Effects of differential blockade of the renin-angiotensin system in postinfarcted rats

The present study compared short-term effects of the AT(1)-receptor antagonist, irbesartan with the angiotensin-converting enzyme (ACE) inhibitor, enalapril on systemic haemodynamics and cardiac remodelling in post-myocardia-infarcted (MI) rats. MI Sprague-Dawley rats were orally treated for 4 weeks with irbesartan (50 mg/kg/day) or enalapril (10 mg/kg/day). Then, cardiac and systemic haemodynamics were measured. Compared with the sham-operated group, left ventricular end-diastolic pressure (LVEDP), diastolic pressure (LVDP), heart weight to body weight ratio were all significantly increased in the MI group while the LV contractility (dP/dt) and pulsatile arterial pressure were significantly reduced. Both drugs reduced the elevated LVEDP and LVDP and prevented cardiac hypertrophy. Furthermore, irbesartan attenuated the right shift of the pressure-volume curves, prevented postinfarction-induced increase in urinary cyclic guanosine monophosphate and reduced urinary aldosterone excretion. Although both drugs were able to prevent further cardiac hypertrophy and improved cardiac filling pressure, only irbesartan limited LV dilatation. These data indicate that blockade of the renin-angiotensin system at the level of AT1 receptors may have a better cardioprotective benefit than reducing angiotensin II levels by ACE inhibition.     

缬沙坦对自发高血压大鼠左室肥厚心肌Kv4．2表达的影响

目的：探讨缬沙坦对自发高血压大鼠（SHR）左室肥厚心肌Kv4．2表达的影响。方法：将16只10周龄雄性SHR随机分成缬沙坦组和非缬沙坦组各8只;8只10周龄Wistar—Kyoto大鼠为对照组。喂药8周后分别测定各组大鼠动脉收缩压、左室质量指数（LVMI）、左室心肌Kv4．2的表达。结果：非缬沙坦组和缬沙坦组LVMI明显大于对照组（3．7±0．02mg／gand3．2±0．03mg／gVS2．5±0．03mg／g,P〈0．001）,非缬沙坦组LVMI明显大于缬沙坦组（3．7±0．02mg／gVS3．2±0．03mg／g,P〈0．001）：非缬沙坦组和缬沙坦组左心室心肌Kv4．2表达明显低于对照组（P〈0．01）,缬沙坦组左心室心肌Kv4．2的表达明显高于非缬沙坦组（P〈0．01）。结论：缬沙坦通过逆转SHR左室心肌肥厚提高左室心肌Kv4．2的表达。     

急性心肌梗死患者经皮冠状动脉介入治疗术后早期心室重构及心功能变化相关研究

目的探讨急性心肌梗死患者经皮冠状动脉介入术后早期心脏结构及心功能的变化。方法直接行经皮冠状动脉介入治疗的急性心肌梗死患者40例(AMI组),行冠状动脉造影术证实存在左冠状动脉支配区域冠心病患者40例(对照组),2组均于术前1d、AMI组于术后1周行心脏超声检查,检测心脏结构及功能。结果术前AMI组左心室质量、左心室质量指数及舒张早期峰值速度/舒张晚期峰值速度高于对照组(P<0.05);AMI组术后左心房内径、右心室内径较术前明显增大,舒张早期峰值速度、舒张晚期峰值速度、E峰下降时间较术前明显增加,左心室质量、左心室质量指数较术前明显减小(P<0.05)。结论急性心肌梗死后早期即可发生心室重构,对心室重构进行早期评价及防治是再灌注治疗的关键。     

