2008年·第121卷第01期

The new European guidelines on the management of non-ST segment elevation acute coronary syndromes (NSTE-ACS) were published in June 2007, two months before the American College of Cardiology-American Heart Association (ACC-AHA) guideline update on the same topic.1'2

Abstract：Background In-stent restenosis (ISR) has become one of the most challenging problems in patients with coronary heart disease. At present, using non-invasive methods to assess ISR is a hol topic. In this investigation we attempted to explore the potential of magnetocardiography (MCG) in diagnosis of in-stent restenosis.Methods MCG was analyzed in 52 patients with coronary artery disease for three times: before stenting, one month and 7 months after successful intracoronary stenting.Results The average classification of total maps (ACTM) and the ratio of abnormal maps (RAM) were Iower in 1 month after intracoronary stenting compared with that obtained before stent planting (2.91 vs 2.52, 65.74% vs 42.80%, P＜0.01),while complex ventricular excitation Index (CVEI) increased from -42.63 to -20.05 (P＜0.01). In ISR subgroup (n=16),RAM decreased in 1 month after intracoronary stenting compared to it before stenting (68.99% vs 45.26%, P＜0.05).ACTM increased in 7 months compared to that obtained in 1 month after stenting (3.15 vs 2.51, P＜0.05). According to the ROC curve, ACTM showed its unique diagnostic value in restenosis patients. The sensitivity and specificity of ACTM were 80.0%, 69.40%, respectively. Its positive predictive value and negative predictive value were 54.6% and 88.5%,respectively.Conclusions After successful intracoronary stenting, most parameters of MCG were improved. ACTM was of prognostic value in diagnosing ISR。

Abstract：Background Even carrying an identicai gene mutation, inter- and intra-family variations have been noticed worldwide in the presence and the severity of left ventricular hypertrophy and sudden death in patients with hypertrophic cardiomyopathy (HCM). Modifier genes may contribute to the diversity. Angiotensin-converting enzyme 2 (ACE2) gene has been established to be associated with parameters of left ventricular hypertrophy in Community based male subjects.The objective of the present study was to investigate the association of ACE2 gene polymorphisms with the phenotype of HCM.Methods A total of 261 consecutive HCM patients and 609 healthy controls were enrolled into this study. The polymorphism of rs2106809 and rs6632677 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by sequencing. Logistic regression model and multivariate analysis were used to determine the odds ratio (OR) and 95% confidence intervals (CI) of variations of ACE2 for HCM.Results The T allele of rs2106809 and C allele of rs6632677 conferred increasing risk for HCM (OR 1.34, 95% CI 1.01-1.77, P=0.04; OR 1.11, 95% CI 1.03-1.21, P=0.002, respectively), and the 2 single nucleotide polymorphisms (SNPs) were in strong linkage disequilibrium (LD), the TC haplotype was independently associated with a higher OR for HCM (OR=1.59, 95% CI 1.21-1.87) after adjusted for conventional risk factors. And the risk alleles were associated with thicker interventricular septal thickness of HCM ((20.0±6.3) mm vs (17.9±5.5) mm, P=0.03 and (21.3±5.9) mm vs (17.9±5.8) mm, P=O.04, respectively). No association was found between the two polymorphisms with female patients with HCM.Conclusion Minor alleles of ACE2 gene might be the genetic modifier for the magnitude of left ventricular hypertrophy in male patients with HCM。

