缬沙坦对慢性心房快速起搏犬血小板和内皮功能的影响

目的探讨缬沙坦对慢性心房快速起搏诱发心房颤动(房颤)犬血小板和内皮功能的影响。方法2001-09~2003-06对哈尔滨医科大学14只犬植入实验用心房固定频率型高频起搏器(400/min)心房快速起搏6周,建立房颤犬模型,随机分为对照组和缬沙坦组。缬沙坦组犬起搏前1周开始服用缬沙坦(30mg·kg-1·d-1),直至起搏结束。起搏前、后采静脉血测定二磷酸腺苷、肾上腺素、胶原、花生四烯酸诱导的犬血小板最大聚集率以及血浆血管性血友病因子(vWF)、内皮素1(ET-1)和血管紧张素Ⅱ(AngⅡ)的变化。结果(1)起搏6周后,对照组和缬沙坦组犬血浆AngⅡ水平均明显增高,提示肾素-血管紧张素系统激活。(2)长期心房快速起搏使对照组犬二磷酸腺苷、肾上腺素、胶原和花生四烯酸诱导的血小板最大聚集率较起搏前明显增加,缬沙坦能够部分抑制起搏引起的血小板激活。(3)快速起搏使犬血浆vWF和ET-1水平明显升高,提示内皮功能受损,缬沙坦能够改善内皮功能,降低房颤犬血浆vWF和ET-1水平。结论缬沙坦能够防治心房快速起搏引起的血小板聚集和内皮功能受损。     

依那普利和氯沙坦对心肌梗死大鼠心室重构影响的比较

目的 研究比较血管紧张素转换酶抑制剂(ACEI)及选择性血管紧张素Ⅱ受体拮抗剂(AT_1受体拮抗剂)对心肌梗死大鼠心室重构的影响.方法Wistar大鼠冠脉结扎制成心肌梗死模型,24小时后随机分为依那普利(enalapril)治疗组,氯沙坦(losartan)治疗组,安慰剂(placebo)组,治疗6周.假手术组为对照.6周后测定体重、梗死区重量、心脏重量/体重、血浆及心肌的血管紧张素Ⅱ(AngⅡ)浓度、心肌胶原含量及血浆内皮素浓度.结果enalapril及losartan治疗组中心脏重量/体重及心脏胶原含量高于假手术组,而低于安慰剂组.在三个梗死组中,梗死区的重量无显著差异.enalapril治疗组血浆AngⅡ浓度降低,而losartan治疗组中血浆AngⅡ浓度升高.梗死后安慰剂组心脏局部AnsⅡ浓度明显高于假手术组、enalanril和losartan治疗组.enalanril及losartan可降低血浆ET-1浓度.结论血管紧张素转换酶抑制剂及血管紧张素Ⅱ受体拮抗剂对阻止心室重构的发展具有相同作用.     

心房颤动犬心房肌肾素-血管紧张素系统改变

目的探讨慢性心房快速起搏诱发心房颤动(房颤)犬心房肌肾素血管紧张素系统(RAS)的改变。方法13只犬随机分为假手术组(n=6)和起搏组(n=7)。起搏组犬无菌开胸后在右心房缝植5对心外膜记录电极,电极尾端经皮下由犬背部穿出;在右心耳缝植螺旋型起搏电极,连接实验用AOO高频起搏器(400次/min),心房快速起搏6周,建立房颤犬模型;假手术组犬仅缝植心外膜记录电极和起搏电极而不起搏。经心外膜电极记录各组犬房颤诱发情况;采用放射免疫方法检测两组犬左心房及右心房组织血管紧张素Ⅰ(AngⅠ)、血管紧张素Ⅱ(AngⅡ)含量及肾素活性;采用逆转录聚合酶链反应(RTPCR)检测两组犬心房肌肾素、血管紧张素原和血管紧张素转换酶mRNA表达水平改变。结果(1)起搏组7只犬均经短阵快速刺激(burstpacing)诱发出房颤,房颤诱发率和平均持续时间较假手术组显著增加(P<0.01);(2)起搏组犬心房肌AngⅠ、AngⅡ含量较假手术组犬心房肌明显升高(P<0.01),肾素活性亦显著增加(P<0.01);同一组犬左心房与右心房组织AngⅠ、AngⅡ含量及肾素活性差异无统计学意义(P>0.05);(3)起搏组犬心房肌肾素、血管紧张素原和血管紧张素转换酶mRNA表达较假手术组犬心房肌显著上调(P<0.01)。结论慢性心房快速起搏诱发房颤犬心房肌AngⅠ、AngⅡ含量及肾素活性显著增加,可能是局部RAS基因表达上调的结果,提示房颤伴随心房肌RAS激活。     

