ROLE OF CONTROLLED CARDIAC REOXYGENATION IN REDUCING NITRIC-OXIDE PRODUCTION AND CARDIAC OXIDANT DAMAGE IN CYANOTIC INFANTILE HEARTS

Cardiopulmonary bypass (CPB) is used increasingly to correct cyanotic heart defects during early infancy, but myocardial dysfunction is ofte n seen after surgical repair. This study evaluates whether starting CP B at a conventional, hyperoxic pO(2) causes an ''unintentional'' reoxy genation (ReO2) injury. We subjected 2-wk-old piglets to ventilator hy poxemia (FIO2 similar to 0.06, pO(2) similar to 25 mmHg) followed by 5 min of ReO2 on CPB before instituting cardioplegia. CPB was begun in hypoxemic piglets by either abrupt ReO2 at a pO(2) of 400 mmHg (standa rd clinical practice) or by maintaining pO(2) similar to 25 mmHg on CP B until controlling ReO2 with blood cardioplegic arrest. The effects o f abrupt vs. gradual ReO2 without surgical ischemia (blood cardioplegi a) a ere also compared. Myocardial nitric oxide (NO) production (chemi luminescence measurements of NO2- + NO3-) and conjugated diene (CD) ge neration (spectrophotometric A(233) measurements of lipid extracts) us ing aortic and coronary sinus blood samples were assessed during cardi oplegic induction. 30 min after CPB, left ventricular end-systolic ela stance (Ees, catheter conductance method) was used to determine cardia c function. CPB and blood cardioplegic arrest caused no functional or biochemical change in normoxic (control) hearts. Abrupt ReO2 caused a depression of myocardial function (Ees = 25 +/- 58 of control). Functi onal depression was relatively unaffected by gradual ReO2 without bloo d cardioplegia (34% recovery of Ees), and abrupt ReO2 immediately befo re blood cardioplegia caused a 10-fold rise in cardiac NO and CD produ ction, with subsequent depression of myocardial function (Ees 21 +/- 2 % of control). In contrast, controlled cardiac ReO, reduced NO product ion 94%, CD did not rise, and Ees was 83 +/- 8% of normal. We conclude ReO2 injury is related to increased NO production during abrupt ReO2, nullifies the cardioprotective effects of blood cardioplegia, and tha t controlled cardiac ReO2 when starting CPB to correct cyanotic heart defects may reduce NO production and improve myocardial status postope ratively.