Atorvastatin use and coronary flow reserve in patients with coronary slow flow / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the impact of statin use on coronary flow reserve (CFR) in patients with slow coronary flow.</p><p><b>METHODS</b>A total of 91 patients with chest pain and coronary slow flow but normal coronary angiography were included in this study, patients were divided into statin group (atorvastatin 20 mg/d for 8 weeks, n = 51) and non-statin group (n = 40), 26 healthy subjects with normal angiography and negative exercise ECG test served as normal controls. Blood cholesterol was measured. Doppler coronary flow velocity and Doppler reserve measurement of distal left anterior descending were recorded at rest and adenosine infusion (140 microgxkg(-1)xmin(-1)) induced hyperemia state, CFR was calculated by the ratio of maximal hyperemia and baseline peak diastolic coronary flow velocity (hCFV and bCFV) before and after atorvastatin treatment.</p><p><b>RESULTS</b>(1) Eight weeks later, total cholesterol and LDL-C levels were significantly lower in statin group than in non-statin group and control group [TC (3.83 +/- 0.80) mmol/L vs. (5.30 +/- 1.18) mmol/L vs. (5.32 +/- 1.17) mmol/L, P < 0.05; LDL-C (2.26 +/- 0.64) mmol/L vs. (3.28 +/- 0.85) mmol/L vs. (3.30 +/- 0.82) mmol/L, P < 0.05]. (2)Baseline CFR levels were significantly lower in statin group and non-statin group than that in control group (2.32 +/- 0.30 vs. 2.25 +/- 0.33 vs. 3.15 +/- 0.34, P < 0.05). Compared with non-statin group and statin group before treatment, 8 weeks statin treatment was associated with reduced bCFV [(26.06 +/- 3.22) cm/s vs. (29.02 +/- 3.36) cm/s and (26.06 +/- 3.22) cm/s vs. (28.43 +/- 3.40) cm/s, P < 0.05], increased hCFV [(77.63 +/- 8.96) cm/s vs. (65.17 +/- 7.22) cm/s and (77.63 +/- 8.96) cm/s vs. (64.58 +/- 6.26) cm/s, P < 0.05] and increased CFR (3.07 +/- 0.29 vs. 2.28 +/- 0.35 and 3.07 +/- 0.29 vs. 2.32 +/- 0.30, P < 0.05). bCFV, hCFV and CFR of statin group post treatment were similar to those of controls (P > 0.05).</p><p><b>CONCLUSION</b>Patients with coronary slow flow were associated with lower CFR which could be significantly improved by statin therapy.</p>

Outcome of patients with ST-elevation myocardial infarction complicated by pre-hospital cardiac arrest underwent emergency percutaneous coronary intervention / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the outcome of ST-elevation acute myocardial infarction (STEMI) patients complicated pre-hospital cardiac arrest underwent percutaneous coronary intervention (PCI).</p><p><b>METHODS</b>From September 2004 to November 2008, 1446 consecutive patients with acute STEMI underwent PCI in our department. 49 out of 1446 patients complicated by pre-hospital cardiac arrest. Clinical outcome including total mortality, adverse cardiac events, stroke and bleeding events during the hospitalization period and within 1 year after discharge was compared between patients with or without pre-hospital cardiac arrest.</p><p><b>RESULTS</b>PCI success rate was similar (85.7% vs. 88.8%, P = 0.497) while the incidence of in-hospital cardiogenic shock 22.4% vs. 3.0%, P < 0.001 and cardiac arrest (44.9% vs. 5.9%, P < 0.001) and in-hospital mortality (36.7% vs. 2.0%, P < 0.001) were significantly higher in patients with pre-hospital cardiac arrest than patients without pre-hospital cardiac arrest. Time from symptom onset to emergency treatment, asystole as initial rhythm, Glasgow coma scale (GCS ≤ 7) and cardiogenic shock on admission were independent risk factors of in-hospital death in patients with pre-hospital cardiac arrest. During follow up, incidences of overall mortality, re-infarction, revascularization and stroke were similar between the two groups.</p><p><b>CONCLUSIONS</b>STEMI patients with pre-hospital cardiac arrest undergoing emergency PCI are facing higher risk of cardiogenic shock and cardiac arrest and higher in-hospital mortality compared to those without pre-hospital cardiac arrest. However, the post-hospital discharge outcome was similar between the two groups.</p>

