Effects of ectopic pacing on repolarization of the chicken left ventricle

Effects of ectopic pacing on left ventricular repolarization were studied in six anesthetized open-chest chickens. In each animal, unipolar electrograms were acquired from as many as 98 sites with 14 plunge needles (seven transmural locations between epicardium and endocardium in each needle). Activation-recovery intervals (ARIs), corrected to the cycle length, were used for estimating repolarization. At baseline, the nonuniform ARI distribution in the left ventricle resulted in the apicobasal differences being greater than the transmural gradient. Nonuniform ARI prolongation caused by ectopic pacing resulted in decreasing the transmural repolarization gradient and increasing the differences in the apex-to-base direction. The basal, but not apical transmural differences contributed to the total left ventricular transmural gradient. The total left ventricular apicobasal gradient was contributed by the apicobasal differences in mid-myocardial and subendocardial layers more than in subepicardial ones. Thus, in in situ chicken hearts, the transmural and apicobasal ARI gradients exist within the left ventricle with the shortest ARIs in the basal subepicardium and the longest ARIs in the subendocardium of the apical and middle parts of the left ventricle. Apicobasal compared to transmural heterogeneity of local repolarization properties contributes more to the total left ventricular repolarization gradient.     

Increased ventricular repolarization heterogeneity in patients with ventricular arrhythmia vulnerability and cardiomyopathy: a human in vivo study

Increased repolarization heterogeneity can provide the substrate for reentrant ventricular arrhythmias in animal models of cardiomyopathy. We hypothesized that ventricular repolarization heterogeneity is also greater in patients with cardiomyopathy and ventricular arrhythmia vulnerability (inducible ventricular tachycardia or positive microvolt T wave alternans, VT/TWA) compared with a similar patient population without ventricular arrhythmia vulnerability (no VT/TWA). Endocardial and epicardial repolarization heterogeneity was measured in patients with (n = 12) and without (n = 10) VT/TWA by using transvenous 26-electrode catheters placed along the anteroseptal right ventricular endocardium and left ventricular epicardium. Local activation times (AT), activation-recovery intervals (ARI), and repolarization times (RT) were measured from unipolar electrograms. Endocardial RT dispersion along the apicobasal ventricle was greater (P < 0.005) in patients with VT/TWA than in those without VT/TWA because of greater ARI dispersion (P < 0.005). AT dispersion was similar between the two groups. Epicardial RT dispersion along the apicobasal ventricle was greater (P < 0.05) in patients with VT/TWA than in those without VT/TWA because of greater ARI dispersion (P < 0.05). AT dispersion was similar between the two groups. A plot of AT as a function of ARI revealed an inverse linear relationship for no VT/TWA such that progressively later activation was associated with progressively shorter ARI. The AT-ARI relationship was nonlinear in VT/TWA. In conclusion, patients with cardiomyopathy and VT/TWA have greater endocardial and epicardial repolarization heterogeneity than those without VT/TWA without associated conduction slowing. The steep repolarization gradients in VT/TWA may provide the substrate for functional conduction block and reentrant ventricular arrhythmias.     

Activation and repolarization patterns in the ventricular epicardium under sinus rhythm in frog and rabbit hearts

Our study compared the contributions of activation sequence and local repolarization durations distribution in the organization of epicardial repolarization in animals with fast (rabbit) and slow (frog) myocardial activation under sinus rhythm. Activation times, repolarization times and activation-recovery intervals (ARI) were obtained from ventricular epicardial unipolar electrograms recorded in 13 Chinchilla rabbits (Oryctolagus cuniculus) and 10 frogs (Rana temporaria). In frogs, depolarization travels from the atrioventricular ring radially. ARIs increased progressively from the apex to the middle portion and finally to the base (502+/-75, 557+/-73, 606+/-79 ms, respectively; P<0.01). In rabbits, depolarization spread from two epicardial breakthroughs with the duration of epicardial activation being lower than that in frogs (17+/-3 vs. 44+/-18 ms; P<0.001). ARI durations were 120+/-37, 143+/-45, and 163+/-40 ms in the left ventricular apex, left, and right ventricular bases, respectively (P<0.05). In both species, repolarization sequence was directed from apex to base according to the ARI distribution with dispersion of repolarization being higher than that of activation (P<0.001). Thus, excitation spread sequence and velocity per se do not play a crucial role in the formation of ventricular epicardial repolarization pattern, but the chief factor governing repolarization sequences is the distribution of local repolarization durations.     

