Pathological alterations in liver injury following congestive heart failure induced by volume overload in rats

Abstract

Heart failure has emerged as a disease with significant public health implications. Following progression of heart failure, heart and liver dysfunction are frequently combined in hospitalized patients leading to increased morbidity and mortality. Here, we investigated the underlying pathological alterations in liver injury following heart failure. Heart failure was induced using a modified infrarenal aortocaval fistula (ACF) in male Wistar rats. Sham operated and ACF rats were compared for their morphometric and hemodynamic data, for histopathological and ultrastructural changes in the liver as well as differences in the expression of apoptotic factors. ACF-induced heart failure is associated with light microscopic signs of apparent congestion of blood vessels, increased apoptosis and breakdown of hepatocytes and inflammatory cell inifltration were observed. The glycogen content depletion associated with the increased hepatic fibrosis, lipid globule formation was observed in ACF rats. Moreover, cytoplasmic organelles are no longer distinguishable in many ACF hepatocytes with degenerated fragmented rough endoplasmic reticulum, shrunken mitochondria and heavy cytoplasm vacuolization. ACF is associated with the upregulation of the hepatic TUNEL-positive cells and proapoptotic factor Bax protein concomitant with the mitochondrial leakage of cytochrome C into the cell cytoplasm and the transfer of activated caspase 3 from the cytoplasm into the nucleus indicating intrinsic apoptotic events. Taken together, the results demonstrate that ACF-induced congestive heart failure causes liver injury which results in hepatocellular apoptotic cell death mediated by the intrinsic pathway of mitochondrial cytochrome C leakage and subsequent transfer of activated caspase 3 into to the nucleus to initiate overt DNA fragmentation and cell death.

Chronic Naltrexone Therapy Is Associated with Improved Cardiac Function in Volume Overloaded Rats

“…Intriguingly, organ/body weight indices of the liver and kidney were not significantly altered in ACF rats which may be due to the large AV fistula itself that affects organ perfusion preventing it from increasing organ weight. Nonetheless, both organs showed overt histopathological changes in the liver [45] and kidney [46], as has been previously published. Secondly, this study was conducted to assess the indirect adverse opioidergic effects in cardiac volume overload.…”

Selective abdominal venous congestion to investigate cardiorenal interactions in a rat model

“…Sections were scanned using the Mirax Desk and observed at 20-times magnification using the Mirax viewer (Carl Zeiss MicroImaging, Germany). Fibrosis was assessed in four randomly chosen sections per rat, as previously described [ 25 , 26 ]. The area of collagen deposition was outlined and quantified using an automated image analysis program (AxioVision 4.6, Carl Zeiss MicroImaging, Germany).…”

The Fibrosis-4 Index Is Useful for Predicting Mortality in Patients with Pulmonary Hypertension due to Left Heart Disease

“…11) In heart failure patients, centrilobular congestion, necrosis, inflammation, sclerosis, fibrosis, and regenerative hyperplasia are pathologically confirmed. [12][13][14] The fibrosis-4 index has been reported to be useful for predicting prognosis in patients with heart failure. 11,15) PH-LHD causes more severe symptoms and a worse prognostic impact, compared with left-sided heart failure with normal pulmonary artery pressure.…”