Acute stress modulates genotype effects on amygdala processing in humans

Probing gene–environment interactions that affect neural processing is crucial for understanding individual differences in behavior and disease vulnerability. Here, we tested whether the current environmental context, which affects the acute brain state, modulates genotype effects on brain function in humans. We manipulated the context by inducing acute psychological stress, which increases noradrenergic activity, and probed its effect on tonic activity and phasic responses in the amygdala using two MRI techniques: conventional blood oxygen level–dependent functional MRI and arterial spin labeling. We showed that only carriers of a common functional deletion in ADRA2B, the gene coding for the α2b-adrenoreceptor, displayed increased phasic amygdala responses under stress. Tonic activity, reflecting the perfusion of the amygdala, increased independently of genotype after stress induction. Thus, when tonic activity was heightened by stress, only deletion carriers showed increased amygdala responses. Our results demonstrate that genetic effects on brain operations can be state dependent, such that they only become apparent under specific, often environmentally controlled, conditions.     

Electrophysiologic effects of unilateral right and left stellate ganglion block on the human heart

To determine the electrophysiologic effects of stellate ganglion (SG) block on the human heart, the two SGs were anesthetized separately, with a 24-hour interval between the two procedures, in 13 patients with episodes of supraventricular tachycardia (six had Kent bundles). Left SG block caused: (1) a lengthening of the AH interval, measured at fixed atrial rates of 10 +/- 12 msec (p less than 0.01); (2) a marked depression of the VA conduction in six of the seven patients with measurable VA interval (in two patients it produced complete VA block); (3) a slowing of 20 to 40 msec of the cycle of an electrically induced reciprocating tachycardia; and (4) failure to modify the QT interval duration. In contrast, right SG block produced asymmetric or opposite changes and prolonged the QT interval (7.6 +/- 8.8 msec, p less than 0.05). Atrial and ventricular refractoriness was not significantly altered by SG block. Retrograde effective refractory period of the Kent bundle changed 20 to 60 msec after unilateral SG blockade. Thus, this study suggests that the human conduction system and the Kent bundles receive an appreciable sympathetic influence from the SG. Like experimental studies, we also found an asymmetric response to unilateral SG block and a dominance, in most of our patients, of the left SG. The influence on myocardial refractoriness was less apparent.     

Dose dependent but non-linear effects of alcohol on the left and right ventricle

OBJECTIVE—To assess the prognostic value of stress echocardiography as an adjunct to exercise electrocardiography in patients with uncomplicated acute myocardial infarction.
DESIGN—496 patients underwent a maximum exercise ECG and pharmacological stress echocardiography (406 dobutamine and 90 dipyridamole) within 15 days of uncomplicated acute myocardial infarction and were followed for a mean of 25 months (range 1-74 months) for reinfarction, unstable angina, and cardiac death. Patients undergoing revascularisation were omitted.
RESULTS—Exercise ECG was positive in 162 patients (32.6%) and low threshold positive (< 100 W) in 91 (18%). Stress echocardiography was positive in 239 patients (48%) (194 with dobutamine and 45 with dipyridamole stress). The agreement between the two tests was 63% (κ = 0.24, 95% confidence interval 0.15 to 0.33). Sixty nine spontaneous events occurred (14 cardiac deaths, 26 reinfarctions, and 29 with unstable angina requiring hospital admission), and 126 patients underwent revascularisation (39 coronary angioplasty and 87 bypass surgery). By receiver operating characteristic curve analysis, stress echocardiography provided incremental prognostic information compared with clinical data. A low threshold positive exercise ECG was associated with a worse outcome, but there was a fivefold increase in risk in patients with positive stress echocardiography who also had a high threshold (> 100 W) positive exercise ECG. Event-free survival of patients with both tests positive was significantly less than in patients with only one positive test or with both tests negative.
CONCLUSIONS—Stress echocardiography provides additional prognostic information after uncomplicated acute myocardial infarction, but the greatest gain is found in patients with a high threshold positive exercise ECG.


