The comparison of the responsiveness of human isolated internal mammary and gastroepiploic arteries to levcromakalim: an alternative approach to the management of graft spasm.
OBJECTIVE
We studied the effectiveness of levcromakalim, a potassium channel opener (KCO), in the prevention and reversal of spasm in arterial grafts used in coronary artery bypass operations, namely, internal mammary artery (IMA) and gastroepiploic artery (GEA).


METHODS
Spasm was mimicked in vitro in arterial rings from 109 patients by increasing the vascular tension with noradrenaline, the thromboxane analogue U46619, endothelin-1 and K+.


RESULTS
GEA displayed considerably higher contractile force to these agents than IMA. Pretreatment with levcromakalim depressed significantly the maximal contractile responses (either absolute or relative) to noradrenaline and U46619 but did not affect those of endothelin-1 and K+ in both of the arteries. Sensitivities (to all agents, except to endothelin-1) decreased significantly after levcromakalim. In experiments evaluating the antispasmodic activity of levcromakalim, a higher relaxant capacity was observed in GEA than IMA (for K+ contraction; IMA: 31.32 +/- 3.83%, n= 13 vs GEA: 98.01 +/- 0.71%, n=7, P<0.05). This different activity of levcromakalim between two arterial grafts was apparent even when GEA rings were contracted to higher force (g) than that of IMA (for K+ contraction; GEA: 72.56 +/- 4.96%, n = 7). Responses to levcromakalim were similar in IMA and GEA when endothelin-1 was used as the spasmogenic agent (IMA: 80.98 +/- 4.85%, n=10 vs GEA: 91.93 +/- 3.17%, n=7, P>0.05).


CONCLUSIONS
Our results provide evidence that levcromakalim may have a therapeutic value in the treatment of spasm of coronary artery bypass grafts, especially GEA.
Akar
F
F
Gazi University, Faculty of Pharmacy, Department of Pharmacology, Ankara, Turkey.
Uydeş-Dogan
B S
BS
Tufan
H
H
Aşlamaci
S
S
Köksoy
C
C
Kanzik
I
I
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001158:Arteries / Q000187:drug effects* / Q000502:physiology / Q000637:transplantation; D001578:Benzopyrans / Q000494:pharmacology*; D001026:Coronary Artery Bypass; D019806:Cromakalim; D019332:Endothelin-1 / Q000494:pharmacology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects* / Q000502:physiology / Q000637:transplantation; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D009852:Omentum / Q000098:blood supply; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology*; D013270:Stomach / Q000098:blood supply; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D019332:Endothelin-1; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011450:Prostaglandin Endoperoxides, Synthetic; D011758:Pyrroles; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019806:Cromakalim; D019335:Nitroarginine; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011188:Potassium; D005905:Glyburide; D009638:Norepinephrine; D007213:Indomethacin