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PubMed2003

Ventricular remodeling.

Ventricular remodeling is an extremely complicated process that is not well understood. There seem to be multiple feedback loops that respond to mechanical events as well as to neurohormonal stimulation, cytokine release, and other, yet unidentified, agents. The progression of ventricular remodeling after the index event includes: Myocyte slippage and thinning of infarct area, chamber dilatation. Fibrosis and scar formation. Collagen strut dissolution and excessive accumulation of interstitial matrix. Increased wall stress. Myocyte hypertrophy. Neurohormonal activation. Cytokine release. Ongoing myocyte hypertrophy. Cell apoptosis and necrosis. Continued deterioration of cardiac function. It is impossible to place the sequence of events in order, because the multiple feedback systems create a complex interactive process. A basic awareness of the pathophysiology of ventricular remodeling can aid in understanding current and future treatments for heart failure. It is clear that therapeutic interventions solely aimed at improving cardiac pump function do not slow the progression of heart failure or reduce mortality. Drugs that block the neuroendocrine contribution to the remodeling process have been shown to have a greater impact. Current therapies with angiotensin-converting enzyme inhibition, beta blockade, and aldosterone antagonism are associated with significant reductions in morbidity and mortality in heart failure. Other therapeutic strategies suggested by knowledge of remodeling mechanisms, such as drugs to block cytokines, endothelins, and MMPs, may offer further benefit to patients with heart failure in the future.

Cytokines↗

PubMed2006

Controversies in ventricular remodelling.

Ventricular remodelling describes structural changes in the left ventricle in response to chronic alterations in loading conditions, with three major patterns: concentric remodelling, when a pressure load leads to growth in cardiomyocyte thickness; eccentric hypertrophy, when a volume load produces myocyte lengthening; and myocardial infarction, an amalgam of patterns in which stretched and dilated infarcted tissue increases left-ventricular volume with a combined volume and pressure load on non-infarcted areas. Whether left-ventricular hypertrophy is adaptive or maladaptive is controversial, as suggested by patterns of signalling pathways, transgenic models, and clinical findings in aortic stenosis. The transition from apparently compensated hypertrophy to the failing heart indicates a changing balance between metalloproteinases and their inhibitors, effects of reactive oxygen species, and death-promoting and profibrotic neurohumoral responses. These processes are evasive therapeutic targets. Here, we discuss potential novel therapies for these disorders, including: sildenafil, an unexpected option for anti-transition therapy; surgery for increased sphericity caused by chronic volume overload of mitral regurgitation; an antifibrotic peptide to inhibit the fibrogenic effects of transforming growth factor beta; mechanical intervention in advanced heart failure; and stem-cell therapy.

Animals↗

PubMed1996

Ventricular remodeling.

Ventricular remodeling is a repair process. It can follow myocardial infarction, mechanical overload (for example, in hypertension or valvular heart disease), and also occurs in inflammation and dilated cardiomyopathy. Remodeling can be an (early) adaptive process followed by a maladaptive (late) phase and involves all cells that are present in the myocardium - the myocyte, the interstitial cells, the vascular endothelium, and the immune cells. Despite the varying etiopathology that these different aspects of heart disease share, a similar sequence of molecular, biochemical and mechanical events that can lead to heart failure, myocyte hypertrophy, extensive extracellular matrix production and fibrosis, even in patients who were previously unaffected by the original disease process (for example, inflammation or infarction). Heart failure can be influenced by treatment of the underlying disease and by modification of the remodeling process, for example, by ACE inhibitors (cardioreparation). In experimental animals it has been clearly demonstrated that ACE inhibitors may even prevent a genetically predetermined left ventricular hypertrophy (cardioprevention).

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2003

Left ventricular remodeling and ventricular arrhythmias after myocardial infarction.

