Early developmental 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure decreases chick embryo heart chronotropic response to isoproterenol but not to agents affecting signals downstream of the beta-adrenergic receptor.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes cardiovascular toxicity in laboratory animals, including alteration in several processes in which beta-adrenergic receptor (beta-AR) signaling plays important roles. Thus, our laboratory investigated the effects of TCDD on beta-AR expression and signal transduction. Fertile chicken eggs were injected with vehicle (corn oil), 0.24 or 0.3 pmol TCDD/g egg on incubation day 0 (D0) or D5. On D10, heart function was assessed by ECG in ovo. Exposure to TCDD increased the incidence of arrhythmias and decreased the positive chronotropic responsiveness of the heart to isoproterenol. The reduced beta-AR responsiveness was, in part, independent of any overt morphological changes in the heart as chick embryos exposed to TCDD on D5 displayed an intermediate responsiveness to beta-AR agonist in the absence of the dilated cardiomyopathy observed in chick embryos exposed to TCDD on D0. TCDD did not decrease the chronotropic response of the heart to agents that stimulate signals downstream of the beta-AR. In fact, TCDD-exposed embryos were more sensitive than controls to forskolin, increasing heart rates (HR) 21.8 +/- 3.5 beats per min (bpm) above baseline versus control values at 6.3 +/- 2.7 bpm above baseline. TCDD exposure also augmented the negative chronotropic response of the heart to verapamil, decreasing HR -23.2 +/- 7.4 bpm relative to baseline versus control embryos at -12.7 +/- 5.9 bpm below baseline. Finally, the mean cardiac beta1-AR mRNA expression in D10 embryos was not significantly altered by exposure to TCDD on D0. These findings establish that a functional end point of the developing chick heart is sensitive to TCDD exposure and that the TCDD-induced reduction in beta-AR responsiveness may result from alterations in signal transduction upstream of adenylyl cyclase.     

Mortality in police and firefighters in New Jersey

A proportionate mortality study of police and firefighters in New Jersey was conducted using the records of a comprehensive retirement system. Three reference populations were used: U.S. general population, New Jersey general population, and police as a reference group for the firefighters. Overall neither group differed from the New Jersey male population in the cause of death. Analyses by latency showed an increase in skin cancer and cirrhosis in firefighters and cirrhosis in police. With increased time from first employment, an inverse association was found between heart disease and time of first exposure. This was reflected in statistically significant increased proportionate mortality rates (PMR) for arteriosclerotic heart disease (ASHD) (ICD 410-414) for both working police (PMR = 1.15) and firefighters (PMR = 1.2). Retired police and firefighters had PMRs of 0.96 and 0.98, respectively. Firefighters had a significant increase in nonmalignant respiratory disease (PMR = 1.98) and leukemia (PMR = 2.76) when the police were used as a reference group. Potential causes of the above findings are discussed.     

Psychological,situational, and gender predictors of cardiovascular reactivity to stress: A multivariate approach

This study examined whether relationships between anger expression, hostility, social evaluative anxiety, and a presumed mechanism for coronary heart disease development, cardiovascular reactivity (CVR) to stress, are moderated by stress situation and gender and whether such relationships are attenuated by inadequate assessments. Subjects (47 men, 47 women) were assigned randomly to either a Harassment or a Social Evaluation condition, under which they performed a reaction time task. SBP, DBP, and HR measures were recorded during baseline and task. Multiple regression analyses indicated that expressed anger was related to CVR only among men in the Harassment condition; that hostile men who express anger showed the most CVR across situations, and that the traits assessed here did not predict CVR among women. Results suggest that assessments of coronary-risk and interventions to reduce risk may need to take into account attitudes, styles of emotional expression, environmental factors, and gender.This research was supported in part by an NIMH predoctoral fellowship (F31MH09836) awarded to John W. Burns and by a grant from the American Heart Association (89-01-3G) awarded to Edward S. Katkin.     