The contribution of ventricular apicobasal and transmural repolarization patterns to the development of the T wave body surface potentials in frogs (Rana temporaria) and pike (Esox lucius)

The study aimed at the simultaneous determination of the transmural and apicobasal differences in the repolarization timing and the comparison of the contributions of these two repolarization gradients to the development of the body surface T wave potentials in animals with the single heart ventricle (fishes and amphibians). Unipolar potentials were measured on the body surface, epicardium and in the intramural (subepicardial, Epi; midmyocardial; and subendocardial, Endo) ventricular layers of 9 pike and 8 frogs. Activation times, repolarization times and activation-recovery intervals were determined. A transmural gradient in repolarization durations in frogs (Endo>Epi, P<0.024) corresponds to the gradient in repolarization times. No significant transmural difference in repolarization duration is observed in pike that produces a repolarization sequence from Endo to Epi (Endo相似文献   

Repolarization of canine ventricular myocardium under the supraventricular rhythm

The ventricular myocardium is characterized by heterogeneity of activation-recovery interval durations. The transmural ARI gradients are present in the right ventricular apex (ARIs monotonically decreased as one moved from the endocardium to the epicardium), and in the left ventricular base (repolarization in the subepicardial layers was significantly shorter than that in the midmyo cardial layers whereas subendocardial ARIs did not differ from the others). The repolarization pattern of these myocardial regions is governed by the distribution of ARIs. In the apical left ventricular and basal right ventricular areas, no significant transmural differences in the repolarization durations were found. The repolarization pattern of these myocardial regions is governed by the activation sequence. In the right ventricle, ARIs were significantly longer at the base and shorter at the apex. In contrast, in the left ventricle, the apical ARIs were prolonged whereas the basal ARIs were abbreviated. The apex-to-base sequence of myocardial repolarization seems to depend on apex-to-base gradient of activation-recovery intervals durations.     

Conduction and refractory disorders in the diabetic atrium

Diabetes mellitus (DM) is an independent risk of atrial fibrillation. However, its arrhythmogenic substrates remain unclear. This study sought to examine the precise propagation and the spatiotemporal dispersion of the action potential (AP) in the diabetic atrium. DM was induced by streptozotocin (65 mg/kg) in 8-wk-old male Wister rats. Optical mapping and histological analysis were performed in the right atrium (RA) from control (n = 26) and DM (n = 27) rats after 16 wk. Rate-dependent alterations of conduction velocity (CV) and its heterogeneity and the spatial distribution of AP were measured in RA using optical mapping. The duration of atrial tachyarrhythmia (AT) induced by rapid atrial stimulation was longer in DM (2.4 ± 0.6 vs. 0.9 ± 0.3 s, P < 0.05). CV was decreased, and its heterogeneity was greater in DM than control. Average action potential duration of 80% repolarization (APD(80)) at pacing cycle length (PCL) of 200 ms from four areas within the RA was prolonged (53 ± 2 vs. 40 ± 3 ms, P < 0.01), and the coefficient of variation of APD(80) was greater in DM than control (0.20 ± 0.02 vs. 0.15 ± 0.01%, P < 0.05). The ratio of APD(80) at PCL shorter than 200 ms to that at 200 ms was smaller (P < 0.001), and the incidence of APD alternans was higher in DM than control (100 vs. 0%, P < 0.001). Interstitial fibrosis was greater and connexin 40 expression was lower in DM than control. The remodeling of the diabetic atrium was characterized as follows: greater vulnerability to AT, increased conduction slowing and its heterogeneity, the prolongation of APD, the increase in spatial dispersion and frequency-dependent shortening of APD, and increased incidence of APD alternans.     

