Search

The age-related decline in T-cell function among elderly individuals remains unclear. We thus investigated the interrelationship between T-cell subsets and age to identify the changes in T-cell phenotypes and develop an age prediction model for the elderly population. A total of 127 individuals aged >60 years were divided into three groups (youngest-old group, 61–70 years, n = 34; middle-old group, 71–80 years, n = 53; and oldest-old group, ≥ 81 years, n = 40). The percentage of CD8+CD28− cells (P = 0.001) was highest in the oldest-old group and then followed by the middle-old group, while the youngest-old group was the lowest. Both females and males demonstrated significant decreases in the absolute counts of CD4+CD45RA+ cells (P = 0.020; P = 0.002) and CD8+CD28+ cells (P = 0.015; P = 0.005) with age. Multivariate linear regression showed that the percentage of CD8+CD28− cells (P < 0.001) was an independent predictor of aging after adjusting for sex, body mass index, hospitalization duration, smoking, drinking, chronic medical illness, and medications at admission. In conclusion, our results suggest that aging in elderly individuals is accompanied by a decrease in the counts of T-cell subpopulations. CD8+CD28− cells may be potential targets for elderly individuals in antiaging-related immunosenescence.

Background Our study aimed to investigate the prognostic value of a novel inflammatory index, systemic immune-inflammation index (SII), with the clinical outcomes of patients infected with coronavirus disease 2019 (COVID-19).Methods We evaluated a cohort study of COVID-19 patients (18–95 years old) in Tongji Hospital of Huazhong University of Science and Technology from January 28th 2020 to February 29th 2020. The enrolled patients were divided into two groups (including low-SII group and high-SII group) according to the cut-off point which is analyzed by receiver operating characteristic (ROC) curve. Univariate and multivariate COX regression analysis were performed to identify the factors associated with the outcomes of patients with COVID-19 infection. The primary and secondary outcome were in-hospital mortality and the development of acute respiratory distress syndrome (ARDS), respectively.Results A number of 326 adult patients (43.87% males, 61.22 ± 0.86 years) were enrolled in the final analyses. There were 147 cases (45.09%) died in hospital and 116 patients (35.58%) developed ARDS. ROC curve analysis indicated that the SII had a greater prediction accuracy in predicting the in-hospital mortality (area under the curve [AUC] = 0.789, sensitivity = 69.90%, specificity = 70.80%) and the development of ARDS (AUC = 0.736, sensitivity = 67.80%, specificity = 71.10%). Kaplan-Meier analysis revealed that patients in high-SII group had a greater risk of adverse clinical outcomes (all P P = 0.028) and the developed ARDS (HR = 6.832, 95%CI = 2.583–18.074, P

Neferine is an isoquinoline alkaloid isolated from seed embryos of Nelumbo nucifera (Gaertn), which has a variety of biological activities. In this study we examined the effects of neferine on Kv4.3 channels, a major contributor to the transient outward current (Ito) in rabbit heart, and on ex vivo electrophysiology of rabbit hearts. Whole-cell Kv4.3 currents were recorded in HEK293 cells expressing human cardiac Kv4.3 channels using patch-clamp technique. Arterially perfused wedges of rabbit left ventricles (LV) were prepared, and transmembrane action potentials were simultaneously recorded from epicardial (Epi) and endocardial (Endo) sites with floating microelectrodes together with transmural electrocardiography (ECG). Neferine (0.1–100 μmol/L) dose-dependently and reversibly inhibited Kv4.3 currents (the IC50 value was 8.437 μmol/L, and the maximal inhibition at 100 μmol/L was 44.12%). Neferine (10 μmol/L) caused a positive shift of the steady-state activation curve of Kv4.3 currents, and a negative shift of the steady-state inactivation curve. Furthermore, neferine (10 μmol/L) accelerated the inactivation but not the activation of Kv4.3 currents, and markedly slowed the recovery of Kv4.3 currents from inactivation. Neferine-induced blocking of Kv4.3 currents was frequency-dependent. In arterially perfused wedges of rabbit LV, neferine (1, 3, and 10 μmol/L) dose-dependently prolonged the QT intervals and action potential durations (APD) at both Epi and Endo sites, and caused dramatic increase of APD10 at Epi sites. Neferine inhibits Kv4.3 channels likely by blocking the open state and inactivating state channels, which contributes to neferine-induced dramatic increase of APD10 at Epi sites of rabbit heart.

