Carbon monoxide-Releasing Molecule-2 (CORM-2) attenuates acute hepatic ischemia reperfusion injury in rats

<p>Abstract</p> <p>Background</p> <p>Hepatic ischemia-reperfusion injury (I/Ri) is a serious complication occurring during liver surgery that may lead to liver failure. Hepatic I/Ri induces formation of reactive oxygen species, hepatocyte apoptosis, and release of pro-inflammatory cytokines, which together causes liver damage and organ dysfunction. A potential strategy to alleviate hepatic I/Ri is to exploit the potent anti-inflammatory and cytoprotective effects of carbon monoxide (CO) by application of so-called CO-releasing molecules (CORMs). Here, we assessed whether CO released from CORM-2 protects against hepatic I/Ri in a rat model.</p> <p>Methods</p> <p>Forty male Wistar rats were randomly assigned into four groups (n = 10). Sham group underwent a sham operation and received saline. I/R group underwent hepatic I/R procedure by partial clamping of portal structures to the left and median lobes with a microvascular clip for 60 minutes, yielding ~70% hepatic ischemia and subsequently received saline. CORM-2 group underwent the same procedure and received 8 mg/kg of CORM-2 at time of reperfusion. iCORM-2 group underwent the same procedure and received iCORM-2 (8 mg/kg), which does not release CO. Therapeutic effects of CORM-2 on hepatic I/Ri was assessed by measuring serum damage markers AST and ALT, liver histology score, TUNEL-scoring of apoptotic cells, NFkB-activity in nuclear liver extracts, serum levels of pro-inflammatory cytokines TNF-α and IL-6, and hepatic neutrophil infiltration.</p> <p>Results</p> <p>A single systemic infusion with CORM-2 protected the liver from I/Ri as evidenced by a reduction in serum AST/ALT levels and an improved liver histology score. Treatment with CORM-2 also up-regulated expression of the anti-apoptotic protein Bcl-2, down-regulated caspase-3 activation, and significantly reduced the levels of apoptosis after I/Ri. Furthermore, treatment with CORM-2 significantly inhibited the activity of the pro-inflammatory transcription factor NF-κB as measured in nuclear extracts of liver homogenates. Moreover, CORM-2 treatment resulted in reduced serum levels of pro-inflammatory cytokines TNF-α and IL-6 and down-regulation of the adhesion molecule ICAM-1 in the endothelial cells of liver. In line with these findings, CORM-2 treatment reduced the accumulation of neutrophils in the liver upon I/Ri. Similar treatment with an inactive variant of CORM-2 (iCORM-2) did not have any beneficial effect on the extent of liver I/Ri.</p> <p>Conclusions</p> <p>CORM-2 treatment at the time of reperfusion had several distinct beneficial effects on severity of hepatic I/Ri that may be of therapeutic value for the prevention of tissue damage as a result of I/Ri during hepatic surgery.</p

Vascular clamping in liver surgery: physiology, indications and techniques

This article reviews the historical evolution of hepatic vascular clamping and their indications. The anatomic basis for partial and complete vascular clamping will be discussed, as will the rationales of continuous and intermittent vascular clamping

The effect of turbulence on transitional flow in the FDA’s benchmark nozzle model using large-eddy simulation

The Food and Drug Administration's (FDA) benchmark nozzle model has been studied extensively both experimentally and computationally. Although considerable efforts have been made on validations of a variety of numerical models against available experimental data, the transitional flow cases are still not fully resolved, especially with regards to detailed comparison of predicted turbulence quantities with experimental measurements. This study aims to fill this gap by conducting large‐eddy simulations (LES) of flow through the FDA's benchmark model, at a transitional Reynolds number of 2000. Numerical results are compared to previous interlaboratory experimental results, with an emphasis on turbulence characteristics. Our results show that the LES methodology can accurately capture laminar quantities throughout the model. In the pre‐jet breakdown region, predicted turbulence quantities are generally larger than high resolution experimental data acquired with laser Doppler velocimetry. In the jet breakdown regions, where maximum Reynolds stresses occur, Reynolds shear stresses show excellent agreement. Differences of up to 4% and 20% are observed near the jet core in the axial and radial normal Reynolds stresses, respectively. Comparisons between viscous and Reynolds shear stresses show that peak viscous shear stresses occur in the nozzle throat reaching a value of 18 Pa in the boundary layer, whilst peak Reynolds shear stresses occur in the jet breakdown region reaching a maximum value of 87 Pa. Our results highlight the importance in considering both laminar and turbulent contributions towards shear stresses and that neglecting the turbulence effect can significantly underestimate the total shear force exerted on the fluid