Abstract：Background Atrial fibrillation (AF) is accompanied by atrial structural remodeling. Calpain activity is induced during AR To lest a causal relationship between calpain activation and atrial structural changes, N-acetyl-Leu-Leu-Met (ALLM), a calpain inhibitor, was utilized in a canine AF model.Methods Fifteen dogs were randomly divided into 3 groups: sham-operated group, control group and calpain inhibitor group; each with 5 dogs. Sustained AF was induced by rapid right atrium pacing at 600 beats per minute for 3 weeks. ALLM was administered at a dosage of 1.0 mg-kg-1·d-1 in the calpain inhibitor group. Three weeks later, the proteolysis, protein expression of TnT and myosin, calpain l localization and expression and structural changes were examined in left atrial free walls, right atrial free walls and the interatrial septum respectively. Atrial size and contractile function were also measured by echocardiography.Results Long-term rapid atrial pacing induced marked structural changes such as enlarged atrial volume, myolysis, degradation of TnT and myosin, accumulation of glycogen and changes in mitochondrial shape and size, which were paralleled by an increase in calpain activity. The positive correlation between calpain activity and the degree of myolysis (rs=0.90 961, P＜0.0001) was demonstrated. In addition to structural abnormalities, pacing-induced atrial contractile dysfunction was observed in this study. The pacing-induced atrial structural alterations and loss of contractility were partially prevented by the calpain inhibitor ALLM.Conclusions Activation of calpain represents key features in the progression towards overt structural remodeling. Calpain inhibitor, ALLM, suppressed the increased calpain activity and reversed structural remodeling caused by sustained atrial fibrillation in the present model. Calpain Inhibition may therefore provide a possibility for therapeutic Intervention in AF。

Abstract：Background Renin-angiotensin-aldosterone System has been demonstrated to be associated with both congestive heart failure (CHF) and atrial fibrillation (AF). This study investigated the effects of spironolactone, a kind of aldosterone antagonist, on atrial electrical remodeling and fibrosis in CHF dogs induced by chronic rapid ventricular pacing. Methods Twenty one dogs were randomly divided into sham-operated group, control group, and spironolactone group. In control group and spironolactone group, dogs were ventricular paced at 220 beats per minute for 6 weeks. Additionally, spironolactone at 15 mg·kg-1·d-1 was given to dogs 1 week before rapid ventricular pacing until pacing stopped. Transthoracic and transoesophageal echocardiographic examinations were performed to detect structural and functional changes of the atrium. Swan2 Ganz floating catheters were used to measure hemadynamics variances. Atrial effective refractory period (AERP), AERP dispersion (AERPd), intra- and inter-atrium conduction time (CT) and intra-atrium conduction velocity (CV) were determined. The inducibility and duration of AF were also measured in all groups. Finally, atrial fibrosis was quantified with Massen staining.Results AERP did not change significantly after dogs were ventricular paced for 6 weeks. However, AERPd, intra- and inter-atrium CT increased significantly, and CV decreased apparently, which was negatively correlated to the atrial fibrosis (r=-0.74, P＜0.05). Simultaneously, left atriums were enlarged and cardiac hemadynamics worsened in pacing dogs. Although spironolactone could not affect cardiac hemadynamics effectively, it can obviously improve left atrial ejection fraction (P＜0.05). Spironolactone treatment did not alter AERP duration, but this medicine dramatically decreased AERPd (P＜0.05), shortened intra- and inter-atrium conduction time (P＜0.05), and increased atrium CV. Moreover, spironolactone decreased the inducibility and duration of AF (P＜0.05),as well as atrial fibrosis (P＜0.01) induced by chronic rapid ventricular pacing.Conclusion Spironolactone contributes to AF prevention in congestive heart failure dogs induced by chronic rapid ventricular pacing, which is related to atrial fibrosis reduction and independent of hemadynamics。

