Left ventricular function and collagen content after regression of hypertensive hypertrophy

To determine whether regression of hypertensive hypertrophy through blood pressure control also involves left ventricular collagen and consecutive alterations in left ventricular diastolic and systolic function, antihypertensive treatment with the calcium channel blocker nifedipine (30 mg/kg.day) was employed in 20-week-old spontaneously hypertensive rats (n = 15) for a period of 20 weeks. Age-matched (40 weeks old) untreated (n = 13) and 20-week-old spontaneously hypertensive rats representing the state before therapy (n = 14) were used for comparison. Myocardial stiffness was described by the tangent modulus Km of the elastic stiffness-stress relation. Left ventricular collagen was determined by means of hydroxyproline (OH-proline) concentration. Myocardial working capacity of the left ventricle was measured as the peak developed systolic pressure per weight unit muscle mass and systolic peak pump function as the maximum achievable cardiac output under volume loading. After the 20-week course of nifedipine treatment, systolic aortic pressure dropped from 187 +/- 11 to 144 +/- 6 mm Hg (p less than 0.001). Regression of hypertrophy was shown by a left ventricular muscle/body weight ratio of 2.13 +/- 0.18 mg/g (p less than 0.01) in the 40-week-old nifedipine-treated hypertensive rats, whereas the ratios of the 20-week-old and 40-week-old untreated spontaneously hypertensive rats were 2.3 +/- 0.30 and 2.34 +/- 0.18 mg/g, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

长期应用依那普利对高血压病患者左室结构及功能影响

观察了28例Ⅱ期高血压病患者平均口服依那普利平均22个月后左室结构及功能改变。结果显示：用药后血压降低总有效率为89．3％，心率无变化。用药后空间隔、左室后壁及左定重量指数均明显下降（P＜0．05），A峰速度及A／E比值明显下降，E峰速度明显增高（P＜0．05）。提示：依那曾利长期治疗可有效降压，并同时逆转左室肥厚，改善左室舒张功能。     

高血压左室肥厚消退后心肌细胞跨膜电位变化的实验研究

目的　观察高血压左室肥厚消退后心肌细胞跨膜电位的变化。方法　 12周龄自发性高血压大鼠 (SHR) ,分别饲服尼群地平或卡托普利 14周 ,以同龄WKY及不经治疗的SHR鼠为对照。采用传统浮置式玻璃微电极记录在体心脏心室肌细胞的动作电位幅度 (APA) ,静息电位 (RMP) ,动作电位时限 (APD) ,及复极 90 %、75 %、5 0 %、2 5 %时的动作电位时限 (APD90 、APD75 、APD5 0 、APD2 5 ) ,并计算APD的离散度。结果　 (1)左室肥厚心肌细胞APD及其离散性均明显大于对照组 ;(2 )尼群地平和卡托普利治疗消退左室肥厚后 ,左心室肌细胞APD缩短及APD离散性减少。结论　伴随心肌肥厚的消退 ,心室肌细胞电生理异常好转。     

Aortic remodelling following the treatment and regression of hypertensive left ventricular hypertrophy: a cardiovascular magnetic resonance study

