Effects of propofol on ischemia-induced ventricular arrhythmias and mitochondrial ATP-sensitive potassium channels.

AIM: To investigate the potential of propofol in suppressing ventricular arrhythmias and to examine whether mitochondrial ATP-sensitive potassium channels are involved. METHODS: Male Sprague-Dawley rats were pretreated with intravenous infusion of propofol (Prop), a selective mitochondrial KATP channel inhibitor 5-hydroxydecanoate (5-HD), propofol plus 5-HD (Prop+5-HD), a potent mitochondrial K(ATP) channel opener diazoxide (DZ) or NS, respectively. The dosage of each drug was 10 mg/kg. The animals then underwent a 30 min-ligation of the left anterior descending artery. The severity of arrhythmias, the incidence of ventricular fibrillation (VF), and the time of the first run of ventricular arrhythmias were documented using an arrhythmia scoring system. Mitochondrial membrane potential (ΔΨm) was measured in freshly isolated rat cardiomyocytes with a fluorescence microscope. RESULTS: The arrhythmia scores in the Prop and DZ group were 2.6(0-5) and 2.4(0-5), respectively, which were significantly lower than that in the control group [4.9(2-8)]. VF was not observed in both Prop and DZ groups. The first run of ventricular arrhythmias was significantly postponed in the Prop group (10.5±2.2 vs 7.3±1.9 min). Bracketing of propofol with 5-HD eliminated the anti-arrhythmic effect of propofol. In isolated rat cardiomyocytes, propofol (50 µmol/L) significantly decreased ΔΨm, but when propofol was co-administered with 5-HD, the effect on ΔΨm was reversed. CONCLUSION: Propofol preconditioning suppresses ischemia-induced ventricular arrhythmias in the rat heart, which are proposed to be caused by opening of mitochondrial K(ATP) channels.

Propofol and arrhythmias: two sides of the coin.

The hypnotic agent propofol is effective for the induction and maintenance of anesthesia. However, recent studies have shown that propofol administration is related to arrhythmias. Propofol displays both pro- and anti-arrhythmic effects in a concentration-dependent manner. Data indicate that propofol can convert supraventricular tachycardia and ventricular tachycardia and may inhibit the conduction system of the heart. The mechanism of the cardiac effects remains poorly defined and may involve ion channels, the autonomic nervous system and cardiac gap junctions. Specifically, sodium, calcium and potassium currents in cardiac cells are suppressed by clinically relevant concentrations of propofol. Propofol shortens the action potential duration (APD) but lessens the ischemia-induced decrease in the APD. Furthermore, propofol suppresses both sympathetic and parasympathetic tone and preserves gap junctions during ischemia. All of these effects cumulatively contribute to the antiarrhythmic and proarrhythmic properties of propofol.

IL-8 reduces VCAM-1 secretion of smooth muscle cells by increasing p-ERK expression when 3-D co-cultured with vascular endothelial cells.

OBJECTIVE: The goal of this study was to investigate the crosstalk between vascular endothelial cells (ECs) and smooth muscle cells (SMCs) using a three-dimensional (3-D) co-culture model. In addition, the role of IL-8 in this crosstalk was investigated. METHODS: A 3-D co-culture model was constructed using a Transwell chamber system and type I collagen gel. Human umbilical artery smooth muscle cells (HUASMCs) were suspended in the gel and added to the upper compartment of the Transwell. Human umbilical vein endothelial cells (HUVECs) were then grown on the surface of the gel. The growth of HUASMCs was tested with a CFDA SE cell proliferation kit. IL-8 and other bioactive substances were investigated by ELISA and real-time PCR. The alteration of p-ERK expression related to the change in IL-8 levels was also examined by Western blot analysis. RESULTS: The proliferation rate of HUASMCs in the 3-D co-culture model was 0.679 ± 0.057. Secretion and transcription of VEGF, t-PA, NO and VCAM-1 in the 3-D co-culture model were different than in single (2-D) culture. When 3-D co-cultured, IL-8 released by HUVECs was significantly increased (2.35 ± 0.16 fold) (P﹤0.05) and the expression of VCAM-1 from HUASMCs was reduced accordingly (0.55±0.09 fold). In addition, increasing or decreasing the level of IL-8 changed the level of p-ERK and VCAM-1 expression. The reduction of VCAM-1, resulting from increased IL-8, could be blocked by the MEK inhibitor, PD98059. CONCLUSION: Crosstalk between HUVECs and HUASMCs occurred and was probably mediated by IL-8 in this 3-D co-culture model.