西拉普利对房颤犬内皮和纤溶功能的影响

目的观察心房快速起搏诱发心房颤动犬内皮和纤溶功能的变化及西拉普利对其影响,探讨房颤血栓前状态的机制及防治对策。方法2004年1月至8月于哈尔滨医科大学第一临床医学院动物实验中心选杂种犬16只,随机分为对照组(n=8)、西拉普利组(n=8),在右心房以单心房(AOO)模式400/min起搏6周,建立房颤犬模型。西拉普利组起搏前1周开始每天服用西拉普利(1mg/kg),直至起搏结束,分别于起搏前、起搏6周后采静脉血,测血浆血管性血友病因子(vWF)、血管紧张素Ⅱ(AngⅡ)、组织型纤溶酶原激活剂(t-PA)、纤溶酶原激活剂抑制物-1(PAI-1)。结果心房快速起搏6周,对照组犬血浆AngⅡ较起搏前明显增高,[(349·9±28·3)ng/L对(198·4±19·4)ng/L,P<0·01];西拉普利组AngⅡ无明显升高(P>0·05);快速起搏后血浆vWF升高[(109·7%±19·8)%对(33·9±5·9)%,P<0·01),西拉普利起搏后血浆vWF亦升高,但却明显低于对照组(P<0·01)];起搏6周后血浆t-PA、PAI-1抗原均明显升高[t-PA:(12·7±2·1)ng/L对(8·9±1·5)ng/L,P<0·01][PAI-1:(24·4±3·9)ng/L对(15·4±2·4)ng/L,P<0·01];西拉普利组起搏后两者亦升高但两者升高程度低于对照组。结论慢性心房快速起搏导致犬肾素-血管紧张素系统(RAS)激活、内皮功能及纤溶功能失调,西拉普利可以阻断RAS激活,不同程度改善内皮和纤溶功能。血管紧张素转换酶抑制剂(ACEI)可能用于房颤血栓防治。     

螺内酯对心力衰竭犬心房颤动的影响

目的探讨螺内酯对心力衰竭犬心房颤动（房颤）的影响及其作用机制。方法21只犬随机分为3组：假手术组（n=7）、起搏组（n=7）和螺内酯组（n=7）。采用心室快速起搏建立心力衰竭犬模型。假手术组植入起搏器后不起搏;起搏组和螺内酯组以220次／min快速起搏心室6周;螺内酯组起搏前1周给予螺内酯至起搏后6周。通过缝置于左、右心房的4对电极测定房颤诱发次数及持续时间,超声心动图测定心房、心室结构和功能变化,Masson染色测定心房胶原容积分数,Westernblot半定量分析心房肌基质金属蛋白酶．9（MMP-9）、转化生长因子-β1（TGF-β1）及血小板衍生生长因子（PDGF）蛋白含量。结果（1）心室快速起搏6周后,起搏组犬房颤诱发率和持续时间显著增加（P〈0．01）,螺内酯组房颤诱发率显著降低、持续时间显著缩短（P〈0．05）。（2）与假手术组相比,起搏组犬左心室最大容积（LVVmax）及左心房最大容积（LAVmax）显著增加（P〈0．01）,左心房射血分数（LAEF）及左心室射血分数（LVEF）显著降低（P〈0．01）,螺内酯组犬LVVmax、LAVmax显著缩小（P〈0．01）,LAEF及LVEF显著升高（P〈0．01）。（3）与假手术组相比,起搏组犬心房胶原容积分数显著升高（P〈0．01）,TGF-β1、PDGF、MMP-9蛋白质表达量显著增加（P〈0．05）;与起搏组相比,螺内酯组胶原容积分数显著降低（P〈0．01）,TGF-β1、PDGF、MMP-9蛋白表达量显著减少（P〈0．01）。结论螺内酯可以减少心力衰竭后房颤的发生,其机制可能与抑制心房肌PDGF、TGF-β1表达有关。     

