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Ventricular Remodelling (ventricular + remodelling)

Distribution by Scientific Domains

Medical Sciences	80%

Selected Abstracts

IN VITRO INHIBITORY EFFECTS OF ATORVASTATIN ON CARDIAC FIBROBLASTS: IMPLICATIONS FOR VENTRICULAR REMODELLING

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2005
Jennifer Martin
SUMMARY 1.,Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) reduce mortality after myocardial infarction (MI). Although this may be predominantly due to their known anti-ischaemic actions, these drugs are known to have other beneficial effects. 2.,Because pathological deposition of extracellular matrix (ECM) material is a key component of remodelling after MI, we sought to determine whether atorvastatin could inhibit ECM production in vitro. 3.,The addition of atorvastatin to rat cardiac fibroblasts stimulated with either transforming growth factor (TGF)-,1 (TGF-,1) or angiotensin (Ang) II reduced collagen synthesis in a dose-dependent manner (3.7-fold reduction (95% confidence interval (CI) 1.8,15; P < 0.01) and 5.3-fold reduction (95% CI 1.8,7.7; P < 0.01), respectively, compared with stimulant alone). Similar observations were made in human cardiac fibroblast cell culture. Atorvastatin also dose-dependently reduced TGF-,1 and AngII-induced increases in ,(I)-procollagen mRNA (P < 0.01 for both), as well as gene expression of the profibrotic peptide connective tissue growth factor. 4.,Atorvastatin appears to directly inhibit collagen production by cardiac fibroblasts. This antifibrotic action may contribute to the antiremodelling effect of statins. [source]

Correlation of ,-skeletal actin expression, ventricular fibrosis and heart function with the degree of pressure overload cardiac hypertrophy in rats

EXPERIMENTAL PHYSIOLOGY, Issue 3 2006
Donatella Stilli
We have analysed alterations of ,-skeletal actin expression and volume fraction of fibrosis in the ventricular myocardium and their functional counterpart in terms of arrhythmogenesis and haemodynamic variables, in rats with different degrees of compensated cardiac hypertrophy induced by infra-renal abdominal aortic coarctation. The following coarctation calibres were used: 1.3 (AC1.3 group), 0.7 (AC0.7) and 0.4 mm (AC0.4); age-matched rats were used as controls (C group). One month after surgery, spontaneous and sympathetic-induced ventricular arrhythmias were telemetrically recorded from conscious freely moving animals, and invasive haemodynamic measurements were performed in anaesthetized animals. After killing, subgroups of AC and C rats were used to evaluate in the left ventricle the expression and spatial distribution of ,-skeletal actin and the amount of perivascular and interstitial fibrosis. As compared with C, all AC groups exhibited higher values of systolic pressure, ventricular weight and ventricular wall thickness. AC0.7 and AC0.4 rats also showed a larger amount of fibrosis and upregulation of ,-skeletal actin expression associated with a higher vulnerability to ventricular arrhythmias (AC0.7 and AC0.4) and enhanced myocardial contractility (AC0.4). Our results illustrate the progressive changes in the extracellular matrix features accompanying early ventricular remodelling in response to different degrees of pressure overload that may be involved in the development of cardiac electrical instability. We also demonstrate for the first time a linear correlation between an increase in ,-skeletal actin expression and the degree of compensated cardiac hypertrophy, possibly acting as an early compensatory mechanism to maintain normal mechanical performance. [source]

The effects of mild induced hypothermia on the myocardium: a systematic review

ANAESTHESIA, Issue 5 2010
F. E. Kelly
Summary Mild induced hypothermia improves neurological outcome and reduces mortality among initially comatose survivors of out-of-hospital cardiac arrest. Similar pathological processes occur in the heart and the brain, namely ischaemia followed by reperfusion injury. Animal data indicate that mild induced hypothermia results in improved myocardial salvage, reduced infarct size, reduced left ventricular remodelling and better long-term left ventricular function. Several small human studies suggest that infarct size may be reduced by mild induced hypothermia, although this has not reached significance in any human study to date. There are variable reports of harm to the myocardium caused by mild induced hypothermia, including reduced myocardial contractility and cardiac output, electrocardiographic changes and arrhythmias, especially bradycardia. These harmful effects are reversible with rewarming. [source]

Metoprolol Treatment Lowers Thrombospondin-4 Expression in Rats with Myocardial Infarction and Left Ventricular Hypertrophy

