Repeatability of the "flash-replenishment" method in contrast-enhanced ultrasound for the quantitative assessment of hepatic microvascular perfusion

This study aimed to evaluate the feasibility and repeatability of the flash-replenishment method in contrast-enhanced ultrasound (CEUS) perfusion imaging and assess quantitatively microvascular perfusion in the liver. Twenty healthy New Zealand rabbits were submitted to CEUS perfusion imaging with continuous intravenous infusion. Using flash-replenishment kinetics, the dynamic process of depletion and refilling of microbubble contrast agent was recorded. The hepatic microvascular perfusion parameters were calculated, including region of interest, peak intensity (PI), area under the curve (AUC), and hepatic artery to vein transit time (HA-HVTT). A consistency test was performed for multiple measurements by the same operator and blind measurements by two different operators. The hepatic perfusion imaging of 3×108 bubbles/min had minimal error and the best imaging effect and repeatability. The variability of the perfusion parameter measured at 3 cm depth under the liver capsule was at a minimum with coefficient of variation of 3.9%. The interclass correlation coefficient (ICC) of measurements taken by the same operator was 0.985, (95% confidence interval, CI=0.927-0.998). Measurements taken by two operators had good consistency and reliability, with the ICC of 0.948 (95%CI=0.853-0.982). The PI and AUC of liver parenchyma after reperfusion were lower than before blocking; and HA-HVTT was significantly longer than before blocking (P<0.05). The flash-replenishment method in CEUS perfusion imaging showed good stability and repeatability, which provide a valuable experimental basis for the quantitative assessment of hepatic microvascular perfusion in clinical practice.

Ischemic preconditioning vs adenosine vs prostaglandin E1 for protection against liver ischemia/reperfusion injury

Ischemia/reperfusion injury is still a major cause of morbidity and mortality during liver surgery and transplantation. A variety of surgical and pharmacological therapeutic strategies have been investigated to minimize the effects of ischemia/reperfusion. The aim of our study was to analyze and compare preventive influences of ischemic preconditioning, adenosine and prostaglandin E1 in the experimental model of hepatic ischemia/reperfusion injury. Adult chinchilla rabbits were divided into four groups: 10 rabbits subjected to liver ischemic preconditioning (3-min period of inflow occlusion followed by a 5-min period of reperfusion) followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of adenosine followed by 45 min of Pringle maneuver; 10 rabbits subjected to pre-treatment with intraportal injection of prostaglandin E1 followed by 45 min of Pringle maneuver; and control group of 10 rabbits subjected to 45 min of inflow liver ischemia without any preconditioning. On the second postoperative day, blood samples were obtained and biochemical parameters of liver function were measured and compared. Liver tissue samples were also obtained and histopathological changes were compared. Based on biochemical and histopathological parameters, it was demonstrated that ischemic preconditioning provided the best protection against hepatic ischemia/reperfusion injury. This was probably due to a wider range of mechanisms of action of this method oriented to reduce oxidative stress and inflammation, and restore liver microcirculation and hepatocyte energy compared to the examined pharmacological strategies.

Protective mechanisms of hypoxia-inducible factor 1α against liver ischemia reperfusion injury / 中华肝胆外科杂志

Hypoxia-inducible factors 1α (HIF-1α) is the key cellular oxygen-sensitive transcription factors that could activate diverse pathways in regulating cellular metabolism,angiogenesis,proliferation and migration,enabling a cell to generate adaptive responses to a low oxygen or hypoxic environment.HIF-1 α has been shown to play an important role in the pathogenesis of multiple liver diseases.This review explores the impact of HIF1α on liver ischemia-reperfusion injury and liver transplantation as well as its mechanism.

Protection of Intrahepatic Injection of Liposome-mediated VEGF Plasmid against Ischemia-reperfusion Liver Injury / 华中科技大学学报(医学版)

Objective To explore the effect of intrahepatic injection of liposome-mediated VEGF plasmid on ischemia-reper-fusion liver injury and its mechanism. Methods Rabbits were randomly divided into normal group, ischemia-reperfusion group and recombinant VEGF therapy group( liposome-mediated transfer of VEGF plasmid into liver via portal vein 20 min before ischemia of liver). The model of liver ischemia-reperfusion injury was established. Liver function and the activity of SOD.XO in blood were determined at the 0,2nd,6th,12th,and 24th h after operation. RT-PCR technique was applied to detect the expression level of Fas mRNA in liver tissues of every group,and flow cytometry was used to measure cell apoptosis rate at the 6th h after operation. At the 24th h after operation,all rabbits were killed and liver tissues of ischemia were taken to make pathological sections for observing the morphology and microstructure under the light microscopy and electron microscopy. ResuJts The level of ALT in recombinant VEGF therapy group was markedly reduced as compared with ischemia-reperfusion group at the 6th,12th,and 24th h after operation( P<0. 05). The activity of SOD in recombinant VEGF therapy group was significantly higher than in ischemia-reperfusion group at the 6th, 12th,and 24th h after operation. The activity of XO in recombinant VEGF therapy group was significantly lower than that in ischemia-reperfusion group at the 6th,12th,and 24th h after operation(P< 0. 05 or P<0. 01). In addition,there was significant difference in the expression of Fas mRNA and cell apoptosis rate between recombinant VEGF therapy group and ischemia-reperfusion group(P<0. 01). The injury of hepatocytes in recombinant VEGF therapy group was significantly alleviated as compared with that in ischemia-reperfusion group under the light microscopy and e-lectron microscopy. Conclusion Liposome-mediated transfer of VEGF plasmid into liver before ischemia of liver can obviously protect hepatocytes by increasing anti-oxidative ability, decreasing the expression of Fas mRNA, and finally inhibiting hepato-cyte apoptosis.

