Hemodynamic mechanisms of the antianginal action of a novel vasodilator FK409 in dynamic exercise-induced angina.
FK409 is a novel vasodilator with a unique chemical structure. We wished to elucidate the mechanisms of antianginal action of FK409 in dynamic exercise-induced angina. Twelve patients with stable effort angina pectoris were studied before and after a single 40-mg oral dose of FK409. Chest pain was induced in all of 12 patients during the control multistage bicycle ergometer exercise. After FK409 administration, the same workload did not induce chest pain in 6 patients. The ST segment at peak exercise showed less severe depression from 0.15 +/- 0.02 to 0.05 +/- 0.01 mV (p < 0.001). Left ventricular (LV) filling estimated by the Doppler method was reduced, and pulmonary artery wedge pressure decreased significantly (p < 0.001) throughout exercise testing after FK409. Myocardial oxygen uptake and coronary sinus flow throughout exercise testing decreased significantly (p < 0.05) after FK409 administration. The results of the present study demonstrate that decrease in myocardial oxygen demand may be caused by pre- and afterload reduction and that it could be a major mechanism of the antianginal action of FK409. However, other mechanisms such as redistribution of coronary blood flow to the subendocardium, direct dilatation of the stenotic parts of the epicardial arteries, and an increase in collateral blood flow should be considered additional possible mechanisms of the antianginal action of FK409.
Yokota
M
M
Department of Clinical Laboratory Medicine, Nagoya University Hospital, Japan.
Matsunami
T
T
Kodama
Y
Y
Sobue
T
T
Nishinaka
Y
Y
Iwase
M
M
Miyahara
T
T
Koide
M
M
Saito
H
H
Shibata
S
S
D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy* / Q000503:physiopathology; D003326:Coronary Circulation / Q000187:drug effects; D004562:Electrocardiography / Q000187:drug effects; D005080:Exercise Test; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D009574:Nitro Compounds / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects
D009574:Nitro Compounds; D014665:Vasodilator Agents; C061872:FK 409