[Effects of control-releasing arsenic trioxide-eluting stent on intimal smooth muscle cells and type III collagen in canine coronary artery post-stent model].

OBJECTIVE: To study the safety and efficacy of control-releasing arsenic trioxide (As2O3)-eluting stent on intimal smooth muscle cells (SMC) and type III collagen (CIII) in canine coronary artery post-stent model. METHODS: Twenty-four experimental canines were equally divided into 4 groups, the three tested groups were deployed by stents with different dosage of As2O3 (1.6 microg/mm2, 2.4 microg/mm2 and 3.2 microg/mm2 in low, median and high dose groups, respectively) and coated with polybutyl methacrylate/nano silica and poly-lactide-coglycolide in mild oversizing (stent/vessel ratio of 1.3:1) in left anterior descending (LAD) or circumflex coronary arteries (LCX), while the control group only by simple coated stent without As2O3. The effect was assessed 4 weeks after stent implantation in terms of vascular histomorphology, and changes of SMC and C III expressions were detected using immunohistochemical analysis. RESULTS: Subintimal hemorrhage, medial/adventitial necrosis, thrombosis and inflammatory cell infiltration were not found and integral endothelium could be seen under screening electron microscopy in all groups. Positive expression of SMC and CIII in the tested groups, especial in the high dose As2O3 group, was more weaker than that in control group. Histo-morphological analysis showed that the neo-genetic intimal area and vascular stenosis were lower, but the mean luminal diameter was larger in the three tested groups than that in the control group (P < 0.01). Comparisons of various indices between tested groups treated by different doses of As2O3 showed that the difference between high/median dose vs. low dose was significant (P < 0.01), but that between high dose vs. median dose was insignificant (P > 0.05). CONCLUSION: Control-releasing As2O3-eluting stent shows a reliable and safe effect in preventing and treating post-stent restenosis by its dose-dependent inhibition on expressions of SMC and CIII to suppress the neo-genesis of intimal hyperplasia.

Pravastatin attenuates interferon-gamma action via modulation of STAT1 to prevent aortic atherosclerosis in apolipoprotein E-knockout mice.

1. The beneficial effects of pravastatin, beyond that of lowering cholesterol in atherosclerosis, include reducing the action of interferon (IFN)-gamma. Interferon-gamma activates the signal transducer and activator of transcription 1 (STAT1), but it is unclear whether the inhibitory effect of pravastatin in atherosclerosis is via modulation of the IFN-gamma/STAT1 pathway. Thus, the aim of the present study was to determine whether the action of pravastatin in preventing aortic atherosclerosis by attenuation of IFN-gamma action is dependent on STAT1. 2. Male apolipoprotein E-knockout (apoE(-/-)) mice were fed a diet containing 1.25% cholesterol (w/w). Mice were divided into two groups, one of which was supplemented with pravastatin (80 mg/kg per day). Male C57BL/6J mice were fed a normal diet and served as the control group (n = 12 per group). 3. Atherosclerotic lesions in the aortic root were assessed by staining sections haematoxylin and eosin. Serum concentrations of IFN-gamma and IFN-gamma mRNA expression in the thoracoabdominal aorta were determined by ELISA and real-time quantitative polymerase chain reaction methods, respectively. Expression of phosphorylated STAT1 (pSTAT1), interferon regulating factor (IRF)-1 and suppressors of cytokine signalling 1 (SOCS1) was determined in the thoracoabdominal aorta using Western blot analysis. 4. After 8 weeks, pravastatin treatment significantly prevented the formation of atherosclerotic lesions (P < 0.05) and reduced serum IFN-gamma concentrations (P < 0.05) and levels of IFN-gamma mRNA within the aorta (P < 0.01). Pravastatin significantly decreased the expressions of pSTAT1 and IRF-1 within the aorta and significantly increased expression of SOCS1. 5. These results suggest that the actions of pravastatin in attenuating the action of IFN-gamma and subsequently preventing aortic atherosclerosis may depend, at least in part, on modulation of STAT1 activity. This providing us with a new therapeutic approach and a clearer insight into the clinical benefits of pravastatin.

