We compared the effect of an
ATP-sensitive potassium channel opener,
YM934, with that of
nitroglycerin (NTG) on impaired coronary circulation in dogs.
Coronary stenosis was produced in 7 dogs by placing a hydraulic occluder around the proximal left circumflex coronary (LCx) artery and abolishing
reactive hyperemia to compromise the LCx flow. The following parameters were measured: the aortic pressure, LCx flow velocity, LCx vessel diameter, LCx peripheral pressure, and segment length in the LCx area. Subsequently, we occluded the LCx artery for 15 seconds and measured the recovery-interval (time required for the segment shortening to return to the preocclusion value). The measurements were recorded under three study conditions: (1) at baseline without LCx
stenosis; (2) with LCx
stenosis under NTG infusion (3 microg/Kg/min); and (3) with LCx
stenosis after
intravenous administration of
YM934 (0.3 microg/kg). The heart rate and aortic pressure were similar under the three study conditions. Mean LCx flow velocity and segment shortening did not significantly change either. However, LCx peripheral pressure decreased after the induction of
stenosis (P < 0.05) and showed no response to either NTG or
YM934.
YM934 administration significantly increased LCx flow in the presence of LCx
stenosis, (P < 0.05), whereas NTG infusion did not.
YM934 significantly shortened the recovery-interval of the segment shortening after 15-sec LCx occlusion (P < 0.05), whereas NTG did not. These findings suggest that
YM934 improves coronary blood flow and prevents myocardial ischemic damage in severely impaired coronary circulation.