Haemodynamic effects of angiotensin converting enzyme inhibition after cardiopulmonary bypass in dogs.
Recent studies have suggested a possible causative relationship between elevated plasma levels of Angiotensin II (AII) and the vasoconstriction associated with conventional cardiopulmonary bypass. The haemodynamic effects of SQ14225, a specific angiotensin converting enzyme inhibitor, have been studied in a group of five dogs submitted to a 60 min period of cardiopulmonary bypass (CPB). A 20 min infusion of SQ14225 in a dose of 2 microgram .kg-1 .h-1 was administered to each dog 2 h after the end of the period of CPB. Measurements of peripheral vascular resistance index (PVRI), cardiac index (CI) and plasma levels of Angiotensin II were obtained at the start and end of the infusion period. The results in the five blocked dogs were compared with a control series of ten unblocked dogs submitted to an identical cardiopulmonary bypass regine. In the blocked dogs, PVRI fell significantly during infusion of SQ14225 from 38.27 units to 21.70 units (P <0.01). There was a simultaneous significant increase in cardiac index from 3.00 to 3.98 litre.m2 .min-1 (P <0.01). Plasma Angiotensin 11 levels fell in the blocked dogs from 57 to 11.5 pg.cm-2 during the infusion period (normal levels <15 pg.cm-3). In the control unblocked dogs, there was no corresponding fall in PVRI, no rise in cardiac index, and no fall in elevated plasma AII levels. The difference between the groups were statistically highly significant (P <0.005). These results indicate that reduction in elevated plasma AII levels after CPB using converting enzyme inhibitor SQ14225 is associated with a significant fall in peripheral vascular resistance and a significant rise in cardiac index. In addition, the study confirms the causative relationship between elevated plasma levels of Angiotensin II and the increased vasoconstriction associated with non-pulsatile CPB.
D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects*; D011392:Proline / Q000031:analogs & derivatives*; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D011392:Proline; D002216:Captopril