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Journal ArticleDOI

Left ventricular hypertrophy in rats with biliary cirrhosis.

TL;DR: In conclusion, portal hypertension associated to biliary cirrhosis induces marked LV hypertrophy and increased myocardial NO synthesis without detectable fibrosis or functional impairment.
About: This article is published in Hepatology.The article was published on 2003-09-01 and is currently open access. It has received 50 citations till now. The article focuses on the topics: Left ventricular hypertrophy & Portal hypertension.
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TL;DR: In patients with advanced cirrhosis, physical and/or pharmacological stress may reveal a reduced cardiac performance with systolic and diastolic dysfunction and electrophysical abnormalities termed cirrhotic cardiomyopathy, and no specific therapy can be recommended, but it should be supportive and directed against the heart failure.
Abstract: There is a mutual interaction between the function of the heart and the liver and a broad spectrum of acute and chronic entities that affect both the heart and the liver. These can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting the heart and the liver at the same time. In chronic and acute cardiac hepatopathy, owing to cardiac failure, a combination of reduced arterial perfusion and passive congestion leads to cardiac cirrhosis and cardiogenic hypoxic hepatitis. These conditions may impair the liver function and treatment should be directed towards the primary heart disease and seek to secure perfusion of vital organs. In patients with advanced cirrhosis, physical and/or pharmacological stress may reveal a reduced cardiac performance with systolic and diastolic dysfunction and electrophysical abnormalities termed cirrhotic cardiomyopathy. Electrophysiological abnormalities include prolonged QT interval, chronotropic incompetance, and electromechanical uncoupling. No specific therapy can be recommended, but it should be supportive and directed against the heart failure. Numerous conditions affect both the heart and the liver such as infections, inflammatory and systemic diseases, and chronic alcoholism. The risk and prevalence of coronary artery disease are increasing in cirrhotic patients and since the perioperative mortality is high, a careful cardiac evaluation of such patients is required prior to orthotopic liver transplantation.

319 citations

Journal ArticleDOI
TL;DR: Cardiac alterations in cirrhosis present with mild increases in ventricular wall thickness, diastolic dysfunction that worsens with ascites and physical stress, and abnormal systolic response to stress limiting exercise capacity.

267 citations


Cites background from "Left ventricular hypertrophy in rat..."

  • ...Data from hearts from cirrhotic rats have been relevant for the understanding of ventricular hypertrophy in cirrhosis [19]....

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Journal ArticleDOI
TL;DR: The clinical features, general diagnostic criteria, pathogenesis and treatment of cirrhotic cardiomyopathy, which contributes to morbidity and mortality after liver transplantation, are discussed in this review.
Abstract: Liver cirrhosis is associated with several cardiovascular disturbances. These disturbances include hyperdynamic systemic circulation, manifested by an increased cardiac output and decreased peripheral vascular resistance and arterial pressure. Despite the baseline increase in cardiac output, cardiac function in patients with cirrhosis is abnormal in several respects. Patients show attenuated systolic and diastolic contractile responses to stress stimuli, electrophysiological repolarization changes, including prolonged QT interval, and enlargement or hypertrophy of cardiac chambers. This constellation of cardiac abnormalities is termed cirrhotic cardiomyopathy. It has been suggested that cirrhotic cardiomyopathy has a role in the pathogenesis of cardiac dysfunction and even overt heart failure after transjugular intrahepatic portosystemic shunt placement, major surgery and liver transplantation. Cardiac dysfunction contributes to morbidity and mortality after liver transplantation, even in many patients who have no prior history of cardiac disease. Depressed cardiac contractility contributes to the pathogenesis of hepatorenal syndrome, especially in patients with spontaneous bacterial peritonitis. Pathogenic mechanisms underlying cirrhotic cardiomyopathy include cardiomyocyte-membrane biophysical changes, attenuation of the stimulatory beta-adrenergic system and overactivity of negative inotropic systems mediated via cyclic GMP. The clinical features, general diagnostic criteria, pathogenesis and treatment of cirrhotic cardiomyopathy are discussed in this review.

128 citations

Journal ArticleDOI
TL;DR: This review summarizes the current understanding of the direct effects of Ang II on cardiomyocytes and focuses particularly on interaction of components of the renin-angiotensin system with other hormones and cytokines.

98 citations


Cites background from "Left ventricular hypertrophy in rat..."

  • ...ciated with increased eNOS expression and a lack of fibrosis (Inserte et al., 2003)....

    [...]

