Dog model to study the effects of pharmacologic agents on the peripheral circulation: Effect of milrinone

To study the effects of an inotropic agent, milrinone, on the entire cardiovascular system, we developed an intact dog model to assess the responses of the heart, arterial and venous circulations. At a dose that increased left ventricular dP/dt by 30% (P <.001) from 2033 ± 133 to 2688 ± 140 mm Hg/sec, milrinone caused a decrease (P <.001) in mean aortic pressure from 88.4 ± 3.5 to 73.1 ± 3.0 mm Hg and cardiac output from 148.0 ± 14.6 to 134.5 ± 13.9 ml/kg/min. Heart rate increased (P <.01) from 124 ± 8 to 135 ± 8 beats/min. Systemic vascular resistance did not change. Right atrial pressure and left ventricular enddiastolic pressure decreased (P <.01). Total blood volume did not change but central blood volume decreased (P <.01) from 26.1 ± 0.9 to 22.3 ± 0.5 ml/kg. After milrinone administration, mean circulatory filling pressure decreased (P <.01) by 30% from 7.4 ± 0.4 to 5.0 ± 0.2 mm Hg. Vascular or venous compliance increased (P <.05) slightly from 1.96 ± 0.4 to 2.20 ± 0.1 ml/mm Hg/kg. This was accompanied by an increase (P <.01) in unstressed vascular blood volume of 3.3 ± 0.6 ml/kg. Arterial compliance also increased (P <.05). In summary, milrinone produces an increase in inotropy, arterial vasodilatation and venodilatation as evidenced by the increased venous compliance and unstressed vascular volume. These changes result in a decrease in left ventricular end-diastolic pressure and cardiac output in the normal heart but would be expected to improve the hemodynamics and cardiac output in the setting of a failing heart.