BACKGROUND: The relation between left ventricular (LV) remodeling and ventricular arrhythmias after myocardial infarction is poorly documented. We investigated the relations between LV size, hypertrophy, and function and ventricular arrhythmias in 263 patients from the Survival and Ventricular Enlargement (SAVE) study, using quantitative 2D echocardiography and ambulatory ECG monitoring after myocardial infarction. METHODS AND RESULTS: Transthoracic 2D echocardiograms and arrhythmia monitoring were performed at baseline (mean, 11 days) and 1 and 2 years after infarction. LV size, short-axis muscle (mass) area (LVMA), and function were quantified from 2D echocardiograms. The prevalence of ventricular tachycardia (VT) and frequent ventricular ectopy (premature ventricular contractions [PVCs] >10/h) was assessed from ambulatory ECG. VT and PVCs >10/h occurred in 20% and 29% of patients at baseline, in 22% and 35% at 1 year and 23% and 39% at 2 years, respectively. VT and PVCs >10/h at baseline and 1 and 2 years were significantly related to LV size, LVMA, and function. Furthermore, changes in LV size and function from baseline to 2 years predicted both VT and PVCs >10/h. The study was underpowered to detect treatment effect of ACE inhibitors and beta-adrenergic receptor blockers but did not alter the relations between ventricular arrhythmias, LV size, and function. CONCLUSIONS: Quantitative echocardiographic assessment of LV size, LVMA, and function and changes in these measurements over time predict ventricular arrhythmias after infarction. Altered LV architecture and function during postinfarction LV remodeling provide an important substrate for triggering high-grade ventricular arrhythmias.

Adrenergic beta-Antagonists↗

PubMed2002

[Clinical study on effect of Astragalus injection on left ventricular remodeling and left ventricular function in patients with acute myocardial infarction].

OBJECTIVE: To observe the effect of Astragalus injection (AI) on left ventricular remodeling and left ventricular function in patients with acute myocardial infarction (AMI). METHODS: AMI patients were randomly divided into the AI group (54 cases) treated with AI and the control group (54 cases) treated with conventional treatment. Left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), anterior endocardial segmental length (ASL), posterior endocardial segmental length (PSL) were assessed by echocardiogram at the 1st and the 4th week of treatment; and the cardiac systolic and diastolic functions were detected by nuclide gating cardiac blood pool imaging on the 4th week. Besides, the plasmic levels of lipid peroxide (MDA), count of endothelial cell (CEC) and superoxide dismutase (SOD) were determined before and after treatment. RESULTS: At the 4th week, changes of LVEDVI, LVESVI and ASL in the AI group were not obvious, but increased significantly in the control group, the significant difference in comparison between the two groups was shown (P < 0.05). As compared with the control group, in the AI group, the left ventricular ejection fraction, left ventricular peak ejecting rate and left ventricular peak filling rate were higher, and the left ventricular time for peak filling rate was shorter, moreover, MDA and CEC were lower and SOD was higher. The difference between groups and between before and after treatment were significant (P < 0.01 or P < 0.05). CONCLUSION: AI is one of the effective drugs in reversal of left ventricular remodeling and improving left ventricular function in patients with AMI.

Adult↗

PubMed1997

Changes in hemodynamics, ventricular remodeling, and ventricular contractility during normal pregnancy: a longitudinal study.

OBJECTIVE: To investigate the hemodynamic changes occurring in normal pregnancy and to see if these changes were associated with an increase in myocardial contractility. METHODS: In a longitudinal study, primigravidas were studied with echocardiography in early (15 +/- 1.8 weeks), mid (26 +/- 1.2 weeks), and late (36 +/- 1.0 weeks) gestation, as well as at 6 weeks postpartum. Cardiac dimensions were measured with two-dimensional and M-mode echocardiography and hemodynamic indices were calculated. All measurements were made with subjects in the left lateral decubitus position. Statistical analysis was performed with repeated measures analysis of variance. RESULTS: Seventy-six women with normal pregnancy outcomes completed all four studies. From the baseline study to late gestation, an increase in cardiac output of 27% (from [mean +/- standard error] 4.2 +/- 0.1 to 5.8 +/- 0.2 L/min, P = .001), and a decrease in total peripheral resistance of 33% (from 1356 +/- 69 to 941 +/- 37 dynes/second cm-5, P = .001) occurred. Over this same time period, left ventricular function, while demonstrating a small and non-significant increase in velocity of circumferential fiber shortening (from 1.25 +/- 0.02 to 1.27 +/- 0.02 cm/second), revealed a 12% decrease in wall stress (from 36.3 +/- 1.0 to 31.9 +/- 1.0 g/cm2, P = .001) and a 13% decrease in the load-independent wall stress to velocity of circumferential fiber shortening ratio (from 30.0 +/- 1.2 to 26.1 +/- 1.0, P = .01), implying enhanced intrinsic myocardial contractility. CONCLUSION: Normal pregnancy is characterized by enhanced myocardial performance.

