Effects of cyanosis and hypothermic circulatory arrest on lung function in neonatal lambs.
BACKGROUND
Lung function is often impaired after cardiac surgery and cardiopulmonary bypass (CPB), particularly in chronically cyanotic patients. This study aimed to evaluate lung function in a surgically created chronic cyanotic neonatal lamb model after CPB and deep hypothermic circulatory arrest (DHCA) and to assess the role of nitric oxide (NO) in the pathogenesis of increased pulmonary vascular resistance.


METHODS
A chronic cyanosis model was surgically created in 7 lambs (4.7+/-0.8 days old) by anastomosing the pulmonary artery (PA) to the left atrium (LA). Another 7 lambs underwent a sham operation (control). One week later, the animals underwent shunt takedown and CPB with 90 minutes of DHCA at 18 degrees C. Cardiac index (CI), pulmonary vascular resistance index (PVRI), lung dynamic compliance (Cdyn), alveolar-arterial oxygen difference (AaDO2), left atrial plasma nitrate/nitrite (NO metabolites) levels, and pulmonary cGMP production (concentration difference between LA and PA) were measured before CPB and at 1 and 2 hours after reperfusion.


RESULTS
The cyanosis model consistently produced significantly lower arterial oxygen tension (34.8+/-2.3 vs 93.1+/-8.8 torr in control, p < 0.001) and Qp/Qs (0.6+/-0.1 vs 1.0+/-0.0 in control, p < 0.001) than controls. Postoperative PVRI was significantly lower in the cyanosis group than in controls, although CPB with DHCA significantly elevated PVR in both cyanotic and control animals. There were no significant differences in AaDO2 and Cdyn after CPB between groups. The level of NO metabolites did not change before or after CPB in either cyanotic or acyanotic animals. NO metabolite levels tended to be higher in the cyanotic animals (p = 0.08). There was no significant difference in pulmonary cGMP production between both groups.


CONCLUSIONS
These findings suggest that CPB with DHCA, per se, does not affect NO production in cyanotic or acyanotic neonatal lambs but causes increased PVR in both groups. Chronic cyanosis does not result in reduced pulmonary function after CPB with DHCA, and is associated with lower PVR. The mechanism may involve an increased NO production in cyanotic animals.
Nagashima
M
M
Department of Cardiovascular Surgery, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Stock
U
U
Nollert
G
G
Sperling
J
J
Shum-Tim
D
D
Hatsuoka
S
S
Mayer
J E
JE
D000818:Animals; D000831:Animals, Newborn; D002302:Cardiac Output / Q000502:physiology; D002315:Cardiopulmonary Bypass; D002908:Chronic Disease; D003490:Cyanosis / Q000503:physiopathology*; D006152:Cyclic GMP / Q000097:blood; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology; D006324:Heart Arrest, Induced; D008168:Lung / Q000098:blood supply*; D008170:Lung Compliance / Q000502:physiology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000502:physiology*; D009573:Nitrites / Q000097:blood; D011653:Pulmonary Diffusing Capacity / Q000502:physiology; D012756:Sheep; D014655:Vascular Resistance / Q000502:physiology*
D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D006152:Cyclic GMP