Volume 86  ·   Issue 16  ·  2006

Congestive heart failure (heart failure) is a difficult problem in cardiology therapy. It is a serious disease that makes patients lose their ability to work and has a high mortality rate. Thousands of patients die of heart failure every year. In recent decades, the incidence of heart failure is increasing year by year. Epidemiological data show that in the United States, about 4~5 million people suffer from heart failure; The number of patients with heart failure worldwide is as high as 22.5 million, and the number of new cases every year is 2 million. The occurrence of this disease is age-related. According to the investigation from 1988 to 1991, about 10% of people aged over 70 years suffered from heart failure. The mortality rate of heart failure is related to clinical severity. For moderate to severe heart failure, the 5-year mortality rate can reach 30% to 50%. The annual medical expenses caused by heart failure are as high as 20 billion to 40 billion US dollars [1]. According to the epidemiological survey of heart failure in China in 2003, the prevalence rate of heart failure among people aged 35 to 74 years is 0.9%. According to this rate, there are about 4 million patients with heart failure among people aged 35 to 74 years in China, and the annual medical expenses are huge [2].

Atrial fibrillation (AF) is a common clinical arrhythmia. The annual incidence of stroke in patients with non-valvular AF is 3% ~5%, and the fatality and disability rate of stroke combined with AF is high, so the prognosis of AF is poor. Warfarin is an effective means to prevent stroke, but the clinical application rate is low, about 40% ~50% in developed countries in Europe and America, while only about 10% of AF patients receive standard warfarin treatment even in big cities in China.

Atheromatous plaque rupture initiates the event of acute coronary syndrome (ACS), which results in secondary thrombosis, and persistent thrombotic obstruction leads to acute myocardial infarction. Platelets play an important role in this process, and the aggregated platelets form the thrombotic core, which expands the blood clots rich in cellulose and red blood cells upstream and downstream. Platelet-rich thrombi are resistant to thrombolysis and cause reocclusion after thrombolysis.

In recent years, some new large-scale randomized clinical trials and meta-analyses have been published in the field of antihypertensive therapy, which have enriched and developed the core content of hypertension treatment strategies and demonstrated new research directions.

Since 1960s, many large-scale clinical trials of antihypertensive drugs have been carried out internationally, and the clinical trials before 1990s used traditional antihypertensive drugs, namely diuretics and β-blockers, and placebo as a control. Early studies have proved that antihypertensive therapy can significantly reduce the incidence and mortality of cardiovascular and cerebrovascular events in mild to moderate hypertension, senile hypertension and simple systolic hypertension.

Atrial fibrillation (Af) is often one of the clinical manifestations of valvular disease, coronary heart disease and hypertension. The complexity of drug therapy and the uncertainty of long-term therapeutic effect have re-aroused people's interest in seeking surgical treatment of Af. We used radiofrequency ablation partial maze surgery to treat Af, and achieved satisfactory results, which are reported below.

In recent years, with the rapid development of interventional techniques, the treatment mode of congenital heart disease (CHD) has gradually changed, that is, from simple surgery or simple interventional therapy to mosaic therapy combined with both. This new treatment mode reduces the trauma of secondary surgery, compensates for the deficiency of surgery, and shows unique advantages [1]. Especially in the treatment of complex CHD, it has a wide application prospect. From June 1994 to December 2005, Guangdong Institute of Cardiovascular Diseases applied this mode to treat 40 cases of CHD, which is reported as follows.

