Normoxic cardiopulmonary bypass reduces oxidative myocardial damage and nitric oxide during cardiac operations in the adult

AbstractObjective: Hyperoxic cardiopulmonary bypass is widely used during cardiac operations in the adult. This management may cause oxygenation injury induced by oxygen-derived free radicals and nitric oxide. Oxidative damage may be significantly limited by maintaining a more physiologic oxygen tension strategy (normoxic cardiopulmonary bypass). Methods: During elective coronary artery bypass grafting, 40 consecutive patients underwent either hyperoxic (oxygen tension = 400 mm Hg) or normoxic (oxygen tension = 140 mm Hg) cardiopulmonary bypass. At the beginning and the end of bypass this study assessed polymorphonuclear leukocyte elastase, nitrate, creatine kinase, and lactic dehydrogenase, antioxidant levels, and malondialdehyde in coronary sinus blood. Cardiac index was measured before and after cardiopulmonary bypass. Results: There was no difference between groups with regard to age, sex, severity of disease, ejection fraction, number of grafts, duration of cardiopulmonary bypass, or ischemic time. Hyperoxic bypass resulted in higher levels of polymorphonuclear leukocyte elastase (377 ± 34 vs 171 ± 32 ng/ml, p = 0.0001), creatine kinase 672 ± 130 vs 293 ± 21 U/L, p = 0.002), lactic dehydrogenase (553 ± 48 vs 301 ± 12 U/L, p = 0.003), antioxidants (1.97 ± 0.10 vs 1.41 ± 0.11 mmol/L, p = 0.01), malondialdehyde (1.36 ± 0.1 μmol/L, p = 0.005), and nitrate (19.3 ± 2.9 vs 10.1 ± 2.1 μmol/L, p = 0.002), as well as reduction in lung vital capacity (66% ± 2% vs 81% ± 1%, p = 0.01) and forced 1-second expiratory volume (63% ± 10% vs 93% ± 4%, p = 0.005) compared with normoxic management. Cardiac index after cardiopulmonary bypass at low filling pressure was similar between groups (3.1 ± 0.2 vs 3.3 ± 0.3 L/min per square meter). [Data are mean ± standard error (analysis of variance), with p values compared with an oxygen tension of 400 mm Hg. Conclusions: Hyperoxic cardiopulmonary bypass during cardiac operations in adults results in oxidative myocardial damage related to oxygen-derived free radicals and nitric oxide. These adverse effects can be markedly limited by reduced oxygen tension management. The concept of normoxic cardiopulmonary bypass may be applied to surgical advantage during cardiac operations. (J Thorac Cardiovasc Surg 1998;116:327-34

Antwort auf Leserbrief zur Publikation in Lab.med. 12, 403-408 (1988)

Antwort auf den Leserbrief von Dr. Rosenberg und Dr. Schuckließ, Boehringer Mannheim GmbH, Sandhofer Straße 116, 6800 Mannheim: https://doi.org/10.1515/labm.1989.13.2.6

Worst case optimization for interfractional motion mitigation in carbon ion therapy of pancreatic cancer

Introduction: The efficacy of radiation therapy treatments for pancreatic cancer is compromised by abdominal motion which limits the spatial accuracy for dose delivery - especially for particles. In this work we investigate the potential of worst case optimization for interfractional offline motion mitigation in carbon ion treatments of pancreatic cancer. Methods: We implement a worst case optimization algorithm that explicitly models the relative biological effectiveness of carbon ions during inverse planning. We perform a comparative treatment planning study for seven pancreatic cancer patients. Treatment plans that have been generated using worst case optimization are compared against (1) conventional intensity-modulated carbon ion therapy, (2) single field uniform dose carbon ion therapy, and (3) an ideal yet impractical scenario relying on daily re-planning. The dosimetric quality and robustness of the resulting treatment plans is evaluated using reconstructions of the daily delivered dose distributions on fractional control CTs. Results: Idealized daily re-planning consistently gives the best dosimetric results with regard to both target coverage and organ at risk sparing. The absolute reduction of D-95 within the gross tumor volume during fractional dose reconstruction is most pronounced for conventional intensity-modulated carbon ion therapy. Single field uniform dose optimization exhibits no substantial reduction for six of seven patients and values for D-95 for worst case optimization fall in between. The treated volume (D > 95 % prescription dose) outside of the gross tumor volume is reduced by a factor of two by worst case optimization compared to conventional optimization and single field uniform dose optimization. Single field uniform dose optimization comes at an increased radiation exposure of normal tissues, e.g. approximate to 2 Gy (RBE) in the mean dose in the kidneys compared to conventional and worst case optimization and approximate to 4 Gy (RBE) in D-1 in the spinal cord compared to worst case optimization. Conclusion: Interfractional motion substantially deteriorates dose distributions for carbon ion treatments of pancreatic cancer patients. Single field uniform dose optimization mitigates the negative influence of motion on target coverage at an increased radiation exposure of normal tissue. Worst case optimization enables an exploration of the trade-off between robust target coverage and organ at risk sparing during inverse treatment planning beyond margin concepts