STUDIES OF HYPOXEMIC REOXYGENATION INJURY - WITHOUT AORTIC CLAMPING .13. INTERACTION BETWEEN OXYGEN-TENSION AND CARDIOPLEGIC COMPOSITION INLIMITING NITRIC-OXIDE PRODUCTION AND OXIDANT DAMAGE/

This study tests the interaction between oxygen tension and cardiopleg ic composition on nitric oxide production and oxidant damage during re oxygenation of previously cyanotic hearts. Of 35 Duroc-Yorkshire pigle ts (2 to 3 weeks, 3 to 5 kg), six underwent 30 minutes of blood cardio plegic arrest with hyperoxemic (oxygen tension about 400 mm Hg), hypoc alcemic, alkalotic, glutamate/aspartate blood cardioplegic solution du ring 1 hour of cardiopulmonary bypass without hypoxemia (control). Twe nty-nine others were subjected to up to 120 minutes of ventilator hypo xemia (oxygen tension about 25 mm Hg) before reoxygenation on CPB. To simulate routine clinical management, nine piglets underwent uncontrol led cardiac reoxygenation, whereby cardiopulmonary bypass was started at oxygen tension of about 400 mm Hg followed by the aforementioned bl ood cardioplegic protocol 5 minutes later. All 20 other piglets underw ent controlled cardiac reoxygenation, whereby cardiopulmonary bypass w as started at the ambient oxygen tension (about 25 mm Hg), and reoxyge nation was delayed until blood cardioplegia was given. The blood cardi oplegia solution was kept normoxemic (oxygen tension about 100 mm Hg) in 10 piglets and made hyperoxemic (oxygen tension about 400 mm Hg) in 10 others. The cardioplegic composition was also varied so that the c ardioplegic solution in each subgroup contained either KCl only (30 mE q/L) or components that theoretically inhibit nitric oxide synthase by including hypocalcemia, alkalosis, and glutamate/aspartate, Function (end-systolic elastance) and myocardial nitric oxide production, conju gated diene production, and antioxidant reserve capacity were measured . Blood cardioplegic arrest without hypoxemia did not cause myocardial nitric oxide or conjugated diene production, reduce antioxidant reser ve capacity, or change left ventricular functional recovery, In contra st, uncontrolled cardiac reoxygenation raised nitric oxide and conjuga ted diene production 19- and 13-fold, respectively (p < 0.05 vs contro l), reduced antioxidant reserve capacity 40%, and contractility recove red only 21% of control levels. After controlled cardiac reoxygenation at oxygen tension about 400 mm Hg with cardioplegic solution containi ng KCl only, nitric oxide and conjugated diene production rose 16- and 12-fold, respectively (p < 0.05 vs control), and contractility recove red only 43% +/- 5%. Normoxemic (oxygen tension of about 100 mm Hg) co ntrolled cardiac reoxygenation with the same solution reduced nitric o xide and conjugated diene production 85% and 71%, and contractile reco very rose to 55% +/- 7% (p < 0.05 vs uncontrolled reoxygenation). In c omparison, controlled cardiac reoxygenation with an oxygen tension of about 400 mm Hg hypocalcemic, alkalotic, glutamate/aspartate blood car dioplegic solution reduced nitric oxide and conjugated diene productio n 85% and 62%, respectively, and contractility recovered 63% +/- 4% (p < 0.05 vs KCl only). Normoxemic delivery of this solution resulted in negligible nitric oxide and conjugated diene production and 83% +/- 8 % recovery of contractility (p < 0.05 vs all other groups). These data show correlation between nitric oxide production during initial reoxy genation and the extent of oxidant damage (i.e., conjugated diene prod uction) and link functional recovery to suppression of excessive nitri c oxide production and limitation of lipid peroxidation by the interac tion of oxygen tension and cardioplegic composition during initial reo xygenation.