Objective to establish a stable and surviving animal model of chronic ischemic heart failure (CIHF) in minipig by using selective microsphere fractional perfusion in anterior descending coronary artery (LAD). Methods Fifteen Chinese Wuzhishan minipig aged 8-11 months, weighing 20-30 kg, underwent coronary angiography (CAG) with 4F Judkins catheter and superselected LAD. Plastic microsphere suspension (1 ml/time, containing about 1.0×105 microspheres) was injected into LAD in fractional fractions, and the injection was repeated at 10 min intervals until the anterior blood flow of LAD slowed down, TIMI blood flow was ≤2, and LVEDP increased to 15 mm Hg ~18 mm Hg. At the same time, the changes of electrocardiogram, invasive hemodynamic parameters and myocardial injury markers (CK-MB, cTnI) were monitored. mRAP, mRVP, mean right atrial pressure (mRAP), mean right ventricular pressure (mRVP), mean pulmonary arterial pressure (mPAP), pulmonary capillary wedge pressure (PCWP) and CO were measured by Swans-Ganz floating catheter before and 2 months after the operation. The changes of left ventricular end-diastolic pressure (LVEDP) were measured by left ventriculography, and the hemodynamic changes before and after the success of CIHF animal model were compared. The success rate, stability and reproducibility of the model were identified and evaluated. The infarcted myocardial area and pathological examination were measured by cardiac necropsy. Results A total of 11 mini-pigs survived 2 months after the modeling, and 10 of them reached the standard of CIHF animal model (LVEDP>18 mm Hg and CO decreased by more than 30%). The success rate of the model was 66.7% (10/15), the number of microspheres injected (3.2 ± 0.9) times, the total amount (3.2 ± 0.9) ×105. Compared with before the modeling, LVEF decreased by 38.5%, LVEDP increased by 197.8%, and CO decreased by 46.8% (P<0.01) mRAP, mRVP, mPAP and PCWP were all significantly increased (P<0.01). Pathological examination showed that the area of myocardial necrosis accounted for 25.4% ~34.9% of the left ventricle area. Light microscopy showed that translucent microspheres were scattered in the anterior wall of left ventricle and the apical subendocardial myocardial vascular obstruction, accompanied by focal coagulative necrosis, and presented the pathological characteristics of ischemic necrosis of myocardium and chronic fibrocollagen hyperplasia. Conclusion The mini-pig CIHF model made by super-selected coronary artery LAD microsphere fractional perfusion method has the advantages of chest closure, high success rate, stability and good repeatability, and is closer to the pathophysiological characteristics and course of clinical CIHF than the heart failure model induced by drug, coronary artery ligation and pacing.

Objective to observe the changes of endothelial repair, endothelial nitric oxide synthase (eNOS) protein expression and nitric oxide level after implantation of diallyl trisulfide-coated stent into coronary arteries in dogs, and to investigate the effects of the drug stent on the structure and function of vascular endothelium. Methods Eight dogs were subjected to stenting of left circumflex coronary artery, and the diallyl trisulfide-coated stent (drug group) and the control stent (control group) were placed into the distal and proximal ends of left circumflex artery, respectively. The animals were sacrificed 28 days after operation, and the intimal hyperplasia was observed by light microscope, and the endothelial repair was observed by scanning electron microscope. The expression of eNOS protein was measured by immunohistochemistry and Western blot, and the level of nitric oxide was detected by nitrate reductase. Results 28 days after operation, the intimal hyperplasia (intimal thickness 0.12 mm±0.05 mm, intimal area 1.17 mm2±0.25 mm2) was significantly lighter in the drug group than in the control group (intimal thickness 0.35 mm±0.11 mm, intimal area 1.81 mm2±0.36 mm2,P<0.01,P<0.05); The endothelial cells on the surface of the intima of blood vessels were distributed more closely, arranged more neatly and covered more completely than those in the control group; The expression level of eNOS protein in the drug group (11.1±1.9 by immunohistochemistry and 37.5±6.2 by Western blot) was significantly higher than that in the control group (5.6±0.6, 10.4±2.7, all P<0.01), and the level of nitric oxide in the drug group (279 μ mol/L ± 72 μ mol/L) was significantly higher than that in the control group (160 μ mol/L ± 57 μ mol/L, P =0.01). Conclusion The diallyl trisulfide coated scaffold can accelerate endothelialization, promote eNOS expression and increase the level of nitric oxide, which indicates that the drug scaffold can promote the repair of endothelial structure and achieve the recovery and perfection of endothelial function.

