Cardiac performance after deep hypothermic circulatory arrest in chronically cyanotic neonatal lambs

Objectives: It is controversial whether immature cyanotic hearts are more s usceptible to ischemic injury than normoxemic hearts. Acutely induced alveo lar hypoxic stress before cardiopulmonary bypass has been used as a model o f cyanosis and is reported to worsen recovery of immature hearts after subs equent ischemic insult by means of a free radical injury mechanism. Because of concerns about the relevance of acute alveolar repair to the chronic cy anosis encountered clinically, we assessed the effects of chronic cyanosis without alveolar hypoxia, acute alveolar hypoxia, and normoxemia on recover y of cardiac function after deep hypothermic circulatory arrest. Methods: A chronic cyanosis model was created in 8 lambs by an anastomosis between the pulmonary artery and the left atrium (cyanosis group). Eight la mbs underwent sham operation (control). One week later, the animals underwe nt cardiopulmonary bypass with 90 minutes of deep hypothermic circulatory a rrest at 18 degrees C. Another 8 lambs underwent 45 minutes of hypoxic vent ilation before bypass, with arterial oxygen tension being maintained at 30 mm Hg (acute hypoxia group). Cardiac index, preload recruitable stroke work , and tau were measured. Malondialdehyde and nitrate-nitrite, nitric oxide metabolites, were also measured in the coronary sinus. Myocardial antioxida nt reserve capacity at 2 hours of reperfusion was assessed by measuring lip id peroxidation in left ventricular tissue samples incubated with t-butylhy droperoxide at 37 degrees C. Results: Oxygen tension was 35 +/- 3 mm Hg in the acute hypoxia group versu s 93 +/- 7 mm Hg in the control group. In the acute hypoxia group the recov ery of cardiac index, preload recruitable stroke work, and tau were signifi cantly worse than that found in both the control and cyanosis groups. Prelo ad recruitable stroke work at 2 hours of reperfusion was slightly but signi ficantly lower in the cyanosis group than in the control group. The postisc hemic level of nitric oxide metabolites was significantly lower in the acut e hypoxia group than in the cyanosis and control groups. However, malondial dehyde levels in the coronary sinus and myocardial antioxidant reserve capa city were not significantly different among the groups. Conclusion: Recovery of left ventricular function after deep hypothermic ci rculatory arrest in neonatal lambs with chronic cyanosis was slightly worse than that found in acyanotic animals. Acute hypoxia before bypass was asso ciated with significantly worse recovery of left ventricular function, and the mechanism of injury may be related to an impairment of nitric oxide pro duction. Free radical injury does not appear to explain any differences amo ng cyanotic, acyanotic, and acutely hypoxic animals in recovery of left ven tricular function after ischemia.