Effects of atenolol on left ventricular hypertrophy and early left ventricular function in essential hypertension

Echocardiographic studies of left ventricular (LV) hypertrophy indicate clinical benefits of antihypertensive therapy. Therefore, M-mode and Doppler techniques were used to assess changes in LV hypertrophy after 10, 30 and 50 weeks of atenolol therapy (50 or 100 mg once daily) in 19 patients with essential hypertension. After 50 weeks of atenolol treatment, the most notable changes were: for M-mode parameters, increases (p less than 0.05) in diastolic LV internal dimension, radius to thickness ratio and stroke volume, and decreases (p less than 0.01) in total wall thickness and heart rate; for Doppler parameters, increases (p less than 0.01) in slope and peripheral resistance, and decreases (p less than 0.01) in heart rate, stroke volume and cardiac output. The decreased total wall thickness and increased radius to thickness ratio suggest a trend toward regression of LV hypertrophy. These findings, along with improvements in blood pressure, pulse and exercise stress tests, indicate potential benefits of atenolol in managing patients with essential hypertension and LV hypertrophy.     

Effects of bisoprolol on left ventricular hypertrophy in essential hypertension

Summary Previous studies have shown that beta-adrenergic blocking drugs can reverse ventricular hypertrophy in patients with systemic hypertension. Thirty patients with essential hypertension and left ventricular hypertrophy were studied at baseline after withdrawing all previous treatments and after 6 months of treatment with 5–20 mg of bisoprolol, a new beta-selective agent, to assess its possible action on left ventricular mass. Three patients did not finish the study. Blood pressure was reduced to below 160/90 mmHg in 22 of the remaining 27 patients. At the end of follow-up, the left ventricular mass (echocardiography) was reduced from 308.1±89 g to 262.3±51 g (p<0.001) and left ventricular mass index from 165±47.4 g/m² to 141.03±26.7 g/m² (p<0.001). The ratio of E wave/A wave velocity of transmitral blood flow measured by Doppler increased from 0.86±0.44 to 1.07±0.45 (p=0.005). Peak filling rate, derived from nuclear ventriculography, changed from 2.05±0.4 EDV/sec before the treatment to 2.23±0.47 EDV/sec after it (p=0.0046). Serum lipids as well as other biochemical tests were unchanged. Left ventricular volumes and ejection fraction did not change, and treadmill exercise time increased from 343±125 seconds to 420±135 seconds (p=0.002). Maximal systolic blood pressure during exercise decreased from 197.2±19.7 mmHg to 182.9±25.8 mmHg (p=0.011). There were few side effects. We conclude that bisoprolol reduces left ventricular mass, preserves systolic function, and improves diastolic function of the left ventricle in hypertensive subjects with left ventricular hypertrophy.     

Effects of indapamide on left ventricular mass and function in systemic hypertension with left ventricular hypertrophy

Left ventricular hypertrophy (LVH) is frequently associated with hypertension and constitutes a major cardiovascular risk factor, the reduction of which should be considered when initiating antihypertensive therapy. To assess the effects of indapamide on LVH, 18 hypertensive patients were included in the study (11 men and 7 women, age 53.6 +/- 2.9 years, mean +/- standard deviation) whose supine diastolic blood pressure was greater than 95 mm Hg without (n = 11) or with (n = 7:6 beta blockers, 1 calcium antagonist) antihypertensive therapy. All presented with LVH, echocardiographically defined by a left ventricular mass index greater than 110 g/m2. After a 2-week preinclusion period, all patients received indapamide, 2.5 mg/day, for a period of 6 months. Physical examination including blood pressure measurement was performed on selection (M-1/2), before (M0), and after 1 (M1), 3 (M3) and 6 (M6) months of indapamide treatment, and echocardiography was performed at M0 and M6. Quality of life was evaluated by means of questionnaires completed by the patient and the physician, and a visual analog scale was completed by the patient at M-1/2, M0 and M6. All clinical parameters remained stable during the 2-week preinclusion period. Indapamide administration induced a highly significant reduction in both supine systolic and diastolic blood pressures from 173.9 +/- 2.9/100.5 +/- 1.2 mm Hg at M0 to 150.9 +/- 1.9/90.5 +/- 1.3 mm Hg at M1 (p less than 0.001), and 145.0 +/- 1.7/86.0 +/- 1.5 mm Hg at M6 (p less than 0.001). Similar favorable effects were observed in the upright position.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of acute arterial hypertension on myocardial infarct size in dogs without left ventricular hypertrophy

