Background and Methods Aldosterone is important in the pathophysiology of heart failure. In a double-blind study, we enrolled 1663 patients who had severe heart failure and a left ventricular ejection fraction of no more than 35 percent and who were being treated with an angiotensin-converting–enzyme inhibitor, a loop diuretic, and in most cases digoxin. A total of 822 patients were randomly assigned to receive 25 mg of spironolactone daily, and 841 to receive placebo. The primary end point was death from all causes. Results The trial was discontinued early, after a mean follow-up period of 24 months, because an interim analysis determined that spironolactone was efficacious. There were 386 deaths in the placebo group (46 percent) and 284 in the spironolactone group (35 percent; relative risk of death, 0.70; 95 percent confidence interval, 0.60 to 0.82; P<0.001). This 30 percent reduction in the risk of death among patients in the spironolactone group was attributed to a lower risk of both death from prog...

https://www.nejm.org/doi/pdf/10.1056/NEJM199909023411001

The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.

Left ventricular hypertrophy (LVH) is the major risk factor associated with myocardial failure. An explanation for why a presumptive adaptation such as LVH would prove pathological has been elusive. Insights into the impairment in contractility of the hypertrophied myocardium have been sought in the biochemistry of cardiac myocyte contraction. Equally compelling is a consideration of abnormalities in myocardial structure that impair organ contractile function while preserving myocyte contractility. For example, in the LVH that accompanies hypertension, the extracellular space is frequently the site of an abnormal accumulation of fibrillar collagen. This reactive and progressive interstitial and perivascular fibrosis accounts for abnormal myocardial stiffness and ultimately ventricular dysfunction and is likely a result of cardiac fibroblast growth and enhanced collagen synthesis. The disproportionate involvement of this nonmyocyte cell, however, is not a uniform accompaniment to myocyte hypertrophy and LVH, suggesting that the growth of myocyte and nonmyocyte cells is independent of each other. This has now been demonstrated in in vivo studies of experimental hypertension in which the abnormal fibrous tissue response was found in the hypertensive, hypertrophied left ventricle as well as in the normotensive, nonhypertrophied right ventricle. These findings further suggest that a circulating substance that gained access to the common coronary circulation of the ventricles was involved. This hypothesis has been tested in various animal models in which plasma concentrations of angiotensin II and aldosterone were varied. Based on morphometric and morphological findings, it can be concluded that arterial hypertension (i.e., an elevation in coronary perfusion pressure) together with elevated circulating aldosterone are associated with cardiac fibroblast involvement and the resultant heterogeneity in tissue structure. Nonmyocyte cells of the cardiac interstitium represent an important determinant of pathological LVH. The mechanisms that invoke short- (e.g., collagen metabolism) and long-term (e.g., mitosis) responses of cardiac fibroblasts require further investigation and integration of in vitro with in vivo studies. The stage is set, however, to prevent pathological LVH resulting from myocardial fibrosis as well as to reverse it.

Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system.

Arterial stiffness is a growing epidemic associated with increased risk of cardiovascular events, dementia, and death. Decreased compliance of the central vasculature alters arterial pressure and flow dynamics and impacts cardiac performance and coronary perfusion. This article reviews the structural, cellular, and genetic contributors to arterial stiffness, including the roles of the scaffolding proteins, extracellular matrix, inflammatory molecules, endothelial cell function, and reactive oxidant species. Additional influences of atherosclerosis, glucose regulation, chronic renal disease, salt, and changes in neurohormonal regulation are discussed. A review of the hemodynamic impact of arterial stiffness follows. A number of lifestyle changes and therapies that reduce arterial stiffness are presented, including weight loss, exercise, salt reduction, alcohol consumption, and neuroendocrine-directed therapies, such as those targeting the renin-angiotensin aldosterone system, natriuretic peptides, insulin modulators, as well as novel therapies that target advanced glycation end products.

Mechanisms, Pathophysiology, and Therapy of Arterial Stiffness

The effect of spironolactone on morbidity and mortality in patients with severe heart failure

Swynghedauw, Bernard. Molecular Mechanisms of Myocardial Remodeling. Physiol. Rev. 79: 215–262, 1999. — “Remodeling” implies changes that result in rearrangement of normally existing structures. Th...

Molecular Mechanisms of Myocardial Remodeling

Pathological left ventricular hypertrophy in renovascular hypertension is associated with the accumulation of fibrillar collagen within the extracellular space and around intramyocardial coronary arteries. Even though the angiotensin converting enzyme inhibitor captopril was previously found to attenuate this interstitial and perivascular fibrosis, the relative importance of arterial and ventricular systolic pressures versus circulating angiotensin II (AII) and aldosterone (AL) in promoting hypertrophy and collagen accumulation in renovascular hypertension is uncertain. By drawing on the in-parallel arrangement of the right and left ventricles, with respect to their coronary circulation, and the in-series mechanical alignment of the ventricles, with a pressure-overloaded left and a normotensive right ventricle, this study sought to address this uncertainty. Three models of experimental hypertension, each having a different circulating AII and AL profile, were examined and compared with their controls: renovascular hypertension, where both AII and AL are increased; infrarenal aorta banding, where AII and AL are normal; and a chronic infusion of AL, where AII is suppressed or normal and AL is increased. In renovascular hypertension, as well as with AL, we found a significant rise in the interstitial collagen volume fraction and perivascular collagen area of the pressure-overloaded, hypertrophied left ventricle as well as the normotensive, nonhypertrophied right ventricle. This remodeling was not seen in either ventricle with infrarenal aorta banding despite comparable systemic hypertension and left ventricular hypertrophy. Thus, in experimental arterial hypertension in the rat, myocyte and nonmyocyte compartments of the myocardium are under separate controls: myocyte hypertrophy is most closely related to ventricular loading while circulating AII and AL, acting alone or in concert with other humoral factors, regulate the accumulation of collagen within the right and left ventricles.

Remodeling of the rat right and left ventricles in experimental hypertension.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

L B Tan

Author Tools

Chat about Author

Papers

Remodeling of the rat right and left ventricles in experimental hypertension.