Aims Malignant ventricular arrhythmias can arise in a subset of congestive heart failure (CHF) patients after they undergo cardiac resynchronization therapy (CRT), thus counteracting the haemodynamic benefits typically associated with biventricular pacing. This study seeks to assess whether alteration of the ventricular transmural repolarization and conduction due to reversal of the depolarization sequence during epicardial or biventricular pacing facilitate the development of ventricular arrhythmias. Methods and results ECGs and monophasic action potential (MAP) were recorded during programmed stimulation from right ventricle (RV) endocardium (RV-Endo), left ventricle (LV) epicardium (LV-Epi), or both (biventricular, Bi-V) in 15 individuals without structural heart diseases. In patients with severe CHF and CRT (n ¼ 21), ECGs were collected during RV-Endo, LV-Epi, and Bi-V pacing. MAP duration on intracardiac electrogram, the QT, JT, and Tpeak 2 Tend intervals on ECGs at different pacing sites were measured and compared. In subjects with or without structural heart disease, compared with RV-Endo pacing, LV-Epi and Bi-V pacing resulted in a longer JT (341.78+ 61.97 ms with LV-Epi, 325.86+ 59.69 ms with Bi-V vs. 286.14+ 38.68 ms with RV-Endo in CHF individuals, P , 0.0001) or Tpeak 2 Tend interval (121.55+ 19.88 ms with LV-Epi, 117.71+ 42.63 ms with Bi-V vs. 102.28+ 12.62 ms with RV-Endo in normal-heart subjects, P , 0.0001; 199.70+ 62.44 ms with LV-Epi, 184.89+ 74.08 ms with Bi-V vs. 146.41+ 31.06 ms with RV-Endo in CHF patients, P , 0.0001), in addition to prolonged myocardial repolarization time and delayed endocardial activation. During follow-up, sudden death and arrhythmia storm occurred in two CHF patients after CRT. Conclusion Epicardial and biventricular pacing prolong the time and increase the dispersion of myocardial repolarization and delay the transmural conduction. All of these should be considered as potential arrhythmogenic factors in CHF patients who receive CRT.

Salidroside (SAL) is a phenylpropanoid glycoside isolated from the medicinal plant Rhodiola rosea. A recent study has reported that SAL can efficiently decrease atherosclerotic plaque formation in low-density lipoprotein receptor-deficient mice. This study was to investigate the molecular mechanism of antiatherogenic effects of SAL. Given the importance of endothelial nitric oxide synthase (eNOS) in atherosclerosis, we sought to elucidate whether SAL could stimulate eNOS activation and also to explore its upstream signaling pathway. Six-week old apoE(-/-) male mice were fed a high-fat diet for 8weeks and then were administered with SAL for another 8weeks. SAL significantly improved endothelial function associated with increasing eNOS activation, thus reduced the atherosclerotic lesion area. SAL increased eNOS-Ser1177 phosphorylation and decreased eNOS-Thr495 phosphorylation, indicative of eNOS activation in endothelium. The aortic sinus lesions in SAL treated mice displayed reduced inflammation. SAL significantly activated AMP-activated protein kinase (AMPK). Both AMPK inhibitor and AMPK small interfering RNA (siRNA) abolished SAL-induced Akt-Ser473 and eNOS-Ser1177 phosphorylation. In contrast, LY294002, the PI3k/Akt pathway inhibitor, abolished SAL-induced phosphorylation and expression of eNOS. High performance liquid chromatography (HPLC) analysis revealed that SAL decreased cellular ATP content and increased the cellular AMP/ATP ratio, which was associated with the activation of AMPK. SAL was found to decrease the mitochondrial membrane potential (ΔΨm), which is a likely consequence of reduced ATP production. The action of SAL to reduce atherosclerotic lesion formation may at least be attributed to its effect on improving endothelial function by promoting nitric oxide (NO) production, which was associated with mitochondrial depolarization and subsequent activation of the AMPK/PI3K/Akt/eNOS pathway. Taken together, our data described the effects of SAL on mitochondria, which played critical roles in improving endothelial function in atherosclerosis.