During acute myocardial infarction an increase in arterial pressure is common in patients who were previously normotensive and, therefore, do not have left ventricular hypertrophy. However, the effect of hypertension on infarct size in the absence of hypertrophy is uncertain. Thus, 32 open chest dogs underwent a 2 hour occlusion of the mid-left anterior descending coronary artery followed by 3 hours of reperfusion. Immediately after occlusion, 14 dogs were randomized to a hypertension group (intravenous phenylephrine infusion starting 5 minutes after occlusion and terminating at the time of reperfusion, with heart rate kept constant by atrial pacing) and 18 dogs to a control group (equivalent volumes of saline solution intravenously). Twelve of the 32 dogs were excluded from analysis because they developed ventricular fibrillation during coronary occlusion or reperfusion. In the hypertension group (n = 10), the mean arterial pressure increased significantly within 10 minutes of coronary occlusion (146 +/- 7 versus 109 +/- 11 mm Hg in 10 control dogs, p less than 0.01) and was maintained approximately 40 mm Hg higher than in the control group (p less than 0.01) throughout the ischemic period. Heart rate was similar in the two groups throughout the experiment. After the dogs were sacrificed, the region normally supplied by the occluded artery (anatomic "region at risk") was identified by simultaneous perfusion of the aortic root and the coronary artery distal to the occlusion. The heart was sectioned transversely and stained with triphenyltetrazolium-chloride. The infarcted area and the anatomic risk area were determined by video planimetry.(ABSTRACT TRUNCATED AT 250 WORDS)     

一氧化氮、醛固酮对高血压左室肥厚及左室舒张功能的影响

目的:探讨一氧化氮(NO)、醛固酮(ALD)在高血压左室肥厚(LVH)形成中的作用及对左室舒张功能的影响。方法:以超声心动图检查55例原发性高血压(EH)患者和30例正常人并计算左室重量指数(LVMI),测定左室舒张功能等指标,并测定空腹血清NO、ALD水平,进行组间比较。结果:EH组与正常人相比NO水平降低、ALD 水平升高,左室舒张功能降低(P均<0.01)。EH-LVH组与EH组相比NO水平降低、ALD水平升高更明显(P< 0.01)。NO、ALD与LVMI相关系数(r)分别为-0.46和0.50(P<0.05)。NO、ALD与左室舒张指标E/A和PFR/ PAFR的,r分别为0.37、0.43、-0.42、-0.37(P<0.05)。结论:原发性高血压患者NO、ALD水平与LVMI和左室舒张功能减退呈显著相关性。     

卡维地洛长期治疗对原发性高血压左心室肥厚及室性心律失常干预的对比研究

目的探讨β及α受体阻滞剂卡维地洛对原发性高血压(EH)患者左心室肥厚(LVH)及室性心律失常(VA)的干预作用。方法入选经超声心动图、心电图、动态心电图检查证实为EH伴LVH及VA患者72例,随机分配到卡维地洛组(口服25~50mg/d)或卡托普利组(口服25~75mg/d),治疗8个月,治疗前后各检查超声心动图、心电图、动态心电图,对比分析组内治疗前后左心室重量指数及VA变化和两组间的差异。结果①与治疗前比较,EH患者在卡维地洛或卡托普利治疗8个月后,两组收缩压与舒张压明显下降(166/104mmHg至135/86mmHg;162/103mmHg至138/87mmHg)(P均<0.01)。②卡维地洛组治疗后,左心室后壁与室间隔厚度较治疗前显著下降(P<0.05),左心室重量及左心室重量指数下降更显著(P均<0.01);卡托普利组治疗后左心室后壁与室间隔厚度及左心室重量及左心室重量指数下降显著(P均<0.05)。③卡维地洛组治疗后VA及复杂性室性VA的控制率为91.67%(33/36);卡托普利组治疗后VA及复杂性VA的控制率为36.1%(13/36),两组间差异有显著性(P<0.01)。结论EH伴LVH及VA患者在卡维地洛治疗8个月后LVH显著逆转,卡维地洛对VA的干预明显优于卡托普利。     

