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).

Effects of minocycline on parameters of cardiovascular recovery after cardioplegic arrest in a rabbit Langendorff heart model

“…Therefore, it may be a favourable strategy to inhibit MPT and depolarization of mitochondria . Accordingly, a beneficial effect of MTP‐inhibition by cyclosporine was recently demonstrated by the authors . Moreover, it has been described in liver cells that minocycline protects from ischemia/reperfusion injury by suppressing mitochondrial calcium uptake and inhibiting MPT.…”

“…33 Accordingly, a beneficial effect of MTP-inhibition by cyclosporine was recently demonstrated by the authors. 34 Moreover, it has been described in liver cells that minocycline protects from ischemia/reperfusion injury by suppressing mitochondrial calcium uptake and inhibiting MPT. This resulted in diminished mitochondrial swelling and in decreased release of pro-apoptotic factors.…”

“…For cardioplegia experiments mature male Chinchilla rabbits (2000–2500 g) were used. Preparation and perfusion of the hearts according to the Langendorff‐technique was done as described earlier …”

“…Preparation and perfusion of the hearts according to the Langendorff-technique was done as described earlier. 34,36 Briefly, rabbits were anaesthetized with medetomidine (0.2 mg/kg body weight) and ketamine (20 mg/kg body weight). After induction of narcosis heparine (500 IU/kg body weight) was administered intravenously and the thorax was opened.…”

Enalapril protects against myocardial ischemia/reperfusion injury in a swine model of cardiac arrest and resuscitation

“…However, information regarding the application of ACEIs in patients with CA and resuscitation is limited. Recently, Hoyer et al provided evidence that ACE inhibition led to significantly improved myocardial contractility after prolonged CA with Bretschneider's solution ( 36 ). In line with the findings of this study, our data demonstrated that enalapril also successfully decreased myocardial injury in a swine model of CA-resuscitation.…”