双龙丸对实验性心肌梗死形态学和血流动力学的影响

目的探讨活血通络类中药双龙丸对心肌梗死后心脏血流动力学和心肌梗死面积的影响。方法参照Drexler法结扎冠脉左前降支 ,制成急性心肌梗死 (AMI)模型。 66只大鼠分为双龙丸大剂量组 (18只 )、双龙丸小剂量组 (19只 )、正常对照组 (10只 )和心肌梗死对照组 (19只 )。各组半数治疗 2周 ,半数治疗至 4周 ,治疗结束时分别行股动脉和颈总动脉插管 ,应用 8导生理记录仪检测心脏血流动力学参数 ,Masson’s染色测定心肌梗死面积。结果治疗 2周和 4周 ,双龙丸大、小剂量组较同期心肌梗死对照组的左室最大收缩速率增高 (P <0 .0 5或P <0 .0 1) ,且大剂量 2周组较心肌梗死对照组的左室最大舒张速率亦增高 (P <0 .0 5 ) ;大剂量组在 2周和 4周时均较心肌梗死对照组的梗死面积减小 (P <0 .0 5 )。结论双龙丸能提高实验性心肌梗死大鼠的左室最大收缩速率 ,大剂量应用还可改善心肌梗死早期左室舒张功能 ,限制心肌梗死范围的扩展     

急性心肌梗死患者早期血清Ⅲ型前胶原检测的临床价值

目的　观察急性心肌梗死 (acutemyocardialinfarction ,AMI)患者早期血清Ⅲ型前胶原 (procollagenⅢ ,PCⅢ )含量的变化及其对抗心肌纤维化的反应 ,探讨血清PCⅢ检测对AMI心肌纤维化的评估价值。方法　采用放免法检测 4 3例AMI患者血清PCⅢ、血管紧张素Ⅱ (angiotensinⅡ ,AngⅡ )水平 ,酶免疫测定法检测肌酸磷酸激酶同工酶MB(CK MB)水平。并将患者随机分成两组 :常规治疗组 2 2例和苯那普利组 2 1例。后者在常规治疗的基础上加用血管紧张素转换酶抑制剂苯那普利渐增量进行干预治疗。所有患者分别在治疗前 ,治疗后 1、3、7和 14天抽取肘静脉血 ,分离血清 ,检测上述指标。正常健康人同批抽血分离血清 ,进行检测。结果　AMI患者治疗前上述血清学指标与健康对照组比较均显著高于后者 (P <0 .0 1)。常规治疗组在常规治疗 7天后PCⅢ和AngⅡ浓度达到高峰 ,显著高于治疗前和治疗 14天的浓度 (P <0 .0 5 ) ;苯那普利组在治疗 7、14天后PCⅢ浓度显著低于治疗前 (P <0 .0 5 ) ,治疗 3、7和 14天后AngⅡ浓度显著低于治疗前 (P <0 .0 5 )。CK MB浓度在治疗后 1天达到高峰 ,显著高于其他各时间段 (P均 <0 .0 5 ) ;治疗后 3、7和 14天降至正常。AMI患者血清PCⅢ水平与CK MB水平无相关关系 (r =- 0 .2 0 14 ,P >0 .0 5     

骨髓间质干细胞冠脉内移植治疗近期陈旧性心肌梗死伴心功能不全

目的研究自身骨髓间质干细胞经冠脉内移植治疗近期陈旧性心肌梗死伴心功能不全的临床疗效及安全性。方法将本院22例近期陈旧性心肌梗死伴心功能不全患者,随机分为对照组和移植组各11例,两组均予常规药物治疗,移植组给予自身骨髓间质干细胞经梗死相关冠脉内移植,对照组经冠脉注射等量生理盐水。术前、术后48 h、3个月和6个月分别检测血清IL-6、TNF-α和CRP,术前、术后3个月和6个月分别观察血浆BNP、6 min步行试验、超声心动图、动态心电图9、9 mTc-甲氧基异丁基异腈(MIBI)和18F-脱氧葡萄糖(FDG)双核素心肌显像。结果细胞移植组术前、术后48 h、3个月和6个月血清IL-6、TNF-α和CRP与对照组比较差异均无显著性(P>0.05)。术后3个月和6个月,与对照组比较,细胞移植组BNP降低,6 min步行试验增加,与自身术前比较差异亦具显著性,P<0.05。术后3月,细胞移植组左室射血分数增加,与对照组和自身术前比较差异有显著性[(0.40±0.03)vs.(0.37±0.09),(0.35±0.05),P<0.05)。术后6月,细胞移植组左室舒张末容积缩小,与对照组和自身术前比较差异有显著性(4.97±0.54)vs.(5.63±0.80),(5.84±0.75)cm,P<0.05]。双核素心肌显像提示,移植组术后6个月灌流-代谢不匹配节段数增加,与对照组和自身术前比较差异具显著性[(7.60±1.26)vs.(6.20±1.14),(5.80±1.69)个,P<0.05]。围手术期及术后6个月随访中未见任何严重致心律失常发生。结论自身骨髓间质干细胞经冠脉内移植治疗陈旧性心肌梗死伴心功能不全患者,可能改善心功能,延缓心室重塑,增加存活心肌,无明显的致心律失常和免疫炎症反应。     

