Portal hypertension (PHT) is associated with hemodynamic changes in intrahepatic, systemic, and portosystemic collateral circulation. Increased intrahepatic resistance and hyperdynamic circulatory alterations with expansion of collateral circulation play a central role in the pathogenesis of PHT. PHT is also characterized by changes in vascular structure, termed vascular remodeling, which is an adaptive response of the vessel wall that occurs in response to chronic changes in the environment such as shear stress. Angiogenesis, the formation of new blood vessels, also occurs with PHT related in particular to the expansion of portosystemic collateral circulation. The complementary processes of vasoreactivity, vascular remodeling, and angiogenesis represent important targets for the treatment of portal hypertension. Systemic and splanchnic vasodilatation can induce hyperdynamic circulation which is related with multi-organ failure such as hepatorenal syndrome and cirrhotic cadiomyopathy.
Collateral Circulation/physiology ; Endothelial Cells/metabolism ; Hemodynamics ; Hepatic Stellate Cells/metabolism ; Hypertension, Portal/*etiology ; Liver Circulation/physiology ; Liver Cirrhosis/*etiology ; Splanchnic Circulation/physiology

Portal hypertension (PHT) is associated with changes in the intrahepatic, systemic and portosystemic collateral circulations. Alteration in vasoreactivity (vasodilation and vasoconstriction) plays a central role in the pathogenesis of PHT by contributing to increased intrahepatic resistance, hyperdynamic circulation and the expansion of the collateral circulation. PHT is also importantly characterized by changes in vascular structure; termed vascular remodeling, which is an adaptive response of the vessel wall that occurs in response to chronic changes in the environment such as shear stress. Angiogenesis, the sprouting of new blood vessels, also occurs in PHT, especially in the expansion of the portosystemic collateral circulation. These complementary processes of vasoreactivity, vascular remodeling and angiogenesis represent important targets in the research for the treatment of portal hypertension.
Collateral Circulation/physiology ; Endothelial Cells/metabolism ; Hepatic Stellate Cells/metabolism ; Humans ; Hypertension, Portal/*etiology ; Liver Circulation/physiology ; Vascular Resistance

OBJECTIVETo explore the feasibility of establishing an isolated porcine liver machine perfusion model and assess its value in high-intensity focused ultrasound studies.

METHODSTwenty-one isolated porcine livers were perfused with autologous blood for 4 h through dual vessels (portal vein and hepatic artery) cannulation using an extracorporeal circulation machine under a sub-normothermic perfusion condition. The perfusion model was assessed by monitoring the liver color, texture, liver weight gain, hemodynamic parameters, color Doppler flow imaging, bile output and histopathology.

RESULTSNineteen isolated porcine livers were successfully cannulated with dual vessels, and failure of hepatic artery intubation occurred in two porcine livers. After machine perfusion for 4 h, the isolated livers maintained a soft texture with stable hemodynamic levels within relative normal physiological ranges. The bile output was more than 3 ml/h within the initial 3 h of perfusion. Histopathological examination demonstrated no morphological or structural changes of the liver tissues.

CONCLUSIONThe isolated porcine liver perfusion model is stable and feasible, and can be used for high-intensity focused ultrasound studies.

Animals ; Equipment Design ; Extracorporeal Circulation ; instrumentation ; methods ; Hemodynamics ; Liver ; blood supply ; diagnostic imaging ; Liver Circulation ; physiology ; Swine ; Ultrasonography

OBJECTIVETo assess the effect of temporary occlusion of hepatic blood inflow on hepatic cancer treated with diode-laser induced thermocogation (LITT).

METHODSThe carcinoma Walker-256 was implanted in 40 SD rat livers. Twelve days later, the animals were randomly divided into 4 groups. Group A received LITT alone; group B received hepatic artery temporary occlusion during LITT; group C received portal vein temporary occlusion during LITT; group D received hepatic artery and portal vein temporary occlusion during LITT. Tumors were exposed to 810 nm diode-laser light at 0.95 watts for 10 min from a scanner tip applicator placed in the tumor. At the same time, the intrahepatic temperature distribution in rats with liver tumors was measured per 2 min during thermocoagulation. Tumor control was examined immediately 7 and 14 d after thermocoagulation.

RESULTSThere was significant difference of intrahepatic temperature distribution in rats with liver tumors among the 4 groups (P<0.05) except when group C samples were compared with group D samples at each time point, and group B samples were compared with group C samples at 120 s (P>0.05). Light microscopic examination of the histologic section samples revealed three separate zones: regular hyperthermic coagulation necrosis zone, transition zone and reference zone. Compared with the samples in group A and group B, group C and group D samples had more clear margin among the three zones.

CONCLUSIONThe hepatic blood inflow occlusion, especially portal vein hepatic blood inflow occlusion, or all hepatic blood inflow occlusion considerably increased the efficacy of LITT in the treatment of liver cancer.

