STUDIES OF HYPOXEMIC REOXYGENATION INJURY - WITHOUT AORTIC CLAMPING .8. COUNTERACTION OF OXIDANT DAMAGE BY EXOGENOUS GLUTAMATE AND ASPARTATE/

Previous studies show that (1) hypoxemia depletes immature myocardium of amino acid substrates and their replenishment improves ischemic tol erance, (2) reoxygenation on cardiopulmonary bypass causes oxygen-medi ated damage without added ischemia, and (3) this damage may be related to the nitric oxide-L-arginine pathway that is affected by amino acid metabolism. This study tests the hypothesis that priming the cardiopu lmonary bypass circuit with glutamate and aspartate limits reoxygenati on damage. Of 22 immature Duroc-Yorkshire piglets (<3 weeks old), five were observed over a 5-hour period (control), and five others underwe nt 30 minutes of CPB without hypoxemia (cardiopulmonary bypass control ), Twelve others became hypoxemic by reducing ventilator inspired oxyg en fraction to 6% to 7% (oxygen tension about 25 mm Hg) before reoxyge nation on cardiopulmonary bypass for 30 minutes. Of these five were un treated (no treatment), and the cardiopulmonary bypass circuit was pri med with 5 mmol/L glutamate and aspartate in seven others (treatment). Left ventricular function before and after bypass was measured by ins cribing pressure-volume loops (end-systolic elastance). Myocardial con jugated diene levels were measured to detect lipid peroxidation, and a ntioxidant reserve capacity was tested by incubating cardiac muscle wi th the oxidant t-butylhydroperoxide to determine the susceptibility to subsequent oxidant injury, CPB (no hypoxemia) allowed complete functi onal recovery without changing conjugated dienes and antioxidant reser ve capacity, whereas reoxygenation injury developed in untreated heart s. This was characterized by reduced contractility (elastance end-syst olic recovered only 37% +/- 8%), increased conjugated diene levels (1 3 +/- 0.1 vs 0.7 +/- 0.1), and decreased antioxidant reserve capacity (980 +/- 59 vs 471 +/- 30 malondialdehyde nmol/g protein at 2 mmol/L t-butylhydroperoxide). In contrast, priming the cardiopulmonary bypas s circuit with glutamate and aspartate resulted in significantly bette r left ventricular functional recovery (75% +/- 8% vs 37% +/- 8%), mi nimal conjugated diene production (0.8 +/- 0.1 vs 1.3 +/- 0.1), and i mproved antioxidant reserve capacity (726 +/- 27 vs 910 +/- 59 malondi aldehyde nmol/g protein) (*p < 0.05 vs cardiopulmonary bypass control ). We conclude that reoxygenation of immature hypoxemic piglets by the initiation of cardiopulmonary bypass causes myocardial dysfunction, l ipid peroxidation, and reduced tolerance to oxidant stress, which may increase vulnerability to subsequent ischemia (i.e., aortic crossclamp ing). These deja suggest that supplementing the prime of cardiopulmona ry bypass circuit with glutamate and aspartate may reduce these delete rious consequences of reoxygenation.