Injectable hydrogel properties influence infarct expansion and extent of postinfarction left ventricular remodeling in an ovine model

A recent trend has emerged that involves myocardial injection of biomaterials, containing cells or acellular, following myocardial infarction (MI) to influence the remodeling response through both biological and mechanical effects. Despite the number of different materials injected in these approaches, there has been little investigation into the importance of material properties on therapeutic outcomes. This work focuses on the investigation of injectable hyaluronic acid (MeHA) hydrogels that have tunable mechanics and gelation behavior. Specifically, two MeHA formulations that exhibit similar degradation and tissue distribution upon injection but have differential moduli (~8 versus ~43 kPa) were injected into a clinically relevant ovine MI model to evaluate the associated salutary effect of intramyocardial hydrogel injection on the remodeling response based on hydrogel mechanics. Treatment with both hydrogels significantly increased the wall thickness in the apex and basilar infarct regions compared with the control infarct. However, only the higher-modulus (MeHA High) treatment group had a statistically smaller infarct area compared with the control infarct group. Moreover, reductions in normalized end-diastolic and end-systolic volumes were observed for the MeHA High group. This group also tended to have better functional outcomes (cardiac output and ejection fraction) than the low-modulus (MeHA Low) and control infarct groups. This study provides fundamental information that can be used in the rational design of therapeutic materials for treatment of MI.     

重症高血压大鼠左心室肥厚时肾上腺髓质素系统的上调

目的探讨肾上腺髓质素(AM)在重症高血压大鼠左心室心肌肥大中的病理生理作用,包括其配体及酰胺化活性。方法试验分为4组：Wistar-Kyoto大鼠为对照组,有卒中倾向的自然发症高血压大鼠组,用卡托普利治疗8周组,用三氯甲噻嗪治疗8周组。AM前体为无活性的甘氨酸基肾上腺髓质素(AM-Gly),AM-Gly经酰胺化转变为成熟的有活性的AM(AM-m)。通过放射性免疫分析,检测血浆和左心室中AM-m、总AM(AM-m AM-G]y)、心房利钠肽含量,以及AM和心房利钠肽基因水平。结果自然发症高血压大鼠组血压、左心室重量、血浆和左心室中心房利钠肽及其mRNA水平均较对照有所升高。血浆中(AM-m： 31％,总AM： 56％)及心室中(AM-m： 84％,总AM： 31％)的AM-m和总AM均较对照组显升高。在左心室组织中自然发症高血压大鼠组(93．2％)的AM-m／总AM比率明显高于对照组。在左心室中的AM的mRNA水平显高于对照组。卡托普利和三氯甲噻嗪降血压和降低肥大左心室中AM-m、总AM、AM的mRNA含量作用相似。结论此高血压模型的肥大心肌中肾上腺髓质素系统上调。作为一个抗重塑的自分泌和(或)旁分泌因子,AM的上调可能改变左心室肥厚的病理生理过程。     