Animals ; Laser Coagulation ; Liver Circulation ; physiology ; Liver Neoplasms ; blood supply ; surgery ; Rats ; Temperature ; Time Factors

In cirrhotic patients undergoing liver transplantation, reperfusion of a liver graft typically increases portal venous blood flow (PVF) because of a decrease in resistance in the liver graft to the PVF and underlying hyperdynamic splanchnic circulation, which develops due to liver cirrhosis complicated by portal hypertension and persists even after successful liver transplantation. If the liver graft has enough capacity to accommodate the increased PVF, the shear stress inflicted on the sinusoidal endothelial cells of the graft promotes hepatic regeneration; otherwise, small-for-size syndrome (SFSS) develops, leading to poor graft function and graft failure. In particular, a partial graft transplanted to patients undergoing living donor liver transplantation has less capacity to accommodate the enhanced PVF than a whole liver graft. Thus, the clinical conditions that the partial graft encounters determine either hepatic regeneration or development of SFSS. Consistent with this, this review will discuss the two conflicting effects of portal hyperperfusion (hepatic regeneration vs. portal hyperperfusion injury) on the partial grafts in cirrhotic patients suffering from hyperdynamic splanchnic circulation, in addition to normal physiology and pathophysiology of hepatic hemodynamics.
Endothelial Cells ; Hemodynamics ; Humans ; Hypertension, Portal ; Liver Cirrhosis ; Liver Regeneration ; Liver Transplantation ; Liver* ; Living Donors ; Physiology ; Regeneration* ; Reperfusion ; Splanchnic Circulation* ; Transplants*

By hemodynamic monitoring of liver transplantation with Color Doppler ultrasound, we observed the hemodynamic changes pre- and post-operatively and the patency of the anastomotic vessels, to detect or exclude the presence of complications, then assess the prognosis. We measured the hepatic blood flow after orthotopic liver transplantation in recent 6 cases, and observed the patency of anastomostic vessels and the hemodynamic improvement of the portal vein and hepatic arteries. The abnormal liquid and solid echoes were not found around the transplantated liver in all 6 cases. The echoes of hepatic parenchyma and tububes were normal. The direction and speed of blood flow were also normal. Five of anastomoses of portal vein in 6 cases were patent. The rest one was a little stenosed, and the speed of local blood flow was a little faster. There were 11 patent ones and 1 mildly stenosed in the 12 anastomoses of inferior venae cavae. The speed index(SI) and resistance index(RI) of hepatic arterial blood flow distal to the anastomoses were all normal. Liver transplantation is the redical therapying of portal hypertension, and the color Doppler ultrasound is the best non-invasived method for monitoring the hemodynamic changes of transplantated liver.
Adult ; Female ; Humans ; Liver ; diagnostic imaging ; physiology ; Liver Circulation ; Liver Transplantation ; diagnostic imaging ; Male ; Middle Aged ; Monitoring, Physiologic ; Ultrasonography, Doppler, Color ; Vascular Patency

OBJECTIVETo investigate the role of perfusion-weighted magnetic resonance imaging (MRI) in evaluation of cirrhotic liver.

METHODSWith a 4F catheter, 1% diluted carbon tetrachloride (1 ml/kg) was selectively injected into right or left hepatic artery of 12 dogs fortnightly. The half liver into which carbon tetrachloride was injected was called as study side (SS), while the other half liver without carbon tetrachloride injection was called as study control side (SCS). Conventional and perfusion-weighted MRI were performed in every 4 weeks. Via a 4F catheter, 5ml gadolinium diethylentriamine pentaaceti acid (Gd-DTPA) dilution was injected into superior mesenteric artery at the 5th scan. The signal intensity-time curves of SS, SCS, and portal vein were completed in MR workstation. The maximal relative signal increase (MRSI), peak time (tp), and slope of the curves were measured.

RESULTSOn conventional MR images, no abnormalities of externality and signal intensity were observed in both SS and SCS of liver at each stage. The mean tp, MRSI, and slope of intensity-time curves in normal liver were 10.56 seconds, 1.01, and 10.23 arbitrary unit (au)/s, respectively. Three parameters of curves didn't show obvious change in SCS of liver at every stage. Abnormal perfusion curves occurred in SS of liver at the 12th week after the 1st injection. The abnormality of perfusion curve in SS was more and more serious as the times of injection increased. The mean tp, MRSI, and slope intensity-time curves in SS of liver were 19.45 seconds, 0.43, and 3.60 au/s respectively at the 24th week.

CONCLUSIONPerfusion-weighted imaging can potentially provide information about portal perfusion of hepatic parenchyma, and to some degree, reflect the severity of cirrhosis.