Calcium-dependent arrhythmias in transgenic mice with heart failure

Transgenic mice overexpressing the inflammatory cytokine tumor necrosis factor (TNF)-alpha (TNF-alpha mice) in the heart develop a progressive heart failure syndrome characterized by biventricular dilatation, decreased ejection fraction, atrial and ventricular arrhythmias on ambulatory telemetry monitoring, and decreased survival compared with nontransgenic littermates. Programmed stimulation in vitro with single extra beats elicits reentrant ventricular arrhythmias in TNF-alpha (n = 12 of 13 hearts) but not in control hearts. We performed optical mapping of voltage and Ca(2+) in isolated perfused ventricles of TNF-alpha mice to study the mechanisms that lead to the initiation and maintenance of the arrhythmias. When compared with controls, hearts from TNF-alpha mice have prolonged of action potential durations (action potential duration at 90% repolarization: 23 +/- 2 ms, n = 7, vs. 18 +/- 1 ms, n = 5; P < 0.05), no increased dispersion of refractoriness between apex and base, elevated diastolic and depressed systolic [Ca(2+)], and prolonged Ca(2+) transients (72 +/- 6 ms, n = 10, vs. 54 +/- 5 ms, n = 8; P < 0.01). Premature beats have diminished action potential amplitudes and conduct in a slow, heterogeneous manner. Lowering extracellular [Ca(2+)] normalizes conduction and prevents inducible arrhythmias. Thus both action potential prolongation and abnormal Ca(2+) handling may contribute to the initiation of reentrant arrhythmias in this heart failure model by mechanisms distinct from enhanced dispersion of refractoriness or triggered activity.     

Action potential characterization in intact mouse heart: steady-state cycle length dependence and electrical restitution

Transgenic mice have been increasingly utilized to investigate the molecular mechanisms of cardiac arrhythmias, yet the rate dependence of the murine action potential duration and the electrical restitution curve (ERC) remain undefined. In the present study, 21 isolated, Langendorff-perfused, and atrioventricular node-ablated mouse hearts were studied. Left ventricular and left atrial action potentials were recorded using a validated miniaturized monophasic action potential probe. Murine action potentials (AP) were measured at 30, 50, 70, and 90% repolarization (APD(30)-APD(90)) during steady-state pacing and varied coupling intervals to determine ERCs. Murine APD showed rate adaptation as well as restitution properties. The ERC time course differed dramatically between early and late repolarization: APD(30) shortened with increasing S1-S2 intervals, whereas APD(90) was prolonged. When fitted with a monoexponential function, APD(30) reached plateau values significantly faster than APD(90) (tau = 29 +/- 2 vs. 78 +/- 6 ms, P < 0.01, n = 12). The slope of early APD(90) restitution was significantly <1 (0.16 +/- 0.02). Atrial myocardium had shorter final repolarization and significantly faster ERCs that were shifted leftward compared with ventricular myocardium. Recovery kinetics of intracellular Ca(2+) transients recorded from isolated ventricular myocytes at 37 degrees C (tau = 93 +/- 4 ms, n = 18) resembled the APD(90) ERC kinetics. We conclude that mouse myocardium shows AP cycle length dependence and electrical restitution properties that are surprisingly similar to those of larger mammals and humans.     