Keywords: risk stratification; myocardial infarction; stress echocardiography; exercise stress testing     

刺激左右颈部迷走交感干对兔心室电生理特性的影响

目的探讨心脏外在自主神经对心室电生理特性的影响及其在室性心律失常发生中的可能作用。方法新西兰大白兔10只静脉麻醉,将6F电极导管通过右侧颈静脉经三尖瓣置入右室,并给予设定的电程序刺激,记录基础状态下心室有效不应期(VERP)、Q-T间期离散度(Q-Td)、Tpeak-Tend离散度(Tp-ed)、心室颤动阈值(VFT);再分离并暴露双侧颈部迷走交感干,分别给予左右单侧及双侧迷走交感干电刺激使心率较基础状态分别减慢10%、30%、50%,重复上述电刺激,并测量上述电生理指标。结果随着刺激颈迷走交感干强度的增加,与基础状态比较,VERP逐渐延长,至左右单侧刺激强度使心率减慢50%、双侧刺激减慢30%时,VERP延长有统计学意义(P<0.05);Q-Td随刺激强度的增加呈逐渐增大趋势,至左、右单侧刺激强度使心率减慢30%、双侧刺激减慢10%时,Q-Td增大具有统计学意义(P<0.05),随着刺激强度地增加,变化更显著(P<0.01);Tp-ed随刺激强度的增加呈逐渐增大趋势,至左、右单侧及双侧刺激强度使心率减慢30%时,Tp-ed增大有统计学意义(P<0.05);给予实验设定的不同强度的左、右单侧颈迷走交感干刺激,与基础状态比较VFT无明显变化,而同时给予双侧颈迷走交感干刺激时,VFT有逐渐减小趋势,但仍无统计学意义。结论心脏外在自主神经在心室电生理特性变化中亦起重要作用,可能是室性心律失常发生的潜在因素。     

Independent effects of both right and left ventricular function on plasma brain natriuretic peptide

BACKGROUND: Brain natriuretic peptide (BNP) is increased in heart failure; however, the relative contribution of the right and left ventricles is largely unknown. AIM: To investigate if right ventricular function has an independent influence on plasma BNP concentration. METHODS: Right (RVEF), left ventricular ejection fraction (LVEF), and left ventricular end-diastolic volume index (LVEDVI) were determined in 105 consecutive patients by first-pass radionuclide ventriculography (FP-RNV) and multiple ECG-gated equilibrium radionuclide ventriculography (ERNV), respectively. BNP was analyzed by immunoassay. RESULTS: Mean LVEF was 0.51 (range 0.10-0.83) with 36% having a reduced LVEF (<0.50). Mean RVEF was 0.50 (range 0.26-0.78) with 43% having a reduced RVEF (<0.50). The mean LVEDVI was 92 ml/m2 with 22% above the upper normal limit (117 ml/m2). Mean BNP was 239 pg/ml range (0.63-2523). In univariate linear regression analysis LVEF, LVEDVI and RVEF all correlated significantly with log BNP (p<0.0001). In a multivariate analysis only RVEF and LVEF remained significant. The parameter estimates of the final adjusted model indicated that RVEF and LVEF influence on log BNP were of the same magnitude. CONCLUSION: BNP, which is a strong prognostic marker in heart failure, independently depends on both left and right ventricular systolic function. This might, at least in part, explain why BNP holds stronger prognostic value than LVEF alone.     

A critical review of effects on ethanol intake of the dynorphin/kappa opioid receptor system in the extended amygdala: From inhibition to stimulation

The dynorphin (DYN)/kappa opioid receptor (KOR) system has increasingly been investigated as a possible pharmacotherapeutic target for alcohol use disorder, but findings on the direction of its effects have been mixed. Activation of KORs by DYN has been shown to elicit dysphoric effects, and the DYN/KOR system has canonically been considered particularly important in driving alcohol intake through negative reinforcement in dependent states. However, this review also highlights its activity in opposing the positive reinforcement that drives alcohol intake at earlier stages. Both DYN and KORs are concentrated in the extended amygdala, a set of interconnected regions that includes the bed nucleus of the stria terminalis, central nucleus of the amygdala, and nucleus accumbens shell. This review focuses on the role of the DYN/KOR system in the extended amygdala in ethanol use. It begins by examining the effects of ethanol on the expression of DYN/KOR in the extended amygdala, expression of DYN/KOR in alcohol-preferring and alcohol-avoiding animals, and the effects of knocking out DYN/KOR genes on ethanol intake. Then, it examines the effects on ethanol use in both dependent and nondependent states from systemic pharmacological manipulations of DYN/KOR and from specific manipulation of this system in regions of the extended amygdala. We propose that greater expression and binding of DYN/KOR, by reducing the positive reinforcement that drives early stages of intake, initially acts to prevent the escalation of ethanol drinking. However, prolonged, binge-like, or intermittent ethanol intake enhances levels of DYN/KOR in the extended amygdala such that the system ultimately facilitates the negative reinforcement that drives later stages of ethanol drinking. This review highlights the potential of the DYN/KOR system as a target that can affect different outcomes across different stages of ethanol drinking and the development of alcohol use disorder.     

