Efekti otvarača kalijumovih kanala na izolovane bajpas graftove bolesnika sa dijabetes melitusom tip 2

Abstract

Ciljevi studije bili su da ispitamo ulogu različitih kalijumovih (K) kanala u kontroli vaskularnog tonusa i antivazokontriktornoj ulozi na bajpas graftovima dobijenim od pacijenata sa dijabetes melitusom tip 2 (DMT2) nakon bajpas operacije. Preostali segmenti humane vene safene (HVS) i unutrašnje torakalne arterije (ITA) dobijeni su od pacijenata bez i sa DMT2. U eksperimentalnom radu koristili smo sistem za izolovane organe kojim smo ispitivali farmakološka svojstva otvarača K kanala i molekularno-biološke tehnike kako bismo detektovali promene u ekspresiji i lokalizaciji K kanala na ovim graftovima. Farmakološki eksperimenti su pokazali da pinacidil daje uporedivu relaksaciju HVS pacijenata sa i bez DMT2. Takođe, pinacidil produkuje relaksaciju dijabetične ITA uporedivu sa dijabetičnom HVS bez razlike u senzitivnosti. Molekularne tehnike su pokazale smanjenu ekspresiju SUR2B subjedinice kod HVS pacijenata sa DMT2 ukazujući da je povećana osetljivost HVS kod NDM pacijenata uslovljena većom ekspresijom funkcionalnih KATP kanala u vaskularnom glatkom mišiću. Subjedinice Kir6.x koje ulaze u sastav KATP kanala su pokazale smanjenu ekspresiju na dijabetičnoj ITA. Dobijeni rezultati studije pokazali su da pinacidil ima komparabilno vazodilatatorno i antivazokonstriktorno dejstvo na humanim bajpas graftovima kod pacijenata bez i sa DMT2. Podaci mogu biti klinički korisni pružajući dokaz da dijabetes izaziva oslabljenu dilataciju humane vene i arterije i da se efekti pinacidila delimično ostvaruju preko različitih K kanala na glatko-mišićnom sloju grafta. Takođe, njima se može analizirati opravdanost rezultata kliničkih ispitivanja koji favorizuju bajpas operaciju umesto perkutane koronarne intervencije za direktnu revaskularizaciju srca kod pacijenata sa DMT2.

The objectives of our study were to examine the role of different potassium (K) channels in the control of vascular tone and the antivasocontrictive role on bypass grafts obtained from patients with type 2 diabetes mellitus (T2DM) after bypass surgery. Leftover segments of human saphenous vein (HSV) and internal thoracic artery (ITA) were obtained from patients with and without T2DM. In our experimental work, we used an isolated organ system to examine the pharmacological properties of K channel openers and molecular-biological techniques to detect changes in the K channels expression and their localization in bypass grafts. The pharmacological experiments showed that the relaxation caused by pinacidil was comparable in HVS patients with and without T2DM. Also, pinacidil produced relaxation of diabetic ITA comparable to diabetic HVS without difference in the sensitivity. Molecular techniques have shown decreased expression of the SUR2B subunit in HVS T2DM patients indicated that the increased sensitivity of HVS in patients without T2DM is due to higher expression of functional KATP channels in the vascular smooth muscle. Significantly lower expression of the Kir6.x subunits of the KATP channels was observed in diabetic ITA. The obtained results of our study showed that pinacidil has a comparable vasodilatory and antivasoconstrictory effects on human bypass grafts in patients with and without T2DM. These data may be clinically useful since they provide evidence that diabetes causes impaired dilatation of the human vein and artery indicated that the effects of pinacidil are partially mediated through various K channels on the smooth muscle of the graft. They can, also, serve as an objective to justificate the results of clinical trials that favor CABG surgery instead of percutaneous coronary intervention for direct heart revascularization in patients with T2DM.