亚麻木酚素对2型糖尿病小鼠学习记忆的影响及其机制初探

目的:研究亚麻木酚素(Flax ligands,FL)对2型糖尿病模型小鼠空间学习记忆的影响及其初步机制。方法:雄性C57小鼠随机分为对照组(Con)、糖尿病模型组(DM)及亚麻木酚素治疗组(DM+FL),DM与DM+FL组给予高脂饮食加小剂量链脲佐菌素(Streptozotocin,STZ)诱导2型糖尿病模型,之后DM+FL组灌胃给予FL 10 mg/kg,每日一次,连续14天,Con与DM组给予等量生理盐水。通过新物体识别试验、Morris水迷宫试验检测小鼠的学习记忆能力,利用Western blot技术测定小鼠海马脑源性神经营养因子(BDNF)及谷酰胺AMPA受体845位磷酸化(pGluA1-Ser845)蛋白表达水平。结果:与Con组比较,DM组小鼠新物体识别指数显著下降(P<0.01),在Morris水迷宫中逃避潜伏期延长(P<0.05),在目的象限内徘徊时间减少(P<0.01);小鼠海马区BDNF和pGluA1-Ser845的蛋白表达水平均显著低于对照组(P<0.01)。与DM组相比,DM+FL组小鼠新物体识别指数显著提高(P<0.01),在Morris水迷宫中逃避潜伏期明显缩短(P<0.05),目的象限徘徊时间显著增多(P<0.05);小鼠海马区BDNF和pGluA1-Ser845的蛋白表达水平均显著升高(P<0.01)。结论:亚麻木酚素对2型糖尿病小鼠学习记忆有明确改善作用,增加海马BDNF和pGlu-A1-Ser845的表达可能是其潜在作用机制。     

Effect of an increase in coronary perfusion on transmural ventricular repolarization

The effect of increased coronary flow on transmural ventricular repolarization was investigated in six pentobabital-anesthetized sheep. Fresh blood at 10 ml/min was injected into the left circumflex coronary artery (LCX) in addition to the normal coronary flow. Unipolar electrocardiograms were simultaneously registered from epicardium, mid-myocardium and endocardium with fine plunge needles. Activation-recovery interval (ARI) was measured from the unipolar electrocardiograms and was used for estimating the ventricular repolarization duration. It was found that intracoronary blood injection (n=3) prolonged ARI in the epicardium, mid-myocardium and endocardium by an average of 34 +/- 16, 28 +/- 18 and 25 +/- 13 ms, respectively (p<0.01). Pretreatment with nitro-L-arginine (n=3), a nitric synthase inhibitor, diminished the flow-induced ARI prolongation across the ventricular wall. In conclusion, an increase in coronary flow lengthens the duration of transmural ventricular repolarization. These effects appear to be mediated by nitric oxide from the coronary endothelium.     

ECG body surface mapping (BSM) in type 1 diabetic patients

Diabetes mellitus is a risk factor of cardiovascular diseases. ECG of patients with diabetes mellitus type 1 (DM 1) shows tachycardia (block of parasympathetic innervation) and abnormal repolarization (increased QT interval and QT dispersion (QTd)) indicating a risk of ventricular tachycardia and sudden death in young people with DM 1. The aim of the present report was to measure 145 parameters of the heart electric field in 22 patients (14 men, 8 women) with DM 1 without complications (mean age 32.8+/-11.4 years) and in 22 controls (11 men, 11 women, mean age 30.1+/-3.4 years). The duration of diabetes was 13.9+/-7.8 years. The parameters were registered by the diagnostic system Cardiag 112.2 and statistically evaluated by the Student and Mann-Whitney test. Tachycardia (86.3+/-2.7 beats.min(-1)), shortening of both QRS (79.9+/-1.6 ms) and QT (349.0+/-5.9 ms) and increased QT dispersion (115+/-36 ms) were observed in DM 1 when compared with the controls (75.0+/-2.1 beats. min.(-1), QRS 89.9+/-2.7 ms, QT 374.0+/-4.4 ms, QTd 34.0+/-12.0 ms, p<0.01). The QTc was 415.2+/-4.1 ms in DM 1 and 401.4+/-6.6 ms in controls (NS). Other significant findings in DM 1 were: higher maximum of depolarization isopotential maps (DIPMmax) in the initial phase of QRS and less positive in the terminal phase, more negative minimum (DIPMmin) during QRS similarly as the minimum in depolarization isointegral maps (DIIMmin) and the minimum in isointegral map of the Q wave (Q-IIMmin), lower maximum in repolarization isopotential maps (RIPMmax) and less negative minimum (RIPMmin), more negative amplitude of Q wave (Q-IPMAM) and more pronounced spread of depolarization (activation time). Our results confirmed a decreased parasympathetic to sympathetic tone ratio (tachycardia, shortening of the activation time) and revealed different depolarization and repolarization patterns in DM 1. The differences in heart electric field parameters measured by the BSPM method in DM 1 and in the controls indicate the importance of ECG examination of diabetic patients type 1 in the prevention of cardiovascular diseases.     

