Effect of ICI 118,587 on left ventricular function during graded treadmill exercise in conscious dogs

Effect of ICI 118,587 (corwin, ICI), a new cardioselective beta-partial agonist, on left ventricular (LV) function was studied and compared with that of isoproterenol and propranolol in 10 conscious normal dogs, instrumented with a micromanometer and pairs of ultrasonic crystals for analysis of LV wall motion. Heart rate, LV dP/dt and mean circumferential shortening velocity were measured at rest and during 3 levels of treadmill exercise (Ex). Before drug administration (control), the heart rate, dP/dt, percent shortening and mean circumferential shortening velocity were enhanced linearly along with the graded Ex. The Ex response curve shifted upward during isoproterenol infusion and downward after the administration of propranolol. With ICI, hemodynamic and contractile indexes were enhanced at rest as with isoproterenol, while these indexes were depressed during maximal Ex as after propranolol. The Ex response curve after ICI crossed the control response curve at a moderate level of Ex. Thus ICI exerts positive inotropic and chronotropic effects at rest when basal sympathetic tone is low, whereas it exerts negative inotropic and chronotropic properties at maximal Ex when sympathetic tone is high. The inherent dual action of this drug is expected to open a new field of treatment for ischemic heart disease with or without heart failure.