Adult↗

PubMed2003

Targeted deletion of apoptosis signal-regulating kinase 1 attenuates left ventricular remodeling.

Left ventricular remodeling that occurs after myocardial infarction (MI) and pressure overload is generally accepted as a determinant of the clinical course of heart failure. The molecular mechanism of this process, however, remains to be elucidated. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays an important role in stress-induced apoptosis. We used ASK1 knockout mice (ASK-/-) to test the hypothesis that ASK1 is involved in development of left ventricular remodeling. ASK-/- hearts showed no morphological or histological defects. Echocardiography and cardiac catheterization revealed normal global structure and function. Left ventricular structural and functional remodeling were determined 4 weeks after coronary artery ligation or thoracic transverse aortic constriction (TAC). ASK-/- had significantly smaller increases in left ventricular end-diastolic and end-systolic ventricular dimensions and smaller decreases in fractional shortening in both experimental models compared with WT mice. The number of terminal deoxynucleotidyl transferase biotin-dUDP nick end-labeling-positive myocytes after MI or TAC was decreased in ASK-/- compared with that in WT mice. Overexpression of a constitutively active mutant of ASK1 induced apoptosis in isolated rat neonatal cardiomyocytes, whereas neonatal ASK-/- cardiomyocytes were resistant to H2O2-induced apoptosis. An in vitro kinase assay showed increased ASK1 activity in heart after MI or TAC in WT mice. Thus, ASK1 plays an important role in regulating left ventricular remodeling by promoting apoptosis.

Animals↗

PubMed1991

[Echocardiography: a quantitative evaluation method of ventricular remodeling].

Left ventricular remodeling consists of changes in size and geometry of the left ventricular cavity associated with changes in wall thickness. These changes occur in different conditions such as during growth, pressure or volume overload or after myocardial infarction. Echocardiography in M or two dimensional modes provides a means of evaluating global and regional left ventricular function and of measuring variations of wall thickness during the cardiac cycle. Using mathematical models in the parasternal (surface-length method) or apical views (Simpson's method) of the left ventricle, the end diastolic and end systolic volumes and ejection fraction can be calculated with reasonable accuracy, so enabling detection of spontaneous or therapeutically-induced variations of clinical significance. The extent of the akinetic or dyskinetic myocardium can be compared with the diastolic perimeter and expressed as a percentage value. This parameter is one of the quantitative values for expressing "expansion" of the necrosed segment and the changes occurring in the non-infarcted areas. M-mode echocardiography more than the two dimensional mode enables measurement of wall thickness and calculation of myocardial mass, providing the clinician with an assessment of myocardial hypertrophy and its relation to left ventricular chamber size (wall thickness/LV radius ratio). Of the different available methods of cardiac imaging, echocardiography is the most widely used because it is non-invasive and can be used repetitively to document the progressive changes in size and wall thickness of the left ventricle, known as "remodeling".

Cardiomegaly↗

PubMed1993

The effects of chronic oral milrinone therapy on early postinfarction left ventricular remodeling.