Abstract

Background: Increased arterial stiffness independently predicts adverse prognosis. While different antihypertensive strategies produce different magnitudes of left ventricular hypertrophy (LVH) regression, there are no comparative data on how these strategies affect arterial stiffness. The aim was to determine the longitudinal change in aortic stiffness following the treatment of essential hypertension with two mechanistically different antihypertensive treatment strategies. Methods and results: Forty-two patients with essential hypertension and CMR confirmed with LVH were randomly assigned to antihypertensive regimes for 6 months. Treatment strategies were designed either to inhibit the renin–angiotensin–aldosterone system (RAAS) and the sympathetic nervous system (SNS) (valsartan and moxonidine, group VM) or to have neutral effect on these systems (bendroflumethiazide and amlodipine, group BA). Both treatment groups underwent identical baseline and a 6-month follow-up CMR and were compared with a healthy age-matched control group. Baseline aortic distensibility (AD) was lower in both hypertensive groups compared with controls (2.8?×?10^?3?mmHg^?1 in group VM (p?=?0.001) and 3.3?×?10^?3?mmHg^?1 group BA (p?=?0.039) compared with 4.5?×?10^?3?mmHg^?1 in the control group). AD increased after antihypertensive therapy (VM: 2.8?×?10^?3?mmHg^?1–4.2?×?10^?3?mmHg^?1 (p?=?0.001); BA 3.3?×?10^?3?mmHg^?1–4.6?×?10^?3?mmHg^?1 (p?<?0.01)). In both treatment groups AD returned to a level comparable with the normal control group (p?=?0.81) after 6 months. Conclusions: In patients with essential hypertension and LVH, AD was lower than in matched normal controls. Despite the opposing pharmacological mechanisms utilised across the treatment groups, the improvement in AD was similar, suggesting that blood pressure reduction per se may be more important than RAAS and SNS inhibition for the improvement of aortic remodelling.     

Development and regression of left ventricular hypertrophy

Left ventricular hypertrophy is an important adaptive response to chronic pressure or volume overload of the left ventricle. The different types and the pathophysiologic mechanisms of the development of left ventricular hypertrophy in various disease states are reviewed. Detection of left ventricular hypertrophy may be accomplished by electrocardiography and cardiac angiography. Echocardiography, however, is the most accurate noninvasive method to detect the presence and estimate the severity of increased left ventricular mass. The clinical significance of left ventricular hypertrophy and its prognostic implications in several cardiac diseases associated with hypertrophy are discussed. The critical transition stage from adaptive, compensatory and reversible left ventricular hypertrophy to "pathologic" hypertrophy with impaired left ventricular contractility and irreversible myocardial damage is yet unknown. Recent data are presented that provide evidence of regression of left ventricular hypertrophy after medical treatment of patients with hypertension and after aortic valve replacement in patients with aortic valve disease. The clinical importance of regression of hypertrophy and its effects on long-term prognosis remain to be determined.     

The regression of left ventricular hypertrophy following a short antihypertensive treatment]

With the objective of trying to prove the regression of ventricular mass in patients with essential hypertension, with and without left ventricular hypertrophy (LVH), we studied 42 patients of both sexes with echocardiography, measuring the left ventricular mass (LVM), the mean parietal thickness (MPT) and the relative parietal thickness (RPT), before and after one month of random treatment with atenolol, verapamil and xipamide, independently that the blood pressure control was or not satisfactory. We found significant reductions in the MPT with verapamil and atenolol (p = 0.006 and 0.036), although only verapamil induced a significant reduction of the LVM. The RPT did not shown any significant modification, although the tendency was opposed with xipamide and the other two groups, verapamil and atenolol. The factor Adequate control of the blood pressure, with any of the treatments, proved to be helpful in the favorable evolution of the regression. The degree of LVH before treatment does not appear to have any influence in the posterior evolution with the treatment.     

Recovery of coronary function and morphology during regression of left ventricular hypertrophy