肾去交感神经对心力衰竭犬心房基质和心房颤动诱发的影响

目的探讨经导管介入肾去交感神经对心力衰竭(简称心衰)犬心房基质和心房颤动(简称房颤)诱发的影响。方法 22只犬随机分为假手术组(n=7),心衰组(n=8)和肾动脉消融组(n=7)。假手术组犬植入起搏器不起搏,喂养3周;心衰组植入起搏器后以240次/分的频率连续右室起搏3周,于起搏前、3周后分别取静脉血检测血管紧张素Ⅱ(AngⅡ)和醛固酮水平;消融组先行双侧肾动脉消融,喂养8周,起搏器植入同心衰组。其中血清学指标测3次(消融前、消融8周后、起搏3周后)。所有犬在实验基线期和终点均进行心脏彩超、血压及电生理检测;处死动物后迅速取心房组织检测其基质变化。结果心衰组2只死亡,消融组1只未进入试验。①与基线期相比,心衰组和消融组在起搏3周后股动脉血压均明显下降,且两者无明显差异;②与基线期相比,心衰组起搏3周后左室收缩末期压力(LVESP)降低[(167±21)mmHg vs(123±14)mmHg,P0.01],左室舒张末期压力(LVEDP)升高[(2.5±1.3)mmHg vs(25±3.7)mmHg,P0.01]。消融组起搏3周后LVESP也降低,但LVEDP无明显变化;③与基线期相比,心衰组起搏3周后心房有效不应期明显降低,消融组无明显变化。消融组起搏3周后房颤平均诱发次数和时间明显少于心衰组;④与心衰组相比,消融组心房肌胶原容积分数、AngⅡ和转化生长因子-β水平明显降低,血AngⅡ和醛固酮水平也明显降低。结论肾去交感神经可抑制长期快速心室起搏心房基质的改变和房颤的诱发。     

原发性高血压交感神经活性的变化及缬沙坦对其活性的影响

目的通过握力试验分析原发性高血压患者交感神经系统激活时血浆中去甲肾上腺素(NE),血管紧张素Ⅱ(AngⅡ),及内皮素-1(ET-1)的变化规律.评价AngⅡ1型受体拮抗剂缬沙坦(valsartan)干预后对高血压患者交感神经活性的影响.方法测定59例原发性高血压患者(高血压组)握力试验后的血压、心率并与50例正常人(正常对照组)比较,同时测定整个握力过程中NE、ET-1和AngⅡ水平.高血压组中21例接受缬沙坦6周治疗及6个月的长期治疗,并重复进行握力试验及上述血管活性肽测定.结果①高血压组握力试验后血压升高的幅度及血浆NE水平明显高于正常对照组有极显著性差异,P＜0.01.②基础ET-1高血压组高于正常对照组有极显著性差异,P＜0.01,握后10分较握前升高有显著性差异,P＜0.05.而AngⅡ在握前及握后均无明显改变P＞0.05.③缬沙坦治疗使血压下降,治疗6周时,血浆中ET-1降低,而NE、AngⅡ水平反射性增高,6个月后NE水平明显降低,AngⅡ水平轻度升高.结论高血压组血浆NE及ET-1对握力交感神经应激反应明显高于正常对照组.AngⅡ受体拮抗剂缬沙坦在降低血压的同时还可以抑制握力应激后的血压升高及交感应激反应,使血浆中NE及ET-1水平下降.     

