Karola Trescher1, Elda Dzilic2, Maximilian Kreibich2, Harald Gasser2, Klaus Aumayr3, Dontscho Kerjaschki3, Brigitte Pelzmann4, Seth Hallström5, Bruno K Podesser6. 1. Department of Cardiac Surgery, LK St. Pölten, Pölten, Austria Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna Medical University, Vienna, Austria karola.trescher@meduniwien.ac.at seth.hallstroem@medunigraz.at. 2. Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna Medical University, Vienna, Austria. 3. Department of Pathology, Vienna Medical University, Vienna, Austria. 4. Institute of Biophysics, Center of Physiological Medicine, Medical University Graz, Graz, Austria. 5. Institute of Physiological Chemistry, Center of Physiological Medicine, Medical University Graz, Graz, Austria karola.trescher@meduniwien.ac.at seth.hallstroem@medunigraz.at. 6. Department of Cardiac Surgery, LK St. Pölten, Pölten, Austria Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna Medical University, Vienna, Austria.
Abstract
OBJECTIVES: Currently available cardioplegic solutions provide excellent protection in patients with normal surgical risk; in high-risk patients, however, such as in emergency coronary artery bypass surgery, there is still room for improvement. As most of the cardioplegic solutions primarily protect myocytes, the addition of substances for protection of the endothelium might improve their protective potential. The nitric oxide donor, S-nitroso human serum albumin (S-NO-HSA), which has been shown to prevent endothelial nitric oxide synthase uncoupling, was added to the newly developed histidine-tryptophan-ketoglutarat (HTK-N) cardioplegia in an isolated heart perfusion system after subjecting rats to acute myocardial infarction (MI) and reperfusion. METHODS: In male Sprague-Dawley rats, acute MI was induced by ligation for 1 h of the anterior descending coronary artery. After 2 h of in vivo reperfusion hearts were evaluated on an isolated erythrocyte-perfused working heart model. Cold ischaemia (4°C) for 60 min was followed by 45 min of reperfusion. Cardiac arrest was induced either with HTK (n = 10), HTK-N (n = 10) or HTK-N + S-NO-HSA (n = 10). In one group (HTK-N + S-NO-HSA plus in vivo S-NO-HSA; n = 9) an additional in vivo infusion of S-NO-HSA was performed. RESULTS: Post-ischaemic recovery of cardiac output (HTK: 77 ± 4%, HTK-N: 86 ± 7%, HTK-N + S-NO-HSA: 101 ± 5%, in vivo S-NO-HSA: 93 ± 8%), external heart work (HTK: 79 ± 5%, HTK-N: 83 ± 3%, HTK-N + S-NO-HSA: 101 ± 8%, in vivo S-NO-HSA: 109 ± 13%), coronary flow (HTK: 77 ± 4%, HTK-N: 94 ± 6%, HTK-N + S-NO-HSA: 118 ± 15%, in vivo S-NO-HSA: 113 ± 3.17%) [HTK-N + S-NO-HSA vs HTK P < 0.001; HTK-N + S-NO-HSA vs HTK-N P < 0.05] and left atrial diastolic pressure (HTK: 122 ± 31%, HTK-N: 159 ± 43%, HTK-N + S-NO-HSA: 88 ± 30, in vivo S-NO-HSA: 62 ± 10%) [HTK-N + S-NO-HSA vs HTK P < 0.05; in vivo S-NO-HSA vs HTK-N P < 0.05] were significantly improved in both S-NO-HSA-treated groups compared with HTK and HTK-N, respectively. This was accompanied by better preservation of high-energy phosphates (adenosine triphosphate; energy charge) and ultrastructural integrity on transmission electron microscopy. However, no additional benefit of in vivo S-NO-HSA infusion was observed. CONCLUSIONS: Addition of the NO donor, S-NO-HSA refines the concept of HTK-N cardioplegia in improving post-ischaemic myocardial perfusion. HTK-N with S-NO-HSA is a possible therapeutic option for patients who have to be operated on for acute MI.
OBJECTIVES: Currently available cardioplegic solutions provide excellent protection in patients with normal surgical risk; in high-risk patients, however, such as in emergency coronary artery bypass surgery, there is still room for improvement. As most of the cardioplegic solutions primarily protect myocytes, the addition of substances for protection of the endothelium might improve their protective potential. The nitric oxidedonor, S-nitrosohuman serum albumin (S-NO-HSA), which has been shown to prevent endothelial nitric oxide synthase uncoupling, was added to the newly developed histidine-tryptophan-ketoglutarat (HTK-N) cardioplegia in an isolated heart perfusion system after subjecting rats to acute myocardial infarction (MI) and reperfusion. METHODS: In male Sprague-Dawley rats, acute MI was induced by ligation for 1 h of the anterior descending coronary artery. After 2 h of in vivo reperfusion hearts were evaluated on an isolated erythrocyte-perfused working heart model. Cold ischaemia (4°C) for 60 min was followed by 45 min of reperfusion. Cardiac arrest was induced either with HTK (n = 10), HTK-N (n = 10) or HTK-N + S-NO-HSA (n = 10). In one group (HTK-N + S-NO-HSA plus in vivo S-NO-HSA; n = 9) an additional in vivo infusion of S-NO-HSA was performed. RESULTS: Post-ischaemic recovery of cardiac output (HTK: 77 ± 4%, HTK-N: 86 ± 7%, HTK-N + S-NO-HSA: 101 ± 5%, in vivo S-NO-HSA: 93 ± 8%), external heart work (HTK: 79 ± 5%, HTK-N: 83 ± 3%, HTK-N + S-NO-HSA: 101 ± 8%, in vivo S-NO-HSA: 109 ± 13%), coronary flow (HTK: 77 ± 4%, HTK-N: 94 ± 6%, HTK-N + S-NO-HSA: 118 ± 15%, in vivo S-NO-HSA: 113 ± 3.17%) [HTK-N + S-NO-HSA vs HTK P < 0.001; HTK-N + S-NO-HSA vs HTK-N P < 0.05] and left atrial diastolic pressure (HTK: 122 ± 31%, HTK-N: 159 ± 43%, HTK-N + S-NO-HSA: 88 ± 30, in vivo S-NO-HSA: 62 ± 10%) [HTK-N + S-NO-HSA vs HTK P < 0.05; in vivo S-NO-HSA vs HTK-N P < 0.05] were significantly improved in both S-NO-HSA-treated groups compared with HTK and HTK-N, respectively. This was accompanied by better preservation of high-energy phosphates (adenosine triphosphate; energy charge) and ultrastructural integrity on transmission electron microscopy. However, no additional benefit of in vivo S-NO-HSA infusion was observed. CONCLUSIONS: Addition of the NO donor, S-NO-HSA refines the concept of HTK-N cardioplegia in improving post-ischaemic myocardial perfusion. HTK-N with S-NO-HSA is a possible therapeutic option for patients who have to be operated on for acute MI.
Authors: Anne-Kristin Schaefer; Attila Kiss; André Oszwald; Felix Nagel; Eylem Acar; Arezu Aliabadi-Zuckermann; Matthias Hackl; Andreas Zuckermann; Renate Kain; Andrzej Jakubowski; Peter Ferdinandy; Seth Hallström; Bruno K Podesser Journal: Transpl Int Date: 2022-04-13 Impact factor: 3.842