OBJECTIVES: To investigate changes in coronary morphology and haemodynamic function during regression of established left ventricular hypertrophy (LVH) following surgical unloading. METHODS: LVH was induced in guinea-pigs by aortic banding and sham operated animals served as controls. We examined the degree of LVH, coronary haemodynamic function and contemporaneous vessel morphology 42 days post-operation. Identically treated animals were debanded and the same parameters measured after 1, 3 and 6 weeks to assess haemodynamic and morphological changes as hypertrophy regressed. RESULTS: Banding resulted in an aortic pressure gradient of 41+/-9 mmHg and increases in heart/body weight ratio (46%), myocyte size (26%) and a doubling of arteriolar wall thickness, all P<0.01. These changes were accompanied by a reduction in coronary reserve (38%) and significantly (P<0.01) decreased maximal response to acetylcholine (70%), sodium nitroprusside (87%), adenosine (70%) and reactive hyperaemia (52%). Surgical debanding normalised the systemic haemodynamics and removed the aortic gradient after 7 days. There was some limited improvement in coronary structure and, to a lesser extent, function despite the continued presence of significant LVH. This had completely regressed to normal levels 23 days after debanding and was accompanied by normalisation of coronary structure and function, although systolic impedance to flow remained significantly increased. After 44 days, debanding resulted in complete cardiac morphological and functional recovery. CONCLUSION: Left ventricular haemodynamic unloading can result in complete normalisation of LVH, coronary morphology and haemodynamic function. Although morphological and functional recovery were closely correlated, recovery of coronary morphology and function slightly preceded that of the myocardium in this aortic banded/debanded model.     

Time course of regression of left ventricular hypertrophy in hypertensive patients treated with atenolol

Regression of left ventricular hypertrophy occurs with a number of antihypertensive drugs, but the time course of this regression has not been defined clearly. We obtained echocardiograms at baseline and serially (on seven occasions) during a 1 year treatment period with the beta-adrenergic receptor inhibitor atenolol in 12 patients with previously untreated essential hypertension. To ensure control of blood pressure in all patients throughout the study, it was necessary to add a thiazide diuretic to the therapy of five patients. Baseline blood pressure was 155/100 mm Hg and fell to 136/84 mm Hg; there was a 20% reduction in heart rate. Posterior and septal wall thicknesses were reduced from 1.16 +/- 0.03 to 1.06 +/- 0.02 cm (p less than .05) and from 1.28 +/- 0.07 to 1.18 +/- 0.06 cm (p less than .05), respectively; this reduction became significant initially at 4 weeks. Left ventricular mass decreased from 144 +/- 9 to 127 +/- 7 g/m2 (p less than .05) and this fall first became statistically significant at 6 months. Significant reduction in electrocardiographic voltages was also seen at 6 months. Therefore, regression of left ventricular hypertrophy with atenolol-induced blood pressure control occurred as early as 4 weeks after starting therapy and was maintained thereafter without apparent compromise of left ventricular systolic function.     

Risks of electrocardiographic left ventricular hypertrophy in hypertensive individuals and benefits of treatment-induced regression

Left ventricular hypertrophy (LVH), a common complication of hypertension, is an important risk factor for cardiovascular disease. Patients with LVH are at a markedly increased risk for many cardiovascular complications and death. This heightened risk can be mitigated in part by antihypertensive therapy-induced regression of LVH. The electrocardiogram (ECG) is a valuable modality in the identification, risk stratification, and longitudinal follow-up of patients with hypertension and LVH. This article details the prognostic significance of ECG LVH and the benefits associated with treatment-induced LVH regression.     

Clustered metabolic abnormalities blunt regression of hypertensive left ventricular hypertrophy: the LIFE study

Background and aimsClusters of metabolic abnormalities resembling phenotypes of metabolic syndrome predicted outcome in the LIFE study, independently of single risk markers, including obesity, diabetes and baseline ECG left ventricular hypertrophy (LVH). We examined whether clusters of two or more metabolic abnormalities (MetAb, including obesity, high plasma glucose without diabetes, low HDL-cholesterol) in addition to hypertension were associated to levels of ECG LVH reduction comparable to that obtained in hypertensive subjects without or with only one additional metabolic abnormality (no-MetAb).Methods and resultsWe studied 5558 non-diabetic participants without MetAb (2920 women) and 1235 with MetAb (751 women) from the LIFE-study cohort. MetAb was defined by reported LIFE criteria, using partition values from the ATPIII recommendations. Time-trends of Cornell voltage–duration product (CP) over 5 years was assessed using a quadratic polynomial contrast, adjusting for age, sex, prevalent cardiovascular disease and treatment arm (losartan or atenolol). At baseline, despite similar blood pressures, CP was greater in the presence than in the absence of MetAb (p < 0.0001). During follow-up, despite similar reduction of blood pressure, CP decreased less in patients with than in those without MetAb, even after adjustment for the respective baseline values (both p < 0.002). Losartan was more effective than atenolol in reducing CP independently of MetAb.ConclusionsClusters of metabolic abnormalities resembling phenotypes of metabolic syndrome are related to greater initial ECG LVH in hypertensive patients with value of blood pressure similar to individuals without metabolic abnormalities, and are associated with less reduction of ECG LVH during antihypertensive therapy, potentially contributing to the reported adverse prognosis of metabolic syndrome.     