Abstract：Background Urinary trypsin Inhibitor inhibits the enhanced production of pro-inflammatory molecules. Hemeoxygenase-1 induction protects against ischemia/reperfusion injury, oxidative stress, inflammation, transplant rejection, apoptosis, and other conditions. However, it is unknown if a combined hemin and ulinastatin pretreatment could result in protective effects for septic shock. In this study, we investigated the role of hemin pretreatment combined with ulinastatin on septic shock in rats.Methods Eighty healthy, male Sprague-Dawley rats were randomly divided into four groups: group S, group H, group U and group HU. Groups S and U received 1 ml normal saline intraperitoneally, while groups H and HU both received 1 ml (100 mg /kg) hemin. Twenty-four hours later, 0.5 ml (10 mg/kg) E. Coli lipopolysaccharide was injected intravenously to replicate the experimental model of septic shock. After an initial 25% decrease in the mean arterial pressure, corresponding to time point 0, groups HU and U received 0.5 ml 10 000 U/kg ulinastatin intravenously, and the others received 0.5 ml normal saline.Results The number of deaths in groups H and U was Iower than that in the group S (P＜0.05), and was higher than that in group HU (all P＜0.05) respectively. The mean arterial pressure (MAP) in the group S was significantly greater than that in group H (P＜0.05), and was Iower than that in group HU and group U (P＜0.05). The plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr) and blood urea nitrogen (BUN), the malondial-dehyde (MDA) of liver, kidney and lung, and the lung Evans blue (EB) Contents in groups H and U, were greater than that in group HU (all P＜0.05), and were Iower than that in group S (all P＜0.05). In contrast, the plasma levels of CO in groups H and HU were higher than that in groups S and U (all P＜0.05), and SOD of liver, kidney and lung in groups H and U were higher than that in group S, and were Iower than that in group HU (all P＜0.05). The levels of TNF-α, IL-6, IL-8 and β-glucuronidase (GCD) activity of plasma in groups U and HU were Iower than those in groups H and S, all having a P＜0.05, while there were no significant differences between group H and group S, or between group HU and group U (all P＞0.05). The HO-1 mRNA and HO-1 protein levels from hepatic, renal, and pulmonary tissue in groups S and U were Iower than those in groups H and HU (all P＜0.05), but there were no significant differences between groups S and U, or between groups H and HU (all P＞0.05). The HO-2 mRNA and HO-2 protein were not significantly different among the four groups (all P＞0.05).Conclusions Combined pretreatment with hemin and ulinastatin in septic shock rats results in an improved response by the upregulation of HO-1 protein followed by increasing CO with resistance to increased oxidative stress, restraining the release of inflammatory mediators, and inhibiting β-GCD activity。

Abstract：Background Medically unexplained dyspnea refers to a condition characterized by a Sensation of dyspnea and is typically applied to patients presenting with anxiety and hyperventilation without underlying cardiopulmonary pathology. We were interested to know how anxiety triggers hyperventilation and elicits subjective Symptoms in those patients. Using an imagery paradigm, we investigated the role of fearful imagery in provoking hyperventilation and in eliciting Symptoms, specifically dyspnea.Methods Forty patients with medically unexplained dyspnea and 40 normal subjects matched for age and gender were exposed to scripts and asked to imagine both fearful and restful scenarios, while end-tidal PCO2 (PetCO2) and breathing frequency were recorded and subjective Symptoms evaluated. The subject who had PetCO2 falling more than 5 mmHg from baseline and persisting at this low level for more than 15 seconds in the imagination was regarded as a hyperventilation responder.Results In patients with medically unexplained dyspnea, imagination of fearful scenarios, being blocked in an elevator in particular, induced anxious feelings, and provoked a significant fall in PetCO2 (P＜0.05). Breathing frequency tended to increase. Eighteen out of 40 patients were identified as hyperventilation responders compared to 5 out of 40 normal subjects (P＜0.01). The patients reported Symptoms of dyspnea, palpitation or fast heart beat in the same fearful script imagery. Additionally, PetCO2 fall was significantly correlated with the intensity of dyspnea and palpitation experienced during the mental imagery on one hand, and with anxiety Symptoms on the other.Conclusions Fearful imagery provokes hyperventilation and induces subjective Symptoms of dyspnea and palpitation in patients with medically unexplained dyspnea。

