Hemodynamic effects of substance P and its receptor antagonist RP67580 in anesthetized rats with carbon tetrachloride-induced cirrhosis

Cárdenas, Andrés; Lowe, Robert S.; Oh, Seungeun; Bodkin, Sheila; Kenney, T. J.; LaMorte, Wayne W.; Afdhal, Nezam H.

doi:10.1080/00365520701685691

Cited by 6 publications

(4 citation statements)

References 25 publications

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“…Portal pressures and MRE images were obtained serially from the same large animal. In contrast, chronic indwelling portal vein and hepatic vein catheters were not possible in rodents (28,29). …”

Section: Discussionmentioning

confidence: 99%

Portal hypertension correlates with splenic stiffness as measured with MR elastography

Nedredal

Yin

McKenzie

et al. 2011

Magnetic Resonance Imaging

101

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Purpose To investigate the correlation between MRE assessed spleen stiffness and direct portal vein pressure gradient (D-HVPG) measurements in a large animal model of portal hypertension. Materials and Methods Cholestatic liver disease was established in adult canines by common bile duct ligation. A spin echo based EPI MRE sequence was used to acquire 3-D/3-axis abdominal MRE data at baseline, four weeks, and eight weeks. Liver biopsies, blood samples, and D-HVPG measurements were obtained simultaneously. Results Animals developed portal hypertension (D-HVPG: 11.0±5.1 mmHg) with only F1 fibrosis after four weeks. F3 fibrosis was confirmed after eight weeks despite no further rise in portal hypertension (D-HVPG: 11.3±3.2 mmHg). Mean stiffnesses of the spleen increased over two-fold from baseline (1.72±0.33 kPa) to four weeks (3.54±0.31 kPa), and stabilized at eight weeks (3.38±0.06 kPa) in a pattern consistent with changes in portal pressure. A positive correlation was observed between spleen stiffness and D-HVPG (r2 = 0.86, p<0.01). Conclusion These findings indicate a temporal relationship between portal hypertension and the development of liver fibrosis in a large animal model of cholestatic liver disease. The observed direct correlation between spleen stiffness and D-HVPG suggest a non-invasive MRE approach to diagnose and screen for portal hypertension.

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Section: Discussionmentioning

confidence: 99%

Portal hypertension correlates with splenic stiffness as measured with MR elastography

Nedredal

Yin

McKenzie

et al. 2011

Magnetic Resonance Imaging

101

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“…In portal hypertension, one of the main factors responsible for a sustained increase in portal blood inflow is the presence of splanchnic vasodilation that occurs secondary to the excessive release of putative vasodilators such as NO, adenosine, substance P, and endocannabinoids, among others (7,14,18,24). One of the major deleterious consequences of portal hypertension in humans is the development of gastrointestinal bleeding attributable to gastroesophageal varices.…”

Section: Discussionmentioning

confidence: 99%

Vascular stasis, intestinal hemorrhage, and heightened vascular permeability complicate acute portal hypertension in cd39-null mice

Sun¹,

Cárdenas²,

Wu³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…The characteristics of the ideal largeanimal model are: (1) duplication of the morphologic features that appear in human liver cirrhosis; (2) gradual and discrete progression of pathologic changes; (3) a high reproducibility and low mortality; (4) reversibility and irreversibility of fibrotic changes, and (5) development of pathophysiologic sequelae [13,14] . CCl 4 has long been known to produce liver cirrhosis in rats [15] . The CCl 4 -induced rat model has been widely used because it results in severe micronodular cirrhosis and ascites, with low mortality rates [15,16] .…”

Section: Discussionmentioning

confidence: 99%

“…CCl 4 has long been known to produce liver cirrhosis in rats [15] . The CCl 4 -induced rat model has been widely used because it results in severe micronodular cirrhosis and ascites, with low mortality rates [15,16] . However, this model is unfit for surgical operation research [5] .…”

Section: Discussionmentioning

confidence: 99%

Development of a New Animal Model of Liver Cirrhosis in Swine

et al. 2008

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This study aimed to develop a new experimental model of liver cirrhosis in swine by using carbon tetrachloride (CCl₄) and ethanol. Liver cirrhosis was induced by intraperitoneal injection of CCl₄ twice a week for 9 weeks. Maize flour was the only food provided and the animals drunk a 5% alcohol-water mixture. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, bilirubin and portal venous pressure (PVP) levels were determined throughout CCl₄ treatment. The animals were sacrificed under general anesthesia at week 9 and liver samples were collected for histological analysis. 83.3% of the swine had liver cirrhosis and 33.3% had died. There was no change of body weight during the course of the experiment (p > 0.05). The AST and ALT levels increased significantly in the early stage of the study but had a trend to decrease during the late phase. The level of bilirubin increased greatly and albumin decreased during the whole experiment (p < 0.05). PVP levels decreased in the early stage in CCl₄-treated swine, but increased significantly at the late phase. In conclusion, this study was successful in producing liver cirrhosis and offers an ideal experimental model for observing surgical therapeutic efficacy.

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Hemodynamic effects of substance P and its receptor antagonist RP67580 in anesthetized rats with carbon tetrachloride-induced cirrhosis

Abstract: Exogenous SP increases PP and decreases MAP in cirrhotic rats. RP687580 decreases PP and reduces SP-induced hypotension in cirrhotic rats. NO blockade abolishes the effect of SP on PP. SP contributes to splanchnic vasodilatation in cirrhosis and this effect may be mediated by NO.

Cited by 6 publications

References 25 publications

Portal hypertension correlates with splenic stiffness as measured with MR elastography

Portal hypertension correlates with splenic stiffness as measured with MR elastography

Vascular stasis, intestinal hemorrhage, and heightened vascular permeability complicate acute portal hypertension in cd39-null mice

Development of a New Animal Model of Liver Cirrhosis in Swine

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