Amelioration of myocarditis by statin through inhibiting cross-talk between antigen presenting cells and lymphocytes in rats.

Statins, inhibitors of 3-hydroxy-3-methylglutary-coenzyme A (HMG-CoA) reductase, have been recognized as a new type of immunomodulator and reported to have anti-inflammatory effect. To investigate the effect of simvastatin, a lipophilic statin, on myocarditis, we explored whether simvastatin is able to inhibit experimental autoimmune myocarditis (EAM) and adoptive transfer of EAM in rats. We found that administration of simvastatin not only interfered with the development of EAM, but also inhibited the transfer. Antigen presenting cells (APCs) were proved to be important for the development of EAM. The ability of myocarditic splenocytes to transfer myocarditis was enhanced after co-culture with APCs. During co-culture of the myocarditic splenocytes and the APCs, simvastatin not only decreased percentages of CD28 expression in CD4-positive myocarditic splenocytes, and CD80 and CD86 expressions in APCs, but also inhibited the production of tumor necrosis factor (TNF)-partial differential in the CD4-positive myocarditic splenocytes and the APCs. These results indicate that simvastatin was able to ameliorate EAM through the inhibition of cross-talk between lymphocytes and APCs, suggesting beneficial role of simvastatin in the treatment of autoimmune myocarditis.

[Effect of zedoary turmeric oil-eluting stents for post-stenting restenosis prevention and treatment].

OBJECTIVE: To investigate the effect and safety of Zedoary Turmeric Oil (ZTO)-eluting stents for post-coronary stenting restenosis prevention and treatment in the experimental dogs. METHODS: Bare stents, stents coated with polybutyl methacrylate/Nano silica, and stents eluted with 100 microg ZTO were randomly deployed in canine anterior descending or circumflex coronary artery. Four weeks after stent implantation, the dogs were sacrificed and the vascular histomorphologic changes in the stenting segment analyzed. RESULTS: Thickened intima could be seen under light microscope in the bare or coated stents, but thinner in ZTO-duting stent, with no sub-intimal hemorrhage, medial or adventitial necrosis, wall adhesive thrombus, or infiltration of inflammatory cells. Scanning electric microscopy showed the intima was intact. Histomorphologic analysis showed that the thickness and area of neo-intima, and the lumen stenosis percent in artery stented with ZTO eluting stents were significantly lower than those stented with bare or coated stents (P <0.01), and thus the lumen cavity was expanded (P < 0.01), while no statistic significant difference between polymer and bare stents was found (P > 0.05). CONCLUSION: ZTO-eluting stent is available and safe, and it could significantly inhibit the growth of neo-intimal in canine coronary mode after stenting, showing a restenosis preventive and treatment effect.

[Effects of controlled-release arsenic-trioxide-eluting stents on in-stent neointimal hyperplasia in coronary artery: experiment with dog model].

