Intracoronary linsidomine abolishes acetylcholine-induced vasoconstriction of epicardial coronary arteries.
If the vasodilation of the epicardial coronary arteries caused by linsidomine (SIN-1), the active metabolite of molsidomine, is well established, few data are available concerning the effects of SIN-1 on the acetylcholine (ACh)-induced vasoconstriction of epicardial coronary arteries. Fourteen patients with mild lesions of the left anterior descending artery (LAD) were studied. Intracoronary blood flow velocity was measured by a Doppler probe placed in the proximal segment of the LAD, and cross-sectional arterial area was assessed by quantitative angiography. After initial hemodynamic parameters were measured, 12 mg papaverine was injected into the left main coronary artery. When hemodynamic parameters returned to baseline values, three increasing concentrations of ACh (5 x 10(-7), 10(-6), and 5 x 10(-6) M) were selectively administered into the LAD in a 3 min period for each concentration. While the infusion of ACh 5 x 10(-6) M was continued, 1 mg SIN-1 was injected as a bolus in the ostium of the left coronary artery. After the injection of papaverine, blood flow increased by 197 +/- 8%, with a trend toward vasoconstriction of the proximal and distal segments of the LAD (p = NS). The ACh injection induced a dose-dependent vasoconstriction, reaching 51 +/- 20% on the distal segment of the LAD at the maximum concentration (p < 0.001). After an initial increase in coronary blood flow of 47 +/- 10 and 28 +/- 11% during the first two concentrations of ACh, respectively, the values decreased after the last injection to the level of baseline values. The infusion of SIN-1 antagonized the ACh-induced vasoconstriction, leading to vasodilation of 7.5 +/- 3% (p < 0.005) and 16 +/- 7% (p < 0.001) of the proximal and distal segments of the LAD, respectively; this was associated with an increase in intracoronary blood flow by 42 +/- 8%. We conclude that intracoronary administration of SIN-1 can antagonize the ACh-induced vasoconstriction of epicardial coronary arteries.
Dubois-Rande
J L
JL
Departement de Cardiologie et de Physiologie (Unité d'Hémodynamique et de Cardiologie Interventionnelle, Service d'Explorations Fonctionnelles: INSERM U2 and U296), Hôpital Henri Mondor, Creteil, France.
Dupouy
P
P
Geschwind
H
H
Castaigne
A
A
Adnot
S
S
D000109:Acetylcholine / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D008981:Molsidomine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; C002385:linsidomine; D008981:Molsidomine; D000109:Acetylcholine