Left ventricular remodeling following acute transmural myocardial infarction may result in early left ventricular enlargement. To characterize the effects of milrinone on components of early left ventricular dilation, rats (n = 120) underwent left coronary artery ligation or sham surgery. In the immediate postoperative period, rats received either no treatment or milrinone (3.17 +/- 0.08 mg/kg/day) dissolved in drinking water for 20 days. Twenty-one days after the initial surgery, hemodynamic measurements were made. The rats were then put to death and the hearts arrested in diastole were excised and fixed at a constant pressure for morphometric analysis. To examine the effects of milrinone on the relative contribution of infarcted and noninfarcted segments to early left ventricular dilation after acute myocardial infarction, a subgroup of infarcted rats chosen randomly was put to death 3 days after the initial surgery for morphometric analysis. Compared with infarcted untreated rats, infarcted milrinone-treated rats had a lower left ventricular volume (1.41 +/- 0.07 ml/kg vs 2.16 +/- 0.19 ml/kg, p < 0.001), lower left ventricular wall stress (0.64 +/- 0.03 vs 0.91 +/- 0.06, p < 0.001), and a lower expansion index (1.61 +/- 0.12 vs 2.61 +/- 0.22, p < 0.001). Morphometric analysis revealed that the noninfarcted segment length did not differ between the two infarcted groups either 3 days or 21 days after left coronary artery ligation. Infarct segment length also did not differ between the two infarcted groups at 3 days, but at 21 days infarct segment was shorter in the milrinone-treated group compared with the untreated group (p < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed2000

[Interactions between physical training and pharmacologic treatment in the prevention of ventricular remodelling in patients with left ventricular dysfunction].

Exercise training is a recommended treatment for chronic heart failure. So far, randomized clinical trials showed that exercise training can improve peak oxygen consumption and reduce neurohormonal and adrenergic activation, nevertheless, the effect on left ventricular remodeling is still controversial. The present study reviewed the randomized clinical trials that investigated the effects of exercise training on left ventricular remodeling. After a first study that showed a worsening of left ventricular function, the following studies showed a neutral effect, and finally, the ELVD-CHF study showed both a reduction in left ventricular dilation and an improvement of ejection fraction. These different results could be explained by the pharmacological treatment before exercise training: in the first study patients did not assume ACE-inhibitors, in the following studies most patients assumed ACE-inhibitors and, finally, in ELVD-CHF, patients assumed ACE-inhibitors and about one fifth of them were on beta-blockers too. In conclusion, exercise training may improve peak oxygen consumption and reduce neurohormonal and adrenergic activation in patients with chronic heart failure. Further studies are necessary to assess if exercise training, associated with ACE-inhibitors and beta-blockers, can reverse or prevent left ventricular remodeling.

Exercise Therapy↗

PubMed1996

The renin-angiotensin system in left ventricular remodeling.

Left ventricular remodeling is a dynamic process that occurs in reaction to an insult to the myocardium. The response to either loss of cells, as may occur following myocardial infarction, or to hemodynamic overload, as may occur in aortic stenosis, is an attempt to maintain cardiac output and normalize wall tension. This is accomplished through the activation of the renin-angiotensin system and hypertrophy of noninfarcted segments of the myocardium. in the case of moderate or large infarctions these mechanisms fail to normalize wall stress. The stimulus to further remodeling remains, viable myocytes hypertrophy (with greater increases in cell length than width), the mass-to-volume ratio increases, and an exponential increase in wall stress results. This increase in myocyte tension has been associated with premature myocyte cell death. Thus, a vicious cycle is established wherein overstretch of the myocardium while sustaining cardiac output leads to progressive myocyte loss and left ventricular dilation. The renin-angiotensin system plays an integral role in this process. Its inhibition by angiotensin-converting enzyme (ACE) inhibitors both chronically and immediately after myocardial infarction has been shown to decrease left ventricular volumes and reduce mortality. Controversy exists regarding the mechanism through which ACE inhibitors exert their effects. ACE inhibitors reduce afterload/preload, circulating angiotensin II levels, and raise circulating levels of bradykinin. It is not yet clear which mechanism is responsible for the greatest impact on left ventricular dilation and mortality. inhibition of the renin-angiotensin system is clearly beneficial to cardiac performance as well as morbidity and mortality when myocardium is lost and heart failure ensues. Specific modes of action require further definition, including local and systemic effects. Possible benefits of angiotensin receptor blockade versus augmentation of bradykinin requires definition, setting the stage for further study, while the beneficial therapeutic use of these agents continues.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1997

Echocardiographic assessment of left ventricular remodeling: are left ventricular diameters suitable tools?

