Relations of plasma homocysteine to left ventricular structure and function: the Framingham Heart Study.

AIMS: Hyperhomocysteinaemia is a risk factor for congestive heart failure, especially in women. We investigated if homocysteine promotes left ventricular (LV) remodelling. METHODS AND RESULTS: We examined cross-sectional relations of plasma total homocysteine to echocardiographic LV structure and function in 2697 Framingham Heart Study participants (mean age 58 years, 58% women) free of heart failure and previous myocardial infarction. Adjusting for age and height, plasma homocysteine was positively related to LV mass, wall thickness, and relative wall thickness in women (p=0.0004-0.04), but not in men (p=0.28-0.68). Adjusting additionally for other clinical covariates, the relations of plasma homocysteine to LV mass and wall thickness in women remained statistically significant, but the relation to relative wall thickness became of borderline significance (1.92 g, 0.01 cm, and 0.29% increase, respectively, for a 1-SD increase in ln[homocysteine], p=0.01-0.08). LV mass and wall thickness were higher in the fourth quartile of plasma homocysteine compared to the lower three in all models in women (p=0.0003-0.02), but not in men (p=0.25-0.78). Plasma homocysteine was not related to left atrial size or LV fractional shortening in either sex. CONCLUSION: In our community-based sample, plasma homocysteine was directly related to LV mass and wall thickness in women but not in men.     

Evaluation of the aldosterone synthase (CYP11B2) gene polymorphism in patients with myocardial infarction

Left ventricular remodeling after myocardial infarction involves activation of the renin-angiotensin-aldosterone system. Recently, the biallelic -344T/C polymorphism of the aldosterone synthase gene was associated with increased aldosterone levels, arterial hypertension, diastolic dysfunction, and left ventricular dilatation. We hypothesized that this polymorphism may also affect left ventricular geometry and function after myocardial infarction. By using a standardized questionnaire, as well as anthropometric and echocardiographic measurements, we thus studied 606 patients (533 men and 73 women) who had a myocardial infarction before the age of 60 years. The aldosterone synthase gene polymorphism was analyzed after polymerase chain reaction amplification and restriction enzyme digestion. The results demonstrated that there was no association of the aldosterone synthase gene polymorphism with echocardiographically determined left ventricular dimensions, wall thicknesses, or indexes of systolic or diastolic function. Furthermore, anthropometric data, including blood pressure levels, were balanced between the different genotypes. Finally, the allele frequency was similar for patients with myocardial infarction and a sample group from the normal population (n=1675). The data indicate that the allele status of the aldosterone synthase gene polymorphism is not useful for the identification of patients with myocardial infarction who have impaired left ventricular function or unfavorable remodeling.     

Relations of plasma total TIMP-1 levels to cardiovascular risk factors and echocardiographic measures: the Framingham heart study.

AIMS: Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a key regulator of extracellular matrix degradation. We examined relations of plasma total TIMP-1 to cardiovascular risk factors and echocardiographic left ventricular (LV) structure and function in a community-based sample. METHODS AND RESULTS: We studied 1069 Framingham Heart Study participants (mean age 56 years, 58% women) free of heart failure and previous myocardial infarction. Plasma TIMP-1 was higher in men compared with women, and increased with age, body mass index and total/HDL-cholesterol ratio, but decreased with alcohol intake. Plasma TIMP-1 was also directly related to smoking, diabetes and use of anti-hypertensive treatment. Adjusting for age, sex and height, plasma TIMP-1 was positively associated with LV mass, wall thickness, relative wall thickness, end-systolic diameter, and left atrial diameter and the risk of having increased LV end-diastolic diameter or increased wall thickness, and negatively correlated with fractional shortening. Additional adjustment for clinical covariates attenuated the relations of plasma TIMP-1 to most echocardiographic measures. CONCLUSIONS: In our cross-sectional investigation, plasma total TIMP-1 was related to major cardiovascular risk factors and to indices of LV hypertrophy and systolic dysfunction. This raises the possibility that cardiovascular risk factors may influence cardiovascular remodelling via extracellular matrix degradation, which may be reflected in plasma TIMP-1 levels.     