Intracoronary nitroprusside in the prevention of the no-reflow phenomenon in acute myocardial infarction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>No-reflow phenomenon during percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) is a predictive factor of continuous myocardial ischemia, ventricular remodeling and cardiac dysfunction, which is closely associated with a worse prognosis. This study aimed to evaluate intracoronary nitroprusside in the prevention of the no-reflow phenomenon in AMI.</p><p><b>METHODS</b>Ninety-two consecutive patients with AMI, who underwent primary PCI within 12 hours of onset, were randomly assigned to 2 groups: intracoronary administration of nitroprusside (group A, n = 46), intracoronary administration of nitroglycerin (group B, n = 46). The angiographic results were observed. The real-time myocardial contrast echocardiography (RT-MCE), including contrast score index (CSI), wall motion score index (WMSI), transmural contrast defect length (CDL) and serious WM abnormal length (WML) were recorded at 24 hours and 1 week post-PCI. High sensitivity C-reactive protein (Hs-CRP) was examined by immune rate nephelometry. N-terminal prohormone brain natriuretic peptide (NT-proBNP) was tested with enzyme-linked immunosorbent assay. Patients were followed up for six months. Major adverse cardiac events (MACE) were recorded.</p><p><b>RESULTS</b>The incidence of final TIMI-3 flow in group A was much higher than that in Group B (P < 0.05), final corrected TIMI frame count (cTFC) in group A decreased significantly than that in group B (P < 0.01). The CSI, CDL/LV length, WMSI and WL/LV length in group A were significantly lower than that in group B (P < 0.01). Levels of Hs-CRP and NT-proBNP at 1 week post-PCI decreased significantly in group A than that in group B (P < 0.01). Patients were followed up for 6 months and the incidence of MACE in group A was significantly lower than that in group B (P < 0.05).</p><p><b>CONCLUSION</b>Intracoronary nitroprusside can improve myocardial microcirculation, leading to the decrease of the incidence of no-reflow phenomenon and better prognosis.</p>

Probucol attenuates atrial autonomic remodeling in a canine model of atrial fibrillation produced by prolonged atrial pacing / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>We hypothesize that increased atrial oxidative stress and inflammation may play an important role in atrial nerve sprouting and heterogeneous sympathetic hyperinnervation during atrial fibrillation (AF). To test the hypothesis, we examined whether the antioxidant and anti-inflammatory treatment with probucol attenuates atrial autonomic remodeling in a canine model of AF produced by prolonged rapid right atrial pacing.</p><p><b>METHODS</b>Twenty-one dogs were divided into a sham-operated group, a control group and a probucol group. Dogs in the control group and probucol group underwent right atrial pacing at 400 beats per minute for 6 weeks, and those in the probucol group received probucol 1 week before rapid atrial pacing until pacing stopped. After 6-week rapid atrial pacing, general properties including left atrial structure and function, atrial hemodynamics and the inducibility and duration of AF were measured in all the groups. Atrial oxidative stress markers and serum C-reactive protein (CRP) concentration were estimated. The degree of nerve sprouting and sympathetic innervation at the right atrial anterior wall (RAAW) and the left atrial anterior wall (LAAW) were quantified by immunohistochemistry, atrial norepinephrine contents were also detected. Atrial beta-nerve growth factor (beta-NGF) mRNA and protein expression at the RAAW and LAAW were assessed by real-time quantitative RT-PCR and Western blotting respectively.</p><p><b>RESULTS</b>Atrial tachypacing induced significant nerve sprouting and heterogeneous sympathetic hyperinnervation, and the magnitude of nerve sprouting and hyperinnervation was higher in the RAAW than in the LAAW. Atrial beta-NGF mRNA and protein levels were significantly increased at the RAAW and LAAW, and the upregulation of beta-NGF expression was greater at the RAAW than at the LAAW in the control group. The beta-NGF protein level was positively correlated with the density of sympathetic nerves in all groups. Probucol decreased the increase of CRP concentration and attenuated atrial oxidative stress caused by atrial tachypacing. In addition, probucol could effectively inhibit atrial beta-NGF upregulation, significantly attenuate atrial nerve sprouting and heterogeneous sympathetic hyperinnervation, and dramatically reduce the inducibility and duration of AF.</p><p><b>CONCLUSIONS</b>The atrial over-expression of beta-NGF possibly caused by increased oxidative stress and inflammation may be the main mechanism underlying atrial autonomic remodeling during AF. Probucol attenuates atrial autonomic remodeling possibly by its antioxidant and anti-inflammatory actions.</p>