OBJECTIVES: We sought to analyze the value of echocardiographic left ventricular (LV) diameters in assessing LV remodeling. BACKGROUND: LV diameters are easily measured and commonly used as a substitute for volumetric analysis to evaluate LV remodeling caused by ventricular overload or dysfunction. However, the impact of these measurements on outcome is disputed, suggesting that they may not adequately assess LV remodeling. METHODS: M-mode echocardiographically measured LV dimensions and the derived LV ejection fraction and end-systolic wall stress were compared with LV volumes and the derived LV ejection fraction and wall stress using the biplane Simpson rule. These measurements were made prospectively and simultaneously in 463 patients (289 men, 174 women; mean [+/-SD] age 62 +/- 15 years), including 46 normal subjects, 52 with aortic regurgitation, 253 with mitral regurgitation and 112 with LV dysfunction. RESULTS: The correlation between diameter and volume was good at end-systole (r = 0.91, p < 0.0001) and end-diastole (r = 0.86, p < 0.0001). However, the relation was exponential, and the 95% confidence interval increased with increasing diameter. The calculated LV ejection fraction and wall stress using LV diameter and volume correlated linearly with a limited range of error (r = 0.96, SEE = 5%, p < 0.0001 and r = 0.95, SEE = 20 g/cm2, p < 0.0001, respectively). CONCLUSIONS: For assessing LV remodeling, LV diameters measured by M-mode echocardiography allow acceptable estimation of LV ejection fraction and wall stress and correlate significantly with LV volumes but are hindered by a wide range of error for assessment of LV size, especially for enlarged ventricles, suggesting that measurement of LV volume should be the preferred method of echocardiographically assessing LV remodeling.

Aortic Valve Insufficiency↗

PubMed2006

Rapid ventricular remodeling with left ventricular unloading postventricular assist device placement: new insights with strain imaging.

We report the case of a 6-year old girl who presented with severe dilated cardiomyopathy. Cross-sectional echocardiography demonstrated a severely dilated hypokinetic left ventricle with an ejection fraction less than 10%. She developed intractable ventricular tachyarrhythmias and subsequently had a left ventricular assist device implanted. Within 1 week of mechanical support, echocardiography demonstrated dramatic reverse remodeling of the left ventricle with marked improvement in myocardial deformation using strain rate imaging. This report further highlights the potential for rapid remodeling after mechanical support of the failing myocardium.

Cardiomyopathy, Dilated↗

PubMed2001

Relationship between transcardiac extraction of aldosterone and left ventricular remodeling in patients with first acute myocardial infarction: extracting aldosterone through the heart promotes ventricular remodeling after acute myocardial infarction.

