Low-dose simvastatin improves survival and ventricular function via eNOS in congestive heart failure

2006 ◽  
Vol 291 (6) ◽  
pp. H2743-H2751 ◽  
Author(s):  
James J. M. Greer ◽  
Aman K. Kakkar ◽  
John W. Elrod ◽  
Lewis J. Watson ◽  
Steven P. Jones ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Cardiac Hypertrophy ◽  
Cardiac Function ◽  
Pulmonary Edema ◽  
Murine Model ◽  
Low Dose ◽  
Simvastatin Treatment ◽  
Simvastatin Therapy ◽  
Vehicle Treatment

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors increase endothelial nitric oxide synthase (eNOS) activity by multiple mechanisms. We previously reported that genetic overexpression of eNOS improves survival and cardiac function in congestive heart failure (CHF). In the present study, we tested the hypothesis that low-dose treatment with an 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor exerts beneficial effects on survival and/or cardiac function in a murine model of CHF. Mice were subjected to permanent ligation of the left coronary artery and randomized to receive either saline vehicle or simvastatin (0.25 mg/kg) 2 h after myocardial infarction and daily (0.25 mg/kg) for 7 days, followed by 21 days of administration every other day for a total duration of 28 days. Myocardial infarct size was not reduced by simvastatin therapy ( P = not significant between groups). Simvastatin treatment did significantly ( P < 0.05) improve survival (45%) compared with vehicle treatment (25%). In addition, simvastatin treatment significantly improved ( P < 0.01) left ventricular function and significantly ( P < 0.01) abrogated cardiac hypertrophy and pulmonary edema compared with vehicle treatment. The protective effects of simvastatin were abrogated by delayed initiation of treatment or genetic ablation of eNOS. In conclusion, low-dose simvastatin therapy significantly improves survival and cardiac function and reduces both cardiac hypertrophy and pulmonary edema via an eNOS-dependent mechanism in a murine model of CHF.

scholarly journals Animal model of left atrial thrombus in congestive heart failure in rats

2019 ◽  
Vol 317 (1) ◽  
pp. H63-H72
Author(s):  
Jiqiu Chen ◽  
Benjamin Strauss ◽  
Lifan Liang ◽  
Roger J. Hajjar
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Cardiac Function ◽  
Pulmonary Edema ◽  
Left Atrial ◽  
Left Ventricular ◽  
Left Atrial Thrombus ◽  
Aortic Banding ◽  
Atrial Thrombus ◽  
Fibrin Adhesion

The aim of the present study was to develop and study a new model of left atrial thrombus (LAT) in rat with congestive heart failure (CHF). CHF was induced by aortic banding for 2 mo, followed by ischemia-reperfusion (I/R) and subsequent aortic debanding for 1 mo. Cardiac function and the presence of LAT were assessed by echocardiography. Masson’s staining was performed for histological analysis. All CHF rats presented with significantly decreased cardiac function, fibrosis in remote myocardium, and pulmonary edema. The incidence rate of LAT was 18.8% in the rats. LAT was associated with severity of aortic constriction, aortic pressure gradient, aortic blood flow velocity, and pulmonary edema but not myocardial infarction or a degree of left ventricular depression. The progressive process of thrombogenesis was characterized by myocyte hypertrophy, fibrosis, and inflammation in the left atrial wall. Fibrin adhesion and clot formation were observed, whereas most LAT presented as a relatively hard “mass,” likely attributable to significant fibrosis in the middle and outer layers. Some LAT mass showed focal necrosis as well as fibrin bulging. Most LAT occurred at the upper anterior wall of the left atrial appendage. Aortic debanding had no significant impact on large LATs (>5 mm2) that had formed, whereas small LATs (<5 mm2) regressed 1 mo after aortic release. LAT is found in a rat model of aortic banding plus I/R followed by aortic debanding. The model provides a platform to study molecular mechanisms and potential new pathways for LAT treatment. NEW & NOTEWORTHY It is critically important to have a rodent model to study the molecular mechanism of thrombogenesis in the left atrium. Left atrial thrombus (LAT) is not a simple fibrin clot like those seen in peripheral veins or arteries. Rather, LAT is a cellular mass that likely develops in conjunction with blood clotting. Studying this phenomenon will help us understand congestive heart failure and promote new therapies for LAT.

