Effects of captopril on the distribution of left ventricular output with ventricular septal defect.
The renin-angiotensin system is activated by congestive heart failure associated with a ventricular septal defect (VSD). To determine the effect of angiotensin-converting enzyme inhibition on the hemodynamics with VSD, the dose response curve of captopril was measured in lambs. Furthermore, the effect of captopril on the distribution of systemic output was determined by the radionuclide-labeled microsphere technique. A total of 12 lambs (less than 1 month old) with VSD were instrumented and a minimum of five animals was tested for each data point. Captopril (0.05-10 mg/kg) caused dose-dependent vascular changes. At a dose of 2 mg/kg, maximal hemodynamic effects were observed. The systemic resistance fell by 28 +/- 9% (mean +/- SD, p less than 0.05, n = 9), whereas pulmonary arteriolar resistance rose by 113 +/- 34% (p less than 0.05). These vascular changes caused a reduction in the ratio of pulmonary to systemic flow from 3.31 +/- 0.59 to 2.19 +/- 0.29 (-34%, p less than 0.05) and a reduction in left-to-right shunt volume by 30% (p less than 0.05). The left atrial pressure fell from 17.3 +/- 3.4 to 10.8 +/- 2.8 mm Hg (-38%, p less than 0.05). Mean aortic pressure was unchanged (71.2 +/- 8.1 versus 67.4 +/- 9.1). Forward flow from the left ventricle increased from 2.17 +/- 0.46 to 2.86 +/- 0.54 liter/min/M2 (p less than 0.05). Microsphere-determined organ blood flow to the heart, kidney, liver, duodenum, and skeletal muscle was preserved after a 5 mg/kg dose of captopril and, in fact, tended to increase, but the changes were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects*; D006345:Heart Septal Defects, Ventricular / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D011652:Pulmonary Circulation / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep; D014655:Vascular Resistance / Q000187:drug effects
D002216:Captopril