Pre-conditioning with the soluble guanylate cyclase activator Cinaciguat reduces ischaemia-reperfusion injury after cardiopulmonary bypass

• Verfasst von: Radovits, Tamás [VerfasserIn]
• Verfasst von: Korkmaz-İçöz, Sevil [VerfasserIn]
• Verfasst von: Miesel-Gröschel, Christiane [VerfasserIn]
• Verfasst von: Seidel, Beatrice [VerfasserIn]
• Verfasst von: Stasch, Johannes-Peter [VerfasserIn]
• Verfasst von: Merkely, Béla [VerfasserIn]
• Verfasst von: Karck, Matthias [VerfasserIn]
• Verfasst von: Szabó, Gábor [VerfasserIn]
• Titel: Pre-conditioning with the soluble guanylate cyclase activator Cinaciguat reduces ischaemia-reperfusion injury after cardiopulmonary bypass
• Verf.angabe: Tamás Radovits, Sevil Korkmaz, Christiane Miesel-Gröschel, Beatrice Seidel, Johannes-Peter Stasch, Béla Merkely, Matthias Karck, Gábor Szabó
• E-Jahr: 2011
• Jahr: 01 February 2011
• Umfang: 8 S.
• Fussnoten: Gesehen am 08.09.2022
• Titel Quelle: Enthalten in: European journal of cardio-thoracic surgery
• Ort Quelle: Oxford : Oxford Univ. Press, 1987
• Jahr Quelle: 2011
• Band/Heft Quelle: 39(2011), 2, Seite 248-255
• ISSN Quelle: 1873-734X
• DOI: doi:10.1016/j.ejcts.2010.05.025
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1816282715

Abstract

Objective: Activation of the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) pathway can induce potent cardioprotection-like effects against ischaemia-reperfusion injury and nitro-oxidative stress. We investigated the effects of pharmacological pre-conditioning with Cinaciguat (BAY 58-2667), a novel sGC activator on peroxynitrite-induced endothelial dysfunction in vitro, as well as on myocardial and coronary vascular function during reperfusion in a canine model of cardioplegic arrest and extracorporeal circulation. Methods: Isolated coronary arterial rings exposed to peroxynitrite were investigated for vasomotor function. Vehicle- and Cinaciguat-pre-treated (8.33 μg h−1 or 25 μg h−1 intravenous (IV) for 30 min) anaesthetised dogs (n = 6-7 per group) underwent hypothermic cardiopulmonary bypass with 60 min of hypothermic cardioplegic arrest. Left- and right-ventricular end-systolic pressure-volume relationship (ESPVR) was measured by a pressure-volume conductance catheter at baseline and after 60 min of reperfusion. Coronary blood flow, vasodilatation to acetylcholine and myocardial level of adenosine triphosphate were determined. Results: Pre-incubation of coronary rings with Cinaciguat improved peroxynitrite-induced endothelial dysfunction. Compared with control, pharmacological pre-conditioning with Cinaciguat (25 μg h−1) led to higher myocardial adenosine triphosphate content, to a better recovery of left- and right-ventricular contractility (Δ slope of left ventricular ESPVR given as percent of baseline: 102.4 ± 19.1% vs 56.0 ± 7.1%) and to a higher coronary blood flow (49.6 ± 3.5 ml min−1 vs 28.0 ± 3.9 ml min−1). Endothelium-dependent vasodilatation to acetylcholine was improved in the treatment groups. Conclusions: Pre-conditioning with Cinaciguat improves myocardial and endothelial function after cardiopulmonary bypass with hypothermic cardiac arrest. The observed protective effects imply that pharmacological sGC activation could be a novel therapeutic option in the protection against ischaemia-reperfusion injury in cardiac surgery.