Abstract：Background Calcified coronary lesions carry the risk of suboptimal stent expansion, subsequently leading to restenosis. The effectiveness of sirolimus-eluting stents (SES) for the treatment of calcified lesion has not been fully investigated. In the present study, therefore, we evaluated the effectiveness of SES Implantation for the treatment of calcified coronary lesions.Mothods A total of 333 consecutive patients with 453 lesions were enrolled in this study. They were divided into two groups according to whether the lesion treated with SES was calcified or not; no calcification group (n=264) and calcification group (n=189). Lesions treated with SES were subjected to quantitative coronary angiography (QCA) immediately and 8 months following stenting.Results Baseline clinical, demographic or angiographic characteristics were well balanced in both groups. Angiographic follow-up at 8 months, the in-stent restenosis and in-segment restenosis rates were not significantly different between the two groups; in-stent restenosis: 3.8% vs 4.2%; P=0.081; in-segment restenosis: 8.7% vs 10.6%, P=0.503. The target lesion revascularization (TLR) was also not significantly different between the two groups; 4.9% vs 6.9%, P=0.378. In addition, the in-stent late loss was similar in both groups; (0.16±0.40) mm vs (0.17±0.33) mm, P＞0.05. Meantime, overall thrombosis rates were also similar in both groups; 1.6% vs 1.6%, P＞0.05.Conclusion Although calcified coronary lesion was hard to stent, successful percutaneous coronary intervention with SES stenting for calcified lesions was conferred by the similar favorable results that were seen when comparing non-calcified and calcified coronary lesions。

Abstract：Background There are few reviews on the clinical features and prognosis of young patients with papillary thyroid cancer and bilateral cervical metastases. We have investigated the long-term impact of initial surgical and medical therapy on such patients.Methods A retrospective study was performeojon 24 young patients (11 females and 13 males) with papillary thyroid cancer and bilateral cervical lymph node metastases, ranging in age from 11 to 20 years (mean age, 16.6 years), who were treated in our Institution from 1 January 1970 to 31 December 1985.Results All the patients in this group were followed up for 20 years. The survival of the patients at 20 years was 91.7%. The recurrence of local tumor and distant metastases was 20.8% and 12.5%, respectively. Based on analysis of the clinical data, we determined that the completeness of the surgical excision had a significant correlation with tumor recurrence.Conclusion These young patients with papillary thyroid cancer and cervical metastases have a good prognosis after suitable treatment。

Abstract：Background Angiostrongyliasis cantonensis is a worldwide-existing parasitic disease. However, the relevant reports on its radiological appearances are limited. In this study, we investigated magnetic resonance imaging (MRI) features of eosinophilic meningoencephalitis in a group of consecutive patients caused by human infection with Angiostrongylus cantonensis after eating freshwater snails.Methods We performed brain MR imaging on 74 patients with angiostrongyliasis cantonensis. The Scanner was a 0.5T unit. For each patient MR pulse sequences of SE T1-weighted image (T1WI) and FSE T2-weighted image (T2WI) were used. After intravenous administration of gadolinium chelate (Gd-DTPA) repeated T1-weighted images were obtained. MRI features of the lesions in the brain and meninges were analyzed and recorded after observing initial and follow-up MR images. The classification of the types of angiostrongyliasis cantonensis infection was done on the basis of locations of the disorders.Results Forty-one (55%) normal and 33 (45%) abnormal MRI appearances in the brain were found. According to locations of the disorders, the types of angiostrongyliasis cantonensis infection were determined as follows: seventeen cases of type meningitis, three of type myeloencephalitis, one of type neuritis and twelve of mixed type (eight of type ventriculitis and five of type pneumonitis were among them). In type meningitis, abnormal leptomeningeal enhancement was visualized. In type myeloencephalitis, lesions in the brain parenchyma may have iso- or slightly Iow Signal intensity on T1WI and high Signal intensity on T2WI. Enhanced nodules in various shapes were shown on gadolinium-enhanced T1 Wl, a few lesions appeared as crescent enhancements and some lesions did not reveal abnormal enhancement. Other than brain lesions, an enhanced nodule was seen in the cervical spinal cord in one patient. In type ventriculitis, brain ventricular enlargement was demonstrated. In type neuritis, a nodule and abnormal enhancement in the right optic nerve was revealed. In type pneumonitis, patchy ground-glass opacity and consolidative lesions at the periphery of the lungs were seen. Follow-up results indicated that most lesions in the brain could resolve in 2 to 8 weeks. Conclusions Angiostrongyliasis cantonensis presented as both single type and mixed type. Nodular enhancing lesions in the brain and/or linear enhancement in the leptomeninges were the main findings, while crescent enhancement would be the characteristic sign of the disease on gadolinium-enhanced T1WI. Focal edematous changes without contrast enhancement in the brain could be seen on MRI in some cases。

