Effects of hepatic ischaemia/reperfusion injury in a rabbit model of Indocyanine Green clearance

Seifalian, Alexander M.; El-Desoky, Hamid; Delpy, David T.; Davidson, Brian R

doi:10.1042/cs1020579

Cited by 7 publications

(5 citation statements)

References 25 publications

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“…Rather, the improved hepatic oxygenand a reduction in hepatic oxygenation (6,7,23). We have confirmed these findings in the present study and ation we observed must have resulted largely from the marked increase in portal oxygenation, augmented furhave further shown that similar changes in portal blood HYPEROXIA AND PORTAL ARTERIALIZATION 807 ther by the increase in portal blood flow.…”

Section: Discussionsupporting

confidence: 81%

“…Plasma glucose was estimated by the glucose oxidase method on a Cobas Mira autoanalyzer (Roche, deoxyhemoglobin (Hb), and cytochrome oxidase (Cyt Ox), an intracellular marker of cellular oxygenation, as Welwyn Garden City, Herts. UK) on blood samples collected from amputated tail tips under anesthesia after previously described (5,7,23). The data were calculated as 1-min averages at baseline and at the end of each 5-7 days to confirm hyperglycemia.…”

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confidence: 99%

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Effect of Inspired Oxygen on Portal and Hepatic Oxygenation: Effective Arterialization of Portal Blood by Hyperoxia

et al. 2004

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Because hypoxia may compromise the survival of intraportally transplanted pancreatic islets, we have measured portal blood flow and both portal and hepatic oxygenation in normal and diabetic rats breathing graded inspired oxygen concentrations. Portal blood flow and hepatic tissue oxygenation were measured using a transonic flowmeter and near infrared spectroscopy while gas analysis was carried out on portal venous blood samples. The effects of breathing 13%, 21%, 50%, or 100% oxygen were compared in animals with steptozotocin-induced diabetes and in controls. In diabetic rats breathing 21% oxygen, portal blood flow was significantly lower than in controls (7.2 ± 0.7 vs. 9.1 ± 0.8 ml/min, p < 0.05). In both groups, breathing 100% oxygen significantly increased portal flow (to 8.4 ± 1.0 and 12.2 ± 0.7 ml/min, respectively). This effect was not secondary to hepatic arterial vasoconstriction because it was not prevented by hepatic artery ligation. In controls, breathing 100% oxygen increased portal pO 2 from 5.0 ± 0.9 to 14.4 ± 1.4 kPa (p < 0.05) and portal venous oxygen saturation (PSaO 2 ) from 53.9 ± 12.1% to 92.9 ± 1.4% (p < 0.05), a value not significantly different from peripheral (arterial) saturation. Similarly, in diabetic animals pO 2 rose from 5.6 ± 0.3 to 11.7 ± 0.4 kPa (p < 0.01) and SO 2 from 55.5 ± 5.2% to 88.5 ± 0.6% (p < 0.05). Hepatic oxyhemoglobin rose and deoxyhemoglobin fell reciprocally as a function of the inspired oxygen concentration. Improved hepatic oxygenation observed in animals breathing oxygen-enriched gas mixtures results from an increase in splanchnic blood flow coupled with a marked increase in portal oxygen saturation. This effective arterialization of portal blood may have important consequences for the success of intraportal transplantation of pancreatic islets.Key words: Experimental transplantation; Islets; Hyperoxia; Portal oxygenation INTRODUCTIONever, the mechanism underlying this effect was not clear. We would not expect that increasing the concenPancreatic islet transplantation potentially offers an tration of oxygen in inspired air would have a significant effective cure for insulin-dependent (type I) diabetes effect on arterial hemoglobin saturation, but hypothemellitus. Shapiro and Lakey have recently reported insusized that hyperoxia might nevertheless exert selective lin independence in 43 consecutive patients transplanted effects on splanchnic blood flow. We therefore studied using a steroid-free immunosuppressive regimen (22,24).the effect of the concentration of inspired oxygen on However, they have had to use an average of two transportal blood oxygenation and flow as well as on hepatic plants per recipient, suggesting that an insufficient numtissue oxygenation. Because oxygen tensions in islets ber of islets survive transplantation. Consistent with this transplanted into various sites, including the liver, are concept, we have previously estimated that only ϳ50% lower in diabetic than in control rats (3) we included islets survive intraportal transplantation in ...