波生坦对慢性低氧性肺动脉高压大鼠右心室肥厚及缝隙连接蛋白(Cx)43表达的影响

目的:研究波生坦(bosentan,BST)对慢性低压低氧性肺动脉高压(HPH)大鼠右心室肥厚及缝隙连接蛋白43(Cx43)表达量的影响。方法:将24只实验动物随机分为正常组、HPH组、安慰剂组和BST治疗组,每组各6只。正常组:常压常氧下饲养6周;其他3组大鼠置于低压低氧仓内8h/d,共6周,从第4周开始,每天给BST治疗组大鼠BST(100mg/kg)灌胃,安慰剂组生理盐水灌胃。6周后,所有大鼠测定血流动力学指标:如平均肺动脉压力(mPAP)、右心室收缩压(RVSP)、右心室收缩压上升最大速率(dp/dtmax),以及右心室肥厚度[如右心室质量/(左心室质量+室间隔质量),RV/(LV+S)]和右心室质量/体质量(RW/BW)。收集动脉血检测血浆内皮素-1(ET-1)和一氧化氮(NO)水平。Masson染色观察心肌胶原纤维容积百分比的变化,免疫组化染色法和Westernblot观察Cx43的变化。结果:BST治疗组大鼠的mPAP、RVSP、RV/(LV+S)、RW/BW及心肌胶原纤维容积百分比均较HPH组显著降低(P0.05),但血浆NO、ET-1的水平和心肌Cx43表达量显著升高(P0.05)。结论:BST在降低肺动脉压力的同时,还可抑制右心室肥厚和Cx43表达量的降低。     

老年高血压伴左室肥厚对左心功能的影响

目的 :探讨老年高血压伴左室肥厚对心功能的影响。方法 :应用核素心血池扫描的方法 ,对老年高血压伴左室肥厚和无左室肥厚的患者 ,进行了左室射血分数 (LVEF)、左室高峰射血率 (PER)、左室高峰充盈率(PFR)、1/ 3充盈分数 (1/ 3FF)及相角程 (PA)的测定 ,并进行比较。结果 :伴左室肥厚的患者PFR、1/ 3FF明显低于无左室肥厚的患者 ,PA明显高于无左室肥厚的患者。结论 :老年高血压伴左室肥厚对心功能的影响 ,主要表现为对舒张功能的影响 ;左室肥厚导致的心室肌纤维化、顺应性下降和运动协调性异常 ,是影响舒张功能的重要原因     

Effects of exercise on coronary circulation in left ventricular hypertrophy caused by hypertension

Exercise is known to promote myocardial vascularity. We therefore studied whether it could prevent coronary abnormalities of hypertensive left ventricular (LV) hypertrophy. Female Sprague-Dawley 1 clip-2 kidneys Goldblatt hypertensive rats (RHR) and their appropriate controls (Sham-SH), were either made to swim (RHR-SW, SH-SW) or kept sedentary (RHR-SED, SH-SED) for 9 weeks. Maximal coronary blood flow (LV CBF, ml/min/gm) and minimal coronary resistance after carbochrome (total LVCR/LV mmHg/ml/min), an index of the functional cross sectional area (CSA) of coronary resistance vessels, were determined in conscious rats by microspheres. Results (m +/- SD) (n = 12 in all groups): (Table: see text). Exercise increased functional coronary CSA in normotensive rats only. This beneficial effect did not occur in hypertension, probably because of functional changes in the coronary vessels of RHR.     

Effects of nitrendipine on diastolic left ventricular function and hypertrophy in patients with hypertension

To assess the effects of antihypertensive therapy on the heart, left ventricular mass and performance indices (determined by M-mode and pulsed Doppler echocardiography) were compared before and after 4-5 months of nitrendipine therapy in 19 primary hypertensive patients (stage I and II). MAP was reduced from 17.1 +/- 1.7 to 14.5 +/- 1.7 kPa (128.5 +/- 12.7 to 109.0 +/- 13.1 mm Hg), P less than 0.001. The heart rate increased from 68 +/- 8 to 70 +/- 8 beats/min (P greater than 0.05). None of the indices for systolic function (SV, SI, CO, CI, EF, FS) changed significantly (P greater than 0.05). But the indices for diastolic function (RFF, RFR, VLef, IRP, EFv, A/E) improved remarkably (P less than 0.001 or 0.05). Furthermore, a positive correlation between the increasing rate of VLef and decreasing rate of MAP (r = 0.58, P less than 0.005) was noticed. Therefore, the decreasing in arterial pressure is considered as a major relative factor in the improvement of diastolic dysfunction. The patients were divided into two groups according to LVMI: group A, 11 patients with LVMI greater than or equal to 125 g/m2; while group B, 8 patients with LVMI less than 125 g/m2. The LV diastolic relaxation index IRP improved to a greater degree in group B (P less than 0.05), although the reduction of MAP was more markable in group A (P less than 0.05). This means that factors other than arterial pressure may influence the LV diastolic relaxation. In group A, the LVMI decreased from 155.1 +/- 29.9 to 144.4 +/- 33.0 g/m2 (a reduction of 7.0 +/- 9.0%). It suggests that LV hypertrophy can be "reversed" following nitrendipine therapy in some of the hypertensive patients.     