Hepatic microcirculatory failure / Falência microcirculatória hepática

Liver ischemia has been considered a frequent problem in medical practice, and can be associated to a number of surgical and clinical situations, such as massive hepatic resections, sepsis, liver trauma, circulatory shock and liver transplantation. After restoring blood flow, the liver is further subjected to an additional injury more severe than that induced by ischemia. On account of the complexity of mechanisms related to pathophysiology of ischemia and reperfusion (I/R) injury, this review deals with I/R effects on sinusoidal microcirculation, especially when steatosis is present. Alterations in hepatic microcirculation are pointed as a main factor to explain lower tolerance of fatty liver to ischemia-reperfusion insult. The employment of therapeutic strategies that interfere directly with vasoactive mediators (nitric oxide and endothelins) acting on the sinusoidal perfusion seem to be determinant for the protection of the liver parenchyma against I/R. These approaches could be very suitable to take advantage of marginal specimens as fatty livers, in which the microcirculatory disarrangements hamper its employment in liver transplantation.

A isquemia hepática é um problema relativamente freqüente na prática clínica, sobrevindo em situações diversas como ressecções hepáticas maciças, sepse, trauma hepático extenso, choque circulatório e transplante hepático. Durante a restauração do fluxo sanguíneo, o fígado é submetido a uma agressão adicional ainda mais intensa que aquela imposta pela isquemia. Devido à complexidade dos diversos mecanismos envolvidos na fisiopatologia da lesão por isquemia e reperfusão (I/R) hepática, esta revisão se limitará a discorrer sobre os efeitos da I/R na microcirculação sinusoidal, com ênfase para as alterações microvasculares que tomam lugar no fígado esteatótico pós-isquêmico. O desarranjo microcirculatório é apontado como um importante fator para explicar a reduzida tolerância do fígado esteatótico ao insulto isquêmico. O desenvolvimento de estratégias terapêuticas capazes de interferir diretamente com os mediadores vasoativos (óxido nítrico e endotelinas) relacionados ao déficit perfusional será determinante para a proteção do parênquima hepático frente às alterações induzidas pela I/R. Esses recursos seriam de especial interesse para o aproveitamento de fígados marginais, cuja falência microcirculatória compromete sobremaneira sua utilização para o transplante hepático.

Protective Effect of Peroxisome Proliferator-Activated Receptor ? Activator 15-Deoxyprostaglandin J_2 in Rat Hepatic Ischemia-Reperfusion Injury and Its Mechanism / 中国普外基础与临床杂志

Objective To investigate the protective effect of peroxisome proliferator-activated receptor ?(PPAR?) activator 15-deoxyprostaglandin J2(15d-PGJ2) in rat hepatic ischemia-reperfusion injury and its mechanism.Methods The models of 70% warm ischemia-reperfusion injury were established in SD rats,rats were randomly divided into 4 groups: sham operation group,ischemia-reperfusion group,15d-PGJ2 group and 15d-PGJ2+GW9662 group.After reperfusion,serum AST and ALT levels were determined;the liver tissues were removed for measurement of activity of NF-?B and myeloperoxidase(MPO),TNF-? content and expression of ICAM-1.Results Compared with sham operation group,the serum levels of ALT and AST,and the activities of MPO and NF-?B,TNF-? content and expression of ICAM-1 in ischemia-reperfusion group,15d-PGJ2 group and 15d-PGJ2+GW9662 group were greatly improved(P

Significance of TLR2 expression in ischemic liver tissue after liver ischemia/reperfusion in mice / 中国普通外科杂志

Objective To explore Toll like receptor 2 (TLR2) expression after partial liver ischemia/ reperfusion (I/R) in BALB/c mice and its relationship with liver function impairment. Methods All the animals were randomly divided into ischemia/reperfusion injury (I/R) and sham operation (S) groups. Total RNA was extracted from the liver samples and the expression of TLR2 mRNA was analyzed quantitatively by real time PCR method. Membrane protein was extracted, and the expression of TLR2 protein was detected by western blot method. Portal vein serum and plasma were taken for further detection of the levels of alanine aminotransferase (ALT), tumor necrosis factor alpha (TNF ?) and endotoxin . Results After 1h of partial liver ischemia and 4 h of reperfusion, the expression of TLR2 mRNA and TLR2 protein were both remarkably upregulated in tissues of ischemic liver lobes in I/R group compared with that in S group (value of TLR2mRNA: 1.06?0.91vs5.08?1.32,P0.05). Conclusions TLR2mRNA and TLR2 protein expression were upregulated in tissues of ischemic liver lobes after partial I/R injury in mice, and were associated with increased levels of portal vein ALT and TNF ?,and impairment of liver function.