Heart failure in pressure overload hypertrophy. The relative roles of ventricular remodeling and myocardial dysfunction

OBJECTIVES: We sought to explore the relative contributions of ventricular remodeling and myocardial dysfunction to heart failure in pressure overload hypertrophy (POH). BACKGROUND: The mechanism that underlies heart failure in POH is adverse left ventricular (LV) chamber remodeling or decreased myocardial function, or a combination of these. METHODS: Twenty weeks after suprarenal aortic banding in rats, animals with POH were classified as those with heart failure (POH-HF) or those with no heart failure (POH-NHF). The LV chamber and myocardial systolic and diastolic functions were determined from in vivo and ex vivo experiments. RESULTS: The LV mass was similar in both POH groups. Chamber remodeling in the POH-HF group was characterized by marked LV enlargement with a normal relative wall thickness (eccentric remodeling), whereas remodeling in the POH-NHF group was characterized by a normal chamber size and increased relative wall thickness (concentric remodeling). The LV systolic function, as determined in vivo from the end-systolic pressure-diameter relationship and ex vivo from the pressure-volume relationship, was lower in the POH-HF group than in the POH-NHF and sham-operated control groups. In contrast, myocardial function was similar in both POH groups, as determined in vivo from the stress-midwall fractional shortening relationship and myocardial systolic stiffness, and ex vivo from the slope of the LV systolic stress-strain relationship. The diastolic chamber stiffness constant was lower in the POH-HF group than in the POH-NHF group, but the myocardial stiffness constant was similar in the two POH groups. CONCLUSIONS: The two POH groups differed primarily in their remodeling process, which led to a chronically compensated state in one group and to heart failure in the other. Hence, heart failure in POH is more closely related to deleterious LV remodeling than to depressed myocardial function.     

Special features of pathogenesis and pharmacotherapy of chronic heart failure in women

At present in Europe number of deaths due to diseases of cardiovascular system in women has exceeded number of deaths in men. It has been established that process of cardiac remodeling proceeds differently in women and men. This determines different prognosis of the course of chronic heart failure. So after acute myocardial infarction in women more often develops chronic heart failure with preserved systolic left ventricular function while in men prevails chronic heart failure with systolic dysfunction. Substantial differences exist in efficacy of pharmacotherapy: for instance thrombolysis in women is less effective than in men, women are less sensitive to angiotensin converting enzyme inhibitors, administration of digoxin, some antiarrhythmic drugs cause complications in women more often than in men.     

Aldosterone receptor blockers in the treatment of heart failure

Opinion statement Heart failure is associated with neurohormonal activation, including activation of the renin-angiotensin-aldosterone system. Plasma aldosterone levels are elevated in patients with heart failure in spite of the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers because of angiotensin-independent stimuli for aldosterone production. In addition to its long recognized role in sodium retention, aldosterone has a number of other deleterious effects, including the increase in myocardial and vascular fibrosis and myocardial remodeling in patients with heart failure. Based on strong clinical trial data, low-dose aldosterone receptor blockers are recommended to improve morbidity and mortality in patients with severe chronic heart failure due to left ventricular systolic dysfunction and in patients with heart failure associated with left ventricular systolic dysfunction after acute myocardial infarction, and in patients already on standard therapy including ACE inhibitors (or angiotensin receptor blockers) and β blockers. In view of the potential for serious hyperkalemia with the use of aldosterone receptor blockers, it is essential to monitor serum potassium closely and to adjust the dose of aldosterone antagonists based on serum potassium levels. Close adherence to the dosing regimens used in the clinical trials (RALES [Randomized Aldactone Evaluation Study] and EPHESUS [Eplerenone Post-AMI Heart Failure Efficacy and Survival Study]) is recommended. These agents should not be initiated in patients with severe renal insufficiency and closer monitoring is warranted in those with mild to moderate renal insufficiency or diabetes.     

Increased prevalence of concentric left ventricular hypertrophy in African-Americans: Will an epidemic of heart failure follow?