低温对离体大鼠心室肌复极时程的影响及其机制

目的: 观察低温对离体大鼠心室肌复极时程及Kir2.1蛋白表达的影响,探讨Kir2.1蛋白在其中的作用。 方法:18只健康雄性SD大鼠, 随机分为3组(n=6),即正常对照组(C组)、35℃低温组(H₁组)和32℃低温组(H₂组)。制备Langendorff离体心脏灌注模型,37℃ K-H液平衡灌注15 min后,C组继续灌注37℃ K-H液30 min;H₁组继续灌注35℃的K-H液30 min,H₂组继续灌注32℃的K-H液30 min。记录各组平衡灌注15 min(T₁)和继续灌注30 min(T₂)时HR、左心室前壁三层心肌单相动作电位,计算单相动作电位复极50％、90％的时程(MAPD₅₀、MAPD₉₀)和跨室壁复极离散度(TDR),同时记录心律失常发生情况。取测量电生理的心室肌部位组织以Western blot测定Kir2. 1蛋白表达,以免疫组织化学法测量Kir2. 1蛋白的平均光密度值(AOD)及分布情况。结果: 与T₀比较,T₁时H₁组和H₂组HR显著减慢(P＜0.05), MAPD₅₀、MAPD₉₀显著延长(P＜0.05),TDR显著增大(P＜ 0.05);与C组比较,T₁时H₁组和H₂组HR显著减慢(P＜0.05),MAPD₉₀显著延长(P＜0.05),TDR显著增大(P＜ 0.05),Kir2.1蛋白表达显著减少(P＜0.05), AOD值显著减少(P＜0.05)。与H₁组比较,T₁时H₂组心率显著减慢(P＜0.05),MAPD₅₀、MAPD₉₀显著延长(P＜0.05),TDR显著增大(P＜0.05)。C组Kir2.1蛋白分布正常,H₁、H₂组蛋白分布紊乱。结论: 低温会延长心室复极时程,增加复极离散度,其机制与低温下调Kir2.1蛋白表达、改变Kir2.1蛋白分布有关。     

Attenuation of I(K,slow1) and I(K,slow2) in Kv1/Kv2DN mice prolongs APD and QT intervals but does not suppress spontaneous or inducible arrhythmias

Overexpression of a truncated Kv1.1 or Kv2.1 channel polypeptide in the heart (Kv1DN or Kv2DN) resulted in mice with a prolonged action potential duration (APD) due to marked attenuation of rapidly activating, slowly inactivating K+ current (I(K,slow1)) or slowly inactivating outward K(+) current (I(K,slow2)) in ventricular myocytes. ECG monitoring, optical mapping, and programmed electrical stimulation of Kv1DN mice revealed spontaneous and inducible reentrant ventricular tachycardia due to spatial dispersion of repolarization and refractoriness. Recently, we demonstrated upregulation of I(K,slow2) in apical cardiomyocytes derived from Kv1DN mice. We therefore hypothesized that the selective upregulation of Kv2.1-encoded currents underlies the apex-to-base dispersion of repolarization and the reentrant arrhythmias. To test this hypothesis, the Kv1DN line was crossbred with the Kv2DN line to produce Kv1/Kv2DN lines. Whole cell voltage-clamp recordings from left ventricular cells of Kv1/Kv2DN confirmed that the 4-aminopyridine- and tetraethylammonium-sensitive components of IK,slow were eliminated, resulting in marked APD prolongation compared with wild-type, Kv1DN, and Kv2DN cells. Telemetric ECG recordings revealed prolongation of the corrected QT in Kv1/Kv2DN compared with Kv1DN and Kv2DN mice. However, attenuation of Kv2.1-encoded currents in Kv1DN mice did not suppress the arrhythmias. Thus, the elimination of I(K,slow2) prolongs APD and the QT intervals, but does not have an antiarrhythmic effect.     