Echocardiographic assessment of left ventricular hypertrophy and function in renal hypertensive dogs

To investigate the performance of the hypertrophied left ventricle, M-mode echocardiographic measurements were performed 2 to 3 times weekly on 8 unanesthetized dogs for several weeks before and for 6 months after the induction of perinephritic hypertension. Four dogs with sham-wrapping and contralateral nephrectomy served as the controls. From a baseline value of 7.7 +/- 0.4 mm (mean +/- SD), left ventricular wall thickness increased to 9.0 +/- 0.6 mm (p less than 0.001) by the 4th week after the induction of hypertension and reached a plateau of 10.2 +/- 1.2 mm (p less than 0.001) by week 10. Fractional shortening of left ventricular dimension (% delta D) increased during early left ventricular hypertrophy and remained elevated for 6 months in the surviving 6 hypertensive dogs. In hypertensive dogs, left ventricular concentric hypertrophy became detectable by week 6 of hypertension. Control dogs did not show these changes. At autopsy, the left ventricular weight of hypertensive and normotensive control dogs was (6.2 +/- 1.4 g/kg and 4.3 +/- 0.5 g/kg (p less than 0.05). In summary, during the early stage of left ventricular hypertrophy in renal hypertensive dogs cardiac performance increased. There is no evidence for deterioration of left ventricular performance as concentric left ventricular hypertrophy develops and becomes chronic.     

Vasodilators and regression of left ventricular hypertrophy. Hydralazine versus prazosin in hypertensive humans

Long-term treatment of hypertensive rats with arterial vasodilators may further increase left ventricular hypertrophy. Since left ventricular hypertrophy may be an important determinant of outcome in hypertension, the long-term effects of arterial vasodilation with hydralazine on left ventricular mass and function were compared with those of an alternative third-line drug, the alpha1 blocker prazosin, in patients still hypertensive despite combined diuretic and beta blocker therapy. A single-blind, randomized, two-group parallel design was employed. Both treatments induced a sustained antihypertensive effect, with hydralazine showing more effect on supine blood pressure, and prazosin having more effect on standing pressure. Heart rate, cardiac output, and volume status showed only minor changes. Plasma norepinephrine showed a sustained increase when measured in both the supine and standing positions, but the increases were similar for the two treatments. Supine and standing plasma renin activity increased only during long-term treatment with hydralazine. Prazosin induced a progressive decrease in left ventricular mass over time (-34 +/- 15 g/m2 at 12 months), but hydralazine did not (-9 +/- 10 g/m2 after 12 months). Stepwise regression indicated that a decrease in systolic blood pressure was associated with a decrease in left ventricular mass with both treatments, but an increase in plasma norepinephrine was associated with an increase in left ventricular mass only with hydralazine, suggesting that increased sympathetic activity may affect left ventricular mass via cardiac alpha1 receptors. Thus, if regression of left ventricular hypertrophy is a worthwhile therapeutic goal, hydralazine and analogous arterial vasodilators are not drugs of choice.     

长期应用奥美沙坦与福辛普利对高血压左室肥厚和心功能的影响

长期高血压可导致心脏和血管的结构和功能改变,这是发生高血压靶器官损害和心脑血管并发症的基础.     