Animals ; Carbon Tetrachloride Poisoning ; Dogs ; Gadolinium DTPA ; Image Enhancement ; instrumentation ; Liver ; pathology ; ultrastructure ; Liver Circulation ; physiology ; Liver Cirrhosis, Experimental ; diagnosis ; physiopathology ; Magnetic Resonance Imaging ; instrumentation ; methods

With the increased temporal resolution available in dynamic computed tomography (CT) and magnetic resonance imaging (MRI), hepatic arterioportal shunts are now more frequently encountered than in the past. The condition occurs in various hepatic diseases in which portal or hepatic venous flow is compromised. The underlying mechanism and the degree of shunt affect its appearance at dynamic imaging. The dynamic CT and MRI findings have been summarized as early enhancement of peripheral portal veins, and wedge-shaped transient parenchymal enhancement during the hepatic arterial phase. Recognition of arterioportal shunt can suggest the presence of a previously unsuspected disorder and avoids false-positive diagnosis or overestimation of a hepatic disease. Familiarity with the pathophysiology of arterioportal shunt also allows investigation of the hepatic hemodynamic changes occurring in various hepatic diseases.
Arteriovenous Fistula/*diagnosis/etiology/physiopathology ; Carcinoma, Hepatocellular/complications ; Chemoembolization, Therapeutic/adverse effects ; *Hepatic Artery ; Human ; Liver Circulation/physiology ; Liver Diseases/complications ; Liver Neoplasms/complications ; *Magnetic Resonance Imaging ; Portal System/physiology ; *Portal Vein ; *Tomography, X-Ray Computed

The purpose of the present study was to assess the correlation that likely exists among increased portal pressure (Pp), portal blood flow quantity (Qp) and ETA and ETB receptor mRNA expression in human cirrhosis. In situ hybridization and reverse-transcription polymerase chain reactions (RT-PCR) were performed to determined the expression of ETA and ETB receptor mRNA in liver tissues from traumatic subjects (n = 10) and cirrhotic patients (n = 15) in whom hepatic hemodynamic values were measured. The expression of the two transcripts was significantly higher in liver samples of cirrhotic patients than in those obtained from traumatic subjects. It has shown that ETA receptor mRNA predominantly located in hepatic stellate cells (HSCs) and vascular smooth muscle cells of intrahepatic arteries and portal veins, ETB receptor mRNA in HSCs, sinusoidal endothelial cells and Kuppfer cells. There was a highly significant direct relationship between ETA and ETB receptor mRNA and Pp and Qp in cirrhotic patients. It suggests that liver paracrine endothelin system may be overactivated in human cirrhosis accompanied with increased expression of ETA and ETB receptor mRNA which may play an important role in the pathogenesis and maintenance of splanchnic hyperdynamics.
Female ; Gene Expression ; Hemodynamics ; Humans ; Hypertension, Portal ; metabolism ; Liver Cirrhosis ; genetics ; metabolism ; Male ; Portal Vein ; physiopathology ; Receptors, Endothelin ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Splanchnic Circulation ; physiology

Hyperdynamic circulation in patients with liver cirrhosis is characterized by increased cardiac output and heart rate, and decreased systemic vascular resistance with low arterial blood pressure and currently focused on understanding the pathogenesis because of possibility of developing novel treatment modality. Basically, these hemodynamic alternations arise from portal hypertension. Portosystemic collaterals develop to counterbalance the increased intrahepatic vascular resistance to portal blood flow and induce an increase in venous return to heart. Increased shear stress in vascular endothelial cell related high blood flow by portosystemic shunting contributes to this up-regulation of eNOS resulting in NO overproduction. Additionally, bypassing through portosystemic collaterals and escaping degradation of over-produced circulating vasodilators in the diseased liver can promote the peripheral arterial vasodilation. Vasodilation of the systemic and splanchnic circulations lead to a reduced systemic vascular resistance, and increased cardiac output and splanchnic blood flow. Furthermore, neurohumoral vasoconstrictive systems including systemic nervous system, rennin angiotensin aldosterone system, and vasopressin are intensively activated secondary to vasodilation. However, hyperdynamic circulation would be more aggravated by the activated vasoconstrictive systems. With the progression of the cirrhotic process, hyperdynamic alternations can be more profound due to hyporesponsiveness to vasoconstrictors and increased shunt formation in conjunction with autonomic neuropathy. Eventually, splanchnic arterial vasodilation results in an increase portal venous inflow, maintaining the elevated portal venous pressure. Hyperdynamic circulation is intimately involved in portal hypertension with liver cirrhosis, therefore it is reasonable to have an interest in complete understanding of the pathogenensis of hyperdynamic circulation to develop novel treatment modality.
Blood Circulation/*physiology ; Blood Flow Velocity/physiology ; Humans ; Hypertension, Portal/etiology/*physiopathology ; Liver/blood supply/physiopathology ; Liver Cirrhosis/drug therapy/etiology/*physiopathology ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type III/metabolism ; Vasodilation