血管紧张素-(1-7)对压力负荷增高大鼠心肌胶原网络重塑的影响

目的　探讨血管紧张素 ( 17)〔Ang ( 17)〕对压力负荷增高大鼠心肌胶原网络重塑的影响。方法　腹主动脉缩窄术制备压力负荷增高大鼠模型 ,75只 SD大鼠随机分为假手术组、模型组、Ang ( 17)治疗组 ( 2 5 μg· kg- 1· h- 1 ,持续静脉给药 )。各组分别于术后 1周和 4周处死部分大鼠 ,检测左心室质量 /体质量比以及心肌胶原容积分数 ,并采用逆转录聚合酶链反应检测左心室心肌 、 型胶原 m RNA的表达水平。结果　与假手术组比较 ,模型组和 Ang ( 17)治疗组术后 1周 、 型胶原 m RNA表达均明显增高 ,Ang ( 17)治疗组增高的幅度明显低于模型组 ;模型组和 Ang ( 17)治疗组术后 4周的左心室质量 /体质量比、心肌胶原容积分数均高于假手术组 ,但 Ang ( 17)治疗组上述指标低于模型组。结论　给予外源性Ang ( 17)能减轻压力负荷增高所致的心肌胶原网络重塑。     

Binding of KRH-594, an antagonist of the angiotensin II type 1 receptor,to cloned human and rat angiotensin II receptors

We studied the binding properties of KRH-594, a new selective antagonist of angiotensin II (AII) type 1 (AT1) receptors, to rat liver membranes and to recombinant AT1 and AT2 receptors. Preincubation of rat liver membranes with KRH-594 produced maximal inhibition of [125I]-AII binding when the preincubation time was 1-2 h. Preincubation with KRH-594 for 2 h decreased the B(max) value and increased the Kd value. For human AT1, human AT2, rat AT1A and rat AT1B receptors, the Ki values for KRH-594 were 1.24, 9360, 0.67, and 1.02 nm, respectively. The rank order of K1 values for human AT1 receptors was KRH-594 > EXP3174 > candesartan = AII. The order of specificities for human AT1 and AT2 receptors was candesartan > EXP3174 > KRH-594. Although a 2-h preincubation of human AT2 receptors with KRH-594 (30 microM) or CGP 42112 (a selective AT2 receptor antagonist; 0.3 nM) inhibited binding of [125I]-AII, the suppression by KRH-594 was not significant. These results indicate that KRH-594 binds potently to AT1 receptors in an insurmountable manner, and that at a very high dose (30 microM) it may also bind to AT2 receptors, but in a surmountable manner.     