Stem cells transplantation is a promising strategy in cardiology. This meta-analysis summarizes the efficacy and safety of stem cells transplantation on top of standard medication on chronic heart failure patients.The following databases were searched, including Cochrane Library (Issue 4, 2011), PubMed (1980 to 2011), Embase (1990 to 2011), CBM (1978 to 2011), CNKI (1994 to 2011), VIP (1989 to 2011), and WanFang Data (1998 to 2011). Search criteria:studies were screened and the quality was evaluated according to predefined inclusion and exclusion criteria. Intervention measures: the treatment group using stem cell transplantation therapy on top of standard drug treatment, while the control group using standard drug treatments.A total of 31 studies involving 2375 patients were included. The results show that the improvement of LVEDV in the stem cell treatment group is greater than in the control group [SMD = -11.8% (95%CI: -0.223 - 0.013), P = 0.027] and the relative-risk of cardiac events is lower in stem cell treatment group [RR = 0.77 (95%CI: 0.66 - 0.90), P0.01] than in control group.Stem cells therapy is effective in improving cardiac remodeling and reducing the relative-risk of cardiac events in patients with chronic heart failure.

The transmural dispersion of APD (TD-APD) and heterogeneous changes in L-type calcium current (I Ca.L ) in rabbit hearts were examined 3 months after myocardial infarction. Compared to the control group, APDs of cells from the epimyocyte, midmyocyte, and endomyocyte layers remote from the infarct site were all lengthened: TD-APD was increased (288.32±19.56 ms vs. 210.32±17.43 ms in the control group; P 0.05). Compared to the control group, I Ca.L density was decreased in the infarct group, the reduction being most prominent in cells from the endomyocyte layer (from 16.12±1.60 pA.pF -1 to 8.73±0.06 pA.pF -1 , decreased 45.82%), with reductions in cells from the midmyocyte and epimyocyte layers of 39.72% and 37.01%, respectively. There was no significant difference in I Ca.L density between the sham-operated and control groups (P>0.05).

To investigate the effect and potential mechanism of lysophosphatidic acid (LPA) and antiarrhythmic peptide (AAP10) on rabbit ventricular arrhythmia.Twenty-four rabbits were randomly divided into three groups (n = 8 each): control group, LPA group and AAP10 + LPA group. Using arterially perfused rabbit ventricular wedge preparations, transmural ECG and action potentials from both endocardium and epicardium were simultaneously recorded in the whole process of all experiments with two separate floating microeletrodes. The incidence of ventricular arrhythmia post S1S2 stimulation was recorded. Protein levels of nonphosphorylated Cx43 and total Cx43 were evaluated by Western blot. The distribution of nonphosphorylated Cx43 was observed by confocal immunofluorescence microscopy.Compared with the control group, the QT interval, endocardial action potential duration, transmural repolarization dispersion (TDR) and incidence of ventricular arrhythmia were significantly increased and nonphosphorylated Cx43 expression was significantly upregulated in the LPA group. Compared with the LPA group, cotreatment with AAP10 can reduce the QT interval, endocardial action potential duration, TDR and incidence of ventricular arrhythmia (25.0% vs 62.5%, P0.01) and downregulate nonphosphorylated Cx43.LPA could promote the arrhythmia possibly by upregulating nonphosphorylated Cx43 and subsequent gap junction transmission inhibition. Gap junction enhancer AAP10 could attenuate the pro-arrhythmic effect of LPA probably by downregulating myocardial nonphosphorylated Cx43 expression.