多平面经食道超声心动图对心血管疾病的诊断价值

为了评价多平面经食道超声心动图（ＴＥＥ）的临床应用价值，对３６例临床经胸超声心动图（ＴＴＥ）检查尚未完全明确诊断的心血管疾病患者进行了ＴＥＥ检查。结果显示：①２６例（７２％）患者ＴＥＥ补充或纠正了ＴＴＥ诊断；②９例手术患者ＴＥＥ诊断符合率１００％；③对感染性心内膜炎小赘生物的检出、间隔缺损部位、数目、合并畸型、心腔内血栓、大动脉瘤等ＴＥＥ的诊断价值明显高于ＴＴＥ。     

EFFECTS OF LOSARTAN ON THE CARDIOVASCULAR SYSTEM, RENAL HAEMODYNAMICS AND FUNCTION AND LUNG LIQUID FLOW IN FETAL SHEEP

1. The angiotensin type 1 (AT₁) receptor antagonist, losartan (10 mg/kg) was infused intravenously into nine chronically catheterized fetal sheep (125–132 days gestation). Losartan reduced the fetal systolic (P < 0.01) and diastolic (P < 0.01) pressor response to 5 μg angiotensin II (AngII) i.v. from 27.4 ± 1.5 to 7.4 ± 0.9 and from 17.5 ± 1.3 to 5.4 ± 0.6 mmHg, respectively, after 1h and to 6.1 ± 0.5 and 4.4 ± 0.5 mmHg, respectively, after 2h. Maternal pressor responses to 5 μg AngII i.v. were unchanged. Fetal mean arterial pressure decreased (P < 0.05) after losartan administration, but fetal heart rate did not change. 2. Fetal haematocrit increased (P < 0.05), fetal PO₂ decreased (P < 0.01), PCO₂ did not change and pH decreased (P < 0.01), as did plasma bicarbonate levels (P < 0.01) following administration of losartan. Thus, losartan induced a fetal metabolic acidosis. 3. Fetal placental blood flow did not change following administration of losartan. In the fetal kidney, losartan caused a decrease in vascular resistance (P < 0.01) and an increase in blood flow (P < 0.05). Glomerular filtration rate decreased (P < 0.05); thus, filtration fraction decreased (P < 0.01). There was no change in the fractional reabsorption of sodium and glomerulotubular balance was maintained. Free water clearance decreased (P < 0.01) and became negative. Urine flow decreased (P < 0.01), the excretion rates of sodium, potassium and chloride did not change, but the urinary sodium:potassium ratio decreased (P < 0.05). There was a decrease in lung liquid flow (P < 0.05) following losartan. 4. It is concluded that the fetal renin-angiotensin system (RAS) is important in the maintenance of fetal arterial pressure, the regulation of fetal renal blood flow and is essential in the maintenance of fetal glomerular function. Further, these actions of AngII are mediated via functional AT₁ receptors. These effects of losartan on the fetal cardiovascular system, renal blood flow and function are similar to those observed following captopril administration. Thus, the effects of angiotensin converting enzyme (ACE) inhibition in the foetus are due to the blockade of the fetal RAS and are independent of any direct effects on bradykinin or prostaglandin levels.     

基于十年随访的心血管代谢性危险因素聚集与社区≥55岁人群全因死亡风险关系的队列研究

背景 心血管代谢性危险因素聚集（CRFC）是老年人常见的健康问题,目前相关研究主要集中在流行病学分布特征的描述,有关CRFC与人群全因死亡风险的研究鲜有报道。目的 探讨CRFC与社区≥55岁人群全因死亡风险的关系,为开展≥55岁人群社区保健提供参考。方法 于2011年9—11月采用典型抽样法选取宁夏回族自治区吴忠市和银川市5个社区的1 046名≥55岁人群作为研究对象,对其开展一般情况问卷调查、体格检查、超声检查、实验室检查和CRFC评价[纳入中心性肥胖、高胆固醇血症、高三酰甘油血症、高低密度脂蛋白血症、低高密度脂蛋白血症、高血压、糖尿病、高尿酸血症、非酒精性脂肪性肝病（NAFLD）共计9项心血管代谢性危险因素后,控制一般情况变量,通过构建多因素Cox比例风险回归模型,估计各个心血管代谢性危险因素的回归系数β,以回归系数β为权重将所有心血管代谢性危险因素的评分相加得出心血管代谢危险因素危险总评分],将心血管代谢危险因素危险总评分按照四分位数分为三组：P75组;分别于2017年,2019年和2021年通过面访和死因监测系统搜索的方式完成随访。采...     