Journal ArticleDOI
TL;DR: This study suggests that elevated markers of diastolic dysfunction during pre-LTx echocardiographic evaluation are associated with an excess risk of HF and may predict post- LTx survival.
Abstract: BACKGROUND: Liver transplantation (LTx) is a life-saving treatment of end-stage liver disease. Cardiac complications including heart failure (HF) are among the leading causes of death after LTx. THE AIM: The aim is to identify clinical and echocardiographic predictors of developing HF after LTx. METHODS: Patients who underwent LTx at the University of Nebraska Medical Center (UNMC) between January 2001 and January 2009 and had echocardiographic study before and within 6 months after transplantation were identified. Patients with coronary artery disease (>70% lesion) were excluded. HF after LTx was defined by clinical signs, symptoms, radiographic evidence of pulmonary congestion, and echocardiographic evidence of left ventricular dysfunction (left ventricle ejection fraction <50%). RESULTS: Among 107 patients (presented as mean age [SD], 55 [10] years; male, 70%) who met the inclusion criteria, 26 (24%) patients developed HF after LTx. The pre-LTx left ventricle ejection fraction did not differ between the HF (69 [7]) and the control groups (69 [7] vs. 67 [6], P=0.30). However, pre-LTx elevation of early mitral inflow velocity/mitral annular velocity (P=0.02), increased left atrial volume index (P=0.05), and lower mean arterial pressure (P=0.03) were predictors of HF after LTx in multivariate analysis. Early mitral inflow velocity/mitral annular velocity greater than 10 and left atrial volume index 40 mL/m2 or more were associated with a 3.4-fold (confidence interval, 1.2-9.4; P=0.017) and 2.9-fold (confidence interval, 1.1-7.5; P=0.03) increase in risk of development of HF after LTx, respectively. CONCLUSIONS: This study suggests that elevated markers of diastolic dysfunction during pre-LTx echocardiographic evaluation are associated with an excess risk of HF and may predict post-LTx survival.

85 citations

References
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Journal ArticleDOI
TL;DR: The stimulation of the renin‐angiotensin‐aldosterone system, vasopressin release and sympathetic nervous system associated with cirrhosis is not consonant with primary volume expansion, and favors the “overflow” hypothesis.

1,475 citations

Journal ArticleDOI
TL;DR: The phenotypic changes of cardiac cells in response to Ang II in vitro closely mimic those of growth factor response in vitro and of load-induced hypertrophy in vivo, and all biological effects of Ang II examined here are mediated primarily by the AT1 receptors.
Abstract: Increasing evidence suggests that angiotensin II (Ang II) may act as a growth factor for the heart. However, direct effects of Ang II on mammalian cardiac cells (myocytes and nonmyocytes), independent of secondary hemodynamic and neurohumoral effects, have not been well characterized. Therefore, we analyzed the molecular phenotype of cultured cardiac cells from neonatal rats in response to Ang II. In addition, we examined the effects of selective Ang II receptor subtype antagonists in mediating the biological effects of Ang II. In myocyte culture, Ang II caused an increase in protein synthesis without changing the rate of DNA synthesis. In contrast, Ang II induced increases in protein synthesis, DNA synthesis, and cell number in nonmyocyte cultures (mostly cardiac fibroblasts). The Ang II-induced hypertrophic response of myocytes and mitogenic response of fibroblasts were mediated primarily by the AT1 receptor. Ang II caused a rapid induction of many immediate-early genes (c-fos, c-jun, jun B, Egr-1, and c-myc) in myocyte and nonmyocyte cultures. Ang II induced "late" markers for cardiac hypertrophy, skeletal alpha-actin and atrial natriuretic factor expression, within 6 hours in myocytes. Ang II also caused upregulation of the angiotensinogen gene and transforming growth factor-beta 1 gene within 6 hours. Induction of immediate-early genes, late genes, and growth factor genes by Ang II was fully blocked by an AT1 receptor antagonist but not by an AT2 receptor antagonist. These results indicate that: (1) Ang II causes hypertrophy of cardiac myocytes and mitogenesis of cardiac fibroblasts, (2) the phenotypic changes of cardiac cells in response to Ang II in vitro closely mimic those of growth factor response in vitro and of load-induced hypertrophy in vivo, (3) all biological effects of Ang II examined here are mediated primarily by the AT1 receptor subtype, and (4) Ang II may initiate a positive-feedback regulation of cardiac hypertrophic response by inducing the angiotensinogen gene and transforming growth factor-beta 1 gene.