Objective to investigate the protective mechanism of protein kinase C on isolated rabbit heart. Methods Using the activator and blocker of protein kinase C, the cardiac function indexes, myocardial CK-MB, LDH, MDA, SOD contents were measured by Langendroff isolated rabbit heart perfusion model, the myocardial water content was calculated, and the apoptotic cells were detected, so as to understand the effect of protein kinase C on cardiac function CK-MB (233.6 U/g±24.6 U/g,285.9 U/g±21.4 U/g), LDH (83.9 U/g±6.5 U/g,91.2 U/g±5.4 U/g and SOD (201.0 U/g±17.4 U/g,91.9 U/g±22.1 U/g) The levels were higher than those in the control group (132.5 U/g±24.8 U/g,74.1 U/g±7.4 U/g,180.3 U/g±16.8 U/g) and the activation-blocking group (135.1 U/g±28.8 U/g,75.1 U/g±8.8 U/g,184.5 U/g±16.9 U/g) (P<0.05), The content of MDA and myocardial water content were significantly lower than those in the control group and the activation-blocking group (P<0.05). Conclusion Protein kinase C has a positive protective effect on the isolated rabbit heart.

Objective to observe the effect of coronary artery calcification on intimal hyperplasia after drug-eluting stent implantation by intravascular ultrasound. Methods 97 patients with coronary artery disease (99 lesions) were measured by intravascular ultrasound (IVUS) 8 months after drug-eluting stent implantation. The cross-sectional area (CSA) of the external elastic membrane (EEM) of the proximal end of the stent, the distal end of the stent and the smallest part of the lumen of the stent, the CSA in the stent, the CSA in the lumen, the area of neointima, the maximum and minimum diameter of the stent, and the stent symmetry index was estimated. According to the detection of vascular calcification by IVUS, the vessels in the stent implantation segment were divided into calcified lesion group and non-calcified lesion group, and the effect of calcified lesion on intimal hyperplasia after stent implantation was observed. Results 14 patients had intimal hyperplasia in the 99 lesions. Compared with the non-calcified group, the CSA in the stent at both ends of the stent after stent implantation in the calcified lesion group was similar: (7.30±1.94) mm2 and (6.58±1.96) mm2 at the proximal end of the stent, (6.74±2.02) mm2 and (6.14±1.82) at the distal end of the stent However, the intimal area was significantly reduced (0.53±1.50) mm2 and (0.02±0.20) mm2. Conclusion the extent of stent expansion and symmetry were poor in the treatment of calcified lesions with coronary drug-eluting stent, but the intimal hyperplasia was reduced compared with the non-calcified lesions.

Objective to summarize the clinical experience and efficacy of covered endovascular stent placement in the treatment of perforating descending aortic ulcer.Methods From August 2002 to February 2006, 14 cases of perforating descending aortic ulcer were male, with an average age of 60.2 years (34~79 years). Except one case was asymptomatic, all the other cases had different degrees of chest and abdominal pain; 3 cases were accompanied by hemoptysis; Eleven patients with history of hypertension were diagnosed by CT enhancement or MRI before surgery. One femoral artery was incised under local anesthesia, and covered endovascular stent was placed under DSA monitoring. Results 16 stents were placed, all of which were successful. Two patients were treated with 2 stents, 11 Talent stents and 5 Aegis stents, respectively. The diameter of the stent was 32mm ~38mm, which was 10% ~20% larger than the diameter of the proximal normal aorta. Immediate angiography showed complete occlusion in 12 cases, and a small amount of contrast overflow in 2 cases. The average follow-up was 17.2 months (1-42 months). CT scan showed that the ulcer and pseudoaneurysm disappeared, and the intramural hematoma was basically absorbed in 2 cases. 1 case died of rupture of pseudoaneurysm at the distal end of the stent 1 month after surgery. Conclusion Descending aortic perforating ulcer can develop into intramural hematoma, local dissection, pseudoaneurysm and rupture, which needs active clinical treatment. Covered endovascular stent placement is a safe and effective method, especially for patients with high surgical risk and high mortality.