OBJECTIVES: The purpose of this study was to evaluate whether plasma aldosterone (ALD) is extracted or produced through the heart in patients with acute myocardial infarction (AMI) and to determine the relationship between transcardiac extraction of plasma ALD and left ventricular (LV) remodeling. BACKGROUND: Although we demonstrated that circulating ALD was extracted through the failing heart and that transcardiac extraction of ALD correlated with LV end-diastolic volume index (LVEDVI) in patients with congestive heart failure, the existence and increase of ALD synthase in the hearts of infarct rats were reported, suggesting cardiac production of ALD in patients with AMI. METHODS: We measured plasma ALD in the aortic root (Ao) and coronary sinus (CS) in 57 consecutive patients who received successful revascularization and enalapril, with first AMI at acute phase and after one month. We also measured plasma procollagen type III aminoterminal peptide (PIIINP) in the CS. RESULTS: Plasma ALD was significantly lower in the CS than it was in the Ao at the acute phase (84.7 +/- 6.3 pg/ml vs. 105.5 +/- 8.0 pg/ml, p < 0.0001). Significant positive correlations exist between the transcardiac gradient of ALD at the acute phase and the LVEDVI at one month. Moreover, the transcardiac gradient of plasma ALD at the acute phase has a significant correlation with plasma PIIINP, a biochemical marker of fibrosis, after one month. Stepwise multivariate analysis showed that transcardiac extraction of plasma ALD at the acute phase had an independent and significant positive relationship with a large LVEDVI after one month. CONCLUSIONS: These results indicate that plasma ALD is extracted through the heart in patients with AMI at the acute phase and that the extracted ALD plays an important role in modulating post-infarct LV remodeling.

Acute Disease↗

PubMed2002

Pathophysiologic role of myocardial apoptosis in post-infarction left ventricular remodeling.

Left ventricular (LV) remodeling and heart failure (HF) complicate acute myocardial infarction (AMI) even weeks to months after the initial insult. Apoptosis may represent an important pathophysiologic mechanism causing progressive myocardiocyte loss and LV dilatation even late after AMI. This review will discuss the role of apoptosis according to findings in animal experimental data and observational studies in humans in order to assess clinical relevance, determinants, and mechanisms of myocardial apoptosis and potential therapeutic implications. More complete definition of the impact of myocardiocyte loss on prognosis and of the mechanisms involved may lead to improved understanding of cardiac remodeling and possibly improved patients' care. Mitochondrial damage and bcl-2 to bax balance play a central role in ischemia-dependent apoptosis while angiotensin II and beta(1)-adrenergic-stimulation may be major causes of receptor-mediated apoptosis. Benefits due to treatment with ACE-inhibitors and beta-blockers appear to be in part due to reduced myocardial apoptosis. Moreover, infarct-related artery patency late after AMI may be a major determinant of myocardial apoptosis and clinical benefits deriving from an open artery late post AMI (the "open artery hypothesis") may be, at least in part, due to reduced myocardiocyte loss.

Animals↗

PubMed2004

Differences in atrial versus ventricular remodeling in dogs with ventricular tachypacing-induced congestive heart failure.

BACKGROUND: Congestive heart failure (CHF) causes arrhythmogenic remodeling in both atria and ventricles, but differences between atrial and ventricular remodeling in CHF have not been well characterized. METHODS AND RESULTS: We examined atrial and ventricular tissues from dogs with CHF induced by ventricular tachypacing (220-240/min) for 0 (control) or 24 h, or 1, 2 or 5 weeks. Histopathology was used to assess apoptosis, fibrosis, white blood cell infiltration and cell death, ELISA to measure angiotensin-II concentration and Western blot to evaluate protein expression. Ventricular tachypacing-induced CHF was associated with substantially more fibrosis in left atrium (maximum 10 +/- 1% at 5 weeks) than in left ventricle (0.4 +/- 0.1% at 5 weeks, P < 0.01 versus left atrium). Tissue angiotensin-II concentration increased to steady state in atrial tissue at 24 h but increased more slowly in left ventricle, with a maximum that was significantly higher in atrium than ventricle. Ventricular tachypacing caused tissue apoptosis, inflammatory cell infiltration and cell death, with maximum changes in left atrium being faster, transient and larger than in left ventricle. Mitogen activated protein kinase activation was rapid (within 24 h) in left atrium, but smaller and slower (p38, c-Jun N-terminal kinase) or non-significant (extracellular signal-related kinase) in left ventricle. The 25-kDa activated form of transforming growth factor-beta1, a particularly important profibrotic mediator in atrium, increased significantly in left atrium, from 2.6 +/- 0.6 (control) to 9.2 +/- 1.7 (24 h) and 8.1 +/- 1.8 optical density units (1 week), but was not significantly changed in ventricle. CONCLUSIONS: There are qualitative and quantitative differences in atrial versus ventricular remodeling in experimental ventricular tachypacing-induced CHF, with potentially important consequences for understanding underlying mechanisms and developing new therapeutic approaches.

