Cardiac performance after deep hypothermic circulatory arrest in chronically cyanotic neonatal lambs.
OBJECTIVE
It is controversial whether immature cyanotic hearts are more susceptible to ischemic injury than normoxemic hearts. Acutely induced alveolar hypoxic stress before cardiopulmonary bypass has been used as a model of cyanosis and is reported to worsen recovery of immature hearts after subsequent ischemic insult by means of a free radical injury mechanism. Because of concerns about the relevance of acute alveolar repair to the chronic cyanosis encountered clinically, we assessed the effects of chronic cyanosis without alveolar hypoxia, acute alveolar hypoxia, and normoxemia on recovery 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 lambs underwent sham operation (control). One week later, the animals underwent cardiopulmonary bypass with 90 minutes of deep hypothermic circulatory arrest at 18 degrees C. Another 8 lambs underwent 45 minutes of hypoxic ventilation 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 antioxidant reserve capacity at 2 hours of reperfusion was assessed by measuring lipid peroxidation in left ventricular tissue samples incubated with t-butylhydroperoxide at 37 degrees C.


RESULTS
Oxygen tension was 35 +/- 3 mm Hg in the acute hypoxia group versus 93 +/- 7 mm Hg in the control group. In the acute hypoxia group the recovery of cardiac index, preload recruitable stroke work, and tau were significantly worse than that found in both the control and cyanosis groups. Preload recruitable stroke work at 2 hours of reperfusion was slightly but significantly lower in the cyanosis group than in the control group. The postischemic level of nitric oxide metabolites was significantly lower in the acute hypoxia group than in the cyanosis and control groups. However, malondialdehyde levels in the coronary sinus and myocardial antioxidant reserve capacity were not significantly different among the groups.


CONCLUSIONS
Recovery of left ventricular function after deep hypothermic circulatory arrest in neonatal lambs with chronic cyanosis was slightly worse than that found in acyanotic animals. Acute hypoxia before bypass was associated with significantly worse recovery of left ventricular function, and the mechanism of injury may be related to an impairment of nitric oxide production. Free radical injury does not appear to explain any differences among cyanotic, acyanotic, and acutely hypoxic animals in recovery of left ventricular function after ischemia.
Nagashima
M
M
Department of Cardiovascular Surgery, Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Nollert
G
G
Stock
U
U
Sperling
J
J
Hatsuoka
S
S
Shum-Tim
D
D
Takeuchi
K
K
Nedder
A
A
Mayer
J E
JE
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002315:Cardiopulmonary Bypass; D003490:Cyanosis / Q000503:physiopathology*; D004195:Disease Models, Animal; D006439:Hemodynamics; D007036:Hypothermia, Induced; D000860:Hypoxia / Q000503:physiopathology*; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000378:metabolism; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism; D012756:Sheep; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*
D009569:Nitric Oxide; D008315:Malondialdehyde