12周运动康复程序对急性期后心肌梗死患者身体机能的影响

目的:探讨康复运动对急性期后心肌梗死患者(PMIP)身体机能的影响。方法:101例男性PMIP参加了12周有氧多样化运动康复程序,程序前后通过递增负荷运动实验对其身体机能、运动能力等指标进行了测定分析。结果:受试者在康复训练后血胆固醇由5.9mmol/L降低到5.4mmol/L(P<0.01);对应跑台各级负荷时的摄氧量(VO2)、心率(HR)、心率-血压乘积(RPP)和主观用力感觉(RPE)在康复程序后有显著的下降(P<0.01或P<0.05);峰值HR、峰值%HRmax和峰值RPP分别增长了7.5%、8.5%和11.7%。结论:PMIP参加12周运动康复程序后,有氧工作能力有所增强、心血管机能有所改善。     

心肌损伤标志物联合检测在急性心肌梗死诊断中的价值

目的评价心肌损伤标志物肌钙蛋白T/I(cTnT/I)、肌红蛋白(Myo)、肌酸激酶同工酶(CK-MB)在急性心肌梗死(AMI)中的诊断价值。方法对150例AMI患者进行心肌标志物和心肌酶谱比较。结果心肌标志物在AMI发病早期升高的幅度较心肌酶谱升高显著,差异有统计学意义(P0.01)。结论心肌损伤标志物cT-nT/I、Myo、CK-MB在AMI早期诊断中具有重要的临床价值。     

Effect of valsartan on erythropoietin and hemoglobin levels in stage III-IV chronic kidney disease patients

Angiotensin-converting enzyme inhibitors (ACEIs) were accepted as a potential cause of inadequate epoetin response in chronic kidney disease (CKD) patients. We aimed to determine the effects of valsartan, an angiotensin receptor blocker (ARB), on serum ertyhropoietin levels and on certain biochemical and haematological parameters in hypertensive CKD patients. Twenty-two stage III-IV CKD patients (mean age; 56.8 +/- 8.9 years, 12 male 10 female) were included in the study. Before initiating the treatment, current anti-hypertensive treatments (if any) were discontinued, and blood samples were collected after a washout period of 3 weeks. Valsartan 80 mg/day was started, and additional anti-hypertensive agents were given according to study protocol if needed. One way Anova and paired t-tests were used for statistical comparisons. Serum blood urea nitrogen (BUN), creatinine, uric acid, potassium, haemoglobin and erythropoietin values were measured, and glomerular filtration rates were calculated before and 3, 6 and 90 days after valsartan treatment, a significant reduction in EPO level was observed at 3rd (19.6 +/- 24.0 vs. 13.8 +/- 8.5, p = 0.010), 6th (12.1 +/- 7.6, p = 0.009), and 90th days (8.3 +/- 5.4, p = 0.007). When pre-treatment values were compared with 90th day results, no significant change was observed in terms of hgb, htc, serum BUN, creatinine, uric acid, potassium, and GFR values. In conclusion, valsartan, an ARB, did not decrease haemoglobin levels in stage III-IV CKD patients despite significant reduction in serum erythropoietinlevels, so ARBs may be preferred to ACEIs in CKD patients when indicated.     

心脏磁共振可评估急性心肌梗死患者的早期心功能状态

目的  探讨心脏磁共振对急性心肌梗死患者早期心功能状态评估价值。方法  选择2022年6月~2022年12月在我科住院并确诊的急性ST段抬高型心肌梗死患者24例,男性22例,女性2例,年龄55.3±11.3岁。所有患者均在入院后行冠状动脉介入手术,并在术后5~7 d行心脏磁共振检查。应用电影成像技术分析心功能状态、是否存在反向运动和室壁瘤;组织追踪技术分析心肌各节段的应变能力;延迟强化技术分析心肌梗死部位、梗死面积大小和是否存在微循环障碍。结果梗死节段心肌应变分析显示：24例患者中,21例患者径向应变下降,18例患者周向应变下降,21例患者纵向应变下降,16例患者三向应变均下降;整体心肌应变分析显示：15例患者径向应变下降,10例患者周向应变下降,20例患者纵向应变下降,9例患者三向应变均下降;梗死节段心肌平均径向应变和周向应变低于整体心肌平均径向应变和周向应变（P < 0.05）,梗死节段与整体心肌纵向应变的差异无统计学意义（P > 0.05）。13例患者出现心肌反向运动;左室射血分数（LVEF）下降者10例;LVEF未下降的14例中,心肌反向运动6例,梗死节段三向心肌应变下降6例,梗死区内微循环障碍7例,NT-proBNP水平升高7例。出现反向运动组患者LVEF、梗死节段心肌和整体心肌平均周向应变、纵向应变均小于未出现反向运动组患者（P < 0.05）。相关性分析显示：LVEF与心肌整体应变、梗死节段应变和左房射血分数呈正相关关系,与心肌梗死面积、左室收缩末期容积/体表面积比值、NT-proBNP水平和Genisini评分呈负相关关系（P < 0.05）。二元Logistic回归显示,梗死节段纵向应变的降低可以独立预测患者是否出现心肌反向运动。结论  心脏磁共振技术可以多角度评价心功能状态,对急性心肌梗死患者术后早期心功能评估、治疗和干预,改善患者的预后提供参考依据。     

