Glabridin Relaxes Vascular Smooth Muscles by Activating BK_(Ca) Channels and Inhibiting Phosphodiesterase in Human Saphenous Vein

The aim of the current study was to investigate the pharmacological activity of glabridinon the isolated human saphenous vein (SV) and explore the underlying mechanisms. Samples of patients' SVs were removed during bypass surgery, and 4-mm lengths of the vessels were placedin Krebs solution at ±4℃ and hung in an isolated organ bath to assess their contraction/relaxationresponses. The contraction/relaxation responses were recorded to observe if the cyclic guanosinemonophosphate (cGMP)/protein kinase G (PKG) pathway mediates the relaxant effect of glabridinafter treatment with blockers like ODQ (a guanylate cyclase inhibitor), KT5823 (a PKG inhibitor),isobutylmethylxanthine [IBMX, a phosphodiesterase (PDE) inhibitor], and cantharidin [Cant,a myosin light-chain phosphatase (MLCP) inhibitor]. Moreover, nitric oxide (NO), cGMP, andPKG levels in SV tissues were determined by ELISA after incubation with glabridin, N(o)-nitro-L-arginine methyl ester (L-Name, a NO synthetase inhibitor), phenylephrine (PE), ODQ, IBMX,and KT5823. The results showed that glabridin relaxed the vascular smooth muscle of humanSV pretreated with PE in a dose-dependent manner, which was independent of the endothelium.The vasorelaxant effect of glabridin was only inhibited by iberiotoxin (IbTX), Cant, and KT5823.Glabridin increased cGMP and PKG levels in SV homogenates, whereas it did not alter the NOlevel. The enhancing efects of cGMP and PKG levels by glabridin were abolished by ODQ andKT5823. In conclusion, glabridin has a vasorelaxant effect, which is associated with the activationof BKc. channels and inhibition of PDE.

Percutaneous coronary intervention of totally occluded coronary venous bypass grafts:An exercise in futility?

BACKGROUND Percutaneous coronary intervention(PCI)of diseased saphenous vein grafts(SVG)continues to pose a clinical challenge.Current PCI guidelines give a class III recommendation against performing PCI on chronically occluded SVG.However,contemporary outcomes after SVG intervention have incrementally improved with distal protection devices,intracoronary vasodilators,drug-eluting stents,and prolonged dual antiplatelet therapy.AIM To reassess the procedural and long-term outcomes of PCI for totally occluded SVG with contemporary techniques.METHODS This was a retrospective observational study conducted at a single university hospital.The study population consisted of 35 consecutive patients undergoing PCI of totally occluded SVG.Post-procedure dual antiplatelet therapy was continued for a minimum of one year and aspirin was continued indefinitely.Clinical outcomes were assessed at a mean follow-up of 1221±1038 d.The primary outcome was freedom from a major adverse cardiac event(MACE)defined as the occurrence of any of the following:death,myocardial infarction,stroke,repeat bypass surgery,repeat PCI,or graft reocclusion.RESULTS The study group included 29 men and 6 women with a mean age of 69±12 years.Diabetes was present in 14(40%)patients.All patients had Canadian Heart Classification class III or IV angina.Clinical presentation was an acute coronary syndrome in 34(97%)patients.Mean SVG age was 12±5 years.Estimated duration of occlusion was acute(<24 h)in 34%of patients,subacute(>24 h to 30 d)in 26%,and late(>30 d)in 40%.PCI was initially successful in 29/35 SVG occlusions(83%).Total stent length was 52±35 mm.Intraprocedural complications of distal embolization or no-reflow occurred in 6(17%)patients.During longer term follow-up,MACE-free survival was only 30%at 3 years and 17%at 5 years.CONCLUSION PCI of totally occluded SVG can be performed with a high procedural success rate.However,its clinical utility remains limited by poor follow-up outcomes.

Iatrogenic Disruption of Left Main Coronary Artery during Aortic Valve Replacement

This aortic valve replacement (AVR) remains the gold standard for symptomatic aortic stenosis. Peri-operative complications like dissection, stenosis involving coronary artery are well described in many series. We present a rare iatrogenic complication of disrupted left main coronary artery during the delivery of cardioplegia while performing AVR in a 54 year male patient for severe calcific aortic stenosis. The inadvertent injury to the artery was timely noticed and managed successfully with long saphenous vein graft.