Pioglitazone Ameliorates Acute Endotoxemia-Induced Acute on Chronic Renal Dysfunction in Cirrhotic Ascitic Rats

Endotoxemia-activated tumor necrosis factor (TNFα)/nuclear factor kappa B (NFκB) signals result in acute on chronic inflammation-driven renal dysfunction in advanced cirrhosis. Systemic activation of peroxisome proliferator-activated receptor gamma (PPARγ) with pioglitazone can suppress inflammation-related splanchnic and pulmonary dysfunction in cirrhosis. This study explored the mechanism and effects of pioglitazone treatment on the abovementioned renal dysfunction in cirrhotic rats. Cirrhotic ascitic rats were induced with renal dysfunction by bile duct ligation (BDL). Then, 2 weeks of pioglitazone treatment (Pio, PPAR gamma agonist, 12 mg/kg/day, using the azert osmotic pump) was administered from the 6th week after BDL. Additionally, acute lipopolysaccharide (LPS, Escherichia coli 0111:B4; Sigma, 0.1 mg/kg b.w, i.p. dissolved in NaCl 0.9%) was used to induce acute renal dysfunction. Subsequently, various circulating, renal arterial and renal tissue pathogenic markers were measured. Cirrhotic BDL rats are characterized by decreased mean arterial pressure, increased cardiac output and portal venous pressure, reduced renal arterial blood flow (RABF), increased renal vascular resistance (RVR), increased relative renal weight/hydroxyproline, downregulated renal PPARγ expression, upregulated renal inflammatory markers (TNFα, NFκB, IL-6, MCP-1), increased adhesion molecules (VCAM-1 and ICAM-1), increased renal macrophages (M1, CD68), and progressive renal dysfunction (increasing serum and urinary levels of renal injury markers (lipocalin-2 and IL-18)). In particular, acute LPS administration induces acute on chronic renal dysfunction (increasing serum BUN/creatinine, increasing RVR and decreasing RABF) by increased TNFα-NFκB-mediated renal inflammatory markers as well as renal M1 macrophage infiltration. In comparison with the BDL+LPS group, chronic pioglitazone pre-treatment prevented LPS-induced renal pathogenic changes in the BDL-Pio+LPS group. Activation of systemic, renal vessel and renal tissue levels of PPARγ by chronic pioglitazone treatment has beneficial effects on the endotoxemia-related TNFα/NFκB-mediated acute and chronic renal inflammation in cirrhosis. This study revealed that normalization of renal and renal arterial levels of PPARγ effectively prevented LPS-induced acute and chronic renal dysfunction in cirrhotic ascitic rats.

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Effect of Two Models of Portal Hypertension on Splanchnic Organ Blood Flow in the Rat

Clinical Science ◽

10.1042/cs0680023 ◽

1985 ◽

Vol 68 (1) ◽

pp. 23-28 ◽

Cited By ~ 47

Author(s):

D. Lebrec ◽

L. Blanchet

Keyword(s):

Blood Flow ◽

Cardiac Output ◽

Portal Hypertension ◽

Portal Vein ◽

Arterial Blood Flow ◽

Organ Blood Flow ◽

Portal Vein Stenosis ◽

Arterial Blood ◽

Duct Ligation ◽

Vein Stenosis

1. Splanchnic organ blood flow and cardiac output were measured by the microsphere method in fasted rats with prehepatic portal hypertension due to portal vein stenosis, in rats with intrahepatic portal hypertension due to bile duct ligation, and in unoperated normal rats. 2. Portal venous pressure was higher in both groups of portal hypertensive rats than in normal rats. Cardiac output was significantly higher in portal hypertensive rats than in normal rats. 3. In rats with portal vein stenosis, splanchnic blood flow was higher than in controls. This increase was caused by increased perfusion of all organs drained by the portal vein, and by increased hepatic arterial blood flow. In rats with bile duct ligation, splanchnic blood flow was not significantly higher than in normal rats: haemoperfusion of all organs contributing to the portal circulation decreased, whereas hepatic arterial blood flow increased. As cardiac output rose similarly, the differences observed between the two types of portal hypertension depend mainly on the difference in distribution of flow within the splanchnic bed.