Objective to investigate the efficacy and safety of linear ablation of circumferential pulmonary vein under the guidance of three-dimensional mapping system in the treatment of chronic atrial fibrillation (AF). Methods From August 2004 to November 2005, 100 consecutive patients with chronic atrial fibrillation were treated with linear ablation of circumferential pulmonary vein under the guidance of three-dimensional mapping system (CARTO system or EnSite NavXTM system). The main endpoint of ablation was electrical isolation of pulmonary vein. Successful follow-up was defined as the absence of any atrial arrhythmia attack for at least 3 months without taking antiarrhythmic drugs. The factors affecting the success rate were analyzed by statistical related variables. Results The average follow-up was 9.7 ± 5.7 months, and the cumulative success rate was 70% (70 cases). The proportion of isthmus ablation and mean ejection fraction in patients with recurrence were lower than those without recurrence of atrial fibrillation. The main complications included cardiac tamponade in 3 cases (3%), stroke in 1 case (1%) and asymptomatic pulmonary vein stenosis in 2 cases (2%).

Objective to evaluate the changes of cardiac function and myocardial ischemic area in patients with acute inferior wall myocardial infarction after transplantation of autologous bone marrow mononuclear cells through coronary artery (BM-MNC). Methods Forty patients with acute inferior wall myocardial infarction with first ST segment elevation were randomly divided into cell transplantation group (n =20) and control group (n =20) after successful PCI. At the same time, autologous BM-MNC suspension or equal amount of heparin saline were injected into the distal end of the infarction-related artery by microcatheter at the same time. The end point of the study was to measure left ventricular function and myocardial ischemic area by delayed enhanced MRI perfusion scan (CMR) at 6 months after operation. Results The changes of left ventricular ejection fraction (LVEF), left ventricular end diastolic volume (LVEDV) and myocardial ischemic area were recorded by CMR. The results showed that LVEF was significantly increased in both groups compared with that before operation (control group 47.9%±6.7% vs 43.4%±6.7%, P =0.001; cell transplantation group △ LVEF) was significantly higher than that in the control group (6.95% ± 3.33% vs 4.05% ± 1.68%, P =0.047), Conclusion Transplantation of autologous bone marrow mononuclear cells in the coronary artery can significantly improve the left ventricular systolic function and myocardial perfusion in patients with acute inferior wall myocardial infarction and reduce the myocardial ischemic area.

Objective to compare the intimal proliferation after treatment with rapamycin drug-eluting stent (DES) and bare metal stent (BMS) by optical coherence tomography (OCT). Methods 19 patients with coronary artery disease were reviewed by coronary angiography from 5 to 93 months after intracoronary stenting. OCT imaging was performed on 21 vessels and 23 stents after angiography. Drug stent group A was performed from 6 to 10 months after DES; 5~10 months after BMS, bare metal stent group B; The results of OCT imaging showed that there were statistically significant differences in the thickness of maximum intimal proliferation, loss of vascular lumen diameter and cross-sectional area and restenosis of diameter and cross-sectional area after stent between the three groups. The maximum intimal proliferation thickness of group A was significantly smaller than that of group B (0.20 mm±0.13 mm vs 0.81 mm±0.46 mm, P =0.019) and group C (0.91 mm±0.27 mm, P =0.007). The loss of vascular lumen diameter in group A was significantly less than that in group B (0.27 mm ± 0.17 mm vs 1.12 mm ± 0.79 mm, P =0.009) and group C (1.20 mm ± 0.31 mm, P =0.013); The diameter restenosis in group A was significantly smaller than that in group B (8%±4% vs 36%±24%, P =0.009) and group C (35%±6%, P =0.017); The loss of cross-sectional area in group A was significantly smaller than that in group B (1.14 mm2±0.9 mm2 vs 3.96 mm2±2.62 mm,P =0.009) and group C (4.66 mm2±1.66 mm2,P =0.006); The restenosis of cross-sectional area in group A was significantly smaller than that in group B (P =0.017) and group C (P =0.009). Almost all of the 13 BMS stents were covered by intima, but the intima proliferation was less after DES implantation, and some of the stents were still not covered by intima even after 29 months after stenting. Conclusion OCT imaging technique can clearly show the proliferation of intima on the support rod and the surface of the stent, which is of great significance to evaluate the therapeutic effect of drug-eluting stents.