Effects of regression of left ventricular hypertrophy following atenolol or bunazosin therapy on ischemic cardiac function and myocardial metabolism in spontaneously hypertensive rats.

The effects of regression of left ventricular hypertrophy following atenolol and bunazosin therapy on ischemic cardiac function and myocardial metabolism in spontaneously hypertensive rats (SHR) were studied. Atenolol (50 mg/kg/day) and bunazosin (5 mg/kg/day) were administered to SHR from 19 to 26 weeks of age, whereas tap water was given to control SHR and normotensive Wistar-Kyoto rats (WKY). Both atenolol and bunazosin significantly decreased arterial blood pressure and significantly decelerated the increase in left ventricular weight in SHR. At the end of the long-term treatment, hearts were removed and perfused by the working heart technique for 15 min, and then global ischemia was induced for either 10 or 30 min. The ischemic heart was reperfused for 30 min. The pressure-rate product and the extent of recovery of the coronary flow after reperfusion following 30 min of ischemia in the bunazosin-treated SHR were significantly higher than those in the control SHR and the atenolol-treated SHR. The levels of adenosine triphosphate (ATP), creatine phosphate (CrP), and energy charge potential in the SHR heart reperfused after 30 min of ischemia were significantly lower than those in the reperfused WKY. Both atenolol and bunazosin improved the restoration of ATP and CrP in SHR after reperfusion following 30 min of ischemia. In conclusion, antihypertensive therapy with either atenolol or bunazosin was effective in preventing cardiac hypertrophy and ischemic damage caused by different mechanisms. Factors resulting from stimulation of the cardiac alpha 1 adrenoceptor may play an important role in the development of hypertensive cardiac hypertrophy, just as factors resulting from stimulation of the beta 1-adrenoceptor do.     

Usefulness of plasma cardiotrophin-1 in assessment of left ventricular hypertrophy regression in hypertensive patients

OBJECTIVE: We investigated whether regression of left ventricular hypertrophy (LVH) in response to antihypertensive treatment is associated with plasma cardiotrophin-1 (CT-1) in hypertensive patients. METHODS: The study was performed in 47 patients with mild to moderate essential hypertension, and LVH was assessed echocardiographically. The family doctor gave antihypertensive treatment and followed all patients. LVH regression was diagnosed if the baseline left ventricular mass index (LVMI) decreased to normal values after 1 year of treatment. Plasma CT-1 was determined by an enzyme-linked immunosorbent assay. RESULTS: The LVMI was normalized in 23 patients (49%) and persisted at an abnormally increased level in 24 patients (51%) after 1 year of treatment, whereas the reduction in clinic and home blood pressure was similar in the two groups: CT-1 decreased (-48%, P < 0.005) and increased (+35%, P < 0.05) in patients in whom LVH regressed and LVH persisted, respectively. Final values of CT-1 were inversely correlated (r = 0.534, P < 0.001) with the decrease in LVMI after treatment in all patients. A significant association (chi2 = 16.87, P < 0.001) was found between normalization of CT-1 and regression of LVH with treatment. A cut-off value of 41 fmol/ml for CT-1 provided a relative risk of 43.13 (95% confidence interval, 4.88-380.48) for detecting LVH regression. CONCLUSION: These results show an association between treatment-induced decrease of plasma CT-1 and LVH regression in essential hypertension. Although preliminary, these findings suggest that the determination of plasma CT-1 may be useful for the follow-up of hypertensive heart disease in routine clinical practice.     

