title: Acute hemodynamic effects of angiotensin- converting enzyme inhibition after prolonged cardiac arrest with Bretschneider's solution.
abstract: Evidence as to how ACE inhibitors attenuate ischemia-reperfusion injury (IR) after cardioplegic arrest remains scarce. Twenty-four rabbit hearts were perfused on a Langendorff apparatus. Control hearts (n = 6) were arrested with pure histidine-tryptophan-ketoglutarate (HTK)-Bretschneider. Treatment groups received added to the cardioplegic solution (n = 6) captopril (100 μmol/l) and losartan (100 μmol/l) for selective AT1-receptor antagonism or BQ123 (100 nmol/l) for selective ETA-receptor antagonism. Pre-ischemic equilibration of 45 min was followed by 90 min of cardioplegic arrest and 30 min of reperfusion. Indices of myocardial contractility (LVP, dp/dt max, dp/dt min), coronary flow, heart rate, and O2 consumption were recorded before and after ischemic arrest. Tissue adenosine triphosphate (ATP) and malondialdehyde (MDA) contents were measured to evaluate energy content and oxidative stress, respectively. After selective cardiac arrest with Bretschneider, captopril-treated hearts showed improved hemodynamics compared to control and the other treatment groups. Oxygen consumption was significantly decreased during early reperfusion in captopril-treated hearts (34 ± 3 μmol/min/g/mmHg) compared to controls and losartan- and BQ123-treated hearts (controls: 77 ± 9 μmol/min/g/mmHg, p = 0.003; losartan: 54 ± 9 μmol/min/g/mmHg, p = 0.015; BQ123: 64 ± 13 μmol/min/g/mmHg, p = 0.046). The ATP content of the reperfused tissue was significantly elevated after captopril treatment compared to control group (24 ± 2 vs. 16 ± 2 μmol/g, p = 0.033), whereas the level of MDA was substantially decreased (0.58 ± 0.163 vs. 1.5 ± 0.28 μmol/g, p = 0.009). ACE inhibition leads to a significantly greater and faster recovery of myocardial contractility after prolonged cardiac arrest with Bretschneider solution. Due to decreased oxygen consumption, myocardial protection is enhanced. The association between ACE and ischemia cannot be clarified by selective blockade of angiotensin-II receptor type 1 (AT1-R) or ETa receptor (ETa-R).
authors.affiliation: Department of Cardiac Surgery, University of Leipzig, Heart Center Leipzig, Struempellstrasse 39, 04289, Leipzig, Germany, alexandrohoyer@googlemail.com.
authors.forename: Alexandro
authors.initials: A
authors.lastname: Hoyer
authors.forename: Jörg
authors.initials: J
authors.lastname: Kempfert
authors.forename: Patrick
authors.initials: P
authors.lastname: Pritzwald-Stegmann
authors.forename: Friedrich-Wilhelm
authors.initials: FW
authors.lastname: Mohr
authors.forename: Stefan
authors.initials: S
authors.lastname: Dhein
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D065128:Endothelin Receptor Antagonists / Q000494:pharmacology; D005947:Glucose / Q000008:administration & dosage; D006323:Heart Arrest / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008353:Mannitol / Q000008:administration & dosage; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D010101:Oxygen Consumption / Q000187:drug effects; D010456:Peptides, Cyclic / Q000494:pharmacology; D011189:Potassium Chloride / Q000008:administration & dosage; D011343:Procaine / Q000008:administration & dosage; D011817:Rabbits
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; C039984:Bretschneider cardioplegic solution; D065128:Endothelin Receptor Antagonists; D010456:Peptides, Cyclic; D008353:Mannitol; D008315:Malondialdehyde; D011343:Procaine; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D002216:Captopril; D005947:Glucose; D019808:Losartan; C072247:cyclo(Trp-Asp-Pro-Val-Leu)