The aim of this study is to observe the effect of combined amiodarone and antiarrhythmic peptide (AAP10) use on the incidence of induced ventricular arrhythmias in healed myocardial infarction (MI) rabbits.Twenty Japanese rabbits underwent thoracotomy without coronary artery ligation (Sham, group A), the middle left circumflex branch were ligated to induce MI in 180 Japanese rabbits. Eight weeks after operation, 124 rabbits survived MI operation and were divided into four groups: control group (group B, n = 31), amiodarone group (group C, n = 31), AAP10 group (group D, n = 31) and amiodarone plus AAP10 group (group E, n = 31). The A and B and D groups were treated with saline 2 ml/d, the C and E groups were treated with 2 ml saline containing amiodarone 100 mg×kg(-1)×d(-1). All rabbits were examined by echocardiogram at 12 weeks after operation, then anesthetized by sodium barbital, the left wedge ventricular preparations were cannulated and artery perfused by Tyrode's solution in vitro in the absence (Group A, B and C) and presence of AAP10 (500 nmol/L, Group D and E). The volume electrocardiogram, QT Interval, QRS interval, effective refractory period (ERP), the T-peak to T-end interval (T(p-e)), and ventricular tachycardia episodes induced by programmed stimulation were recorded. The T(p-e)/QT ratio was calculated. After perfusion, gap junctions protein connexin 43 (Cx43) expression was detected by Western blot and immunofluorescence.The incidence of induced ventricular tachycardia episodes of group A, B, C, D, E was 0, 62.5%, 26.9%, 40.0%, 22.2% respectively. The incidence of induced ventricular tachycardia episodes of group E was less than group B. The T(p-e)/QT ratio in group B, C, D were greater than in group A. The T(p-e)/QT ratio of group E was less than group B. The myocardial Cx43 in the group B was down-regulated and disorganized compared to group A, up-regulated in group C and E compared to group B, up-regulated in group E compared to group D. The Cx43 in the heart of group D and E were well organized than in group B and C.The artery perfused rabbits wedge preparations with healed myocardial infarction with high incidence of induced ventricular tachycardia episodes are good platform for ventricular arrhythmias research. Combined amiodarone and AAP10 use could decrease the T(p-e)/QT ratio and the incidence of induced ventricular tachycardia episodes. Amiodarone and AAP10 have synergistic effects on upregulating Cx43 and preventing ventricular arrhythmias in this rabbit model of healed myocardial infarction.

To study the Kv1.3 channel expression changes after CD4(+) and subsets CD28(null)/CD28(+)T cells activation in peripheral blood of patients with acute coronary syndrome (ACS).CD4(+)T cell in 27 ACS patients and CD4(+)CD28(null)/CD4(+)CD28(+)T cells in 12 out of these 27 ACS patients were isolated from peripheral blood with magnetic cell sorting. The whole-cell Kv1.3 currents for three T cells were recorded with patch-clamp technique before and 72 hours after activation by purified anti-human CD3 Interferon gamma, tumor necrosis factor alpha (TNF-alpha), granzyme B mRNA expression were determined by reverse transcription-PCR before and 72 hours after activation by purified anti-human CD3 in the presence or absence of recombinant Margatoxin (rMgTX, 0.1, 1, 10 nmol/L), a specific Kv1.3 channel blocker.Peak Kv1.3 channel currents of CD4(+), CD4(+)CD28(null), CD4(+)CD28(+)T cells were significantly increased and the mean Kv1.3 channel numbers per cell of these cells were increased by about 90%, 60%, 80% (402 +/- 88 vs. 752 +/- 275, 553 +/- 328 vs. 874 +/- 400, 392 +/- 133 vs. 716 +/- 251, all P0.05) after activation compared to baseline values. Baseline CD4(+)CD28(null)T cell numbers were about 40% more than those of CD4(+)CD28(+)T cell (P0.05) and were similar after activation (P = 0.102). The mRNA expression of interferon gamma, TNF-alpha and granzyme B were dose-dependently down-regulated by rMgTX.Kv1.3 channels of peripheral CD4(+)T cell and CD28(null)/CD28(+)T cells from ACS patients significantly increased after activation and Kv1.3-specific channel blocker rMgTX could effectively abolish this effect suggesting a potential role of Kv1.3 channel blocker on plaque stabilization in ACS patients.