Impaired left ventricular functional reserve in hypertensive patients with left ventricular hypertrophy

To determine whether patients with hypertension and especially those with left ventricular hypertrophy have subtle changes in cardiac function, we measured the increase in left ventricular ejection fraction and in systolic blood pressure to end-systolic volume index ratio with exercise in 40 hypertensive patients and 16 age-matched normotensive volunteers. Twenty-two hypertensive patients without hypertrophy had normal end-systolic wall stress at rest and exercise responses. In contrast, the 18 patients with echocardiographic criteria for left ventricular hypertrophy demonstrated a significant increase in end-systolic wall stress at rest compared with normal subjects (69 +/- 16 vs. 55 +/- 15 10(3) x dyne/cm2, p less than 0.05) despite having normal resting left ventricular size and ejection fraction. In patients with left ventricular hypertrophy, the increase in ejection fraction with exercise was less than in the normotensive control subjects (7 +/- 7 vs. 12 +/- 8 units, p less than 0.05), and delta systolic blood pressure to end-systolic volume with exercise was reduced (3.3 +/- 3.8 vs. 8.3 +/- 7.7 mm Hg/ml/m2, p less than 0.05). The hypertensive patients with hypertrophy displayed a shift downward and to the right in the relation between systolic blood pressure to end-systolic volume ratio and end-systolic wall stress compared with control subjects and hypertensive patients without left ventricular hypertrophy. Thus, hypertensive patients with left ventricular hypertrophy by echocardiography and normal resting ejection fraction exhibit abnormal ventricular functional responses to exercise. This finding may have implications in identifying patients at higher risk for developing heart failure.     

Comparison of ketanserin and celiprolol on regression of left ventricular hypertrophy in older hypertensive patients

Summary The effects of ketanserin, a specific serotonin₂-receptor agonist, and celiprolol, a new, highly cardioselective % MathType!MTEF!2!1!+-% feaafeart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaGaeqOSdi2aaS% baaSqaaiaaigdaaeqaaaaa!3874!\[\beta _1 \] blocker with partial % MathType!MTEF!2!1!+-% feaafeart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaGaeqOSdi2aaS% baaSqaaiaaikdaaeqaaaaa!3875!\[\beta _2 \] agonist activity and peripheral vasodilating properties, on left ventricular (LV) structure and function were assessed in 60 older hypertensive patients (>55 years) with clinical LV hypertrophy (LV mass indes >130 g/m²). The patients were studied using echocardiography after 1 month of placebo treatment, and 6 and 18 months of monotherapy with active drug. Ketanserin and celiprolol lowered blood pressure to normal levels. Heart rate did not change with ketanserin and fell moderately (-5%) with celiprolol (p<.001). Regression of LV hypertrophy was achieved with the use of either medication (p<.0001), although the magnitude of reduction in LV mass was greater with celiprolol at both 6 months (-10% vs-5%, p=.001) and 18 months (-13% vs-7%, p=.002). While LV volume did not change with either drug, celiprolol tended to decrease it, resulting in a 5% reduction in cardiac index (p=.01), which was associated with mild bradycardia. Ketanserin did not change LV ejection fraction, whereas celiprolol caused a slight (1.5%) long-term improvement (p=.003). Systolic wall stress and total peripheral resistance decreased with both agents (p<.01), with no between-group differences. In conclusion, antihypertensive treatment of older persons with ketanserin or celiprolol achieves regression of LV hypertrophy without associated deleterious effects on LV function.     

Beta blockers & left ventricular hypertrophy regression

Left ventricular hypertrophy (LVH) particularly in hypertensive patients is a strong predictor of adverse cardiovascular events. Identifying LVH not only helps in the prognostication but also in the choice of therapeutic drugs. The prevalence of LVH is age linked and has a direct correlation to the severity of hypertension. Adequate control of blood pressure, most importantly central aortic pressure and blocking the effects of cardiomyocyte stimulatory growth factors like Angiotensin II helps in regression of LVH. Among the various antihypertensives ACE-inhibitors and angiotensin receptor blockers are more potent than other drugs in regressing LVH. Beta blockers especially the newer cardio selective ones do still have a role in regressing LVH albeit a minor one. A meta-analysis of various studies on LVH regression shows many lacunae. There have been no consistent criteria for defining LVH and documenting LVH regression. This article reviews current evidence on the role of Beta Blockers in LVH regression.