Left ventricular hypertrophy (LVH), used in this review to denote abnormally increased left ventricular (LV) mass, is an important cardiac trait because of its association with numerous adverse cardiovascular outcomes including myocardial infarction and heart failure. LV mass is typically assessed by noninvasive cardiac imaging (echocardiography or MRI); electrocardiography is an insensitive measure. There are two predominant types of hypertrophy: concentric, where LV wall thickness is increased relative to cavity dimensions, and eccentric, where LV wall thickness is not increased relative to cavity dimensions. Several large studies indicate that the prevalence of concentric LVH is higher in African-Americans versus whites. Although there are data to suggest that concentric LVH results in systolic heart failure in animal models, such data are lacking in humans. How concentric LVH affects the prevalence of systolic and diastolic heart failure in African-Americans needs further study. Given the large burden of LVH among African-Americans, such data are needed to estimate the expected burden and type of heart failure which will occur in the future in this population.     

Optimizing care of heart failure after acute MI with an aldosterone receptor antagonist

The presence of heart failure or left ventricular systolic dysfunction in the setting of acute myocardial infarction is associated with poor prognosis. Aldosterone is an important downstream mediator of the reninangiotensin-aldosterone system that promotes myocardial collagen deposition, myocardial fibrosis, apoptosis, ventricular remodeling, and endothelial dysfunction. It may play an important role in the increased morbidity and mortality and the development and progression of heart failure after acute myocardial infarction. Extending the findings from the Randomized Aldactone Evaluation Study (RALES) in patients with chronic heart failure, the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) demonstrated that the selective aldosterone blocker eplerenone offered a significant survival benefit, attenuation of progression of heart failure, and prevention of sudden cardiac death when used in addition to optimal medical therapy. The current evidence-based guidelines now suggest that aldosterone blockade should be an integral component of heart failure therapy to improve outcomes in this high-risk population.     

Aldosterone receptor blockade prevents the transition to cardiac pump dysfunction induced by beta-adrenoreceptor activation

The transition from compensated to decompensated left ventricular hypertrophy (LVH) in hypertension involves excessive beta-adrenoreceptor (beta-AR) stimulation. To explore whether aldosterone receptor activation contributes toward beta-AR-induced left ventricular (LV) decompensation in hypertensive LVH, the effect of spironolactone (SPIRO; 80 mg x kg(-1) x day(-1)) on LV cavity dimensions, function, and chamber remodeling mechanisms was evaluated in spontaneously hypertensive rats (SHR) receiving a low dose of the beta-AR agonist isoproterenol (ISO) at 0.02 to 0.04 mg x kg(-1) . day for 4.5 months. ISO administered to SHR resulted in an increased 24-hour urinary aldosterone excretion and LV cavity dimensions, a right shift in LV diastolic pressure-volume relations, a decreased LV relative wall thickness, and increased total, noncross-linked, type I and type III myocardial collagen concentrations without further enhancing increased myocardial norepinephrine (NE) release. ISO reduced pump function without modifying intrinsic myocardial systolic function or inducing further myocyte necrosis or apoptosis. ISO only increased LV cavity volumes after prolonged periods of administration. SPIRO abolished ISO-induced chamber dilatation, wall thinning, and pump dysfunction and reduced total, noncross-linked, type I and type III myocardial collagen concentrations but failed to modify blood pressure, volume preloads, intrinsic myocardial systolic function, myocardial NE release, or the degree of necrosis or apoptosis. In conclusion, these results suggest that aldosterone receptor blockade, through load-independent effects, may be useful in preventing the transition from compensated LVH to dilatation and pump dysfunction mediated by chronic beta-AR activation.     

Effect of left ventricular geometric remodeling on restrictive filling pattern and survival in ischemic cardiomyopathy

