Acute hemodynamic effects of angiotensin- converting enzyme inhibition after prolonged cardiac arrest with Bretschneider%26apos;s solution

作者：Hoyer Alexandro^*; Kempfert Joerg; Pritzwald Stegmann Patrick; Mohr Friedrich Wilhelm; Dhein Stefan

来源：Naunyn-Schmiedeberg's Archives of Pharmacology, 2014, 387(12): 1221-1229.

DOI：10.1007/s00210-014-1052-7

• Captopril
• HTK solution
• Cardioprotection
• Endothelin
• Angiotensin

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 mu mol/l) and losartan (100 mu mol/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 O-2 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 mu mol/min/g/mmHg) compared to controls and losartan- and BQ123-treated hearts (controls: 77 +/- 9 mu mol/min/g/mmHg, p = 0.003; losartan: 54 +/- 9 mu mol/min/g/mmHg, p = 0.015; BQ123: 64 +/- 13 mu mol/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 mu mol/g, p = 0.033), whereas the level of MDA was substantially decreased (0.58 +/- 0.163 vs. 1.5 +/- 0.28 mu mol/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 (AT(1)-R) or ETa receptor (ETa-R).

• 出版日期2014-12