = 12).</p><p><b>RESULTS</b>Wall motion improvement was found to be 94.5%, 45.5% and 16.1% respectively (P < 0.01) in homogenous, patchy and absent contrast opacification segments. At baseline, there was no significant difference in LV volume and global function between the two groups. After revascularization, group B had significantly larger LV end-diastolic volume (LVEDV) and LV end-systolic volume (LVESV), lower LV ejection fraction (LVEF) and higher wall motion score index (WMSI) than those of group A (all P < 0.05). Revascularization was followed by significant improvement of LV volume and recovery of global LV function in group A (all P < 0.01); however, in group B, after revascularization, deterioration of LVEDV (P < 0.05) was observed, moreover LVESV, WMSI and LVEF did not change significantly.</p><p><b>CONCLUSIONS</b>The maintenance of myocardial microcirculation detected by RT-MCE can predict functional recovery and LV remodeling after revascularization in patients with ischemic heart disease, which might be helpful in clinical decision-making and risk stratification.</p>

Assessment of left ventricular systolic synchronicity by real-time three-dimensional echocardiography in patients with dilated cardiomyopathy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recent advances in real-time three-dimensional echocardiography (RT3DE) offer the potential to assess the left ventricular (LV) dyssynchrony simultaneously by analyzing the 17 segments time-volume curves. The purpose of this study was to test the feasibility and accuracy of RT3DE for quantitative evaluation of left ventricular systolic synchronicity.</p><p><b>METHODS</b>Twenty-four patients with dilated cardiomyopathy (DCM) and twenty-five healthy volunteers were enrolled in this study. Full volume RT3DE was performed by using Philips IE33 with X3-1 probe. The global and 17-segmental time-volume curves were obtained by the on-line Qlab software (version 4.2). The time to minimal systolic volume in each segment (T(msv)) was taken to derive the following indexes of systolic asynchrony: T(msv) 16-SD, T(msv) 16-Dif, T(msv) 12-SD, T(msv) 12-Dif, T(msv) 6-SD and T(msv) 6-Dif, which meant the standard deviation or the maximal difference of T(msv) among the 16, 12 and 6 segments of the left ventricle respectively. The software also provided with each of the above parameters as a percentage of the cardiac cycle.</p><p><b>RESULTS</b>T(msv) 16-SD, T(msv) 12-SD and T(msv) 6-SD were all significantly larger in the DCM group than those of the control group [T(msv) 16-SD: (52.9 +/- 40.6) ms vs (8.8 +/- 6.2) ms; T(msv) 12-SD: (29.5 +/- 30.8) ms vs (6.9 +/- 4.0) ms; T(msv) 6-SD: (28.9 +/- 34.6) ms vs (7.0 +/- 4.7) ms, all P < or = 0.001]. T(msv) 16-Dif, T(msv) 12-Dif and T(msv) 6-Dif were also significantly larger in the DCM group. There were close negative relations between the LVEF determined by RT3DE and each of the indexes of systolic asynchrony, among which the indexes of T(msv)-16-SD% and T(msv)-16-Dif% correlated most closely (r = -0.703 and r = -0.701, respectively). The DCM patients had significantly larger EDV and ESV, with significantly reduced LVEF compared with the healthy subjects.</p><p><b>CONCLUSION</b>RT3DE provides a simple, useful and unique approach to assess the systolic synchronicity of all the left ventricular segments simultaneously.</p>

