Hemodynamic consequences of inotropic support with digoxin or amrinone in lambs with ventricular septal defect

Inotropic support with digoxin is commonly used in patients with left ventricular volume overload due to ventricular septal defect (VSD). However, the hemodynamic consequences of inotropic agents with VSD have not been experimentally explored. We studied two inotropic agents, digoxin and amrinone, in chronically instrumented lambs with left ventricular volume overload due to a surgically created VSD. Intravenous digoxin (40 micrograms/kg) produced serum levels of 3.5 +/- 0.9 ng/ml (mean +/- SD) in seven lambs 60 min after administration, reduced the heart rate by 16% (172 to 149 beats/min, p less than 0.05), increased the stroke volume 16% (29.8 to 34.5 ml/beat, p less than 0.05) but did not significantly alter the systemic flow index (Qs), the pulmonary flow index (Qp), or the volume of left to right shunt (QL-R, 6.74 to 6.77 liter/min/m2). The mean left atrial pressure (LA) was unchanged (17.6 versus 17.1 mm Hg) following digoxin. Chronic digoxin use in four lambs for 4 days (25 +/- 8 micrograms/kg/8 h) produced trough serum levels of 1.2 +/- 0.2 ng/ml. There was no additional hemodynamic effect compared to acute digoxin, the Qp/Qs ratio was unchanged (3.10 versus 3.08) and evidence of left ventricular volume overload (LA - 14.0 versus 13.4) was unchanged. Amrinone lowered the systemic resistance index in a dose dependent fashion. The peak reduction of 20% (25.3 to 20.3 U/m2, p less than 0.01) occurred at 20 min after an intravenous (3 mg/kg) bolus in seven lambs. The Qs increased from 2.58 to 3.10 liter/min/m2 (p less than 0.01). The Qp was unchanged, thus the Qp/Qs ratio was lowered by 16% (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)