Effects of spironolactone on electrical and structural remodeling of atrium in congestive heart failure dogs / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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 x kg(-1) x 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 Masson staining.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Effects of chronic trimetazidine treatment on atrial energy metabolism in a canine model of chronic atrial fibrillation / 中华心血管病杂志

<p><b>OBJECTIVE</b>Aim of the present study was to investigate the effect of chronic trimetazidine treatment on atrial energy metabolism and endothelial function in a canine model of chronic atrial fibrillation (AF).</p><p><b>METHODS</b>Eighteen canines were randomly divided into sham-operated group (n = 6), atrial pacing group (n = 6), and trimetazidine group (n = 6). In atrial pacing group and trimetazidine group, dogs were atrial paced at 400 beats per minutes for 6 weeks. Trimetazidine at 5 mgxkg(-1)xd(-1) was given one day before rapid atrial pacing for 6 weeks. Creatine phosphate (CrP), adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) in atrial tissue were analyzed by high-performance liquid chromatography. Total adenosine (TAN) was calculated. The expression of endothelial nitric oxide synthase (eNOS) in atrial tissue was determined by Western blot and immunohistochemical staining. In addition, plasma levels of von Willebrand factor (vWF) was quantified with enzyme-linked immunoadsorbent assay and NO(2)(-)/NO(3)(-) (NOx) was determined by nitrate reductase method.</p><p><b>RESULTS</b>Atrial CrP (P < 0.01) and CrP/ATP were significantly decreased in paced atrium compared to atrium from sham-operated group (P < 0.05) while ATP, ADP, AMP and TAN remained unchanged (all P > 0.05). Plasma vWF was significantly increased and plasma NOx significantly decreased in paced animals compared to sham-operated animals. Atrial expression of eNOS was also significantly reduced in paced animals (P < 0.01). Trimetazidine treatment did not alter the contents of CrP, ATP, ADP, AMP and TAN, but significantly increased atrial eNOS expression (P < 0.05), decreased plasma vWF (P < 0.01) and increased plasma NOx concentration.</p><p><b>CONCLUSION</b>Trimetazidine treatment affect chronic AF induced disturbance in energy metabolism but may improve endothelial function through a NOx depended manner.</p>

The efficacy of percutaneous coronary intervention combined percutaneous thrombectomy on coronary thrombotic lesions in patients with acute myocardial infarction / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy of percutaneous coronary intervention (PCI) combined percutaneous thrombectomy on coronary thrombotic lesions in patients with acute myocardial infarction (AMI).</p><p><b>METHODS</b>PCI were performed in 56 patients with AMI and positive coronary thrombus shown by angiography and these patients were randomly divided into PCI therapy group (n = 28) and PCI combined percutaneous thrombectomy group (n = 28). Real-time myocardial contrast echocardiography (RT-MCE) was performed at 24h and 1 week after PCI. Contrast score index (CSI), regional wall motion score index (WMSI), endocardial length of contrast defect (CDL), and wall motion abnormality (WML) were calculated. The plasma level of hs-CRP was measured by immunonephelometry. The plasma concentration of N-terminal proB-type natriuretic peptide (NT-proBNP) and matrix metalloproteinase-9 (MMP-9) were detected by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>CSI, WMSI, CDL and WML at 24 hours and 1 week post procedure as well as the levels of hs-CPR and NT-proBNP at 1 week post procedure [(4.56 +/- 1.98) mg/L vs. (5.96 +/- 2.03) mg/L, P < 0.05; (544.7 +/- 185.3) pmol/L vs. (897.6 +/- 215.9) pmol/L, P < 0.01] were significantly lower in PCI combined percutaneous thrombectomy group than those in PCI group in various time points. There were no differences in the plasma level of MMP-9 between the two groups [(672.7 +/- 175.9) microg/L vs. (609.6 +/- 196.5) microg/L, P > 0.05] at 1 week after PCI.</p><p><b>CONCLUSIONS</b>PCI combined percutaneous thrombectomy can significantly reduce no-reflow phenomenon, improve microcirculation and myocardial dysfunction. Thus PCI combined percutaneous thrombectomy is a feasible therapy in patients with AMI.</p>