Abstract：Background Although it is recognized that bronchial smooth muscle cells (BSMCs) play a key role. In airway remodeling during chronic asthma, it is not well understood how BSMCs exert their inflammatory functions. The extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway is an important signaling pathway in chronic asthma, but its influence on secretion by BSMCs has not been well-studied. We investigated the impact of ERK1/2 signaling pathway on secretion by BSMCs in a rat model of chronic asthma in this study.Methods To create a rat model of chronic asthma, Wistar rats underwent ovalbumim (OVA) injection and eight weeks of inhalation. BSMCs were isolated and cultured in vitro. Epidermal growth factor, PD98059 and ERK1/2 antisense oligonucleotide were used to explore the role of ERK1/2 signaling pathway. The expression of P-ERK1/2 (phospho-ERK1/2) in BSMCs was analyzed by Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). Secretion of BSMCs was detected by enzyme-linked immunosorbent assay (ELISA).Results Phospho-ERK1/2 expression was increased in BSMCs of chronic asthmatic rats compared with the controls. PD98059 inhibited expression of phospho-ERK1/2 protein, while treatment with an antisense oligonucleotide inhibited the expression of P-ERK1/2 mRNA and protein. BSMCs obtained from the chronic asthma group secreted significantly greater quantities of growth factors (transforming growth factor (TGF)-β1, vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF)), cytokines (regulated upon activation, normal T cell-expressed and secreted (RANTES) and eotaxin), and extracellular matrix (fibronectin and collagen l) compared with normal controls. Epidermal growth factor stimulated secretion in both groups, but the response of the chronic asthma group was more intense. Both PD98059 and antisense oligonucleotide suppressed secretion by BSMCs in chronic ashmatic rats. Antisense oligonucleotide reduced the level of RANTES nearly to that of normal controls, while PD98059 could not. Conclusion These results suggest that ERK1/2 signaling pathway may play an important role in the augmented secretion of BSMCs in chronic asthmatic rats, and ERK1/2 antisense oligonucleotide effectively inhibits the process。

Abstract：Background Many patients with acute coronary syndrome (ACS) develop recurrent angina (RA) during hospitalization. The aim of this non-randomized, prospective study was to investigate the predictive factors of RA in unselected patients with ACS enrolled in the global registry acute coronary events (GRACE) during hospitalization in China. Methods Between March 2001 and October 2004, enrolled were 1433 patients with ACS, including ST segment elevation myocardial infarction (662, 46.2%), non-ST segment elevation myocardial infarction (239, 16.7%) and unstable angina (532, 37.1%). The demographic distribution, medical history and clinical data were collected to investigate the predictive factors of RA by Logistic regression.Results During hospitalization 275 (19.2%) patients were documented with RA including unstable angina (53.2%), non-ST segment elevation myocardial infarction (27.5%), ST segment elevation myocardial infarction (19.3%). A comorbidity of dyslipidemia, prior angina, percutaneous coronary Intervention (PCI) within 6 months was more common in patients with RA, P＜0.05. In the patients with RA, a significantly higher proportion of patients with acute pulmonary edema was observed, 23 (8.4%) versus 43 (3.7%), P=0.001. Acute renal failure was present in 8 (2.9%) of patients with RA versus 19 (1.6%) of patients without RA,P=0.165. Hemorrhagic events were present in 6 (2.2%) of patients with RA versus 8 (0.7%) of patients without RA, ventricular tachycardia/ ventricular fibrillation events in 12 patients (4.3%) versus 22 patients (1.9%), congestive heart failure in 69 patients (25.0%) versus 94 patients (8.1%), myocardial re-infarction in 28 patients (10.1%) versus 15 patients (1.3%), P＜0.05, respectively. A lower proportion of patients with RA underwent in-hospital PCI, 687 (59.3%) versus 114 (41.5%), P=0.000. A higher proportion of patients with RA received heparin, 260 (94.5%) versus 1035 (89.4%), P=0.006; and beta-blockers 176(64.0%) versus 864 (74.5%), P=0.000. Multivarible regression analysis showed that RA was associated with prior angina (OR 2.086, 95% Cl 1.466-2.967), in-hospital PCI (OR 0.579, 95% Cl 0.431-0.778), in-hospital congestive heart failure (OR 2.410, 95% Cl 1.634-3.555), myocardial re-infarction (OR 7.695, 95%Cl 3.701-15.999), beta-blocker (OR 0.626, 95%Cl 0.458-0.855), and heparin (OR 3.411, 95%Cl 1.604-7.382).Conclusions In-hospital congestive heart failure, myocardial re-infarction, prior angina history and use of heparin are stronger independent predictors of RA; beta-blockers and PCI are also important predictive factors for RA。