OBJECTIVE: To study the safety and efficacy of controlled-release arsenic-trioxide (As(2)O(3))-eluting stents to reduce in-stent neointimal hyperplasia in coronary artery. METHODS: As(2)O(3) was sprayed onto the stainless steel coated with polybutyl methacrylate/nano-silica and poly-lactide-co-glycolide so as to make the controlled-release As(2)O(3)-eluting stents with the As(2)O(3) concentrations of 0, 1.6, 2.4, and 3.2 microg/mm(2). Thirty adult dogs were randomly divided into 5 equal groups to undergo deployment of bare stent, coated stent, and As(2)O(3)-eluting stent of low dose (1.6 microg/mm(2)), medium dose (2.4, microg/mm(2)), and high dose (3.2 microg/mm(2)) into the left anterior descending artery or circumflex coronary artery respectively, and aspirin 250 mg/day was given 3 days before operation until 4 weeks after operation. Four weeks after the operation the dogs underwent angiography and then killed. The coronary artery, heart, liver, spleen, lung, kidney, and brain were taken out for pathological examination. RESULTS: The mean injury scores were similar in all groups. The values of mean neointimal thickness of the high-, medium-, and low-dose groups were (0.14 +/- 0.05) mm, (0.15 +/- 0.04) mm, and (0.27 +/- 0.03 mm) respectively, all significantly lower than those of the coated stent and bare stent groups [(0.39 +/- 0.06) mm and (0.33 +/- 0.02) mm respectively, all P < 0.01], with significant differences between the high and medium groups and low dose group (both P < 0.01). The neointimal areas of the high, medium, and low dose groups were (1.09 +/- 0.11) mm(2), (1.33 +/- 0.10) mm(2), and (1.93 +/- 0.29) mm(2) respectively, all significantly smaller than those of the coated stent and bare stent groups [(2.44 +/- 0.15) mm(2) and (2.40 +/- 0.32) mm(2), all P < 0.01] with significant differences between the high and medium groups and low dose group (both P < 0.01). The stenosis rates of the high, medium, and low dose groups were (19.54 +/- 3.59)%, (22.18 +/- 3.3)%, and (36.22 +/- 5.17)% respectively, all significantly lower than those of the coated stent and bare stent groups [(50.39 +/- 3.03)%, and (46.88 +/- 5.85)% respectively, all P < 0.01] with significant differences between the high and medium groups and low dose group (both P < 0.01). The luminal areas of the high, medium, and low dose groups were (5.14 +/- 0.55) mm(2), (4.97 +/- 0.38) mm(2), and (3.75 +/- 0.39) mm(2) respectively, all significantly larger than those of the coated stent and bare stent groups [(2.62 +/- 0.22) mm(2) and (3.10 +/- 0.66) mm(2) respectively, both P < 0.01] with significant differences between the high and medium groups and low dose group (both P < 0.01). Pathological examination did not find intraintimal hemorrhage, medial and adventitial necrosis, aneurysm, thrombosis, and inflammatory cell infiltration in all groups. CONCLUSION: Capable of inhibiting neointimal hyperplasia in the coronary arteries dose-dependently after implantation, controlled-release As(2)O(3)-eluting stents is safe and applicable in treating coronary diseases.

[Electrocardiographic and angiographic characteristics of patients with acute solitary posterior myocardial infarction].

OBJECTIVE: To investigate electrocardiographic (ECG) and angiographic characteristics of patients with acute solitary posterior myocardial infarction. Patients complicated by inferior wall or right ventricular infarction were excluded. METHOD: ECG and angiographic changes in 11 patients with acute solitary posterior myocardial infarction admitted to our emergency room from 2001 to 2006 were analyzed. RESULTS: Besides typical ST segment elevation in V(7)-V(9) leads, other ECG manifestations in these patients included V(1)-V(2) R/S > or = 1 (9/11, 81.8%), 1 - 2 mm ST depression in V(1)-V(4) (5/11, 45.5%), 0.5 - 1.5 mm ST elevation in I, aVL leads (4/11, 36.4%) and 0.5 - 1.5 mm ST elevation in V(5)-V(6) leads (5/11, 45.5%). Coronary angiography showed that left circumflex artery (LCX) was the infarction related artery in all cases. The infarction area located before OM1 origination in 1 patient with a 95% pipe-like stenosis (1/11), after OM1 origination in 6 patients (6/11, 4 with total occlusion, 1 with sub-total occlusion and 1 with 90% long length stenosis), in OM1 in 4 patients (4/11, 2 with total occlusion, 1 with sub-total occlusion and 1 with 95% local stenosis). There were 3 patients (27.3%) with single vessel lesion, 4 patients (36.4%) combined with left anterior descending artery (LAD) lesion, 2 patients (18.2%) combined with right coronary artery (RCA) lesion and 2 patients (18.2%) combined with LAD and RCA lesions. CONCLUSIONS: Acute posterior myocardial infarction should be suspected with V(1)-V(2) R/S > or = 1 and V(1)-V(4) ST depression in standard 12 leads ECG. Besides symptoms and cardiac enzyme measurements, recording posterior leads electrocardiogram and performing coronary angiography will help to make the correct diagnosis.

[Effect of early and non-early controlled-release of arsenic-trioxide eluting stents on restenosis inhibition in a canine model].