Determinants of left ventricular hypertrophy in arterial hypertension

A long term study (2-7 years, mean 3.6 years) monitoring 112 clinical and echocardiographic pattern in 593 hypertensives and 156 normotensives was performed in order to find associations to left ventricular hypertrophy (LVH) developing later. 49% of the hypertensives developed echocardiographic signs of LVH (wall thickness of 12 mm and more), in contrast to 5.1% of normotensive persons. Multivariate analysis revealed the following parameters examined at entry were associated with LVH on follow-up: male sex, prolonged hypertensive history, higher diastolic blood pressure, frequent lipid-metabolism disturbances, uncharacteristic chest pain and less effective antihypertensive treatment. Thus, LVH development can be regarded as a multifactorial process.     

The assessment of left ventricular hypertrophy in hypertension

The presence of left ventricular hypertrophy (LVH) in hypertension, as detected by the electrocardiogram or echocardiography, is associated with an increased risk of mortality and morbidity several times above and beyond the risk of hypertension alone. The LIFE (Losartan Intervention For Endpoint reduction in hypertension) study confirmed that pharmacological agents, which reduce LVH, confer further reduction in morbidity and mortality. This makes the identification of patients with LVH all the more important. In this article we describe the various methods available to diagnose the presence of LVH in patients with hypertension, and consider their strengths and their place in clinical practice and in research.     

Effects of verapamil and aspirin on experimental chronic hypoxic pulmonary hypertension and right ventricular hypertrophy in rats.

Rats made hypoxic by confinement in hypoxic cages for 4 weeks developed pulmonary hypertension and right ventricular hypertrophy. Treatment with Verapamil or aspirin reduced both chronic hypoxic pulmonary hypertension and the hypertrophy of the right ventricle. The antihypertensive effect of Verapamil is explained by the involvement of the transmembrane calcium flux in pulmonary vascular smooth muscle in the hypoxic vasoconstrictory response. Part of the antihypertensive effect of inhibition of prostaglandin synthesis is attributed to a decrease in packed cell volume produced in hypoxic, aspirin treated rats.     

Cardioreparative effects of lisinopril in rats with genetic hypertension and left ventricular hypertrophy.

BACKGROUND. In genetic and acquired hypertension, a structural remodeling of the nonmyocyte compartment of the myocardium, including the accumulation of fibrillar collagen within the interstitium and adventitia of intramyocardial coronary arteries and a medial thickening of these vessels, represents a determinant of pathological hypertrophy that leads to ventricular dysfunction. METHODS AND RESULTS. To evaluate the benefit of angiotensin converting enzyme inhibition in reversing this interstitial and vascular remodeling in the rat with genetic spontaneous hypertension (SHR) and established left ventricular hypertrophy (LVH), we treated 14-week-old male SHR with oral lisinopril (average dose, 15 mg/kg/day) for 12 weeks. Myocardial stiffness and coronary vascular reserve to adenosine (800 micrograms/min) were examined in the isolated heart; myocardial collagen and intramural coronary artery architecture were analyzed morphometrically. In lisinopril-treated SHR compared with 14-week-old baseline or 26-week-old untreated SHR and age- and sex-matched Wistar-Kyoto (WKY) controls, we found 1) a regression in LVH and normalization of blood pressure, 2) a complete regression of interstitial fibrosis, represented by a decrease of interstitial collagen volume fraction from 7.0 +/- 1.3% to 3.2 +/- 0.3% (p less than 0.025; WKY, 2.8 +/- 0.5%), 3) normalization of myocardial stiffness constant from 19.5 +/- 0.9 to 13.7 +/- 1.3 (p less than 0.025; WKY, 13.8 +/- 2.2), 4) a reversal of intramural coronary artery remodeling, including a decrease in the ratio of perivascular fibrosis to vessel lumen size from 1.4 +/- 0.2 to 0.4 +/- 0.1 (p less than 0.025; WKY, 0.6 +/- 0.1) and medial thickening from 12.3 +/- 0.6 to 7.4 +/- 0.5 microns (p less than 0.005; WKY, 7.4 +/- 0.4 microns), and 4) a restoration of coronary vasodilator response to adenosine from 12.3 +/- 0.9 to 26.0 +/- 1.4 ml/min/g (p less than 0.005; WKY, 21.8 +/- 2.2 ml/min/g). Thus, in SHR with LVH and adverse structural remodeling of the cardiac interstitium, lisinopril reversed fibrous tissue accumulation and medial thickening of intramyocardial coronary arteries and restored myocardial stiffness and coronary vascular reserve to normal. CONCLUSIONS. These cardioreparative properties of angiotensin converting enzyme inhibition may be valuable in reversing left ventricular dysfunction in hypertensive heart disease.     