Abstract：Background Invasive intravascular ultrasound (IVUS) is current dlagnostic Standard for myocardial bridging (MB).Non-invasive multislice computerized tomography coronary angiography (MSCT) technique has provided a good anatomical view of the tunnel arten/ now.Methods A total of 51 consecutive patients with atypical or typical angina scheduled for IVUS were enrolled in this study and MSCT was performed 7 days before IVUS. Coronary imaging was quantified using IVUS and MSCT. Four main vessels (left main artery (LMA), left anterior descending (LAD), left circumflex (LCX), right coronary artery (RCA)) were examined.Results Forty-one out of 51 (80%) patients received metaprolol (25 mg) before the MSCT scan and 25 of them were current beta-blocker users. The mean heart rate was (64±3) beats per minute. A total of 51 patients underwent IVUS examination (30 with MB and 21 without MB) were chosen for this study. Twenty-eight out of 30 MB cases were correctly diagnosed by MSCT and 2 patients with MB were not detected. Comparison with IVUS, the sensitivity of detection by MSCT was 93%, specificity was 100%. The lumen diameter of the tunnel artery derived from MSCT and IVUS significantly decreased from (2.9±0.3) mm to (2.4±0.4) mm (P＜0.001) and from (3.3±0.3) mm to (2.6±0.5) mm (P＜0.001),respectively. Minimal and maximal diameters of MB derived from MSCT were significantly smaller than those from IVUS ((2.4±0.4) mm vs (2.6±0.5) mm, P＜0.05 and (2.9±0.3) mm vs (3.3±0.3) mm, P＜0.05), respectively.Conclusions MSCT offers a reliable non-invasive method for MB in LAD and atherosclerosis diagnosis with diagnostic accuracy comparable with invasive IVUS。

Abstract：Background Autoantibodies against angiotensin AT1 receptor have been discovered in patients with preeclampsia or malignant hypertension. Some studies have demonstrated that the autoantibodies are involved in the immunopathogenesis of hypertension and have an agonist effect similar to angiotensin II.Methods Autoantibodies against AT1 receptor were purified from sera of patients with primary hypertension by affinity chromatography. Proliferation of cultured rat vascular smooth muscle cells was detected by bromodeoxyuridine incorporation and activation of signalling molecules detected by Western blotting and electrophoretic mobility shift assay. Resuits The AT1-Rab caused a significant proliferation similar to the Ang II during first 24 hours. The levels of nuclear factor-KB (NF-κB), phosphorylated JAK2, phosphorylated STAT1 (pSTATI) and phosphorylated STAT3 (pSTAT3) molecules were increased in response to the autoantibodies. In contrast, the activations of NF-κB and JAK-STAT were blocked by losartan, pyrrolidinedithiocarbamate (a specific Inhibitor of NF-κB) and AG490 (a specific Inhibitor of the JAK2 tyrosine kinase). The expressions of NF-κB, pSTATI and pSTATS reached peak levels at different times. Moreover, the relative densities of electrophoretic bands showed that activation of pSTAT3 was more significant than STAT1 induced by AT1-Rab.Conclusions These results suggest that the autoantibodies against AT1 receptor have an agonist effect similar to Ang II in proliferation of VSMCs and the NF-κB and JAK-STAT proteins play essential roles. The effect is different from Angll in that STAT3 is the main downstream activating molecule in JAK-STAT signalling pathway。

U sing targeted toxins is a promising approach for the therapy of cancer and autoimmune diseases, as well as other disorders.1