Usefulness of dobutamine stress myocardial contrast echocardiography for assessing coronary artery disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Quantitatively assessing myocardial perfusion and its reserve is of great importance for the diagnosis and stratification of patients with coronary artery disease (CAD), and represents an important goal of myocardial contrast echocardiography. In this study we sought to test the usefulness of low dose dobutamine stress real-time myocardial contrast echocardiography (RT-MCE) in the assessment of CAD, and to explore the relationship between perfusion reserve and contractile reserve.</p><p><b>METHODS</b>Twenty-six patients with suspected or clinical diagnosed CAD were enrolled and underwent RT-MCE at baseline and under low dose dobutamine stress, and subsequent coronary angiography. RT-MCE images were analyzed quantitatively from microbubble replenishment curves for myocardial perfusion and its reserve.</p><p><b>RESULTS</b>At baseline, significant differences in beta (0.28 +/- 0.12, 0.25 +/- 0.09, 0.22 +/- 0.06, 0.20 +/- 0.07 respectively, P < 0.01) and A x beta (1.37 +/- 0.46, 1.28 +/- 0.47, 1.13 +/- 0.37, 0.91 +/- 0.32, respectively, P < 0.01) were observed among four segment groups with graded coronary artery stenosis severity (normal; 30% - 69% stenosis; 70% - 90% stenosis; and beyond 90% stenosis), but not observed in parameter A. When under stress, significant differences in A (5.73 +/- 1.28, 5.63 +/- 1.01, 4.96 +/- 0.81, 4.57 +/- 0.62, respectively, P < 0.01), beta (0.67 +/- 0.17, 0.55 +/- 0.19, 0.32 +/- 0.13, 0.25 +/- 0.08, respectively, P < 0.01) and A x beta (3.81 +/- 1.20, 3.11 +/- 1.17, 1.59 +/- 0.82, 1.12 +/- 0.37, respectively, P < 0.01) were observed among the formerly mentioned groups. Graded decreases in A reserve (1.20 +/- 0.53, 1.11 +/- 0.16, 0.98 +/- 0.12, 0.99 +/- 0.13, respectively, P < 0.01), beta reserve (2.65 +/- 1.07, 2.32 +/- 0.82, 1.44 +/- 0.40, 1.29 +/- 0.34, respectively, P < 0.01) and A x beta reserve (3.05 +/- 1.63, 2.59 +/- 1.01, 1.42 +/- 0.44, 1.27 +/- 0.34, respectively, P < 0.01) could also be observed with increasing coronary stenosis severity. In five segments groups scored by WMS (1 - 5), concordance between contractile function and myocardial perfusion could be found both at rest (beta: 0.28 +/- 0.11, 0.22 +/- 0.08, 0.21 +/- 0.05, 0.17 +/- 0.05, 0.19 +/- 0.06, respectively, P < 0.01; A x beta: 1.29 +/- 0.48, 0.98 +/- 0.45, 0.94 +/- 0.29, 0.76 +/- 0.30, 0.92 +/- 0.32, respectively, P < 0.01) and under stress (beta: 0.59 +/- 0.20, 0.35 +/- 0.15, 0.27 +/- 0.08, 0.17 +/- 0.05, 0.20 +/- 0.05, respectively, P < 0.01; A x beta: 3.07 +/- 1.38, 1.62 +/- 0.82, 1.28 +/- 0.40, 0.78 +/- 0.24, 0.93 +/- 0.22, respectively, P < 0.01). This concordance is also valid in terms of the reserves, and the MCE parameters in segments with ameliorated contractile function are significantly higher than in those without.</p><p><b>CONCLUSIONS</b>Quantitative RT-MCE in conjunction with dobutamine stress shows promise in identifying and stratifying CAD and in exploring the perfusion-contractile correlation.</p>

Value of low dose dobutamine real-time myocardial contrast echocardiography in the assessment of coronary artery disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the value of quantitative real-time myocardial contrast echocardiography (RT-MCE) combined with low dose dobutamine stress test in the detection of coronary artery disease (CAD), and to assess the contribution of collateral blood flow (CBF) to myocardial perfusion.</p><p><b>METHODS</b>Twenty-six hospitalized patients referred for coronary angiography and subsequent revascularization underwent routine echocardiography, RT-MCE at baseline and after low dose dobutamine administration. The images of RT-MCE were analyzed quantitatively from microbubble replenishment curves for myocardial perfusion and its reserve by using the QLab software.</p><p><b>RESULTS</b>At baseline, both beta and A x beta (but not A) were decreased with the increase of severity of coronary stenosis (P < 0.01). Under dobutamine stress, A, beta and A x beta values were decreased with the increase of severity of coronary stenosis (P < 0.01), Graded decreasing in the reserves of A, beta and A x beta were observed with increasing coronary stenosis severity (P < 0.01). Furthermore, significant differences in beta, A x beta, and WMS were observed between segments with CBF and those without.</p><p><b>CONCLUSION</b>Quantitative RT-MCE in conjunction with dobutamine stress can be used as a sensitive measure to identify and stratify CAD as well as to assess the contribution of collateral blood flow.</p>