The purpose of our study is to observe the voltage-gated potassium channel Kv1.3 expression on CD4+CD28null T cells from the peripheral blood of ACS patients by the patch clamp technique.Kv1.3 potassium channels expression from 17 patients with ACS and 11 healthy age-matched normal controls was detected in single cell (CD4+CD28null T cells and CD4+CD28+ T cells) by fluorescence microscopy and patch clamp.The percent of CD4+CD28nullT cells are higher in the ACS (6.97% +/- 2.05%) than that in the controls (1.38% +/- 0.84%, P0.05). The concentration of hsCRP is directly correlated with the number of the CD4+CD28null T cells in the ACS (r = 0.52, P0.05). The conductance [(6.89 +/- 1.17) nS vs. (3.36 +/- 0.66) nS], dens [(1.95 +/- 0.80) n/microm2 vs. (1.13 +/- 0.57) n/microm2] and numbers [(574.5 +/- 97.6) n/cell vs. (280.3 +/- 55.3) n/cell] of the Kv1.3 channels on the CD4+CD28null T cells are significantly higher than those on the CD4+CD28+ T cells (all P0.01) in ACS patients, but were similar on CD4+CD28+ T cells between ACS patients and controls.The CD4+CD28null T cells in the ACS and the numbers of Kv1.3 channels on the CD4+CD28null T cells from the ACS patients are significantly upregulated and might contribute to the pathogenesis of ACS.

To determine current density of voltage-gated potassium channels and Kv1.3 express in T-lymphocyte derived from patients with acute coronary syndrome (ACS).Peripheral blood mononuclear cells were collected from 12 patients with ACS and 10 control donors. Whole-cell patch clamp technique was used to record the outward K(+) currents (IK) and western blots technique was used to detect the express of Kv1.3 protein in lymphocyte.(1) The current density of voltage-gated potassium channel was significantly higher in ACS patients [(269 +/- 94) pA/pF] than in controls [(191 +/- 64) pA/pF, P0.01] while membrane capacitance was similar between the two groups. (2) Kv1.3 protein expression was also significantly increased in ACS patients than in controls (P0.01).The lymphocyte voltage-gated potassium channel is upregulated in patients with ACS suggesting a role of Kv activation in the pathophysiology of ACS.

To investigate the effect of KN-93, a calmodulin kinase II inhibitor, on ventricular arrhythmias in rabbits with cardiac hypertrophy.Female New Zealand white rabbits were randomly divided into four groups (n = 10 each): Sham; LVH; LVH + KN-92 and LVH + KN-93 group. LVH was induced by partially constricting the abdominal aorta. In Sham group, the abdominal aorta was exposed without constriction. Eight weeks later, the arterially perfused left ventricular wedge preparations were made and transmembrane action potentials (TAP) from epicardium and endocardium and transmural ECG were simultaneously recorded. Incidence of early after depolarization (EAD) and torsade de pointes (Tdp), QT interval, action potential duration (APD) and transmural depolarization dispersion (TDR) at different cycle lengths were observed under slow stimulation (2000 - 4000 ms), hypokalemic (2 mmol/L) and hypomagnesaemic (0.25 mmol/L) Tyrode's solution perfusion.Left ventricular hypertrophy was detected in LVH group by echocardiography and not affected by KN-92 and KN-93. Perfused with hypokalemic, hypomagnesaemic Tyrode's solution and under slow stimulation (2000 - 4000 ms), the incidences of EAD and Tdp in Sham group, LVH group, LVH + KN-92 group (0.5 micromol/L) and LVH + KN-93 group (0.5 micromol/L) were 0/10, 10/10, 9/10, 5/10 and 0/10, 5/10, 4/10, 1/10, respectively. With 1 micromol/L KN-92 and KN-93, the incidences of EAD and Tdp in LVH + KN-92 and LVH + KN-93 group were 9/10, 3/10 and 4/10, 1/10 respectively. The QT interval, APD and TDR were not affected by KN-93.The calmodulin kinase II inhibitor KN-93 can effectively suppress ventricular arrhythmias in rabbits with cardiac hypertrophy by decreasing EAD.