Effects of losartan and atenolol on left ventricular mass and neurohormonal profile in patients with essential hypertension and left ventricular hypertrophy

OBJECTIVE: To compare the effects of the angiotensin II antagonist, losartan, with those of atenolol on left ventricular hypertrophy (LVH), blood pressure and neurohormone concentrations in hypertensive patients with LVH. DESIGN: A multinational, randomized, double-blind trial. SETTING: Hospital. PATIENTS: Hypertensive patients with an echocardiographically documented left ventricular mass index (LVMI) 120 g/m(2) (men) or 105 g/m(2) (women). INTERVENTIONS: Patients allocated randomly to groups received either losartan or atenolol 50 mg/day for 36 weeks, with possible titration to 100 mg/day, and addition of hydrochlorothiazide 12.5 or 25 mg/day. MAIN OUTCOME MEASURES: Changes in LVMI and sitting systolic (SBP) and diastolic (DBP) blood pressures after 36 weeks of treatment (study powered for non-inferiority hypothesis). All echocardiographic data were read in a central laboratory by staff blinded to the treatments and sequence of echocardiographic tapes. RESULTS: The estimated treatment difference between the losartan and atenolol regimens (mean change from baseline at week 36) in LVMI was -2.5 g/m(2) [95% confidence interval (CI) -7.36 to 2.37 g/m(2) ] in favor of losartan, indicating that losartan was significantly non-inferior ( 0.001, non-inferiority limit 8 g/m(2) ) and numerically superior to atenolol in reducing LVMI. The losartan-based regimen significantly reduced LVMI after 36 weeks compared with baseline (-6.56 g/m(2) , 95% CI -10.24 to -2.88 g/m(2) , P<0.001), whereas the atenolol-based regimen had no significant effect (-3.71 g/m, 95% CI -7.75 to 0.32 g/m(2) , P= NS). In a subset of 82 patients, significant changes in serum concentrations of atrial natriuretic peptide, brain natriuretic peptide and immunoreactive amino-terminal pro-brain natriuretic peptide were recorded in losartan-treated ( 0.01) but not atenolol-treated patients. Losartan and atenolol significantly decreased SBP and DBP from baseline after 6, 12, 24 and 36 weeks. The changes from baseline in DBP were greater in the atenolol group at weeks 6 and 36 [difference -2.6 mmHg ( P= 0.016) at week 36]. However, both treatment regimens achieved similar SBP/DBP values at week 36 (141.1 +/- 12.8/86.8 +/- 8.2 mmHg for losartan and 141.4 +/- 17.2/85.0 +/- 10.1 mmHg for atenolol, respectively). Overall, losartan treatment was associated with significantly fewer drug-related clinical adverse events, compared with atenolol (10 and 22%, respectively, P= 0.028). CONCLUSIONS: Both losartan- and atenolol-based regimens effectively decreased blood pressure. Losartan was non-inferior and numerically superior to atenolol in regression of LVH. The reduction in hypertrophy with losartan treatment was accompanied by reductions in circulating concentrations of cardiac natriuretic peptides. Losartan, by specifically blocking angiotensin II, may therefore have effects on the heart beyond those expected from the decrease in blood pressure alone. Losartan was better tolerated than atenolol.