Microarray analysis of extracellular matrix genes expression in myocardium of mouse with Coxsackie virus B3 myocarditis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Extracellular matrix (ECM) orchestrates cell behaviour including growth, death, apoptosis, adhesion, migration, and invasion by activating several signalling pathways. Certain components of ECM, such as integrins, may act as receptors or co-receptors of enterovirus. ECM-activated gene expressions in myocardium of viral heart disease including myocarditis and partial cardiomyopathy remain elusive. This study was to investigate the expression of ECM-activated genes in myocardium of mouse with viral myocarditis.</p><p><b>METHODS</b>BALB/c mice were infected with Coxsackie virus B3 (CVB3) to establish an animal model of myocarditis. Uninfected mice were also prepared and served as controls. Specific mRNA expression pattern in myocarditic mouse heart was analysed by an in-house cDNA microarray containing 8,192 genes. Overexpressed ECM genes were selected and subsequently confirmed by Northern blot analysis.</p><p><b>RESULTS</b>Nine ECM genes were isolated, from the array of 8,192 genes, as overexpressed genes in hearts of myocarditic mice in comparison with controls. Subsequent Northern blot analysis confirmed that four of the nine genes were highly expressed. Expression of these four genes, Fin15, ILk, Lamr1 and ADAMTS-1, has not been reported previously to be induced by Coxsackie virus.</p><p><b>CONCLUSION</b>CVB3-induced myocarditis is associated with gene expression profiles of certain ECM components.</p>

The role of inflammatory stress in acute coronary syndrome / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To summarize current understanding of the roles of anti-inflammatory and proinflammatory mechanisms in the development of atherosclerosis and acute coronary syndrome and to postulate the novel concept of inflammation stress as the most important factor triggering acute coronary syndrome. Moreover, markers of inflammation stress and ways to block involved pathways are elucidated.</p><p><b>DATA SOURCES</b>A literature search (MEDLINE 1997 to 2002) was performed using the key words "inflammation and cardiovascular disease". Relevant book chapters were also reviewed.</p><p><b>STUDY SELECTION</b>Well-controlled, prospective landmark studies and review articles on inflammation and acute coronary syndrome were selected.</p><p><b>DATA EXTRACTION</b>Data and conclusions from the selected articles providing solid evidence to elucidate the mechanisms of inflammation and acute coronary syndrome were extracted and interpreted in the light of our own clinical and basic research.</p><p><b>DATA SYNTHESIS</b>Inflammation is closely linked to atherosclerosis and acute coronary syndrome. Chronic and long-lasting inflammation stress, present both systemically or in the vascular walls, can trigger acute coronary syndrome.</p><p><b>CONCLUSIONS</b>Inflammation stress plays an important role in the process of acute coronary syndrome. Drugs which can modulate the balance of pro- and anti-inflammatory processes and attenuate inflammation stress, such as angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers, statins, and cytokine antagonists may play active roles in the prevention and treatment of acute coronary syndrome when used in addition to conventional therapies (glycoprotein IIb/IIIa receptor antagonists, mechanical intervention strategies, etc).</p>

Identification of syndrome X using intravascular ultrasound imaging and Doppler flow mapping / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The purpose of this study was to assess the morphological changes and physiological function of coronary arteries in patients presenting with chest pain but having normal coronary angiograms, using intravascular ultrasound imaging (IVUS) and intracoronary Doppler (ICD) flow measurements, in order to elucidate the mechanism of syndrome X.</p><p><b>METHODS</b>A total of 126 patients [67 males, 59 females, mean age (53.1 +/- 13.0) years] who experienced chest pain but had normal coronary angiograms were included in this study. ICD flow measurements of the left anterior descending coronary artery (LAD) were performed using a Cardiometrics FloMap II system. Coronary flow velocity reserve (CFVR) was defined as the ratio of the average peak velocity during hyperemia to that at baseline, induced by an intracoronary bolus injection of 18 microg adenosine. A 3.2F or 2.9 F 30 MHz mechanical rotating ultrasound catheter (CVIS, Boston Scientific) or a 3.0 F 20 MHz electronic ultrasound catheter (Endosonics) was used for IVUS.</p><p><b>RESULTS</b>The mean CFVR value of the LAD was 2.71 +/- 0.74. Reduction of CFVR (< 3.0) was found in 82 of 126 (65.1%) patients. IVUS images of the LAD were available for 109 patients. Plaque formation was detected in 76/109 (69.7%) patients. Based on the presence or absence of plaque formation as well as the reduction or non-reduction of CFVR, patients were divided into four groups: Group I (n = 10), normal IVUS findings and normal CFVR; Group II (n = 23), normal IVUS findings with reduction in CFVR; Group III (n = 29), IVUS evidence of plaque formation but normal CFVR; and Group IV (n = 47), IVUS evidence of plaque formation with reduction in CFVR.</p><p><b>CONCLUSION</b>This study shows the important clinical value of a combination of IVUS and ICD in diagnosing patients with angiographically normal coronary arteries. Only 10% of patients studied (Group I) were found to be truly free of coronary disease, while 20% of patients (Group II) would be diagnosed as suffering from syndrome X.</p>