Negative inotropic effects of amrinone in the neonatal piglet heart

Cardiac mechanical function and coronary flow (CF) were measured in isovolumically beating hearts from neonatal piglets 0.5 to 12 days of age. The hearts were perfused retrogradely at 70 cm H2O with a recirculating modified Krebs-Henseleit solution containing washed adult pig red cells (hematocrit, 25%). They were electrically paced (180 beats/min), and left ventricular developed pressure (delta P), maximum rate of rise of pressure (dP/dt), CF, and myocardial oxygen consumption were measured. These parameters were found to remain stable for at least 60 minutes. In one group, a single dose of amrinone was added to the perfusate to yield a concentration of 50 micrograms/ml. Within 5 minutes delta P decreased from 104.0 +/- 7.1 to 65.3 +/- 8.6 mm Hg (p less than 0.001), and dP/dt fell from 1,160 +/- 96 to 658 +/- 78 mm Hg/sec (p less than 0.001). In a second group, successive doses of amrinone were added to yield concentrations ranging from 5 to 50 micrograms/ml. There was a progressive decrease in delta P and dP/dt to 66.5 +/- 4.2% and 57.6 +/- 4.8% of initial values, respectively. CF increased progressively from 3.2 +/- 0.2 to 6.8 +/- 0.5 ml/min/g. In 3 experiments, amrinone was washed out after achieving the maximum concentration. Depressed mechanical function reversed and delta P and dP/dt returned to control values in each heart. Additionally, CF decreased from 7.6 +/- 0.3 to 5.0 +/- 0.2 ml/min/g. It is concluded that amrinone has concentration-dependent negative inotropic actions in the neonatal piglet heart. Hence, the drug may not be useful in treating heart failure in the human neonate.