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Section: Discussionsupporting

confidence: 81%

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confidence: 99%

Effect of Inspired Oxygen on Portal and Hepatic Oxygenation: Effective Arterialization of Portal Blood by Hyperoxia

et al. 2004

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“…The delayed uptake of fluorescein following I/R injury is consistent with a previous study that showed delayed uptake and clearance of indocyanine green (ICG) in the rabbit liver following I/R injury. 37 Another recent study also found a reduced uptake and clearance of perfused rhodamine 123 in the rat liver after I/R injury. 38 To our knowledge, we are the first to use intravital imaging to visualize and model the uptake and clearance of a fluorescent compound to assess liver function following I/R injury.…”

Section: Discussionmentioning

confidence: 99%

“…37 In addition, another study reports that I/R injury is associated with a reduction in sinusoid density within the liver, 39 which is believed to impair hepatic microcirculation. 40 Therefore delayed fluorescein uptake may be due to a decrease in sinusoid diameter that impairs blood flow and thus availability of the dye to the hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

Intravital multiphoton microscopy can model uptake and excretion of fluorescein in hepatic ischemia-reperfusion injury

et al. 2013

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Abstract. The liver is important in the biotransformation of various drugs, where hepatic transporters facilitate uptake and excretion. Ischemia-reperfusion (I/R) injury is a common occurrence in liver surgery, and the developing oxidative stress can lead to graft failure. We used intravital multiphoton tomography, with fluorescence lifetime imaging, to characterize metabolic damage associated with hepatic I/R injury and to model the distribution of fluorescein as a measure of liver function. In addition to measuring a significant increase in serum alanine transaminase levels, characteristic of hepatic I/R injury, a decrease in the averaged weighted lifetime of reduced nicotinamide adenine dinucleotide phosphate was observed, which can be attributed to a changed metabolic redox state of the hepatocytes. I/R injury was associated with delayed uptake and excretion of fluorescein and elevated area-under-the-curve within the hepatocytes compared to sham (i.e., untreated control) as visualized and modeled using images recorded by intravital multiphoton tomography. High-performance liquid chromatography analysis showed no differences in plasma or bile concentrations of fluorescein. Finally, altered fluorescein distribution was associated with acute changes in the expression of liver transport proteins. In summary, multiphoton intravital imaging is an effective approach to measure liver function and is more sensitive in contrasting the impact of I/R injury than measuring plasma and bile concentrations of fluorescein.

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“…The fluorophores can either come from exogenous probes used to stain the tissue or from the intrinsic autofluorescence of certain biomolecules. Previously, using optical imaging techniques IRI was quantified in different organs [7,8], while hepatic IRI was investigated in animal models using near-infrared spectroscopy of indocyanine green [9] and molecular imaging of flavins [10].…”

Section: Introductionmentioning

confidence: 99%

Optical imaging for the assessment of hepatocyte metabolic state in ischemia and reperfusion injuries

Cour¹,

Mehrvar²,

Kim³

et al. 2017

Biomed. Opt. Express

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Deterioration in mitochondrial function leads to hepatic ischemia and reperfusion injury (IRI) in liver surgery and transplantation. 3D optical cryoimaging was used to measure the levels of mitochondrial coenzymes NADH and FAD, and their redox ratio (NADH/FAD) gave a quantitative marker for hepatocyte oxidative stress during IRI. Using a rat model, five groups were compared: control, ischemia for 60 or 90 minutes (Isc60, Isc90), ischemia for 60 or 90 minutes followed by reperfusion of 24 hours (IRI60, IRI90). Ischemia alone did not cause a significant increase in the redox ratio; however, the redox ratio in both IRI60 and IRI90 groups was significantly decreased by 29% and 71%, respectively. A significant correlation was observed between the redox ratio and other markers of injury such as serum aminotransferase levels and the tissue ATP level. The mitochondrial redox state can be successfully measured using optical cryoimaging as a quantitative marker of hepatic IR injury.

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Effects of hepatic ischaemia/reperfusion injury in a rabbit model of Indocyanine Green clearance

Cited by 7 publications

References 25 publications

Effect of Inspired Oxygen on Portal and Hepatic Oxygenation: Effective Arterialization of Portal Blood by Hyperoxia

Effect of Inspired Oxygen on Portal and Hepatic Oxygenation: Effective Arterialization of Portal Blood by Hyperoxia

Intravital multiphoton microscopy can model uptake and excretion of fluorescein in hepatic ischemia-reperfusion injury

Optical imaging for the assessment of hepatocyte metabolic state in ischemia and reperfusion injuries

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