Comparison of the effects of levosimendan and papaverine on human internal mammary artery and saphenous vein.
OBJECTIVE
Internal mammary artery (IMA) and saphenous vein (SV) are two most common vessels used in coronary artery bypass grafting (CABG). In the present study, the effect of levosimendan (a novel inotropic/vasodilator compound) and papaverine are compared, using IMA and SV obtained from CABG patients.


METHODS
Unused segments of IMA and SV of each patient were cut into two rings of 3 mm length. Four rings (two from IMA, two from SV) were suspended in an organ bath, contracted with norepinephrine and then the responses to the cumulative concentrations of levosimendan and papaverine were recorded.


RESULTS
Levosimendan relaxed IMA but failed to relax SV completely. In addition, its IC50 value (concentration which reduced 50% of initial contraction) to relax SV was about 300 times higher than the IC50 value for IMA. Its arteriodilating concentration was in the range of its clinically effective inotropic concentration. Papaverine relaxed both vascular preparations completely. Its IC50 value was about 2.4 times higher toward SV in comparison to that of IMA.


CONCLUSIONS
It is concluded that levosimendan is much more potent to relax norepinephrine-induced contraction of human IMA in comparison to its effect on human SV. It may have the potential to be used as a mixed inotropic/arteriodilator compound in several clinical settings including CABG in which it can increase cardiac contractility and prevent IMA vasospasm.
Mirkhani
Hossein
H
Department of Pharmacology, Shiraz University of Medical Sciences, PO Box 71345-1649, Shiraz, Iran. mirkhanh@sums.ac.ir
Shafa
Masih
M
Khazraei
Hajar
H
D000368:Aged; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects*; D008875:Middle Aged; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D012501:Saphenous Vein / Q000187:drug effects*; D000077464:Simendan; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D006835:Hydrazones; D011724:Pyridazines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000077464:Simendan; D010208:Papaverine; D009638:Norepinephrine