BackgroundTo evaluate the effects of Left ventricular remodeling patterns in patients with left ventricular restrictive filling pattern (RFP; E/A>2) in ischemic cardiomyopathy (ICM) on prognosis.MethodsPatient data was retrospectively analyzed over a period of 4.5 years to determine the effect of LV geometry by Echocardiographic parameterson survival and re-admission for heart failure. All patients with previous history of transmural myocardial infarction were studied and all were on guideline directed medical therapy. None underwent device therapy or surgery. The stored 2D Echocardiograms were studied. Left ventricular dimensions were noted, including the relative wall thickness (RWT). The patients were grouped based on RWT<0.34 and ≥ 0.34 and were compared for clinical outcomes of mortality and re-admissions for heart failure, over a period of 54 months.ResultsThere were 102 ICM patients who had baseline RFP. We identified two sub-groups based on geometric phenotypes of left ventricular eccentric remodeling and dilated remodeling based on the relative wall thickness (RWT >0.34 or <0.34). The patients with preserved RWT had significantly more dilated ventricles (LVIDd and LVIDs), greater pulmonary artery systolic pressures (PASP), greater diatolic dysfunction (E/A) and less left ventricular ejection fraction (LVEF); p < 0.001. The number of deaths was higher in the reduced RWT patients, as were the number of re-admissions, although the time to survival and time to re-admission was not significant.ConclusionsIn this pilot study on ICM patients in advanced heart failure with baseline RFP, the presence of preserved RWT indicative of eccentric remodelling demonstrated a better clinical outcome.     

Associations between circulating components of the renin-angiotensin-aldosterone system and left ventricular mass.

OBJECTIVE: Cardiac growth may be modulated in part by the trophic effects of neurohormones. The aim of the present study was to investigate the relation between the basal activity of the renin-angiotensin-aldosterone system and left ventricular mass. DESIGN: A population based sample of 615 middle-age subjects was studied by standardised echocardiography; anthropometric measurements; and biochemical quantification of renin, pro-renin, angiotensinogen, angiotensin converting enzyme (ACE), and aldosterone. RESULTS: Echocardiographic left ventricular mass index correlated significantly with arterial blood pressure, age, and body mass index. In addition, in men ACE activity was significantly related to left ventricular mass index in univariate (P = 0.0007) and multivariate analyses (P = 0.008). Men with left ventricular hypertrophy presented with significantly higher serum ACE concentrations than those with normal left ventricular mass index (P = 0.002). In both men and women serum aldosterone was strongly related to septal and posterior wall thickness. Furthermore, in women serum aldosterone was positively and independently associated with left ventricular mass index (P = 0.0001). This effect was most prominent in hypertensive women. Finally, women with left ventricular hypertrophy presented with significantly higher serum aldosterone (P = 0.01). No significant associations with left ventricular mass index were observed for angiotensinogen, renin, or pro-renin. CONCLUSIONS: The data suggest that the variability of serum ACE or aldosterone, as occurred in this large population based sample, may contribute to the modulation of left ventricular mass.     

Effect of aldosterone blockade in patients with systolic left ventricular dysfunction: implications of the RALES and EPHESUS studies

Aldosterone blockade has been shown to be effective in reducing total mortality as well as hospitalization for heart failure in patients with systolic left ventricular dysfunction (SLVD) due to chronic heart failure and in patients with SLVD post acute myocardial infarction. The evidence for the effectiveness of aldosterone blockade in chronic heart failure comes from the randomized aldactone evaluation study (RALES) while that for patients post infarction from the eplerenone post acute myocardial infarction efficacy and survival study (EPHESUS). These studies suggest that mineralocorticoid receptor activation remains important despite the use of an angiotensin converting enzyme-inhibitor/angiotensin receptor blocking (ARB) agent and a beta blocker. Increasing evidence suggest that aldosterone blockade has important effects not only on the kidney but on ventricular remodeling, myocardial fibrosis, autonomic balance, fibrinolysis, oxidative stress, and activation of the NF-kappaB and AP-1 signaling pathways. The results of these studies in patients with SLVD has important implications not only for patients with chronic heart failure and post infarction but also for the therapy of patients with essential hypertension and other cardiovascular diseases.     

福辛普利对急性心肌梗死大鼠心室重构的影响

目的 观察福辛普利对急性心肌梗死大鼠心室重构的防治作用。方法 大鼠结扎左冠状动脉前降支造成急性心肌梗死,同时应用福辛普利进行治疗,给药4周后测定心室重构大鼠血液动力学、生化学及形态学参数。结果 福辛普利对急性心肌梗死心室重构大鼠,能明显升高左心室内压最大上升和下降速率(±dp/dtmax)及其校正值(±dp/dtmax/LVSP),降低左心室收缩压(LVSP)及左心室舒张末压(LVEDP),亦能明显降低左心室容积(LVV)、左心室长轴(LVLA)长度、左心室短轴(LVSA)长度、左心室绝对重量(LVAW)、左心室相对重量(LVRW)、左心室绝对重量(RVAW)和右心室相对重量(RVRW),但对心率(HR)、收缩压(SBP)、舒张压(DBP)、平均动脉压(MAP)及体重(BW)均无明显影响。此外,可明显降低血清脂质过氧化物(LPO)及心肌血管紧张素Ⅱ(Ang Ⅱ)和肾上腺素(E)含量,提高超氧化物歧化酶(SOD)及谷胱甘肽过氧化物酶(GSH-Px)活性。结论 福辛普利能有效防治急性心肌梗死大鼠的心室重构。     

