STUDIES OF HYPOXEMIC REOXYGENATION INJURY - WITHOUT AORTIC CLAMPING .9. IMPORTANCE OF AVOIDING PERIOPERATIVE HYPEROXEMIA IN THE SETTING OF PREVIOUS CYANOSIS/

This study of an in vivo infantile piglet model of compensated hypoxem ia tests the hypothesis that reoxygenation on hyperoxemic cardiopulmon ary bypass produces oxygen-mediated myocardial injury that can be limi ted by normoxemic management of cardiopulmonary bypass and the interva l after cardiopulmonary bypass. Twenty-five immature piglets (<3 weeks old) were placed on 120 minutes of cardiopulmonary bypass and five pi glets served as a biochemical control group without cardiopulmonary by pass. Five piglets underwent cardiopulmonary bypass without hypoxemia (cardiopulmonary bypass control). Twenty others became hypoxemic on ca rdiopulmonary bypass for 60 minutes by lowering oxygen tension to abou t 25 mm Hg. The study was terminated in five piglets at the end of hyp oxemia, whereas 15 others were reoxygenated at an oxygen tension about 400 mm Hg or about 100 mm Hg for 60 minutes. Oxygen delivery aas main tained during hypoxemia by increasing cardiopulmonary bypass flow and hematocrit level to avoid metabolic acidosis and lactate production, M yocardial function after cardiopulmonary bypass was evaluated from end -systolic elastance (conductance catheter) and Starling curve analysis , Myocardial conjugated diene production and creatine kinase leakage w ere assessed as biochemical markers of injury, and antioxidant reserve capacity was determined by measuring malondialdehyde after cardiopulm onary bypass in myocardium incubated in the oxidant, t-butylhydroperox ide, Cardiopulmonary bypass without hypoxemia caused no oxidant or fun ctional damage. Conversely, reoxygenation at an oxygen tension about 4 00 mn Hg raised myocardial conjugated diene level and creatine kinase production (CD: 3.5 +/- 0.7 A(233) mn/min/100 g, creatine kinase: 8.5 +/- 1.5 U/min/100 g, p < 0.05 vs cardiopulmonary bypass control), redu ced antioxidant reserve capacity (malondialdehyde: 1115 +/- 60 nmol/g protein at 4.0 mmol t-butylhydroperoxide, p < 0.05 vs control), and pr oduced severe postbypass dysfunction (end-systolic elastance recovered only 39% +/- 7%, p < 0.05 vs cardiopulmonary bypass control). Lowerin g oxygen tension to about 100 mm Hg during reoxygenation avoided conju gated diene production and creatine kinase release, retained normal an tioxidant reserve, and improved functional recovery (80% +/- 11%, p < 0.05 vs oxygen tension about 400 mm Hg). These findings show that conv entional hyperoxemic cardiopulmonary bypass causes unintended reoxygen ation injury in hypoxemic immature hearts that may contribute to myoca rdial dysfunction after cardiopulmonary bypass and that normoxemic man agement may be used to surgical advantage.