Quinaprilat during cardioplegic arrest in the rabbit to prevent ischemia-reperfusion injury.
OBJECTIVE
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 +/- 200 g) were randomly assigned to four groups. Two groups received quinaprilat (1 microg/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(-1). 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 micromol/g vs 1.81 +/- 0.12 micromol/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).


CONCLUSIONS
These experimental findings have clinical relevance regarding prevention of postoperative myocardial stunning and low coronary reflow in patients undergoing heart surgery.
Korn
Peter
P
Department of Cardiothoracic Surgery, Allgemeines Krankenhaus Wien, Waeringer Guertel 18-20, A-1090 Vienna, Austria.
Kröner
Andreas
A
Schirnhofer
Jan
J
Hallström
Seth
S
Bernecker
Oliver
O
Mallinger
Rudolf
R
Franz
Maximilian
M
Gasser
Harald
H
Wolner
Ernst
E
Podesser
Bruno K
BK
D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001784:Blood Gas Analysis; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D006324:Heart Arrest, Induced / Q000379:methods*; D006439:Hemodynamics; D007546:Isoquinolines / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000648:ultrastructure; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D011817:Rabbits; D044005:Tetrahydroisoquinolines
D000806:Angiotensin-Converting Enzyme Inhibitors; D002314:Cardioplegic Solutions; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C054501:quinaprilat