Editorial commentDifferential, time-dependent effects of perivenous application of fibrin glue on medial thickening in porcine saphenous vein grafts

The study presented by Wan and co-workers explores the effect of extravascular support of venous anastomosis by perivenous injection of fibrin glue on medial thickening 1 and 4 months after intervention in a porcine model. Although this study was negative and, in fact, showed detrimental results with use of this technique, the authors should be commanded for their initiative of testing in an in vivo relevant model, a hypothesis that was raised under ex vivo nonpulsatile flow conditions. Such research initiatives are mandatory to avoid the pitfalls of empirism based on nonphysiological models devoid of the complex habitat and systems interaction including the inflammatory reaction after surgical trauma found in humans. Although the number of successful experiments is low, the results are clear enough at 4 months to demise the use of fibrin glue administered at the tested dose and conditions. The mechanisms evoked by the authors for initial positive results at 1 month, i.e. preferential migration of medial vascular smooth muscle cells towards the adventitia is attractive yet slightly naive considering the complexity of processes occurring at the site of a vascular anastomosis. Development of intimal hyperplasia is a necessary phenomenon in thin venous grafts submitted to arterial pressure, which increases wall thickness in order to normalize wall tension. Factors influencing this process include rheological and mechanical factors such as angle of anastomosis, anastomotic compliance, flow patterns, shear stress, and vortexes all which can influence local release of nitric oxide (NO) which has a inhibitory effect on smooth muscle cell proliferation and migration. Endogenous production of NO by the conduit itself, superior in internal mammary arteries versus veins, as well as integrity of the endothelium and of the internal elastic lamina after surgical manipulation may also contribute to the process of intimal hyperplasia. Although testing of the perivascular support hypothesis is worthwhile for improvement of graft patency in venous grafts, this purely mechanical approach may be difficult to control and reproduce. Pharmacological interventions are more likely to produce reliable and durable results and also influence the progression of disease in native coronary arteries, the other common cause of long-term graft failure, and need for re-intervention. Finally, even though venous grafts are still used in 2006, the clear superiority of use of bilateral mammary arteries and the potential benefits of all arterial grafting strategies, yet to be demonstrated in properly designed studies, are routes of equal and perhaps superior importance to pursue in the quest for improvement in the long term results of surgical myocardial revascularization.

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