Mineralocorticoid receptor antagonism and cardiac remodeling in ischemic heart failure

Aldosterone production in the heart as well as aldosterone plasma levels are increased after myocardial infarction and in congestive heart failure, correlating with the severity of disease. Aldosterone promotes sodium and water retention, sympathoadrenergic activation, endothelial dysfunction, and cardiovascular fibrosis and hypertrophy. Even maximally recommended doses of ACE inhibitors do not completely prevent formation of aldosterone. The Randomized Aldactone Evaluation Study (RALES) and the Eplerenone Post acute myocardial infarction Heart failure Efficacy and SUrvival Study (EPHESUS) demonstrated that aldosterone receptor blockade markedly reduces mortality among patients with heart failure. This review summarizes recent clinical and experimental data on the effect of aldosterone antagonists on left ventricular remodeling and function in ischemic heart failure with special emphasis on potential underlying mechanisms. While reduction of excessive extracellular matrix turnover leading to decreased fibrosis appears to be the most important effect of mineralocorticoid receptor antagonism in heart failure, other mechanisms such as regression of hypertrophy, improvement of endothelial function, reduction of superoxide formation, and enhanced renal sodium excretion may contribute. Recent data showed that in rats with left ventricular dysfunction after extensive myocardial infarction, eplerenone on top of ACE inhibition more effectively improved cardiac remodeling and molecular alterations than ACE inhibition alone.     

Congestive heart failure with preserved left ventricular systolic function after acute myocardial infarction: clinical and prognostic implications

AIMS: To characterise the prevalence, in-hospital complications, management, and long-term outcome of patients with congestive heart failure but preserved left ventricular systolic function after acute myocardial infarction. METHODS: 3166 consecutive patients screened for entry in the Bucindolol Evaluation in Acute Myocardial Infarction Trial with definite acute myocardial infarction and echocardiographic assessment of left ventricular systolic function were included between 1998 and 1999 in this prospective observational study. Main outcome measures were occurrences of in-hospital complications and all cause mortality. RESULTS: Congestive heart failure was seen during hospitalisation in 1464 patients (46%), 717 patients had preserved left ventricular systolic function (wall motion index > or =1.3 corresponding to ejection fraction > or =0.40), and 732 patients had systolic dysfunction (wall motion index <1.3). One year mortality in patients with no heart failure, heart failure with preserved systolic function, and heart failure with systolic dysfunction were 6, 22 and 35%, P<0.0001. Unadjusted risk of death from all causes associated with heart failure and preserved systolic function was 3.3 (95% CI 2.8-4.0), and after adjustment for baseline characteristics and left ventricular systolic function in multivariate Cox proportional hazards analysis the risk was 2.1 (95% CI 1.7-2.6), P<0.0001. CONCLUSIONS: Congestive heart failure is frequently present in patients with preserved left ventricular systolic function, and is associated with increased risk of in-hospital complications and death following acute myocardial infarction.     

Cellular basis of ventricular remodeling after myocardial infarction.