Effects of adenovirus-mediated gene transfer of ICOSIg fusion protein on experimental autoimmune myocarditis in Lewis rats / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the effects of adenovirus vector-mediated gene transfer of ICOSIg fusion protein on experimental autoimmune myocarditis (EAM) in Lewis rats.</p><p><b>METHODS</b>Expression vector containing ICOSIg (p-Adeno-ICOSIg) was constructed by fusion of human ICOS and IgGFc segment. Adenovirus vector was digested by PacI enzyme and transfected into HEK 293 cells. Adenovirus expressing ICOSIg was produced. EGFP was constructed into adenovirus vector and used as control. EAM was induced in Lewis rats by injection of porcine cardiac myosin. All immunized Lewis rats were divided into 4 groups. Group A (n = 15) and B (n = 15) received adenovirus containing ICOSIg on day 0 and day 14 respectively to study the effects of costimulatory molecules gene therapy on T cell activation and inflammation; group C (n = 10) and group D (n = 10) received adenovirus containing EGFP on day 0 and day 14 respectively as controls. Group E (n = 10) was normal controls that did not receive immunization. On day 28, all rats were killed after echocardiography examination. Histopathological examination was performed to observe myocardial inflammation. Protein levels of ICOS, ICOSL, B7-1 and B7-2 were detected by Western blot. INF-gamma, IL-2 and IL-4 mRNA were determined by realtime RT-PCR.</p><p><b>RESULTS</b>On day 28, cardiac function was significantly improved and myocardial inflammation significantly attenuated in group B compared to group A, C and D (all P < 0.05). B7-1 expression at protein level was significantly lower in group B than that of group C (P < 0.05). ICOS and ICOSL expressions at protein level were significantly decreased in both group A and B compared with group C and D (P < 0.05). IFN-gamma mRNA level significantly decreased and IL-4 mRNA significantly increased in group A and B compared to group C and D (P < 0.05).</p><p><b>CONCLUSIONS</b>Blockade of costimulatory pathway with gene therapy of ICOSIg alleviated autoimmune inflammatory damage and improved cardiac function in Lewis rats with EAM. Down-regulated costimulatory molecules in the myocardium and reduced inflammatory cytokine secretion might be responsible for the beneficial effects of ICOSIg in this model.</p>

Chronic effects of percutaneous transmyocardial laser revascularization in patients with refractory angina / 中华心血管病杂志

<p><b>OBJECTIVE</b>Conflicting results exist on the therapeutic effects of percutaneous myocardial laser revascularization (PMR) in patients with refractory angina pectoris. This study assessed the effects of PMR on myocardial innervation and perfusion in patients with refractory angina pectoris.</p><p><b>METHODS</b>Patients with refractory angina unsuitable for standard revascularization treatment (PTI and CABG) were randomly divided into medication plus PMR (PMR, n = 17) and medication group (M, n = 13). Coronary sinus noradrenaline (NE) and epinephrine (E) levels, heart rate variability (HRV), total ischemic burden (TIB), and ischemic ST segmental events (STI), myocardial perfusion were evaluated at pre-, immediately post and 12 months post treatment (mean followed up time = 11.6 +/- 4.9 months).</p><p><b>RESULTS</b>In PMR group, one patient developed non-persistent ventricular tachycardia, 2 developed pericardial tamponade and another one patient developed heart failure at 24 h after operation. Coronary sinus NE and E were significantly lower 60 min post PMR compared to pre-PMR and HRV was significantly increased 24 h post PMR. One year post treatments, angina grade was significantly decreased in PMR (1.7 +/- 0.3) than that in M group (0.4 +/- 0.2, P < 0.05) while other parameters were similar between the groups.</p><p><b>CONCLUSIONS</b>PMR induced an early transient denervation and decreased angina grade one year post treatment in patients with refractory angina.</p>