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2010
Erja Mustonen
In this study, we characterised left ventricular thrombospondin-1 and -4 expression in rats treated with a beta-blocker metoprolol during the remodelling process in response to pressure overload and acute myocardial infarction. Left ventricular thrombospondin-1 and thrombospondin-4 mRNA levels increased 8.4-fold (p < 0.001) and 7.3-fold (p < 0.001) post-infarction, respectively. Metoprolol infusion by osmotic minipumps (1.5 mg/kg/hr) for 2 weeks after myocardial infarction decreased thrombospondin-1 and thrombospondin-4 mRNA levels (55% and 50%, respectively), improved left ventricular function, and attenuated left ventricular remodelling with reduction of left ventricular atrial natriuretic peptide and brain natriuretic peptide gene expression. Thrombospondin-1 and -4 mRNA levels correlated positively with echocardiographic parameters of left ventricular remodelling as well as with atrial natriuretic peptide and brain natriuretic peptide gene expression. Moreover, there was a negative correlation between left ventricular ejection fraction and thrombospondin-1 mRNA levels. In 12-month-old spontaneously hypertensive rats with left ventricular hypertrophy, metoprolol decreased left ventricular thrombospondin-4 levels and attenuated remodelling while thrombospondin-1, atrial natriuretic peptide and brain natriuretic peptide mRNA levels as well as left ventricular function remained unchanged. In metoprolol-treated spontaneously hypertensive rats, thrombospondin-4 gene expression correlated with parameters of left ventricular remodelling, while no correlations between thrombospondins and natriuretic peptides were observed. These results indicate that thrombospondin-1 expression is linked exclusively to left ventricular remodelling process post-infarction while thrombospondin-4 associates with myocardial remodelling both after myocardial infarction and in hypertensive heart disease suggesting that thrombospondins may have unique roles in extracellular matrix remodelling process. [source]

Growth hormone, acromegaly, and heart failure: an intricate triangulation

CLINICAL ENDOCRINOLOGY, Issue 6 2003
Luigi Saccà
Summary Short-term GH or IGF-I excess provides a model of physiological cardiac growth associated with functional advantage. The physiological nature of cardiac growth is accounted for by the following: (i) the increment in cardiomyocyte size occurs prevalently at expense of the short axis. This is the basis for the concentric pattern of left ventricular (LV) hypertrophy, with consequent fall in LV wall stress and functional improvement; (ii) cardiomyocyte growth is associated with improved contractility and relaxation, and a favourable energetic setting; (iii) the capillary density of the myocardial tissue is not affected; (iv) there is a balanced growth of cardiomyocytes and nonmyocyte elements, which accounts for the lack of interstitial fibrosis; (v) myocardial energetics and mechanics are not perturbed; and (vi) the growth response is not associated with the gene re-programming that characterizes pathologic cardiac hypertrophy and heart failure. Overall, the mechanisms activated by GH or IGF-I appear to be entirely different from those of chronic heart failure. Not to be neglected is also the fact that GH, through its nitric oxide (NO)-releasing action, contributes to the maintenance of normal vascular reactivity and peripheral vascular resistance. This particular kind of interaction of GH with the cardiovascular system accounts for: (i) the lack of cardiac impairment in short-term acromegaly; (ii) the beneficial effects of GH and IGF-I in various models of heart failure; (iii) the protective effect of GH and IGF-I against post-infarction ventricular remodelling; (iv) the reversal of endothelial dysfunction in patients with heart failure treated with GH; and (v) the cardiac abnormalities associated with GH deficiency and their correction after GH therapy. If it is clear that GH and IGF-I exert favourable effects on the heart in the short term, it is equally undeniable that GH excess with time causes pathologic cardiac hypertrophy and, if it is not corrected, eventually leads to cardiac failure. Why then, at one point in time in the natural history of acromegaly, does physiological cardiac growth become maladaptive and translate into heart failure? Before this transition takes places, the acromegalic heart shares very few features with other models of chronic heart failure. None of the mechanisms involved in the progression of heart failure is clearly operative in acromegaly, save for the presence of insulin-resistance and mild alterations of lipoproteins and clot factors. Is this enough to account for the development of heart failure? Probably not. On the other hand, it must be stressed that GH and IGF-I activate several mechanisms that play a protective role against the development of heart failure. These include ventricular unloading, deactivation of neurohormonal components, antiapoptotic effect and enhanced vascular reactivity. Ultimately, all data available concur to hypothesize that acromegalic cardiomyopathy represents a progressive model of cardiac hypertrophy in which the cardiotoxic and pro-remodelling effect is intrinsic to the excessive and unrestrained myocardial growth. [source]