Haemodynamic effects of RO 13-6438, a new inotropic agent with vasodilating properties

The chemical class 1,5-dihydroimidazo (2,1-6) guinazolin-2(3H)ones has been shown to have positive inotropic activity, some of its members displaying a favourable ratio between positive inotropic and chronotropic activity. This study was designed to determine the cardiovascular properties of Ro 13-6483, a non-glycoside, non-catechol positive inotropic agent, in anaesthetized, open chest mongrel dogs. Ro 13-6483 (1 mg/kg) was administered intravenously over a 5-min period to 6 dogs. Haemodynamic changes were measured continuously over a period of 45 min. Ro 13-6483 increased stroke volume by 61.9% (p < 0.001) and cardiac output by 53.3% (p < 0.001). Systolic and diastolic blood pressure decreased significantly (p < 0.01). Heart rate did not change. The lowering of the blood pressure, without a significant increase in heart rate, observed after Ro 13-6483 administration might prove to be of value in patients with congestive heart failure, since Ro 13-6483 would reduce afterload and improve the competency of the heart, in addition to the positive inotropic effects.