IL-10 gene modification on immature dendritic cells induces antigen-specific tolerance in experimental autoimmune myocarditis / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate whether IL-10 gene modification on immature dendritic cells (iDC) could induce autoimmune tolerance in rat experimental autoimmune myocarditis (EAM).</p><p><b>METHODS</b>EAM was induced by cardiac myosin immunization on day 0 and day 7 in rats. A total of 2 x 10(6) mature DC (mDC), iDC, pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or PBS were injected intravenously at 5th immunization day. Three weeks later, echocardiography and HE staining were performed to observe the cardiac function and myocardial inflammation. Th1/Th2 cytokines were detected by ELISA and MHC-II molecules, costimulatory molecules were identified by flow cytometry. In vitro T lymphocyte proliferation assay and adoptive transfer of DCs were performed to determine the antigen specific tolerance induced by IL-10 gene modification on iDCs.</p><p><b>RESULTS</b>EAM rats treated with pcDNA3-IL-10 transfected iDC showed improved cardiac function and reduced inflammatory cells infiltration into myocardium. Moreover, lower Th1 and higher Th2-type response was induced, MHC-II and costimulatory molecules down-regulated and antigen specific immunological responses towards cardiac myosin inhibited in pcDNA3-IL-10-iDC treated EAM rats.</p><p><b>CONCLUSION</b>Treatment with IL-10 gene modified iDCs could ameliorates EAM by inducing Th2 polarization and down-regulation of MHC-II molecules and costimulatory molecule expressions.</p>

Antigen-specific tolerance induced by IL-10 gene modified immature dendritic cells in experimental autoimmune myocarditis in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Experimental autoimmune myocarditis (EAM) in rats is a T-cell-mediated disorder. The initiation and maintenance of autoimmune responses in EAM depend on the maturation state of dendritic cells. IL-10 is a pleiotrophic immunomodulatory cytokine that functions at different levels of the immune response, so it has emerged as a promising therapeutic factor for the treatment of autoimmune/inflammatory diseases. This study was designed to test the hypothesis that IL-10 gene modified bone marrow-derived immature dendritic cells (iDCs) ameliorate EAM and to explore the underlying mechanisms.</p><p><b>METHODS</b>EAM was induced using the methods of cardiac myosin immunization on day 0 and day 7. Immature and mature bone marrow-derived dendritic cells (BMDCs) were generated without or with the stimulation by lipopolysaccharide (LPS) and the phenotype was analyzed by flow cytometry. Some of the iDCs were transfected by pcDNA3-IL-10 plasmid. 2 x 10(6)/per rat mature DC (mDC), immature DC (iDC), pcDNA3 transfected iDC, pcDNA3-IL-10 transfected iDC or phosphate buffered saline (PBS) were injected intravenously for treatment 5 days after the first immunization. On day 21, HE staining was performed to detect the myocardial inflammation and T lymphocyte proliferation assay was used to determine the effects of IL-10 gene transfected iDC on autoreactive T cell proliferation. Expression of IkappaB, the inhibitor of NF-kappaB pathway, was determined by Western blot.</p><p><b>RESULTS</b>BMDCs generated in a medium supplemented with granulocyte-macrophage-colony-stimulating factor (GM-CSF) were relatively immature, as determined by flow cytometry. However, stimulation with LPS induced these cells to become mature (m) DCs with higher levels of surface major histocompatibility complex (MHC)-II and costimulatory molecules. Intravenous administration of iDCs, especially pcDNA3-IL-10 transfected iDC, ameliorated the histopathological severity of the myosin induced-EAM, and the effect was lost after the DCs underwent maturation induced by in vitro exposure to LPS. IL-10 gene modified iDC inhibited the antigen specific T cell responses towards cardiac myosin. IkappaB protein was up-regulated significantly in the IL-10 gene modified iDC group.</p><p><b>CONCLUSIONS</b>IL-10 gene modified iDC induced antigen-specific tolerance in EAM. The underlying mechanisms may be related to costimulatory molecules down-regulation and NF-kappaB pathway inhibition.</p>