心力衰竭患者血管内皮功能和脑钠素的变化及缬沙坦的干预效应

目的:探讨充血性心力衰竭(CHF)患者血循环内皮细胞计数(CEC)、血浆脑钠素(BNP)、内皮素-1(ET -1)及6-酮-前列腺素F1α(6-Keto-PGF1α)含量的变化及血管紧张素Ⅱ受体拮抗剂缬沙坦的干预效应。方法: 35例CHF患者服用缬沙坦8周,并检测用药前、后外周血CEC、BNP、ET-1、血管紧张素Ⅱ(Ang Ⅱ)及6-Keto -PGFI1α的含量,30例健康体检者为对照组。结果:CHF患者CEC、血浆ET-1、Ang Ⅱ及BNP水平明显升高,6 -K-PGF1α。明显降低(P均<0.01)。缬沙坦治疗使CEC、血浆ET-1及BNP水平明显降低及Ang Ⅱ与6-Keto -PGF1α含量显著增加(P<0.01)。结论:缬沙坦具有保护血管内皮及改善心脏功能的作用。     

慢性快速心房起搏心房颤动犬内皮型一氧化氮合酶mRNA表达变化的研究

为研究慢性快速心房起搏心房颤动(简称房颤)犬模型中心内膜内皮型一氧化氮合酶(eNOS)mRNA表达的变化,探讨其与心房结构重构、血栓形成的关系。13只健康犬随机分为假手术组和起搏组,应用埋藏式高频率心脏起搏器快速起搏心房(400次 /分) 6周,取左、右心房,左、右心耳及主动脉内膜。通过逆转录 聚合酶链反应 (RT PCR),以β actin为内参照,测定犬心内膜eNOSmRNA表达的变化,同时检测血浆NO代谢产物硝酸盐 (NOx)的含量。结果:正常犬心脏eNOSmRNA表达存在差异,左房、左心耳明显高于右房、右心耳;起搏 6周后左房、左心耳eNOSmRNA表达起搏组明显低于假手术组,而右房、右心耳、主动脉无明显差别,血浆NOx起搏组亦明显低于假手术组。结论:正常犬心脏eNOS基因表达是不平衡的,左房明显高于右房。房颤犬eNOSmRNA表达降低可能是心房结构重构,血栓形成的重要因素之一。     

福辛普利对心力衰竭患者血浆内皮素-1和降钙素基因相关肽的影响

目的 了解心力衰竭患者血浆内皮索-1(ET-1)、血管紧张素Ⅱ(AngⅡ)和降钙素基因相关肽(CGRP)的变化,并观察福辛普利对其的影响.方法 测定40名健康者(正常对照组)和90例心力衰竭患者血浆ET-1、AngⅡ和CGRP浓度,随后90例心力衰竭患者被随机分成常规治疗组和福辛普利组(常规治疗+福辛普利10 mg,1次/d),每组45例.治疗14 d后复测血浆ET-1、AngⅡ和CGRP浓度,同时应用彩色多普勒超声显像仪测量正常对照组和心力衰竭患者治疗前后的左心室射血分数(LVEF).结果 与正常对照组相比较,心力衰竭患者血浆ET-1、Ang Ⅱ明显升高(P＜0.01),ET-1和AngⅡ与LVEF呈负相关(r=-0.71,r=0.62,P＜0.01),ET-1和AngⅡ呈正相关(r=0.69,P＜0.01).治疗14 d后,福辛普利组血浆ET-1和AngⅡ明显下降(P＜0.01),CGRP显著升高,(P＜0.01),LVEF得到改善(P＜0.05),而常规治疗组无明显变化(P＞0.05).结论 心力衰竭患者血浆ET-1、AngⅡ浓度明显升高,且与LVEF呈负相关,血浆CGRP显著下降.福辛普利具有降低ET-1和Ang I、升高CGRP并改善LVEF的作用.     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Serological survey of HIV and syphilis in pregnant women in Madagascar

Objectives Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy. Methods Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays. Results Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum. Conclusions Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.