Electrophysiological properties of ventricular muscle obtained from spontaneously diabetic mice.

The electrophysiological properties of cardiac muscle in KK/Ta mouse (hereafter referred to as KK mouse), an animal model of human non-insulin-dependent diabetes mellitus, were investigated, and the findings compared with those obtained from a non-diabetic control mouse (C57BL/6J mouse; referred to as B6 mouse). The ages of the B6 mice were 23.9 +/- 5.4 weeks (n = 24) and those of the KK mice used were 25.7 +/- 10.8 weeks (n = 34). The KK mice had mild obesity, hyperglycemia and hyperinsulinemia. Ventricular muscles from both mice were examined by light microscopy. Partial myocardial fibrosis and filament disorder in the ventricular muscles were found only in the KK mice. The resting membrane potential of the ventricular muscle was less negative in the KK mice than in the control mice. The maximum rate of rise in the upstroke of the action potential was significantly decreased in the KK mice compared with that of the control mice. These suggest a decrease in a time-independent K+ current (IK1) in the KK mice. The duration of the action potential (APD) at all levels of repolarization was significantly longer in the KK mice than in the B6 mice. A blocker of transient outward current (I(to)), 4-aminopyridine, significantly prolonged the APD of the B6 mice, but failed to prolong it in the KK mice, suggesting that Ito in the diabetic mice is very small. A Ca2+ channel blocker, CoCl2, dramatically lengthened all levels of APD in both groups, suggesting that there is no difference between B6 mice and KK mice in L-type Ca2+ current via Ca2+ channels. These suggest the malfunction or deficiency of ionic channels which carry, at least Ito and IK1 in diabetic mice.     

Effect of Resveratrol on Behavioral Performance of Streptozotocin-induced Diabetic Mice inAnxiety Tests

The aim of this study was to evaluate with anxiety tests the effect of resveratrol (RSV) on streptozotocin (STZ)-induced diabetic mouse behavioral performance at the second and fourth week of treatment. Confirmed diabetic mice (>250 mg/dl of glucose in blood after STZ injection) were treated with RSV (RDM, n=12) or control treated (DM, n=12) for 4 weeks. DM and RDM were tested in the Open Field Test (OFT) and Elevated Plus Maze (EPM). In the second week of RSV treatment, a higher grooming frequency (P<0.05) and a lower defecation and rearing frequency (P<0.05) were detected in the OFT in the RDM group compared with the DM. There was a higher grooming frequency (P<0.05) and higher percentage of entries in open arms (P<0.05) in the RDM group than in the DM group in the EPM. However, in the fourth week of RSV treatment, the only effect observed was a higher grooming frequency in the RDM group than in the DM group (P<0.05) in the EPM. In conclusion, RSV treatment in diabetic mice provoked anxiolytic-like effects in both tests (OFT and EPM), and these effects were observed in a short time window (2 weeks). It is suggested that RSV may help diabetic animals to adapt to new stressing and anxiety situations and thus to improve their welfare.     

Sympathetic stimulation increases dispersion of repolarization in humans with myocardial infarction