OBJECTIVE: To observe the safety and efficacy of early or non-early controlled-release arsenic-trioxide (As(2)O(3))-eluting stents on reducing in-stent neointimal hyperplasia. METHODS: Bare stents, stents coated with polybutyl methacrylate/Nano silica (containing 200 microg of As(2)O(3) per stent or not), stents coated with polybutyl methacrylate/Nano silica inside (containing 200 microg of As(2)O(3) per stent or not) and poly-lactide-co-glycolide (PLGA) outside were deployed with mild oversizing in left anterior descending (LAD) and circumflex coronary arteries (LCX)of 30 canines (n = 6, 12 stents for each group). RESULTS: The mean injury scores were similar in all groups at 4 weeks post stents implantation while the mean neointimal thickness, neointimal area and degree of stenosis were significantly reduced and the lumen area significantly increased in canines receiving single coating stents containing As(2)O(3) compared with single or double coating stents and bare stents groups (all P < 0.01). These effects were further enhanced in canines implanted with double coating stents containing As(2)O(3) (all P < 0.01 vs. single coating stents containing As(2)O(3)). No intraintimal hemorrhage, medial and adventitial necrosis, aneurysm, thrombosis, inflammatory cells infiltration were observed in all stenting groups. CONCLUSIONS: Controlled-release As(2)O(3)-eluting stents resulted in a significant inhibition of neointimal hyperplasia in the canine coronary arteries 4 weeks after stents implantation and the effects is more significant with controlled-release of As(2)O(3) at non-early stage than that at early stage.

[Endothelial progenitor cells related gene expression changes before and early after revascularization in patients with acute myocardial infarction].

OBJECTIVE: The purpose of this study was to observe the endothelial progenitor cells (EPCs) related gene expression changes before and early after revascularization in patients with acute myocardial infarction. METHODS: Peripheral blood samples were taken from patients with acute anterior myocardial infarction 6 hours and 7 days after PCI and stenting. Mononuclear cells (MNCs) were isolated by Ficoll-density centrifugation and cultured in M-199 medium. After 14 days culture, attaching cells incorporated DiI-acetylated low-density lipoprotein (EPCs) were collected and RNA was isolated by Trizol for microarray analysis on 24 genes associated with permissibility/vessel tone (angiotensin system: ACE, AGTR-1, AGTR-2; NO system: eNOS; prostacyclin system: COX-2; endothelin system: ET-1, ETA, ETB; superoxide anions system: SOD-1), angiogenesis (adhesion molecule: CDH5; growth factors and receptors: VEGFR1, VEGFR2, VEGF) and endothelial cell activation (adhesion molecules expression: ICAM1, ICAM2, ICAM3, PECAM-1, E-Selectin, L-Selection, VCAM1; change phenotype from antithrombotic to prothrombotic: tPA, uPA, PAI, vWF). VEGFR2, PECAM-1 and VE-cadherin positive cells were identified by flow cytometry. RESULT: Eight gene expressions (AGTR-1, AGTR-2, COX-2, eNOS, ET-1, ETA, VEGF) were significantly downregulated 7 days post PCI compared to pre-PCI (P < 0.05). Flow cytometry results showed that VEGFR2 positive cells were also significantly reduced post PCI than that of before PCI (P < 0.05). CONCLUSION: PCI down-regulated endothelial progenitor cells related gene expressions in patients with acute myocardial infarction.

[Blood pressure changes post liver transplantation in 206 recipients].

OBJECTIVE: To study the blood pressure (BP) changes in the liver transplant recipients. METHODS: A total of 206 patients without preoperation hypertension received liver transplantation in our hospital from February 2001 to July 2005. The BP level and serum immunosuppressant concentration at preoperation and various time points post operation were determined. RESULTS: Compared with the preoperation, the average systolic and diastolic pressure was significantly increased at the 2 week, 1, 2, 4 and 6 months post operation. The mobility of hypertension increased significantly after liver transplantation, with the highest mobility (46.49%) at the 1st month post operation. There was no linear correlation between the immunosuppressant (FK506) concentration and the BP level at any time point. CONCLUSION: There was a high hypertension incidence after liver transplantation. Although the use of immunosuppressive drugs accompanied with the BP increase, there was no linear correlation between the immunosuppressant concentration and the BP level post operation.

[Histopathological changes post cryoablation in canine myocardium].

OBJECTIVE: The purpose of this study was to observe histopathological changes post cryoablation in canine myocardium, to characterize the specific ablation lesion post cryoablation. METHODS: Cryothermal ablation was applied on myocardium (both epicardium and endocardium) of 14 mongrel dogs with different ablation parameters (-25 degrees C x 4 min, -50 degrees C x 4 min, -75 degrees C x 4 min, -75 degrees C x 2 min, -75 degrees C x 6 min, -75 degrees C x 8 min). Lesion dimensions and histopathologic changes were observed. RESULTS: The discrete, sharply delimited lesions were detected in cryoablated myocardium. Histologically, cryoablation in all temperatures studied induced heterogeneous necrosis of the myocardium. Lesion dimensions are related to freezing time and temperature. CONCLUSION: Cryoablation is a feasible and preferably choice for clinical application due to its controllable myocardium lesions.