Effects of losartan and valsartan on left ventricular hypertrophy and function in essential hypertension

This study compared the effect of losartan and valsartan on left ventricular mass (LVM) and function in patients with untreated essential hypertension and concentric left ventricular hypertrophy (LVH). Thirty patients (17 men and 13 women; mean age, 48±8 years) with untreated essential hypertension and concentric LVH, as determined by echocardiographic assessment, were randomly assigned in equal numbers and double-blind fashion to receive either losartan 50 to 100 mg/d or valsartan 80 to 1 60 mg/d. Doppler echocardiograms were obtained from each patient before treatment, at the time of initial blood pressure control, and then after 6 months. A significant reduction (P<.01) in LVM index was observed in both the losartan group (from 57.1±7.2 g/m^2.7 to 51.5±6.1 g/m^2.7) and the valsartan group (from 58.1±8.4 g/m^2.7 to 48.2±6.2 g/m^2.7), but the reduction was higher (P<.05) in the valsartan group. The predicted midwall fractional shortening improved significantly in both the losartan group (from 81±8% to 89±9%, P<.05) and the valsartan group (from 78±7% to 91 ±9%, P<.01). Similarly, the early peak/peak atrial velocity ratio improved significantly both in the losartan group (from 0.78±0.4 to 0.88±0.3, P<.05) and the valsartan group (from 0.84±0.3 to 0.94±0.4, P<.01). These results indicate that valsartan is more effective than losartan in reducing LVM index in hypertensive patients with concentric LVH. This effect is associated with improvement in midwall systolic performance and left ventricular diastolic function.     

早期新型心脏康复模式对急性心肌梗死PCI术后患者心肌血流灌注及心肺功能的影响

目的探讨早期新型心脏康复模式对急性心肌梗死经皮冠状动脉介入(PCI)术后患者的干预效果。方法选取2018年1月至2020年1月收治的80例急性心肌梗死PCI手术患者,将其随机分为对照组和观察组,各40例。对照组采用常规心脏康复模式干预,观察组采用早期新型心脏康复模式干预。比较两组的心肌血流灌注、心肺功能指标及生活质量评分。结果干预后,观察组的TIMI血流分级优于对照组(P<0.05)。干预后,两组的CO、LVEF均较干预前升高,PAP均较干预前降低,且观察组优于对照组(P<0.05)。干预后,两组患者的SF-36各维度评分均较干预前升高,且观察组高于对照组(P<0.05)。结论给予急性心肌梗死PCI术后患者早期新型心脏康复模式,有助于促进心肌血流灌注及心肺功能改善,提高生活质量,值得临床推广应用。     