Endogenous Endothelin-1 Participates in the Maintenance of Cardiac Function in Rats With Congestive Heart Failure

Circulation ◽  
1996 ◽  
Vol 93 (6) ◽  
pp. 1214-1222 ◽  
Author(s):  
Satoshi Sakai ◽  
Takashi Miyauchi ◽  
Takeshi Sakurai ◽  
Yoshitoshi Kasuya ◽  
Masaki Ihara ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Cardiac Function ◽  
Endothelin 1

Acute Pulmonary Edema Complicating Tonsillectomy and Adenoidectomy

PEDIATRICS ◽  
1985 ◽  
Vol 75 (1) ◽  
pp. 112-114
Author(s):  
ARTHUR N. FEINBERG ◽  
CHARLES L. SHABINO
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Continuous Positive Airway Pressure ◽  
Pulmonary Edema ◽  
Airway Pressure ◽  
Positive Airway Pressure ◽  
Medical Personnel ◽  
Acute Onset ◽  
Respiratory Support ◽  
Acute Pulmonary Edema

In summary, we have presented two cases to illustrate the problem of postoperative pulmonary edema following tonsillectomy and adenoidectomy. Furthermore, we have discussed the difficulty in predicting those patients who will develop this complication. Because of the potential seriousness and unpredictability of acute pulmonary edema following tonsillectomy for chronic obstruction, it is important that medical personnel, including pediatricians caring for patients after tonsillectomy, be able to readily recognize this phenomenon of acute onset of congestive heart failure and treat it rapidly with diuretics, continuous positive airway pressure, and respiratory support as needed.

Neutrophil-activating peptide-2 in patients with pulmonary edema from congestive heart failure or ARDS

1993 ◽  
Vol 264 (5) ◽  
pp. L490-L495 ◽  
Author(s):  
A. B. Cohen ◽  
M. D. Stevens ◽  
E. J. Miller ◽  
M. A. Atkinson ◽  
G. Mullenbach ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Pulmonary Edema ◽  
High Performance ◽  
Distress Syndrome ◽  
Normal Subjects ◽  
Antigen Concentration ◽  
Fluid Formation

We carried out studies to determine whether the neutrophil-activation peptide-2 (NAP-2) plays a role in the recruitment and/or degranulation of neutrophils into the lungs of patients with the adult respiratory distress syndrome (ARDS) or congestive heart failure (CHF). NAP-2 precursors plus NAP-2 (beta-thromboglobulin-like antigen) were measured in lung fluids and plasmas with a radioimmunoassay, and NAP-2 was separated from its precursors by high-performance liquid chromatography. Pulmonary edema fluids (PEFs) from patients with CHF contained higher concentrations of the beta-thromboglobulin-like antigen than PEFs from patients with ARDS, and bronchoalveolar lavage fluids (BALs) from patients with ARDS contained higher concentrations of beta-thromboglobulin-like antigen than BALs from normal subjects. beta-Thromboglobulin-like antigen concentration was 4.1-fold greater in PEFs from patients with CHF than in their plasmas. Chemotactically active NAP-2 was also demonstrated in PEFs but not in plasmas from patients with CHF and ARDS. These data suggest that significant platelet degranulation occurred into the lungs of the patients with CHF and that NAP-2 and other platelet constituents may contribute to fluid formation in patients with CHF.