右室流出道与右室心尖部起搏对心脏收缩功能和左室重构的影响

目的评价右室流出道(RVOT)和右室心尖部(RVA)起搏对心脏收缩同步性、收缩功能和左室重构的影响。方法82例高度或III度房室传导阻滞患者随机分为RVOT起搏组(A组,n=43)和RVA起搏组(B组,n=39),以术前左室12节段达峰时间标准差(Ts-SD)是否>32.6ms对两组患者进行亚组分组,Ts-SD>32.6ms者为A1亚组与B1亚组,Ts-SD≤32.6ms为A2亚组与B2亚组。于术前及术后6个月分别进行超声心动图检查,测量舒张末左室容积(LVEDV)、收缩末左室容积(LVESV)、左室射血分数(LVEF),并采集组织多普勒图像(TDI)进行脱机分析,测量主动脉瓣射血前时间(APET)、肺动脉瓣射血前时间(PPET)、左室12节段收缩达峰时间(Ts),计算室间电机械延迟(IVMD)和Ts-SD。结果术后6个月,两组的IVMD均较术前增加;两组Ts-SD与术前比无差异。亚组分析表明术前同步性好的A2、B2亚组术后Ts-SD升高;术前同步性差的A1亚组术后Ts-SD降低。术后6个月两组LVEDV、LVESV及LVEF与术前比较均无差异,组间比较亦无差异。结论RVOT和RVA起搏短期内对左室收缩功能及左室重构均无影响,术前收缩不同步者可从RVOT起搏中获益。     

Chronic and acute effects of smoking on left and right ventricular relaxation in young healthy smokers

BACKGROUND: Left ventricular (LV) diastolic dysfunction has been observed in cigarette smokers with coronary artery disease. The aim of the study was to assess LV and right ventricular (RV) diastolic function in healthy, young, and slim smokers before and after smoking one cigarette. MATERIAL AND METHODS: The participants were 66 healthy volunteers (age < 40 years; body mass index < 25 kg/m(2)): 33 smokers (study group [HS]) and 33 nonsmokers (control group). Echocardiographic examination was done in the HS before smoking one cigarette (HS-1) and after smoking one cigarette (HS-2). To assess diastolic function of LV and RV mitral valve flow (MVF), pulmonary venous flow (PVF) and tricuspid valve flow (TVF) were evaluated. RESULTS: MVF early to late phase ratio (E/A) was significantly lower in HS-1 and HS-2 than in the control group. The PVF systolic to diastolic phase ratio (S/D) was significantly higher in HS-1 and HS-2 than in the control group. These changes suggest LV diastolic function impairment in the HS, but the MVF pattern remained within the normal range. PVF S/D showed systolic dominance (S/D > 1) typical for impaired LV relaxation and abnormal for this age group. TVF E/A was significantly lower in HS-2 than in HS-1 and control subjects and suggests RV diastolic dysfunction. CONCLUSIONS: The following conclusion are made: (1) MVF and PVF demonstrate LV relaxation impairment in healthy smokers before and after smoking one cigarette; (2) the assessment of PVF is a good method reflecting LV diastolic function changes, even when MVF remains normal; and (3) TVF shows RV relaxation impairment after smoking one cigarette in healthy smokers.     

Acute effects of low doses of ethanol on left and right ventricular function in young healthy subjects

Background: Moderate‐to‐high blood concentrations of ethanol acutely impair conventional echocardiographic measures of left ventricular (LV) performance, but the effects of low concentrations are unclear. This study explored the acute effects of low blood concentrations of ethanol on sensitive and load‐independent indices of LV and right ventricular (RV) function. Methods: This is a crossover experimental study conducted in 64 young healthy volunteers. Participants were asked to drink a light dose of Italian red wine equivalent to 0.5 mg/kg of ethanol, and an equal volume of fruit juice in separate experiments. The following measurements were taken at baseline and 60 minutes after the challenges: tissue Doppler mitral annulus systolic velocity (S’) and excursion (MAPSE), early diastolic velocity (E’), its ratio to late diastolic velocity (E’/A’), and the ratio of mitral‐to‐myocardial early diastolic velocities (E/E’); and tricuspid annulus systolic velocity (tricuspid S’) and amplitude (TAPSE), early diastolic velocity (tricuspid E’), and its ratio to late diastolic velocity (tricuspid E’/A’). Results: Blood ethanol concentration after wine intake was 0.48 ± 0.06 g/l. Compared with the control challenge, ethanol yielded a decrease in all measures of LV function (S’, ?9.7%; E’, ?11.2%; E’/A’, ?13.4%; MAPSE, ?8.8%; p < 0.05 for all). Among indices of RV function, increases in tricuspid E’/A’ ratio and TAPSE were observed (+24.5% and +9.0%, respectively; p < 0.05 for both). Conclusions: Low blood concentrations of ethanol acutely impair LV function and increase some indices of RV function in young healthy individuals.     