To determine whether acute left ventricular failure associated with myocardial infarction leads to architectural changes in the spared nonischemic portion of the ventricular wall, large infarcts were produced in rats, and the animals were sacrificed 2 days after surgery. Left ventricular end-diastolic pressure was increased, whereas left ventricular dP/dt and systolic pressure were decreased, indicating the presence of severe ventricular dysfunction. Absolute infarct size, determined by measuring the fraction of myocyte nuclei lost from the left ventricular free wall, averaged 63%. Transverse midchamber diameter increased by 20%, and wall thickness diminished by 33%. The number of mural myocytes in this spared region of the left ventricular free wall decreased by 36% and the capillary profiles by 40%. Thus, side-to-side slippage of myocytes in the myocardium occurs acutely in association with ventricular dilation after a large myocardial infarction. In order to analyze the chronic consequences of myocardial infarction on ventricular remodeling, a second group of experiments was performed in which the left coronary artery was ligated and the functional and structural properties of the heart were examined 1 month later. In infarcts affecting an average 38% of the free wall of the left ventricle (small infarcts), reactive hypertrophy in the spared myocardium resulted in a complete reconstitution of functioning tissue. However, left ventricular end-diastolic pressure was increased, left ventricular dP/dt was decreased, and diastolic wall stress was increased 2.4-fold. After infarctions resulting in a 60% loss of mass (large infarcts), a 10% deficit was present in the recovery of viable myocardium. Functionally, ventricular performance was markedly depressed, and diastolic wall stress was increased 9-fold. The alterations in loading of the spared myocardium were due to an increase in chamber volume and a decrease in the myocardial mass/chamber volume ratio that affected both infarct groups. Thus, decompensated eccentric ventricular hypertrophy develops chronically after infarction and growth processes in myocytes are inadequate for normalization of wall stress when myocyte loss involves nearly 40% or more of the cells of the left ventricular free wall. The persistence of elevated myocardial and cellular loads may sustain the progression of the disease state toward end-stage congestive heart failure.     

Targeted overexpression of growth hormone by adenoviral gene transfer preserves myocardial function and ventricular geometry in ischemic cardiomyopathy

BACKGROUND: Post-infarction heart failure is characterized by progressive left ventricular dilatation and wall thinning, with both systolic and diastolic cardiac dysfunction. Human growth hormone (GH) stimulates cardiac hypertrophy when secreted in excess and directly enhances cardiomyocyte contractile function. We hypothesized that local myocardial overexpression of GH could prevent ventricular remodeling and heart failure following myocardial infarction (MI) in rats. METHODS AND RESULTS: Rats underwent ligation of the left anterior descending coronary artery with direct intramyocardial injection of adenovirus encoding human GH (n = 8) or null virus as control (n = 8). Six weeks following MI, Adeno-GH treated animals had significant preservation of both systolic and diastolic cardiac function compared to Null animals (maximum dP/dt GH 2927 +/- 83 vs Null 1622 +/- 159 mmHg/sec, p < 0.001; minimum dP/dt -2409 +/- 82 vs -1195 +/- 179 mmHg/sec, p < 0.01). GH animals had improved ventricular geometry with decreased chamber dilatation (13.2 +/- 0.13 vs 14.4+/-0.15 mm, p < 0.001) and increased wall thickness (2.02 +/- 0.10 vs 1.28 +/- 0.07 mm, p < 0.001), and this was associated with advantageous myocardial hypertrophy with increased cardiomyocyte fiber size. Local myocardial overexpression of GH protein was seen in Adeno-GH animals, while serum levels of human GH were undetectable after 6 weeks. CONCLUSIONS: Treatment with Adeno-GH following MI resulted in reduced ventricular dilatation, increased local myocardial hypertrophy, and preservation of both systolic and diastolic cardiac function. No significant systemic exposure to growth hormone transgene was observed. The induction of regional hypertrophy is a novel approach to treating heart failure, and may be useful to treat or prevent post-infarction ischemic cardiomyopathy.     

Hypertrophic remodeling: gender differences in the early response to left ventricular pressure overload

