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• W2012208614 abstract "Reply to the Editor: I would like to thank Thomas and his colleagues for their interest in our recent article1Ihnken K Winkler A Schlensak C Sarai K Neidhart G Unkelbach U et al.Normoxic cardiopulmonary bypass reduces oxidative myocardial damage and nitric oxide during cardiac operations in the adult.J Thorac Cardiovasc Surg. 1998; 116: 327-334Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar and I appreciate their kind remarks. They are to be congratulated for their excellent clinical results in a subgroup of high-risk patients. Their findings are similar to our results in 37 patients with acute coronary occlusion treated with blood cardioplegic controlled coronary reperfusion.2Beyersdorf F Mitrev Z Sarai K Eckel L Klepzig H Ihnken K et al.Changing patterns of patients undergoing emergency surgical revascularization for acute coronary occlusion: importance of myocardial protection techniques.J Thorac Cardiovasc Surg. 1993; 106: 137-148PubMed Google Scholar This concept of controlling the circumstances of initial reperfusion after ischemia was originally developed by Buckberg,3Buckberg GD Studies of controlled reperfusion after ischemia.J Thorac Cardiovasc Surg. 1986; 92: 483-488PubMed Google Scholar long before we established controlled reoxygenation after hypoxemia.4Morita K Ihnken K Buckberg GD Studies of hypoxemic/reoxygenation injury: with aortic clamping. XII. Delay of cardiac reoxygenation damage in the presence of cyanosis: a new concept of controlled cardiac reoxygenation.J Thorac Cardiovasc Surg. 1995; 110: 1265-1273Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar It is important to distinguish between ischemia-reperfusion and hypoxia-reoxygenation injury, and not to interchange the two terms for different settings.5Ihnken K Morita K Buckberg GD Sherman MP Young HH Studies of hypoxemic/reoxygenation injury: without aortic clamping. III. Comparison of the magnitude of damage by hypoxemia/ reoxygenation versus ischemia/reperfusion.J Thorac Cardiovasc Surg. 1995; 110: 1182-1189Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar Whereas there is normal or increased blood flow with nutritious blood during hypoxia, there is no blood supply to a completely ischemic area, which will become secondarily hypoxemic and acidotic. Reperfusion injury has a multifactorial cause, in which restoration of blood flow with normal blood at systemic pressure (uncontrolled reperfusion) will cause lipid peroxidation, membrane damage, cell swelling, calcium overload, mitochondrial disruption, and myocardial necrosis.3Buckberg GD Studies of controlled reperfusion after ischemia.J Thorac Cardiovasc Surg. 1986; 92: 483-488PubMed Google Scholar Controlled reperfusion incorporates mechanisms to control the composition of the reperfusate (calcium, substrates, osmolarity, pH, oxygen-derived free radical scavengers) and the circumstances of the initial reperfusion period (time, temperature, and pressure). Reduced oxygen content in the reperfusate is only one aspect, but all determinants have to be addressed to obtain the full beneficial effect.3Buckberg GD Studies of controlled reperfusion after ischemia.J Thorac Cardiovasc Surg. 1986; 92: 483-488PubMed Google Scholar Reoxygenation injury after hypoxemia, in contrast, is mainly caused by oxygen-derived free radical production and can be significantly reduced by simply applying the concept of normoxia, without considering pH, calcium levels, osmolarity, or pressure. This is demonstrated in the present study and in our studies of hypoxemic immature hearts.1Ihnken K Winkler A Schlensak C Sarai K Neidhart G Unkelbach U et al.Normoxic cardiopulmonary bypass reduces oxidative myocardial damage and nitric oxide during cardiac operations in the adult.J Thorac Cardiovasc Surg. 1998; 116: 327-334Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar, 6Ihnken K Morita K Buckberg GD Matheis G Sherman MP Allen BS et al.Studies of hypoxemic/reoxygenation injury: without aortic clamping. II. Evidence