1,413 citations

Journal Article
TL;DR: In vivo recent evidence suggest that the activation of mitogen-activated protein kinases and activator protein-1 by Ang II may play the key role in cardiovascular and renal diseases, however, there are still unresolved questions and controversies on the mechanism of Ang II-mediated cardiovascular and kidneys diseases.
Abstract: A growing body of evidence supports the notion that angiotensin II (Ang II), the central product of the renin-angiotensin system, may play a central role not only in the etiology of hypertension but also in the pathophysiology of cardiovascular and renal diseases in humans. In this review, we focus on the role of Ang II in cardiovascular and renal diseases at the molecular and cellular levels and discuss up-to-date evidence concerning the in vitro and in vivo actions of Ang II and the pharmacological effects of angiotensin receptor antagonists in comparison with angiotensin-converting enzyme inhibitors. Ang II, via AT(1) receptor, directly causes cellular phenotypic changes and cell growth, regulates the gene expression of various bioactive substances (vasoactive hormones, growth factors, extracellular matrix components, cytokines, etc.), and activates multiple intracellular signaling cascades (mitogen-activated protein kinase cascades, tyrosine kinases, various transcription factors, etc.) in cardiac myocytes and fibroblasts, vascular endothelial and smooth muscle cells, and renal mesangial cells. These actions are supposed to participate in the pathophysiology of cardiac hypertrophy and remodeling, heart failure, vascular thickening, atherosclerosis, and glomerulosclerosis. Furthermore, in vivo recent evidence suggest that the activation of mitogen-activated protein kinases and activator protein-1 by Ang II may play the key role in cardiovascular and renal diseases. However, there are still unresolved questions and controversies on the mechanism of Ang II-mediated cardiovascular and renal diseases.

992 citations

Journal ArticleDOI
TL;DR: The data suggest that ET-1 induces hypertrophy of cardiomyocytes associated with the induction of muscle-specific gene transcripts through the possible involvement of protein kinase C activation or intracellular Ca2+ mobilization.
Abstract: To determine whether endothelin-1 (ET-1) induces hypertrophy of cardiomyocytes, the effects of ET-1 on the expression of muscle-specific genes and a proto-oncogene, c-fos, in cultured neonatal rat cardiomyocytes were examined by Northern blot analysis. ET-1 (10(-7) M) induced about twofold to fourfold increases in the gene expression of myosin light chain 2, alpha-actin, and troponin I after 6 hours, which continued up to 24 hours. The ET-1-induced increases in mRNA levels for these muscle-specific genes were dose dependent (10(-9) to 10(-7) M). Run-on transcriptional assay showed that the changes in mRNA level for three muscle-specific genes were regulated, at least in part, at the transcriptional level. 12-O-Tetradecanoylphorbol 13-acetate (TPA), a potent protein kinase C activator, and the Ca2+ ionophore ionomycin also increased mRNA levels of three muscle-specific genes. ET-1, TPA, and ionomycin similarly induced the expression of c-fos after 30 minutes, which returned to an undetectable level after 6 hours. ET-1 remarkably and dose-dependently stimulated accumulation of total inositol phosphates in cardiomyocytes. Morphometrical evaluation showed that ET-1 significantly increased surface area of cardiomyocytes without cell proliferation. ET-1 also dose-dependently stimulated the synthesis of protein and DNA, which was unaffected by the L-type calcium channel blocker nicardipine. These data suggest that ET-1 induces hypertrophy of cardiomyocytes associated with the induction of muscle-specific gene transcripts through the possible involvement of protein kinase C activation or intracellular Ca2+ mobilization.

512 citations

Journal ArticleDOI
TL;DR: The primary effects of mechanical stress are focused on: how mechanical stress may be sensed, and which signal transduction pathways may couple mechanical stress to modulation of gene expression, and to increased protein synthesis.
Abstract: Cardiac hypertrophy is a well known response to increased hemodynamic load. Mechanical stress is considered to be the trigger inducing a growth response in the overloaded myocardium. Furthermore, mechanical stress induces the release of growth-promoting factors, such as angiotensin II, endothelin-1, and transforming growth factor-beta, which provide a second line of growth induction. In this review, we will focus on the primary effects of mechanical stress: how mechanical stress may be sensed, and which signal transduction pathways may couple mechanical stress to modulation of gene expression, and to increased protein synthesis. Mechanical stress may be coupled to intracellular signals that are responsible for the hypertrophic response via integrins and the cytoskeleton or via sarcolemmal proteins, such as phospholipases, ion channels and ion exchangers. The signal transduction pathways that may be involved belong to two groups: (1) the mitogen-activated protein kinases (MAPK) pathway; and (2) the janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. The MAPK pathway can be subdivided into the extracellular-regulated kinase (ERK), the c-Jun N-terminal kinase (JNK), and the 38-kDa MAPK (p38 MAPK) pathway. Alternatively, the stress signal may be directly submitted to the nucleus via the cytoskeleton without the involvement of signal transduction pathways. Finally, by promoting an increase in intracellular Ca2+ concentration stretch may stimulate the calcium/calmodulin-dependent phosphatase calcineurin, a novel hypertrophic signalling pathway.

495 citations

Trending Questions (1)
Can cirrhosis spread to other organs?

This observation could be relevant to patients with cirrhosis.