右心室不同部位起搏对心脏收缩同步性及心功能的影响

目的比较右心室流出道（right ventricular outflow tract,RVOT）起搏与右心窀心尖部（riht ventficular apex,RVA）起搏对心脏收缩同步性指标及收缩功能的影响。方法2004年1月至2005年1月在我院植入VVL／VVIR,DDD／DDDR起搏器的患者,随机接受RVA起搏和RVOT起搏。植入前检查12导联体表心电罔及超声心动图,记录QRS时限、左心室舒张末内径（LVEDD）、左心房内径（LAD）、左心事射血分数（LVEF）。植入后记录心室起搏状态下的QRS时限。随访时间为2年,随访内容包括LVEDD、LAD、LVEF,同时应用脉冲组织多普勒技术测定心室问激动延迟（IVMD）以及左心室内收缩同步性指标（Ts-SD）。结果共随访30例患者,其中RVA起搏17例,RVOT起搏13例,两组患者间年龄、性别及心血管疾病等基本情况筹异无统计学意义。植入前两组患者问QRS时限、LVEDD、LAD及LVEF差异无统计学意义,植入后RVOT起搏状态下QRS时限较RVA起搏明显缩短[（140．15±11．36）ms对（160．76±23．68）ms,P=0．033],植入后两组间IVMD[（25．7±9．1）mS对（36．7±10．0）ms,P=0．076]比较差异无统计学意义,两组问Ts—SD（13．34ms对42．96ms,P=0．001）比较差异有统计学意义;植入后随访两年,两组患者间LAD差异无统计学意义[（43±6）ms对（42±9）ms,P=0．759],同RVA组相比,RVOT组LVEDD缩小[（5．10±0．76）mm对（5．28±0．40）mm,P=0．048],LVEF明显增加（0．56±0．04对0．52±0．02,P=0．001）。结论同右心窄流出道起搏相比,右心室心尖部起搏对患者心功能呈负性影响,且加重左心室内不同步收缩。     

Adverse effects of Wolff-Parkinson-White syndrome with right septal or posteroseptal accessory pathways on cardiac function

Aims: Wolff–Parkinson–White syndrome with right septalor posteroseptal accessory pathways causes eccentric septalmechanical activation and may provoke left ventricular (LV)dyssynchrony and dysfunction. The aim of the study was to evaluatethe effect of radiofrequency catheter ablation (RFA) of theaccessory pathways on LV function. Methods and results: Retrospectively, transthoracic echocardiography and electrocardiogramrecordings were analysed in 34 patients (age: 14.2 ±2.5 years) with right septal or posteroseptal accessory pathwaysprior and after (median: 1 day) successful RFA. Results priorto RFA, LV ejection fraction was decreased (<55%) in 19/34patients (56%). After RFA, QRS duration was normalized (129± 23 vs. 90 ± 11, P < 0.0001), LV functionimproved (ejection fraction: 50 ± 10 vs. 56 ±4%, P = 0.0005) and septal-to-posterior wall motion delay asa global measure for LV dyssynchrony decreased (110 ±94 vs. 66 ± 53, P = 0.012). Longitudinal two-dimensionalstrain evaluated in five patients demonstrated a decrease ofleft intraventricular mechanical delay from 292 ± 125to 118 ± 37 ms after RFA. Conclusion: Wolff–Parkinson–White syndrome with right septalor posteroseptal accessory pathways may cause LV dyssynchronyand jeopardize global LV function. Radiofrequency catheter ablationresulted in normalized QRS duration, mechanical resynchronization,and improved LV function. Even in the absence of arrhythmias,RFA of right septal or posteroseptal pathways may be consideredin patients with significantly decreased LV function.     