Enalaprilat,losartan and LU 135252 in coronary blood flow regulation

BACKGROUND: High plasma levels of angiotensin II are found in several pathologies such as hypertension, heart failure and myocardial infarction. The effect of high concentrations of angiotensin II on coronary circulation is not well defined. The aim of the present study was to assess coronary blood flow regulation during tachycardia in the presence of elevated coronary plasma levels of angiotensin II, and the changes induced by ACE inhibition and blockade of angiotensin II and endothelin-A receptors. DESIGN: Left anterior coronary artery was catheterized in 38 pigs to infuse the study drugs. Saline was infused for 15 min. Then, the first atrial pacing was performed. The pigs were distributed to: Group 1 (n = 7) angiotensin II; Group 2 (n = 7) enalaprilat + angiotensin II; Group 3 (n = 9) the bradykinin B2 antagonist HOE 140 + enalaprilat + angiotensin II; Group 4 (n = 7) losartan + angiotensin II; and Group 5 (n = 8) endothelin-A receptor antagonist LU 135252 + angiotensin II. After giving these infusions, a second pacing was repeated. RESULTS: The increase in coronary blood flow induced by pacing with angiotensin II was reduced from 181 +/- 21% to 116 +/- 37% (P = 0.006 vs. saline). Enalaprilat, losartan and LU 135252 restored the capacity of coronary blood flow to increase during pacing (151 +/- 39%, 162 +/- 35% and 161 +/- 16%, respectively; P = NS, vs. saline), while HOE 140 abolished the effect of enalaprilat. CONCLUSIONS: Moderately elevated coronary concentrations of angiotensin II reduced coronary blood flow during pacing. Enalaprilat, losartan and LU 135252 restored the hyperaemic coronary flow to similar values observed with saline. The beneficial effect of ACE inhibition is mediated through an increase in bradykinin.     

大鼠心肌梗死后血清脑钠肽、内皮素-1和一氧化氮的变化及缬沙坦的干预作用

目的通过动物实验发现急性心肌梗死后大鼠脑钠肽（BNP）、内皮素-1（ET-1）和一氧化氮（N0）的变化规律,以及缬沙坦对这些体液因子的干预作用。方法Wistar大鼠90只,经麻醉后行冠脉结扎处理制作心肌梗死模型,术后存活的大鼠分为①对照组（Sham,n=30）;②心肌梗死组（AMI,n=30）;③心肌梗死＋缬沙坦组（AMI＋valsartan,n=30）。心肌梗死＋缬沙坦组于术后将缬沙坦行干预治疗。术后开始计时,于6,12,24h和3,7,30天分别抽大鼠静脉血1ml,测定BNP,ET-1和N0指标,观察各组之间的差异。结果各组间血清BNP,ET-1和N0水平在每个时间点均有明显差异（各P值均〈O．05）,其中BNP和ET-1有单纯心肌梗死组〉心肌梗死＋缬沙坦组〉对照组的大小关系,而N0有单纯心肌梗死组〈心肌梗死＋缬沙坦组〈对照组的大小关系。结论血清BNP,ET-1升高和N0的降低参与了AMI后病情演变过程。缬沙坦能改善AMI后血清BNP,ET-1升高和N0的降低程度,对AMI后病情变化有益。     

心肌标志物联合检测在急性心肌梗死早期诊断中的应用价值

目的探讨高敏C反应蛋白(hs-CRP)、肌钙蛋白I(cTnI)和肌酸激酶同工酶(CK-MB)联合检测在心肌梗死早期诊断中的应用。方法选取2010年1月至2013年12月荆门市第一人民医院收治的2型糖尿病伴心肌梗死住院患者106例,其中60例具有典型心肌梗死症状的患者纳入对照组,46例不典型心肌梗死患者纳入观察组,动态监测两组患者发病后血清hs-CRP、cTnI、CK-MB水平的变化,并比较不同时间点两组患者各指标水平。结果不同时间点两组患者血清hs-CRP、cTnI、CK-MB水平比较,差异均无统计学意义(P0.05);两组患者血清CK-MB水平均于发病后3~12h开始升高,24~48h达到高峰,3~5d基本恢复正常水平;血清hs-CRP水平于发病后3h开始升高,一直保持高水平,3~5d后开始下降;血清cTnI水平于发病后3~6h开始升高,12~24h达高峰,一直持续高水平,5d后开始下降。结论 CK-MB、hs-CRP及cTnI联合检测有助于心肌梗死的早期诊断,尤其可提高症状不明显患者的诊断率,避免漏诊、误诊。