[Effects of antidepressant therapy in patients with suspected "angina pectoris" and negative coronary angiogram complicating comorbid depression].

OBJECTIVE: We observed the therapeutic effectiveness and safety of different antidepressants as well as the correlation between symptomatic improvement of depression and improvement of chest pain in patients with susceptible "angina pectoris" and negative coronary angiogram complicating comorbid depression. METHODS: In this double-blinded randomized study, a total of 123 eligible patients were allocated into three groups: (1) Group F: fluoxetine 20 mg QN (n = 41); (2) Group P: Placebo 1 tablet QN (n = 40); (3) Group F + O: fluoxetine 20 mg + olanzapine 2.5 mg QN for the former 2 weeks and only fluoxetine 20 mg QN for the latter 2 weeks (n = 42). The total therapy duration was 4 weeks. HAMD, HAMA and self-evaluation table of chest pain were obtained before therapy, at the end of 1 and 2 weeks after therapy. RESULTS: Baseline HAMD and HAMA scores and self-evaluation score of chest pain were similar among 3 groups and all scores were significantly improved post various therapies in the order of group F + O > group F > group P. The rate of score decrease were seen after 1 week treatment in group F + O and after 2 week treatment in group F. There was a significant positive correlation between the rates of self-evaluation chest pain score decrease and HAMD (r = 0.867, P < 0.001) and HAMA (r = 0.854, P < 0.001) score decreases after 4 weeks therapies (P < 0.05). During the whole course of treatment, no serious adverse reaction was found in all patients. CONCLUSION: In patients with suspected "angina pectoris" and negative coronary angiogram complicating comorbid depression, the antidepressants were safe and significantly improved the symptoms of depression and anxiety and chest pain. Low dose fluoxetine plus short term olanzapine regimen was superior to fluoxetine alone regimen in terms of stronger and quicker symptom improvement.

[Comparison of different pacing sites of the right ventricle on left ventricular mechanical synchrony and systolic performance using tissue Doppler imaging].

OBJECTIVE: Right ventricular apical pacing may induce cardiac desynchronize and deteriorate left ventricular systolic performance. We hypothesized that right ventricular outflow tract (RVOT) pacing could produce better mechanical synchrony and left ventricular contraction. METHODS: We enrolled nine patients without structural heart disease who underwent electrophysiological studies. The pacing sites (right apex, low septum, free wall and septum of RVOT of the right ventricle) were defined with fluoroscopy and ECG. The atrioventricular sequential pacing was applied every 5 minutes in a random order at a rate of 120 bpm. Tissue Doppler imaging was carried out with GE VIVID 7 for off-line analysis at each pacing site. The global systolic contraction amplitude (GSCA) was calculated as the average shortening amplitude of all 16 segments of left ventricle. RESULTS: The GSCA during pacing was 5.76 mm +/- 0.66 mm at free wall of RVOT and 5.66 mm +/- 1.00 mm at septum of RVOT, respectively. The GSCA at both sites was significantly higher than that at apical pacing 4.82 mm +/- 0.94 mm (P < 0.05) or low septum pacing 4.82 mm +/- 1.06 mm (P < 0.05). Moreover, segmental displacement analysis showed that the longitudinal displacement of lateral, posterior, and inferior walls significantly decreased at apical pacing compared with RVOT pacing, although no difference could be demonstrated in anterior and septum walls. Accordingly, the curve of the myocardial displacement at apical or low septum pacing was M-shaped, and had a negative wave at the end of the diastole in lateral, posterior, and inferior walls. The tissue velocity during isovolumic contraction period was also higher than systolic tissue velocity in these walls. The phenomenon could seldom be seen at RVOT pacing. CONCLUSION: RVOT pacing in patients without structural heart disease is associated with more favorable immediate myocardial contraction and mechanical synchrony compared with right apical pacing or low septum pacing.

[Immediate effect of cardiac resynchronization therapy by tissue synchronization imaging and tissue tracking in patients with congestive heart failure].

