Surgical sealant in the prevention of early vein graft injury in an ex vivo model

BACKGROUND: The amelioration of the adaptation process (arterialisation) of the vein graft wall to the arterial circulation in coronary artery bypass surgery by using extravascular support is clearly established in animal models and in in vitro and ex vivo set-ups. This support consists of some form of external graft-supporting modality like a prosthetic graft of stent. The clinical application of perivenous support, however, is hampered due to the fact that no easy applicable external support is available. Considering that application in the form of a spray is the most convenient modality, we evaluated whether polyethylene glycol is capable of providing adequate perivenous support. Polyethylene glycol is a synthetic, biodegradable product, used in cardiac surgery as a sealant, and is commercially available in the form of a spray. METHODS: Segments of human saphenous vein graft obtained during coronary artery bypass graft (CABG) procedures were placed in an ex vivo model, a side loop of the extracorporeal perfusion circuit, and perfused with autologous blood, making the circumstances identical to the implanted saphenous vein grafts concerning pressure, temperature, level of complement and leukocyte activation and blood pressure. Alternately around every other study vein graft segment polyethylene glycol was applied. Unsupported grafts served as control. After 1 min of solidification, perfusion was started with a pressure of about 60 mmHg (nonpulsatile flow). Perfusion was maintained for 60 min, after which the grafts were collected for light microscopy and electron microscopy. RESULTS: Light microscopy and electron microscopy showed remarkable attenuation of endothelial cell loss and less injury of smooth muscle cells of the circular and longitudinal layer of the media in the supported group compared to the nonsupported vein graft segments. CONCLUSION: Polyethylene glycol is able to provide adequate external vein graft support, preventing overdistension, in an ex vivo model. This provides a basis for clinical application. Further investigation is warranted to evaluate long-term effects

Perivenous support reduces early changes in human vein grafts:Studies in whole blood perfused human vein segments

Background: Patency of vein grafts in coronary artery bypass grafting procedures is generally less favorable than those of selected arterial grafts. However, vein grafts still are needed in cardiac operations. It would be desirable to find measures to improve the patency of vein grafts next to antithrombotic regimens. Animal studies demonstrated that arterial pressure induces overdistention of the thin-walled vein grafts and that prevention of this overdistention with extravascular support ameliorates the arterialization process with, subsequently, more favorable patency. To evaluate whether perivenous stenting of the rather muscular human vein grafts is also beneficial, we designed an in vitro model to study the early effects of perivenous support in human vein grafts. Methods: Seven paired segments of human vein graft obtained during coronary artery bypass grafting procedures were placed in a perfusion circuit and perfused simultaneously with autologous whole blood, with a pressure of 60 mm Hg (nonpulsatile flow). After 30 minutes of perfusion, one segment, and after 60 minutes of perfusion, the remaining segment were taken for histologic and immunohistochemical examination. In the next experiments 7 segments of human vein graft were placed in the circuit and supported with a polytetrafluoroethylene graft to prevent overdistention with 7 unstented segments as controls. Results: In unsupported vein grafts perfused with autologous blood under a pressure of 60 mm Hg, a complete de-endothelialization was shown after I hour of perfusion. In the study vein grafts, with a perivenous polytetrafluoroethylene graft preventing overdistention (n = 7), the endothelium remained intact. Electron microscopic investigation of the media showed severe damage in the circular smooth muscle layer in the unstented group, whereas in the stented group almost no injury was found. Conclusion: In our in vitro closed-loop model, reproducible vessel wall changes were observed in all human vein graft specimens studied. The beneficial effect of perivenous support could also be established for the human greater saphenous vein, providing a basis for clinical application

Perivenous application of fibrin glue reduces early injury to the human saphenous vein graft wall in an ex vivo model

OBJECTIVES: From animal and clinical studies it is known that prevention of 'over-distention' of vein grafts by using extravascular support ameliorates the arterialization process in vein grafts with subsequent more favorable patency. The most ideal support is a biodegradable, porous, elastic graft (Biomaterials, 15 (1994) 83). However, a specific graft meeting these criteria is not available yet. Fibrin glue on the other hand, although used for other purposes in cardiac surgery, theoretically meets the criteria for ideal extravascular support. In this ex vivo study, we evaluated the possible beneficial effect of perivenous application of fibrin glue. METHODS: Segments of human vein graft obtained during CABG procedures in 14 consecutive patients were placed in a side loop of the extracorporeal perfusion circuit. In this way the study vein grafts did meet identical circumstances as the vein grafts implanted. Perfusion in the loop was started with a flow just enough to counteract the collapse of the vein, usually about 8 mm Hg, and alternately around the segments fibrin glue was applied or no perivenous support was administered as control. After 1 min of soldification, perfusion was started with a pressure of about 60 mm Hg (non-pulsatile flow). Perfusion was maintained for 60 min, after which the grafts were collected for light microscopic and electron microscopic assessment. RESULTS: Light microscopy and electron microscopy showed remarkable attenuation of endothelial cell loss and less injury of smooth muscle cells of the circular muscle layer of the media in the fibrin glue supported vein grafts compared to the non-supported group. CONCLUSION: Fibrin glue is able to accomplish adequate external vein graft support, preventing overdistention, in an ex vivo model. This provides a basis for clinical application. Further investigation is necessary to evaluate long-term effects

Production of endothelin-1 and reduced blood flow in the rat kidney during lung-injurious mechanical ventilation

INTRODUCTION: The mechanisms by which mechanical ventilation (MV) can injure remote organs, such as the kidney, remain poorly understood. We hypothesized that upregulation of systemic inflammation, as reflected by plasma interleukin-6 (IL-6) levels, in response to a lung-injurious ventilatory strategy, ultimately results in kidney dysfunction mediated by local endothelin-1 (ET-1) production and renal vasoconstriction. METHODS: Healthy, male Wistar rats were randomized to 1 of 2 MV settings (n = 9 per group) and ventilated for 4 h. One group had a lung-protective setting using peak inspiratory pressure of 14 cm H(2)O and a positive end-expiratory pressure of 5 cm H(2)O; the other had a lung-injurious strategy using a peak inspiratory pressure of 20 cm H(2)O and positive end-expiratory pressure of 2 cm H(2)O. Nine randomly assigned rats served as nonventilated controls. We measured venous and arterial blood pressure and cardiac output (thermodilution method), renal blood flow (RBF) using fluorescent microspheres, and calculated creatinine clearance, urine flow, and fractional sodium excretion. Histological lung damage was assessed using hematoxylin-eosin staining. Renal ET-1 and plasma ETA and IL-6 concentrations were measured using enzyme-linked immunosorbent assays. RESULTS: Lung injury scores were higher after lung-injurious MV than after lung-protective ventilation or in sham controls. Lung-injurious MV resulted in significant production of renal ET-1 compared with the lung-protective and control groups. Simultaneously, RBF in the lung-injurious MV group was approximateIN 40% lower (P < 0.05) than in the control group and 28%, lower (P < 0.05) than ill the lung-protective,e group. Plasma ET-1 and IL-6 levels did not differ among the groups and systemic hemodynamics, such as cardiac Output, were comparable. There was no effect oil creatinine clearance, fractional sodium excretion, urine Output, or kidney histology. CONCLUSIONS: Lung-injurious MV for 4 h in healthy rats results ill significant production of renal ET-1 and in decreased RBF, independent of IL-6. Decreased RBF has no observable effect on kidney function or histology