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Changes in Umbilical Arterial Blood Flow by an Intraamniotic Distilled Water Infusion

Yearbook of Obstetrics Gynecology and Women s Health ◽

10.1016/s1090-798x(08)70024-9 ◽

2007 ◽

Vol 2007 ◽

pp. 30-31

Author(s):

S.H. Ural

Keyword(s):

Blood Flow ◽

Arterial Blood Flow ◽

Distilled Water ◽

Arterial Blood ◽

Water Infusion

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Liver bud transplantation in rats

Magyar Sebészet (Hungarian Journal of Surgery) ◽

10.1556/1046.71.2018.4.3 ◽

2018 ◽

Vol 71 (4) ◽

pp. 163-169

Author(s):

Eiji Kobayashi ◽

Shin Enosawa

Keyword(s):

Fetal Liver ◽

Liver Parenchyma ◽

Arterial Blood Flow ◽

Silk Suture ◽

Cell Sheets ◽

Human Liver Tissue ◽

Arterial Blood ◽

Matrix Cell ◽

Experimental Microsurgery

Abstract: Introduction: Research has made progress in organ fabrication using an extracellular matrix, cell sheets, or organoids. Human liver tissue has been constructed using a 3-dimensional (3D) bioprinter and showed evidence that an in vitro generated liver bud was reformed in a rodent liver model. This study describes the stages of development of rat fetal organs and liver structure and reviews recent progress in liver organoid transplantation. Methods: The authors developed the procedures for creating a transected plane for use in experimental microsurgery in rats. A liver lobe was fixed vertically with gauze and it was ligated with 6-0 silk suture in the cut line; the parenchyma was cut, and major vessels were ligated to create the transected plane. The ligated tissue was carefully resected. Hemostasis was not required and hepatic components remained on the transected plane. The plane was covered by omentum. Results: Using this model, we transplanted fetal liver or a 3D bioprinted liver organoid. This microsurgical method enabled creation of an intact liver parenchyma plane. No bleeding was observed. The transplanted liver components successfully engrafted on the liver. Conclusion: This method may provide an essential environment for growing liver using portal and arterial blood flow.

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Impact of Pre Transplant Transarterial Chemoembolization on Hepatic Arterial Blood Flow and Outcomes in Liver Transplantation

10.26226/morressier.58eb975dd462b80290b50084 ◽

2017 ◽

Author(s):

Siddharth Jain

Keyword(s):

Liver Transplantation ◽

Blood Flow ◽

Transarterial Chemoembolization ◽

Arterial Blood Flow ◽

Hepatic Arterial Blood Flow ◽

Arterial Blood

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Modeling Elastic Walls in Lattice Boltzmann Simulations of Arterial Blood Flow

SNE Simulation Notes Europe ◽

10.11128/sne.23.tn.10189 ◽

2013 ◽

Vol 23 (2) ◽

Author(s):

Xenia Descovich ◽

Giuseppe Pontrelli ◽

Sauro Succi ◽

Simone Melchionna ◽

Manfred Bammer

Keyword(s):

Blood Flow ◽

Lattice Boltzmann ◽

Arterial Blood Flow ◽

Arterial Blood ◽

Lattice Boltzmann Simulations ◽

Elastic Walls

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Sustained Inflation Reduces Pulmonary Blood Flow during Resuscitation with an Intact Cord

Children ◽

10.3390/children8050353 ◽

2021 ◽

Vol 8 (5) ◽

pp. 353

Author(s):

Jayasree Nair ◽

Lauren Davidson ◽

Sylvia Gugino ◽

Carmon Koenigsknecht ◽

Justin Helman ◽

...