Objective to investigate the epidemiological status of hypertension in China in 2002 and lay a foundation for further control of hypertension.Methods A cluster sampling survey was conducted on natural populations from 14 provinces and cities in north and south of China, and the cardiovascular epidemiological survey with hypertension as the main content was conducted among the population.Results 29 076 people were investigated, and 9872 patients suffered from hypertension.After standardization, the total prevalence of hypertension was 27.86%, the prevalence of hypertension in male patients was 34.72%, and that in female patients was 25.34%. The prevalence of hypertension in male patients was higher than that in female patients. The prevalence of hypertension in male patients was higher than that in female patients. Among females, the highest rate is 38.30% in Hebei Province, and the lower in Hubei and Shandong Province, and there is a decreasing trend from north to south. The awareness rate of hypertension is 60.7%, the treatment rate is 37.7% after standardization, and the control rate is 5.7%. Conclusion The prevalence of hypertension in China is relatively high, while the awareness rate, treatment rate and control rate of hypertension are relatively low.

Objective to investigate the relationship between the-344T/C polymorphism of aldosterone synthase gene (CYP11B2) and plasma renin activity (PRA) and the levels of angiotensin Ⅱ (ANG Ⅱ) and aldosterone (Aldo) in patients with essential hypertension (EH). Methods PCR-RFLP was used to detect the-344T/C genotype of CYP11B2 in 421 patients with EH and 207 normal subjects. The concentrations of basal PRA, plasma ANG Ⅱ and Aldo were measured by radioimmunoassay in 328 patients with EH. Results the genotype (P =0.61) and allele frequency (P =0.34) of-344T/C polymorphism were not significantly different between EH and normal subjects. After adjusting age, sex and body mass index, the plasma Aldo concentration (213.5 pmol/L) of TT genotype was significantly higher than that of TC (163.5 pmol/L) and CC (141.5 pmol/L) genotype in 328 patients with EH However, there was no significant difference in basal PRA (P =0.63) and plasma AngⅡ concentration (P =0.28) between different genotypes. The plasma AngⅡ concentration (81.9 pmol/L) of CC genotype was significantly higher than that of TC (52.2 pmol/L) and TT (49.5 pmol/L) genotype (P =0.02) in 279 EH patients at challenge (P =0.02). Conclusion CYP11B2 gene-344T/C polymorphism is significantly correlated with plasma Aldo level and challenge plasma AngⅡ concentration in EH patients.