OBJECTIVE: To evaluate the immediate effect of cardiac resynchronization therapy (CRT) by Doppler tissue imaging (DTI), tissue synchronization imaging (TSI) and tissue tracking imaging (TTI) in patients with congestive heart failure. METHODS: Ten patients with congestive heart failure who had cardiac resynchronization therapy were enrolled. The TSI and TTI imaging were performed by GE vivid 7 with M3s probe. The TTI image was obtained in diastole to determine delayed longitude contraction (DLC). The left ventricular ejection fraction (LVEF), the percentage of delayed longitude contraction segments (DLC), the standard deviation of the time to peak myocardial systolic contraction of 16 segments (Ts-SD), the standard deviation of the time to peak myocardial diastole of 16 segments (Td-SD), the systolic velocity of right ventricule (RV-Sm) and the average systolic velocity of mitral valve annulus (LV-Sm) were measured. The intraventricular dyssynchrony could be semi-quantified by TSI as 4 (red), 3 (orange), 2 (yellow), 1 (green), and the average value of 16 segments was defined as the TSI index. The immediate changes of these parameters were investigated when the pacemaker was turned on and off. The correlation of the Ts and TSI index was also analyzed. RESULTS: When the pacemaker was on, the LVEF improved significantly from (37 +/- 11.30)% to (46 +/- 10.10)% (P < 0.01), and LV-Sm increased significantly from (3.16 +/- 0.87) cm/s to (3.76 +/- 0.74) cm/s (P < 0.01), RV-Sm increased significantly from (6.79 +/- 1.78) cm/s to (7.75 +/- 1.92) cm/s (P < 0.01). DLCs decreased significantly from (35 +/- 6.04)% to (18.13 +/- 9.97)% (P < 0.01), Ts-SD decreased from (83.97 +/- 33.02) ms to (52.67 +/- 19.65) ms, P < 0.05, Td-SD decreased from (87.81 +/- 22.34) ms to (63.45 +/- 31.49) ms, P < 0.05 and TSI index reduced from 2.11 +/- 0.15 to 1.60 +/- 0.33 (P < 0.01) respectively. In addition, the reduction of TSI index correlated significantly with that of Ts-SD (r = 0.75, P < 0.05). CONCLUSIONS: CRT could immediately improve the systolic and diastolic synchrony of the left ventricle and ventricular function. TSI and TTI may be as the new effective modalities to assess the mechanical dyssynchrony. TSI index was direct and reliable in this study.

Inhibition of leptin-induced vascular extracellular matrix remodelling by adiponectin.

Vascular extracellular matrix (ECM) remodelling, which is the result of disruption in the balance of ECM synthesis and degradation, induces vessel fibrosis and thereby leads to hypertension. Leptin is known to promote tissue fibrosis, while adiponectin has recently been demonstrated to be anti-fibrogenic in tissue fibrosis. In this study, we aimed to evaluate the leptin-antagonist function of adiponectin and to further elucidate the mechanisms through which adiponectin dampens leptin signalling in vascular smooth muscle cells, thus preventing excess ECM production, in our already established 3D co-culture vessel models. Our 3D co-culture vessel model, which mimics true blood vessels, is composed of vascular endothelial cells, vascular smooth muscle cells and collagen type I. We validated the profibrogenic effects of leptin and analysed matrix metalloproteinase 2 (MMP2), MMP9, tissue inhibitor of metalloproteinase 1 (TIMP1) and collagen types II/IV secretion in 3D vessel models. The protective/inhibitory effects of adiponectin were re-analysed by inhibiting adiponectin receptor 1 (AdipoR) and AdipoR2 expression in endothelial cells using RNAi technology. In the 3D vessel models, adiponectin blocked the leptin-stimulated secretion of collagen types II/IV and TIMP1 while significantly increasing MMP2/9 activity. In endothelial cells, adiponectin induced phosphorylation of AMPK, thereby suppressing leptin-mediated STAT3 phosphorylation through induction of SOCS3 in smooth muscle cells. Our findings indicate that adiponectin disrupted the leptin-induced vascular ECM remodelling via AdipoR1 and enhanced AMPK signalling in endothelial cells, which, in turn, promoted SOCS3 up-regulation in smooth muscle cells to repress leptin-stimulated phosphorylation of STAT3.