Keyword(s):

Blood Flow ◽

Perinatal Asphyxia ◽

Arterial Blood Flow ◽

Positive Pressure ◽

Optimal Timing ◽

Delayed Cord Clamping ◽

Arterial Blood ◽

Cord Clamping ◽

Sustained Inflation ◽

Near Term

The optimal timing of cord clamping in asphyxia is not known. Our aims were to determine the effect of ventilation (sustained inflation–SI vs. positive pressure ventilation–V) with early (ECC) or delayed cord clamping (DCC) in asphyxiated near-term lambs. We hypothesized that SI with DCC improves gas exchange and hemodynamics in near-term lambs with asphyxial bradycardia. A total of 28 lambs were asphyxiated to a mean blood pressure of 22 mmHg. Lambs were randomized based on the timing of cord clamping (ECC—immediate, DCC—60 s) and mode of initial ventilation into five groups: ECC + V, ECC + SI, DCC, DCC + V and DCC + SI. The magnitude of placental transfusion was assessed using biotinylated RBC. Though an asphyxial bradycardia model, 2–3 lambs in each group were arrested. There was no difference in primary outcomes, the time to reach baseline carotid blood flow (CBF), HR ≥ 100 bpm or MBP ≥ 40 mmHg. SI reduced pulmonary (PBF) and umbilical venous (UV) blood flow without affecting CBF or umbilical arterial blood flow. A significant reduction in PBF with SI persisted for a few minutes after birth. In our model of perinatal asphyxia, an initial SI breath increased airway pressure, and reduced PBF and UV return with an intact cord. Further clinical studies evaluating the timing of cord clamping and ventilation strategy in asphyxiated infants are warranted.

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Combined resection of the hepatic artery without reconstruction in pancreaticoduodenectomy: a case report of pancreatic cancer with an aberrant hepatic artery

Surgical Case Reports ◽

10.1186/s40792-020-00997-5 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Tadao Kuribara ◽

Tatsuo Ichikawa ◽

Kiyoshi Osa ◽

Takeshi Inoue ◽

Satoshi Ono ◽

...

Keyword(s):

Pancreatic Cancer ◽

Hepatic Artery ◽

Locally Advanced ◽

Pancreatic Head ◽

Arterial Embolization ◽

Arterial Blood Flow ◽

Temporary Increase ◽

Combined Resection ◽

Arterial Blood ◽

Arterial Resection

Abstract Background Pancreaticoduodenectomy (PD) is rarely performed for pancreatic cancer with hepatic arterial invasion owing to its poor prognosis and high surgical risks. Although there has been a recent increase in the reports of PD combined with hepatic arterial resection due to improvements in disease prognosis and operative safety, PD with major arterial resection and reconstruction is still considered a challenging treatment. Case presentation A 61-year-old man with back pain was diagnosed with pancreatic head and body cancer. Although distant metastasis was not confirmed, the tumor had extensively invaded the hepatic artery; therefore, we diagnosed the patient with locally advanced unresectable pancreatic cancer. After gemcitabine plus nab-paclitaxel (GnP) therapy, the tumor considerably decreased in size from 35 to 20 mm. Magnetic resonance imaging revealed a gap between the tumor and the hepatic artery. Tumor marker levels returned to their normal range, and we decided to perform conversion surgery. In this case, an artery of liver segment 2 (A2) had branched from the left gastric artery; therefore, we decided to preserve A2 and perform PD combined with hepatic arterial resection without reconstruction. After four cycles of GnP therapy, we performed hepatic arterial embolization to prevent postoperative ischemic complications prior to surgery. Immediately after embolization, collateral arterial blood flow to the liver was observed. Operation was performed 19 days after embolization. Although there was a temporary increase in liver enzyme levels and an ischemic region was found near the surface of segment 8 of the liver after surgery, no liver abscess developed. The postoperative course was uneventful, and S-1 was administered for a year as adjuvant chemotherapy. The patient is currently alive without any ischemic liver events and cholangitis and has not experienced recurrence in the past 4 years since the surgery. Conclusions In PD for pancreatic cancer with hepatic arterial invasion, if a part of the hepatic artery is aberrant and can be preserved, combined resection of the common and proper hepatic artery without reconstruction might be feasible for both curability and safety.

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