New criterion to determine left bundle branch capture on the basis of individualized His bundle or right ventricular septal pacing

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右心室非心尖部起搏与心尖部起搏对左心室功能中远期影响的meta分析

目的：系统评价右室非心尖部（RVNA）起搏与心尖部（RVA）起搏对左心室功能的中远期影响。 方法: 系统检索PubMed,EMBASE数据库和Cochrane图书馆,检索时间截止至2018-01。纳入关于RVNA起搏与RVA起搏对左心室功能中远期的随机对照试验（RCT）。采用RevMan5.3软件进行Meta分析。 结果：纳入26项研究,共包括1926例患者。在左室射血分数（LVEF）（WMD =2.94,95％CI：1.57-4.31,P <0.01）和6分钟步行试验（6MWT）（WMD =23.45,95％CI：0.68-46.22,P =0.04）方面,RVNA组优于RVA组。基础状态LVEF≤40-45％（WMD =5.03,95％CI：4.38-5.69,P <0.01）或随访时间≥12个月（WMD =3.38,95％CI：1.73-5.03,P <0.01）的患者,RVNA组对术后左心室收缩功能的影响小于RVA组。而基础状态LVEF保留（WMD =0.92,95％CI：?0.73-2.56,P =0.27）或随访时间<12个月（WMD =1.81,95％CI：?0.03-3.64,P =0.05）的患者,两组无显著差异。在血N末端脑肽前体（NT-proBNP）或脑利钠肽（BNP）方面（SMD =?0.29,95％CI：?0.70-0.13,P =0.17）,RVNA组与RVA组无显著差异。 结论：对于基础状态LVEF减低（≤40-45％）或随访时间超过一年的永久起搏器置入患者,RVNA起搏比RVA起搏对术后LVEF影响小。     

The effects of isometric stress on left ventricular filling in athletes with isometric or isotonic training compared to hypertensive and normal controls

Hypcrtrophy of the left ventricle may be associated with alteredleft ventricular filling dynamics. To test whether isometricand isotonic training affect left ventricular filling differentlyat rest and during isometric stress, 38 males, 13 long distancerunners, eight weight-lifters, eight hypertensive patients andnine age-matched healthy male controls with a mean age of 30± 7 years, were studied before and after 90 s of 50%maximal handgrip force. Left ventricular Doppler filling parameterswere compared in the four groups while they were resting andduring isometric stress testing, and the results assessed inrelation to left ventricular mass index and wall stress. Allsubjects had normal resting filling patterns except for hypertensivepatients, and peak meridional wall stress was low in both athleticgroups at rest. Weight-lifters had a hypertensive response duringisometric stress testing, associated with a reduction in peakE velocity and a marked increase in peak A velocity, resemblingthe filling pattern in hypertensive subjects. In runners thefilling pattern remained normal. Thus, while the resting left ventricular pattern was normalin all athletes, isometric stress testing was associated witha hypertensive filling pattern only in weight-lifters comparedto normal filling in runners. (Eur Heart J 1996; 17: 457–461)     

Comparison of the effects of nitroprusside and nifedipine on diastolic properties in patients with hypertrophic cardiomyopathy: Altered left ventricular loading or improved muscle inactivation?

The calcium channel blocking agent, nifedipine, has been shown to improve indexes of left ventricular relaxation, diastolic filling and compliance in patients with hypertrophic cardiomyopathy. The mechanism of action of nifedipine on diastolic properties in patients with hypertrophic cardiomyopathy is unclear and could result from an improvement in myocardial inactivation or from systemic vasodilation and left ventricular unloading. To distinguish between these mechanisms, the effects of nifedipine and the vasodilator nitroprusside on left ventricular diastolic properties were compared in 10 patients with nonobstructive hypertrophic cardiomyopathy using simultaneous micromanometer left ventricular pressure and echocardiographic measurements. Left ventricular peak systolic pressure was comparable during nitroprusside infusion (132 +/- 38 mm Hg) and after nifedipine (132 +/- 32 mm Hg). During nitroprusside infusion, the decrease in left ventricular end-diastolic pressure (22 +/- 11 to 17 +/- 11 mm Hg, p less than 0.05) was associated with a decrease in left ventricular end-diastolic dimension. In contrast, the decrease in left ventricular end-diastolic pressure after nifedipine (22 +/- 11 to 18 +/- 10 mm Hg, p less than 0.05) was associated with no reduction of left ventricular end-diastolic dimensions, suggesting an increase in left ventricular distensibility. Compared with nitroprusside, nifedipine was associated with less prolongation of the left ventricular isovolumic relaxation time and less depression of the peak left ventricular posterior wall thinning rate and peak left ventricular internal dimension filling rate. These data suggest that the effects of the calcium channel blocker, nifedipine, on diastolic mechanics in hypertrophic cardiomyopathy result not only from systemic vasodilation but also from improved cardiac muscle inactivation.