Quinaprilat during cardioplegic arrest in the rabbit to prevent ischemia-reperfusion injury

Objectives: This study evaluated intracardiac angiotensin-converting enzyme inhibition as an adjuvant to cardioplegia and examined its effects on hemodynamic. metabolic, and ultrastructural postischemic outcomes. Methods: The experiments were performed With an isolated, erythrocyte-perfused, rabbit working-heart model. The hearts excised from 29 adult New Zealand White rabbits (2950 1 200 g) were randomly assigned to four groups. Two groups received quinaprilat (1 mug/mL), initiated either with cardioplegia (n = 7) or during reperfusion (n = 7). The third group received L-arginine (2 mmol/L) initiated with cardioplegia (n = 7). Eight hearts served as a control group, Forty minutes of preischemic perfusion were followed by 60 minutes of hypothermic arrest and 40 minutes of reperfusion. Results: All treatments substantially improved postischemic recovery of external heart work, (62% +/- 6%, 69% +/- 3%, and 64% +/- 5% in quinaprilat during cardioplegia, quinaprilat during reperfusion, and L-arginine groups, respectively, vs 35% +/- 5% in control group, P <.001) with similarly increased external stroke work and cardiac output. When administered during ischemia, quinaprilat significantly improved recovery of coronary flow (70% +/- 8%, P =.028 vs quinaprilat during reperfusion [49% +/- 5%] and P = .023 vs control [48% +/- 6%]). L-Arginine (55% +/- 7%) showed no significant effect, Postischemic myocardial oxygen consumption remained low in treatment groups (4.6 +/- 1.2 mL . min(-1) . 100 g(-1), 6.0 +/- 2.2 mL . min(-1) . 100 g(-1), and 4.7 +/- 1.6 mL . min 100 g(-1) in quinaprilat during cardioplegia, quinaprilat during reperfusion, and L-arginine groups, respectively. vs 4.2 +/- 0.8 mL . min(-1) . 100 g(-1) in control group), even though cardiac work was markedly increased. High-energy phosphates, which Were consistently elevated in all treatment groups. showed a significant increase in adenosine triphosphate with quinaprilat during ischemia (2.24 +/- 0.14 μmol/g vs 1.81 +/- 0.12 μmol/g, in control group, P =.040). Ultrastructural grading of mitochondrial damage revealed best preservation with quinaprilat during, ischemia (100% [no damage], P =.001 vs control). Conclusion: These experimental findings have clinical relevance regarding prevention of postoperative myocardial stunning and low coronary reflow in patients undergoing heart surgery.