A gene therapeutic approach to inhibit calcium and integrin binding protein 1 ameliorates maladaptive remodelling in pressure overload

2018 ◽  
Vol 115 (1) ◽  
pp. 71-82 ◽  
Author(s):  
Andrea Grund ◽  
Malgorzata Szaroszyk ◽  
Janina K Döppner ◽  
Mona Malek Mohammadi ◽  
Badder Kattih ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Cardiac Function ◽  
Binding Protein ◽  
Treatment Strategies ◽  
Pressure Overload ◽  
Cellular Growth ◽  
Neonatal Rat ◽  
Rat Cardiomyocytes ◽  
Pathological Cardiac Hypertrophy

Abstract Aims Chronic heart failure is becoming increasingly prevalent and is still associated with a high mortality rate. Myocardial hypertrophy and fibrosis drive cardiac remodelling and heart failure, but they are not sufficiently inhibited by current treatment strategies. Furthermore, despite increasing knowledge on cardiomyocyte intracellular signalling proteins inducing pathological hypertrophy, therapeutic approaches to target these molecules are currently unavailable. In this study, we aimed to establish and test a therapeutic tool to counteract the 22 kDa calcium and integrin binding protein (CIB) 1, which we have previously identified as nodal regulator of pathological cardiac hypertrophy and as activator of the maladaptive calcineurin/NFAT axis. Methods and results Among three different sequences, we selected a shRNA construct (shCIB1) to specifically down-regulate CIB1 by 50% upon adenoviral overexpression in neonatal rat cardiomyocytes (NRCM), and upon overexpression by an adeno-associated-virus (AAV) 9 vector in mouse hearts. Overexpression of shCIB1 in NRCM markedly reduced cellular growth, improved contractility of bioartificial cardiac tissue and reduced calcineurin/NFAT activation in response to hypertrophic stimulation. In mice, administration of AAV-shCIB1 strongly ameliorated eccentric cardiac hypertrophy and cardiac dysfunction during 2 weeks of pressure overload by transverse aortic constriction (TAC). Ultrastructural and molecular analyses revealed markedly reduced myocardial fibrosis, inhibition of hypertrophy associated gene expression and calcineurin/NFAT as well as ERK MAP kinase activation after TAC in AAV-shCIB1 vs. AAV-shControl treated mice. During long-term exposure to pressure overload for 10 weeks, AAV-shCIB1 treatment maintained its anti-hypertrophic and anti-fibrotic effects, but cardiac function was no longer improved vs. AAV-shControl treatment, most likely resulting from a reduction in myocardial angiogenesis upon downregulation of CIB1. Conclusions Inhibition of CIB1 by a shRNA-mediated gene therapy potently inhibits pathological cardiac hypertrophy and fibrosis during pressure overload. While cardiac function is initially improved by shCIB1, this cannot be kept up during persisting overload.

Pulmonary Edema I: Cardiogenic Pulmonary Edema

2017 ◽  
Author(s):  
Annette Esper ◽  
Greg S Martin ◽  
Gerald W. Staton Jr
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Pulmonary Edema ◽  
Clinical Characteristics ◽  
Distress Syndrome ◽  
Capillary Permeability ◽  
Treatment Options ◽  
Experimental Models ◽  
Lung Mechanics ◽  
Cardiogenic Pulmonary Edema

There are two categories of pulmonary edema: edema caused by increased capillary pressure (hydrostatic or cardiogenic edema) and edema caused by increased capillary permeability (noncardiogenic pulmonary edema, or acute respiratory distress syndrome). This review focuses on cardiogenic pulmonary edema and describes the general approach to patients with suspected cardiogenic pulmonary edema. The pathogenesis, diagnosis, treatment, and outcome of cardiogenic pulmonary edema are reviewed. Figures include chest scans showing pulmonary edema and noncardiogenic pulmonary edema, an illustration of the differences between cardiogenic and noncardiogenic edema, and a chart comparing lung mechanics and other variables in experimental models of cardiogenic pulmonary edema and noncardiogenic edema. Tables show clinical characteristics of patients with cardiogenic pulmonary edema and treatment options. This review contains 3 figures, 4 tables, and 24 references. Key words: cardiogenic pulmonary edema, congestive heart failure, pulmonary edema, Starling’s law

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