Angiotensin II↗

PubMed1993

[Ventricular remodelling and modifications in ventricular filling in the acute phase of a myocardial infarct].

The importance of infarct expansion in determining global ventricular remodelling and prognosis after myocardial infarction is well known, whereas how infarct expansion affects left ventricular filling dynamics is not defined. To address this issue two-dimensional and Doppler echocardiography was performed in 28 consecutive patients admitted to our Coronary Care Unit for a first acute transmural myocardial infarction 1) within 24 hours of symptoms' onset and 2) at predischarge. A semiquantitative echocardiographic infarct size index was computed, while the infarct and non-infarct segment length was measured in a short-axis papillary muscle section. Peak velocity of early (E) and late (A) transmitral Doppler curves were also measured. An increment in infarct segment length > or = 1.2 cm between baseline and predischarge examination was chosen as target to divide patients with (N = 8) and without (N = 20) infarct expansion. Patients with expansion had a higher echocardiographic infarct size index (3.5 +/- 1.4 versus 2.3 +/- 0.6 segments, p < 0.0001) and a higher CK-MB infarct size (336 +/- 235 versus 129 +/- 87 UI, p = 0.002), while ejection fraction was lower (36 +/- 8% versus 48 +/- 7%, p < 0.001). A linear correlation was found between the increment in infarct segment length and in left ventricular volume between the baseline and the predischarge examination (r = 0.58, p < 0.01). Doppler parameters were not different at baseline examination between patients with and without expansion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2003

Aldosterone receptor blockade improves left ventricular remodeling and increases ventricular fibrillation threshold in experimental heart failure.

OBJECTIVES: To investigate the effects of aldosterone receptor blockade in postinfarction heart failure. METHODS: Eighty-seven rats with moderate myocardial infarction were randomized to receive either no drug or canrenone, the active metabolite of spironolactone, 20 mg/kg/day, or ramipril, 1 mg/kg/day, or a combination of the two drugs. Treatment was initiated 1 month after coronary ligation and lasted 4 weeks. Echocardiography was performed at baseline and after 4 weeks. LV catheterization, isolated heart studies, morphometric histology, myocardial norepinephrine and SERCA-2 mRNA were assessed at the end of the treatment period. RESULTS: Infarct sizes were 33+/-3, 32+/-3, 34+/-3, and 34+/-4% in the placebo, canrenone, ramipril, and combination groups, respectively. Canrenone attenuated LV remodeling, improved LV systolic and diastolic function, and markedly reduced interstitial and perivascular fibrosis. These effects were increased by concomitant ramipril therapy. Moreover, myocardial norepinephrine content was decreased while ventricular fibrillation threshold significantly augmented by canrenone. SERCA-2 levels remained unchanged. CONCLUSIONS: Canrenone attenuated LV dilation and interstitial remodeling, and improved LV filling dynamics and systolic function in the rat model of postinfarction heart failure. Addition of ramipril conferred further cardioprotection. Canrenone also reduced myocardial norepinephrine content and increased ventricular fibrillation threshold. The data provide a potential explanation for the decreased sudden death observed in the RALES study. The mechanisms of action of aldosterone inhibition are still poorly understood, despite its proven efficacy in heart failure. Rats with postinfarction heart failure were randomized to receive for 1 month either no drug or canrenone, or ramipril, or a combination of canrenone and ramipril. Canrenone treatment was associated with a significant attenuation of LV dilation, better LV diastolic and systolic dynamics, and a marked reduction of reactive fibrosis. These effects were enhanced by concomitant ramipril therapy. Moreover, canrenone increased ventricular fibrillation threshold and reduced myocardial norepinephrine content. The data may explain the reduced mortality demonstrated by the RALES.

Animals↗