巨噬细胞功能M1/M2极性化在心血管疾病中的研究进展

巨噬细胞是先天免疫系统的主要细胞,具有可塑性和异质性,在机体的免疫应答、组织稳态、重塑等多方面发挥重要功能。根据功能极性可分为M1(促炎)和M2(抗炎)2个亚型。M1/M2巨噬细胞在响应局部微环境的刺激反应过程中,通过改变其功能极化,获得特定的功能表型并分泌不同的细胞因子。巨噬细胞通过改变代谢重编程以适应其功能变化。M2巨噬细胞以氧化磷酸化和脂肪酸为能量代谢的主要方式,而M1巨噬细胞为无氧糖酵解。目前研究发现在心血管疾病中,巨噬细胞可能通过其功能极性变化引起巨噬细胞激活、组织浸润、释放促炎性细胞因子而参与心血管疾病的发生。本文对巨噬细胞功能极化、代谢重编程在心血管疾病中的作用进行综述。     

An Extension of the Regression of Offspring on Mid-Parent to Test for Association and Estimate Locus-Specific Heritability: The Revised ROMP Method

The Regression of Offspring on Mid-Parent (ROMP) method is a test of association between a quantitative trait and a candidate locus. ROMP estimates the trait heritability and the heritability attributable to a locus and requires genotyping the offspring only. In this study, the theory underlying ROMP was revised (ROMP_rev) and extended. Computer simulations were used to determine the type I error and power of the test of association, and the accuracy of the locus-specific heritability estimate. The ROMP_rev test had good power at the 5% significance level with properly controlled type I error. Locus-specific heritability estimates were, on average, close to simulated values. For non-zero locus-specific heritability, the proposed standard error was downwardly biased, yielding reduced coverage of 95% confidence intervals. A bootstrap approach with proper coverage is suggested as a second step for loci of interest.
ROMP_rev was applied to a study of cardiovascular-related traits to illustrate its use. An association between polymorphisms within the fibrinogen gene cluster and plasma fibrinogen was detected (p < 0.005) that accounted for 29% of the estimated fibrinogen heritability. The ROMP_rev method provides a computationally fast and simple way of testing for association and obtaining accurate estimates of locus-specific heritability while minimizing the genotyping required.     

Family history of hypertension,gender, and cardiovascular reactivity and stereotypy during stress

Thirty subjects with a family history of hypertension and 28 subjects without such a history performed a Stroop Color-Word Interference task, a mental arithmetic task (serial subtraction of sevens), and a shock avoidance task (repeating digits backward while expecting to be shocked for mistakes). Systolic and diastolic blood pressure and pulse rate were recorded while subjects anticipated, undertook, and recovered from the shock avoidance task and undertook and recovered from the Stroop and mental arithmetic tasks. It was found that compared to nonfamily history subjects, family history subjects manifested reliably greater cardiovascular reactivity during each task and in anticipation of the shock avoidance task. These results are congruent with the notion that excessive sympathetic nervous system reactivity—possibly genetically determined—is involved in the development of some form(s) of essential hypertension. Further, the results indicated that family history subjects manifested greater consistency, or stereotypy, of cardiovascular response across the experimental tasks than nonfamily history subjects. The possible role of cardiovascular stereotypy in the development of essential hypertension is also discussed.This investigation was supported by University of Kansas General Research Allocation 3115-xO-0038 to B. Kent Houston.