Objectives. To identify gender differences in left ventricular remodeling, hypertrophy, and function in response to pressure overload due to ascending aortic banding in rats.Background. Gender may influence the adaptation to pressure overload, as women with aortic stenosis have greater degrees of left ventricular hypertrophy and better left ventricular function than men.Methods. Fifty-two weanling rats underwent ascending aortic banding (16 males, 18 females), or sham surgery (9 males, 9 females). At 6 and 20 weeks, rats underwent transthoracic echo Doppler studies, and closed-chest left ventricular pressures with direct left ventricular puncture. Perfusion-fixed tissues from eight rats were examined morphometrically for myocyte cross-sectional area and percent collagen volume.Results. At 6 weeks after aortic banding, left ventricular remodeling, extent of hypertrophy, and function appeared similar in male and female rats. At 20 weeks, male but not female rats showed an early transition to heart failure, with onset of cavity dilatation (left ventricular diameter = 155% vs. 121% of same-sex sham), loss of concentric remodeling (relative wall thickness = 102% vs. 139% of sham), elevated wall stress (systolic stress = 266% vs. 154% of sham), and diastolic dysfunction (deceleration of rapid filling = 251% vs. 190% of sham). Left ventricular systolic pressures were higher in female compared with male rats (186 ± 20 vs. 139 ± 13 mm Hg), while diastolic pressures tended to be lower (14 ± 4 vs. 17 ± 4 mm Hg).Conclusions. Gender significantly influences the evolution of the early response to pressure overload, including the transition to heart failure in rats with aortic stenosis.     

Ethnic differences in left ventricular structure: relations to hemodynamics and diurnal blood pressure variation

BACKGROUND: Previous studies have suggested that African Americans have a greater left ventricular relative wall thickness than whites with similar levels of blood pressure (BP), whereas other investigators have documented an attenuated nocturnal decline in BP and early remodeling of the resistance vessels in African Americans. METHODS: To further evaluate the contributions of diurnal BP variation and vascular remodeling to ethnic differences in left ventricular geometry, we measured ambulatory BP, systemic hemodynamics, minimum forearm vascular resistance, and left ventricular structure in a biracial sample of 171 men and women between the ages of 25 and 45 years. RESULTS: Despite similar resting BPs, African Americans had a greater indexed peripheral resistance, a greater minimal forearm vascular resistance, and a smaller nocturnal decline in BP than white subjects. African Americans also had a greater left ventricular relative wall thickness (0.41 +/- 0.07 v 0.38 +/- 0.08, P =.048) and a trend toward a greater indexed left ventricular mass (41.1 +/- 8.7 v 38.6 +/- 8.6 g/m(2.7), P =.087). Ethnic differences in relative wall thickness were no longer significant when adjusted for either indexed peripheral resistance (P =.173) or sleep systolic BP (P =.124). CONCLUSIONS: In our cohort of young men and women, African Americans had a greater left ventricular relative wall thickness than whites with similar levels of resting BP. This early concentric remodeling of the left ventricle in African Americans may be mediated, in part, by hemodynamic influences, including a greater peripheral vascular resistance and a smaller nocturnal decline in BP.     

Importance of an intact growth hormone/insulin-like growth factor 1 axis for normal post-infarction healing: studies in dwarf rats

Treatment with GH attenuates remodeling and improves left ventricular function in the setting of experimental heart failure following coronary ligation. This study was designed to test the hypothesis that an intact GH/insulin-like growth factor 1 (IGF-1) axis is required for normal myocardial infarction healing. Myocardial infarction was induced by coronary ligation in GH-deficient dwarf rats and in age-matched controls. In dwarf rats, serum IGF-1 levels were reduced by 50%, and grow rate was 50% less than normal littermates, although no differences in myocardial IGF-1 messenger RNA levels were observed compared with controls. All rats underwent transthoracic echocardiography at baseline, 2 weeks, and 6 weeks after myocardial infarction. Left ventricular end-diastolic pressure was obtained by in vivo closed chest catheterization. At 6 weeks, both infarcted groups exhibited similar myocardial infarction size at transthoracic echocardiography and at morphometric histology. In both groups with myocardial infarction, there was significant left ventricular dilation and reduced systolic function. However, the extent of remodeling as assessed by the increase in end-diastolic dimension (%Delta + 36 +/- 5 vs. +19 +/- 4; P: < 0.01) and depression of function (%Delta fractional shortening -12 +/- 2 vs. -7 +/- 1; P: < 0.01) were both greater in the dwarf group. Furthermore, dwarf rats failed to develop compensatory hypertrophy of noninfarcted posterior wall (%Delta posterior wall +5 +/- 1 vs. +15 +/- 3; P: < 0.01). Therefore, pathologic left ventricular remodeling and functional loss following myocardial infarction is more marked in conditions of GH deficiency. An intact GH/IGF-1 axis appears necessary for a normal response to myocardial infarction injury in the rat.