To evaluate the effects of antiarrhythmic peptide (AAP10) on ventricular arrhythmias in rabbits with healed myocardial infarction (OMI).Thirty rabbits were randomly divided into three groups (n = 10 each): Sham group, left thoracotomy was performed without coronary ligation; OMI group and OMI + AAP10 group, the circumflex coronaries were ligated. Three months post operation, the electrophysiological and antiarrhythmic effects of AAP10 were assessed in the arterially perfused rabbit left ventricular wedge preparation. Sham and OMI group were perfused with Tyrode's solution and OMI + AAP10 group was perfused with Tyrode's solution + AAP10 (80 nmol/L). Transmembrane action potentials were recorded simultaneously from endocardium and epicardium together with a transmural ECG by use of 2 separate intracellular floating microelectrodes. The stimulus-response-interval (SRI) of the epicardium and the incidence of ventricular tachycardia (VT) were observed. Whole heart and left ventricular weights, the left ventricular thickness at infarct border zone were measured.Whole heart and left ventricular weights as well as the left ventricular thickness at the infarct border zone significantly increased post infarction. VT was induced in 8 out of 10 rabbits in OMI group and in 2 out of 10 rabbits in OMI + AAP10 group (P0.05). SRI was also significantly shortened in OMI + AAP10 group compared to OMI group [SRI-1: (20.59 +/- 0.79) ms vs. (28.71 +/- 0.55) ms; SRI-2: (30.42 +/- 0.74) ms vs. (38.67 +/- 0.49) ms, all P0.01]. However, the action potential morphology and duration were similar between OMI and OMI + AAP10 groups.The antiarrhythmic peptide (AAP10) can increase gap junctional intercellular conductance without affecting the action potential morphology and duration and decrease the incidence of inducible ventricular tachycardia.

To investigate the effects of imidapril (IMI) on effective refractory period (ERP) and sodium current (I(Na)) of myocytes in ventricular noninfarction zone of healed myocardial infarction (HMI) in rabbit models.Rabbits with left coronary artery ligation were prepared and IMI (0.625 mg x kg(-1) x d(-1), 8 weeks) was orally administered. The ERP and sodium current were recorded.The ERP in HMI heart was prolonged. The ERP in IMI group was lower significantly than that of HMI group. The I(Na) density of myocyte in HMI ventricle decreased obviously. V 1/2 of steady state inactivation of I(Na) shifted to hyperpolarization, and time constant (tau) of recovery from inactivation in HMI ventricular myocyte was longer than that of sham ventricular myocyte. I(Na) density in IMI group increased markedly as compared with that of HMI group.IMI was shown to reverse the abnormal prolongation of ERP in rabbit heart with the HMI and increase I(Na) density. It may be the mechanism of IMI preventing against antiarrhythmia in healed myocardical infarction.

To evaluate the effects of W-7, a calmodulin inhibitor, on transmural dispersion of repolarization (TDR), early after depolarization (EAD) and torsade de pointes (TdP) induction after administration of d-sotalol in isolated rabbit heart.TdP was induced by d-sotalol (30 micromol/L), bradycardia, and hypokalemic (1.5 mmol/L)/hypomagnesaemic (0.35 mmol/L) solution in isolated female rabbit hearts. Thirty six rabbit hearts were divided into 4 groups (n = 9 each): d-sotalol alone, d-sotalol + W-7 (20 micromol/L), d-sotalol + W-7 (50 micromol/L), and d-sotalol + W-7 (100 micromol/L). Monophasic action potentials (MAPs) of the left ventricular epimyocardium (Epi), midmyocardium (M), and endomyocardium (Endo) were recorded simultaneously with ECG. The incidence of EAD and TdP were observed as well.Treatment with d-sotalol alone prolonged ventricular MAP duration and QT interval, increased TDR, and evoked high incidence of EAD (9/9) and spontaneous TdP (7/9) in hypokalemic/hypomagnesaemic solution in female rabbit heart. W-7 concentration-dependently decreased incidence of TdP (4/9 in 20 micromol/L; 2/9 in 50 micromol/L; 1/9 in 100 micromol/L). This effect of W-7 coincided with the decreased incidence of EAD (5/9 in 20 micromol/L; 4/9 in 50 micromol/L; 1/9 in 100 micromol/L). However, the d-sotalol-induced prolongation of QT interval and TDR was not significantly altered by W-7 at the three concentration used.In isolated female rabbit hearts, calmodulin antagonist W-7 suppresses d-sotalol-induced TdP without altering TDR but does suppress EAD. The effects observed with W-7 also suggest a possible important role for calmodulin-activated enzymes in the induction of TdP.