The experimental study on changes of endothelial nitric oxide synthase and plasminogen activator inhibitor-1 protein in the canine atrial fibrillation model / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the changes in the expressions of endothelial nitric oxide synthase (eNOS) and plasminogen activator inhibitor-1 (PAI-1) and the alterations of nitric oxide (NO) concentration in atrial endocardium in atrial fibrillation (AF) in order to investigate the mechanisms that contribute to thrombosis.</p><p><b>METHODS</b>In canine AF was produced with rapid atrial pacing at 400 bpm for 6 weeks, whereas the controls had no atrial pacing. NO production was measured by NO-specific microelectrode. The expression of endocardial eNOS and PAI-1 protein were determined by Western blot analysis and immunohistochemical Staining. Plasma levels of PAI-1 were analysed by Enzyme-linked immunoadsorbent assay.</p><p><b>RESULTS</b>Left atrial NO concentration was decreased in AF than that in controls [(23.4 +/- 5.8)nmol/L vs (63.8 +/- 16.1)nmol/L, P < 0.01]. Endocardial eNOS expression was also significantly decreased (855 +/- 217 vs 2320 +/- 694, P < 0.05), whereas the expression of the PAI-1 was increased (3164 +/- 827 vs 1371 +/- 352, P < 0.01). Neither NO concentration, nor PAI-1, eNOS expression were altered in the right atria at the same time. A significant increase for plasma levels of PAI-1 was also detected in AF group. No correlation was found between eNOS and PAI-1 protein expression (r = 0.217, P > 0.05).</p><p><b>CONCLUSION</b>In the canine model AF was associated with a marked decrease in endocardial NOS expression and NO concentration and with an increase in PAI-1 expression in the left atrium, which may contribute to the thrombosis in AF.</p>

Effects of Losartan on acute atrial electrical remodeling / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Atrial electrical remodeling (AER) contributes to the maintainance of atrial fibrillation (AF). This study was to compare the effects of Losartan with those of Diltiazem on tachycardia-induced acute AER in rabbits.</p><p><b>METHODS</b>Twenty-one rabbits paced with maximal atrial capture rate for 3 hours in the right atrium (RA) were randomly divided into saline group, Diltiazem group and Losartan group. After autonomic blockage, we measured atrial effective refractory period (AERP), AERP rate adapting feature, AERP dispersion and RA conduction time at basic cycle lengths (BCLs) of 200 ms and 150 ms at baseline, 0.5 hour, 1 hour, 2 and 3 hours after rapid atrial pacing.</p><p><b>RESULTS</b>In the saline group, there was a prompt decrease in AERP as a result of rapid atrial pacing, and AERP200 and AERP150 were shortened sharply within 0.5 hour of pacing (30.2 +/- 10.5 ms and 24.1 +/- 9.1 ms, respectively). The AERP did not change dramatically in the Diltiazem and Losartan groups. In the saline group, the value of (AERP200-AERP150)/50 ms in high RA was 0.17 +/- 0.08 at baseline and became significantly smaller at 0.5 hour (0.08 +/- 0.06), 1 hour (0.09 +/- 0.06), 2 hours (0.08 +/- 0.04) and 3 hours (0.09 +/- 0.05) (all P < 0.05), suggesting a reduction of rate adaptation of AERP. The value of (AERP200-AERP150)/50 ms in high RA did not change during the 3 hours of pacing in both Diltiazem and Losartan groups. In the saline group, AERP dispersion increased significantly at 2 and 3 hours (P < 0.05). However, Diltiazem could not prevent the increase of AERP dispersion at 3 hours (P < 0.05). During Losartan infusion, the AERP dispersion was no longer increased after rapid atrial pacing. There was no significant difference in RA conduction time among the three groups.</p><p><b>CONCLUSION</b>Like calcium antagonist Diltiazem, Losartan could prevent AERP shortening and preserve rate adaptation of AERP after rapid atrial pacing. Losartan is more effective than Diltiazem in inhibiting the increase of AERP dispersion.</p>