for reoxygenation damage.J Thorac Cardiovasc Surg. 1995; 110: 1171-1181Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar, 7Morita K Ihnken K Buckberg GD Sherman MP Young HH Studies of hypoxemic/reoxygenation injury: without aortic clamping. IX. Importance of avoiding perioperative hyperoxemia in the setting of previous cyanosis.J Thorac Cardiovasc Surg. 1995; 110: 1235-1244Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar However, cardiac reoxygenation injury during ischemia was avoided only by using oxygen reduced, controlled reoxygenation with substrate-enriched blood cardioplegic protection.4Morita K Ihnken K Buckberg GD Studies of hypoxemic/reoxygenation injury: with aortic clamping. XII. Delay of cardiac reoxygenation damage in the presence of cyanosis: a new concept of controlled cardiac reoxygenation.J Thorac Cardiovasc Surg. 1995; 110: 1265-1273Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, 8Ihnken K Morita K Buckberg GD Sherman MP Ignarro LJ Young HH Studies of hypoxemic/reoxygenation injury: with aortic clamping. XIII. Interaction between oxygen tension and cardioplegic composition in limiting nitric oxide production and oxidant damage.J Thorac Cardiovasc Surg. 1995; 110: 1274-1286Abstract Full Text Full Text PDF PubMed Scopus (13) Google Scholar We must also consider that, contrary to coronary reperfusion, hyperoxia not only affects the myocardium, but may have a whole body effect. Our study1Ihnken K Winkler A Schlensak C Sarai K Neidhart G Unkelbach U et al.Normoxic cardiopulmonary bypass reduces oxidative myocardial damage and nitric oxide during cardiac operations in the adult.J Thorac Cardiovasc Surg. 1998; 116: 327-334Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar was designed to assess the damaging potential of hyperoxic extracorporal circulation. Both patient groups underwent ventilator hyperoxia, which is clinically routine, as mentioned by Thomas and associates. There is evidence that hyperoxia during ventilator support also may have negative effects.9Jacobson RM Feinstein AR Oxygen as a cause of blindness in premature infants: “autopsy” of a decade of errors in clinical epidemiologic research.J Clin Epidemiol. 1992; 45: 1265-1287Abstract Full Text PDF PubMed Scopus (29) Google Scholar It is therefore conceivable that patients have an initial reoxygenation injury before cardiopulmonary bypass (CPB). The results of our study,1Ihnken K Winkler A Schlensak C Sarai K Neidhart G Unkelbach U et al.Normoxic cardiopulmonary bypass reduces oxidative myocardial damage and nitric oxide during cardiac operations in the adult.J Thorac Cardiovasc Surg. 1998; 116: 327-334Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar however, indicate that this was not the case, inasmuch as biochemical markers of injury were low at institution of CPB and rose later. Further investigations will have to address this interesting issue. I believe that hyperoxia is not physiologic, but damaging to all organs, and furthermore unnecessary, especially during CPB.10Ihnken K Hyperoxic cardiopulmonary bypass causes reoxygenation injury and lipid peroxidation.J Thorac Cardiovasc Surg. 1997; 114: 304-305Abstract Full Text Full Text PDF PubMed Google Scholar All clinical situations dealing with reperfusion after ischemia or reoxygenation after hypoxia (for example, transplantation, replantation, and extracorporeal membrane oxygenation) have to take into account the damaging potential of hyperoxia and may benefit from applying normoxia. For example, we could demonstrate that adherence to these concepts can prevent reperfusion injury after prolonged skeletal muscle ischemia.11Ihnken K Beyersdorf F Winkelmann BR Mitrev Z Unkelbach U Experimental application of controlled limb reperfusion after incomplete ischaemia.Br J Surg. 1996; 83: 803-809Crossref PubMed Scopus (8) Google Scholar" @default.
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• W2012208614 title "Controlled cardiac reoxygenation in adults with ischemic heart disease" @default.
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