To investigate the effects of chronic treatment with imidapril on the electrophysiologic heterogeneous change of the noninfarcted myocardium of rabbits after myocardial infarction and the mechanism of its antiarrhythmic efficacy.Rabbits with left coronary artery ligation were prepared and allowed to recover for 8 weeks. Myocytes were isolated from subendocardial, midmyocardial, and subepicardial regions of the noninfarcted left ventricular wall. Action potentials and calcium current were recorded using whole-cell patch clamp technique.The action potential duration of repolarization 90 % (APD90) was more prolonged in midmyocardium rather than in subepicardium and subendocardium with healed myocardial infarction. The transmural dispersion of repolarization (TDR) was increased in the three ventricular regions. The amplitude of I(Ca-L) [was enhanced but its density was decreased in noninfarcted ventricular myocytes due to increased cell membrane capacitance. The increased differences of calcium currents among subepicardium, midmyocardium, and subendocardium were also discovered. Normalization of heterogeneous changes in repolarization after treatment with imidapril was observed and decrease of TDR in noninfarcted area was measured. Early after depolarization (EAD) events of noninfarcted midmyocardium were markedly decreased by imidapril.Imidapril reduced the electrophysiologic heterogeneities in noninfarcted area in rabbits after myocardial infarction. This ability of imidapril may contribute to its antiarrhythmic efficacy.

Objectives The contribution of regulatory T cells (Tregs) to the pathogenesis of acute coronary syndrome (ACS) remains poorly understood. One core obstacleis the lack of Treg-specific markers. A highly conserved CpG enriched element in fork head box P3intron 1 (FOXP3 i l) is unmethylated only in Tregs, and measuring the unmethylation of FOXP3 i l can be used to identify the role of Tregs inclinical diseases. This study investigated whether analysing the demethylation status of FOXP3 i 1 is a more reliablemeans than using Treg-specific surface markers in ACS. Methods We evaluated circulating Tregs percentages on different levels including cell frequencies (CD4 + CD25 high FOXP3 + Tregs and CD4 + CD25 high CD45 + naive Tregs) or FOXP3mRNA, FOXP3 i 1 demethylation status and related cytokine secretion in 89 patients with ACS and 35 controls. Results FOXP3i 1 demethylation assay showed that the amount of Tregs in ACS patients was significantly reduced than that in controls ( p = 0.0005). However, flow cytometry analysis did not identify any reduction of CD4 + CD25 high FOXP3 + Tregs in ACS patients. Notably, younger patients had higherpercentage of CD4 + CD25 high FOXP3 + Tregs but decreased percentage of CD4 + CD25 high CD45 + naive Tregs than either controlsor older patients. Furthermore, a DNA hypomethylation agent increasedthe amount of CD4 + CD25 high FOXP3 + Tregs and Tregs related cytokine IL-10 and suppressed the production of pro-inflammatory cytokin einterferon-γ by inducing FOXP3 i 1 demethylation in vitro . Conclusions A quantitative defect of Tregs, suggestive of decreased peripheral tolerance, could be a potential hallmark of ACS disease. Targeting FOXP3 i l demethylation might elevate the inhibitory activity of Tregs in ACS.