The sympathetic nervous system is thought to play a key role in genesis and maintenance of ventricular arrhythmias. The myocardial effect of sympathetic stimulation on myocardial repolarization in humans is poorly understood. The purpose of this study was to evaluate the effects of direct and reflex sympathetic stimulation on ventricular repolarization in patients with postinfarct cardiomyopathy (ICM). The effects of direct sympathetic stimulation were assessed using isoproterenol, while those of reflex sympathetic stimulation were assessed with nitroprusside infusion in ICM patients (n = 5). Five patients without cardiomyopathy were also studied. Local repolarization was measured from intracardiac electrograms that were used to calculate the activation recovery interval (ARI), a surrogate of action potential duration. Isoproterenol significantly increased heterogeneity in repolarization in patients with ICM; the decrease in ARI from baseline was 72.9 ± 9.1 ms in more viable regions, 64.5 ± 8.9 ms in the scar, and 54.9 ± 9.1 ms in border zones (P = 0.0002 and 0.014 comparing normal and scar to border zones, respectively). In response to nitroprusside, the ARI at the border zones decreased significantly more than either scar or surrounding viable myocardium, which showed an increase in ARI (P = 0.014 and 0.08 comparing normal tissue and scar to border zones, respectively). Furthermore, isoproterenol increased ARI dispersion by 70%, while nitroprusside increased ARI dispersion by 230% when ICM patients were compared to those with structurally normal hearts (P = 0.0015 and P < 0.001, respectively). In humans, both direct and reflex sympathetic stimulations increase regional differences in repolarization. The normal tissue surrounding the scar appears denervated. Dispersion of ARI in response to sympathetic stimulation is significantly increased in patients with ICM.     

2型糖尿病大血管病变患者血清趋化素与hs-CRP的相关性

目的:观察2型糖尿病(type2 diabetes mellitus,T2DM)大血管病变患者血清趋化素(chemerin)和超敏C-反应蛋白(high-sensitivity C-reactive protein,hs-CRP)的水平及其相关性。方法:选择我院2013年4月至2015年4月收治的T2DM患者60例,根据患者血管病变情况分为糖尿病大血管病变组和单纯糖尿病组,每组30例。另选择同期来我院体检的健康志愿者30例作为对照组。检测三组血清chemerin和hs-CRP水平并分析。结果:糖尿病大血管病变组和单纯糖尿病组血清chemerin和hs-CRP水平均显著高于对照组(P0.05);糖尿病大血管病变组血清chemerin和hs-CRP水平均显著高于单纯糖尿病组(P0.05);糖尿病大血管病变组血清chemerin与hs-CRP呈正相关(r=0.451,P0.05)。结论:T2DM大血管病变患者血清chemerin水平显著增高,血清chemerin水平与炎症指标hs-CRP存在正相关,chemerin可能通过介导炎症在T2DM大血管病变过程中发挥作用。     

Coronary occlusion and reperfusion promote early afterdepolarizations and ventricular tachycardia in a canine tissue model of type 3 long QT syndrome

Although long QT syndrome (LQTS) and coronary occlusion-reperfusion (O/R) are arrhythmogenic, they affect ventricular action potential duration (APD) differently. In contrast to the prolonged APD in LQTS, ischemia abbreviates APD after a transient prolongation. Thus we hypothesized that the dynamic interactive effects of ischemia and LQTS on APD and its dispersion would affect ventricular arrhythmogenicity. We mapped transmural distribution of action potentials in 6 groups of 10 isolated wedges of canine ventricular walls: LQTS-O/R, LQTS only, and O/R only, with separate groups for pacing cycle lengths (PCL) of 1,000 and 2,000 ms. We created type 3 LQTS with anemone toxin (ATX) II followed >30 min later by arterial occlusion (40 min) and reperfusion (>100 min). Arterial occlusion initially (first 4 min) prolonged and then shortened APD. Early afterdepolarizations (EADs) occurred during the initial 4 min of occlusion in 4 of the 10 LQTS-O/R wedges at PCL of 2,000 ms but not in the other groups. Reperfusion restored APD in the O/R-only groups but caused APD to overshoot its original duration, indicating depressed repolarization reserve, in the LQTS-O/R group. Reperfusion increased the dispersion of APDs and initiated ventricular tachycardia-fibrillation in 7 of 10 and 6 of 10 LQTS-O/R wedges and in 2 of 10 and 1 of 10 O/R-only wedges at PCLs of 1,000 and 2,000 ms, respectively. The LQTS-only wedges exhibited neither EADs nor ventricular tachycardia. We conclude that coronary O/R increased the arrhythmogenicity of LQTS via cumulative prolongation of APD, increase in repolarization dispersion, and suppression of repolarization reserve.