Functional effects of nitric oxide-releasing aspirin on vein conduits of diabetic patients undergoing CABG.
BACKGROUND
Type 2 diabetes mellitus (DM) is known to negatively affect biological properties of venous vasculature, and, particularly, to reduce endothelium-derived nitric oxide release. This condition might influence venous graft function following coronary artery bypass surgery (CABG). The aim of this study was to evaluate the functional effects of a NO-releasing aspirin (NORA) on vein grafts (VG) of diabetics and control patients undergoing elective CABG.


METHODS
In 40 consecutive ischemic heart disease patients, the effects of NORA were tested on segments of saphenous vein conduits harvested during elective CABG. Twenty patients had type-2 DM (mean age 69+/-2), whereas 20 patients had no DM (NDM) and represented the control group (mean age 67+/-4). Functional responses were tested by exposing VGs to NORA and to standard vasoactive agents in an organ-bath preparation. Histological features of VGs were also assessed by light and electronic microscopy.


RESULTS
Significant impairment of endothelial-dependent vasodilation (acetylcholine induced) was documented in VGs of DM subjects. NORA induced a significant and comparable vascular relaxation in all venous segments of NDM and DM patients (56+/-12% of maximal relaxation vs 61+/-11% in the control group, respectively). Histology showed variable extent of vascular layer and cellular abnormalities in VGs of diabetics (intimal hyperplasia, calcific deposition, endothelial cell degeneration) likely responsible of the endothelial functional impairment, whereas control group VG showed preserved structures.


CONCLUSIONS
This preliminary study confirms the impairment of endothelium-dependent vasodilative property of VGs in DM patients. It also indicates that NORA effectively induces vasodilation of VGs which was effective also in DM patients thereby representing a promising therapy for diabetics undergoing CABG with the use of VGs, although further studies are mandatory to conclusively assess the safety and benefits of this pharmacological agent.
Lorusso
Roberto
R
Experimental Cardiac Surgery Laboratory and Cardiac Surgery Unit, Civic Hospital, Brescia, Italy. roberto_lorusso@iol.it
De Cicco
Giuseppe
G
Beghi
Cesare
C
Gherli
Tiziano
T
Poli
Enzo
E
Corradi
Domenico
D
Maestri
Roberta
R
Bonadonna
Stefania
S
Mancini
Tatiana
T
Giustina
Andrea
A
D000109:Acetylcholine / Q000627:therapeutic use; D000368:Aged; D001241:Aspirin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000150:complications / Q000188:drug therapy / Q000473:pathology / Q000601:surgery*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009599:Nitroprusside / Q000627:therapeutic use; D012501:Saphenous Vein / Q000187:drug effects* / Q000637:transplantation*; D019737:Transplants; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000627:therapeutic use
D005343:Fibrinolytic Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; C102148:nitroaspirin; D000109:Acetylcholine; D001241:Aspirin