Objective to down-regulate the expression of angiotensin Ⅱ1a receptor (AT1a) by RNA interference technique, and to observe its effect on renal vascular hypertension and myocardial hypertrophy remodeling. Methods A two-kidney, one-clip: 2K1C hypertensive rat model was constructed. Plasmids pAT1a-shRNA1 and pAT1a-shRNA2 carrying U6 promoter and AT1a-specific short hairpin RNA (shRNA) coding sequence were administered into the tail vein for a single dose, and unrelated plasmid pGenesil-Con (pCon) containing non-specific shRNA coding sequence and selective AT1 receptor antagonist valsartan were administered daily by gavage for 3 weeks. No intervention was used as a control. The changes of caudal artery pressure, carotid artery pressure level and the ratio of left ventricular weight to body weight (LV/BW) were detected, and the expression of AT1 receptor in tissues was analyzed by Western-blot. Results Compared with before intervention, caudal artery pressure increased by about 25 mm Hg in Blank group and pCon group, while decreased by 15 in pAT1a-shRNA1 and pAT1a-shRNA2 groups Carotid artery pressure and left ventricular/body weight ratio : pAT1a-shRNA1 (194 mm Hg ± 5 mm Hg; 2.27±0.37), pAT1a-shRNA2 (200 mm Hg±5 mm Hg; 2.31±0.26), valsartan group (164 mm Hg±5 mm Hg; 2.26±0.39) were significantly lower than those in control group (234 mm Hg±10 mm Hg; 3.24±0.38) and pCon group (232 mm Hg±7 mm Hg; 2.94±0.06); Compared with the control group, the expression of AT1a receptor in left ventricle (53.3% and 47.8%, respectively) and aorta (58.7% and 49.3%, respectively) was significantly reduced in pAT1a-shRNA1 and pAT1a-shRNA2 groups.Conclusion RNA interference with AT1a receptor can effectively inhibit the progression of renal vascular hypertension and the remodeling of myocardial hypertrophy.RNA interference technology may be a new strategy for gene therapy of hypertension.

In toxicology, carbon monoxide (CO) poisoning is a common cause of death and morbidity, and the symptoms of CO poisoning mainly include vertigo, nausea, weakness, headache, fatigue and confusion, etc. The study by Henry CR and others of Minneapolis Heart Institute Foundation, Minnesota, USA, published in JAMA, 2006, 295: 398-402, January 25, 2006, showed that myocardial injury in patients with moderate to severe CO poisoning is an important signal of aggravation or even death, and for patients with moderate to severe CO poisoning, myocardial injury can assess the mortality of patients.

Left ventricular hypertrophy (LVH) and its secondary congestive heart failure are one of the main causes of human disability and death at present. Obesity is not only a risk factor of cardiovascular disease, but also a main cause of LVH. The causes of obesity are not only related to the hormones that regulate energy metabolism and appetite, but also related to leptin deficiency or receptor insensitivity. Animal experiments have shown that leptin deficiency or insensitivity can lead to LVH, but human obesity is related to hyperleptinemia and leptin insensitivity. Therefore, for humans, leptin supplementation alone is difficult to control obesity and LVH. Is there a factor parallel to leptin that can reverse the heart structure? Researchers led by Shubha V. Y. Raju of Johns Hopkins University School of Medicine in the United States shifted their research focus to ciliary neurotrophic factor (CNTF) to investigate whether activating CNTF receptor can reverse LVH. The results of this study were published recently in the journal Proceedings of the National Academy of Sciences of the United States (PNAS, 2006, 103:4222-4227).

Several randomized clinical trials have confirmed that implantation of rapamycin-eluting stents (SES) can significantly reduce the restenosis rate and the chance of revascularization of target lesions within 3 years compared with ordinary bare metal stents (BMS). The restenosis rate of SES was 0 and 8.9% in RAVEL test and SIRIUS test, respectively. However, in the SIRIUS study, which included many "complex lesions" such as small blood vessels, long lesions and diabetes, compared with BMS group, the effect of SES on in-stent restenosis still showed obvious advantage (42.3% vs 5.9%). In the above trials, the safety of stents was also affirmed. There was no stent thrombosis in RAVEL trial after 6 months follow-up. The SIRIUS trial only used aspirin and clopidogrel for two months, but the incidence of stent thrombosis was only 1.1%, and all occurred within 1 month after surgery. However, the above trials did not include all clinical conditions, and the trials were mostly conducted in experienced large centers. What is the performance of patients with multi-vessel disease, diabetes, left main bifurcation disease, arterial stenosis, grafting disease, etc.? Urban et al. of Switzerland published the 1-year follow-up results of the e-Cypher registration study in Circulation (2006, 113: 1434-1441), showing that rapamycin-eluting stenting is very safe in daily clinical practice, and the incidence of stent thrombosis is similar to the results of previous trials.