Continuous pulmonary infusion of L-arginine during deep hypothermia and circulatory arrest improves pulmonary surfactant integrity in piglets.
BACKGROUND
The integrity of pulmonary surfactant (PS) is impaired during deep hypothermia and circulatory arrest (DHCA), a preferred bypass strategy for infants undergoing complex cardiac operations, due mainly to bypass-induced systemic inflammation. The requirement of L-arginine, a precursor of nitric oxide, is elevated during acute pulmonary inflammation. We hypothesized that continuous intrapulmonary supplementation of L-arginine during DHCA can maintain the integrity of PS metabolism and thus protect the pulmonary function.


METHODS
Sixteen piglets underwent 90-minute circulatory arrest at 18 degrees C before rewarming. During circulatory arrest, antegrade infusion of Ringer's lactate solution alone (n = 8) or containing L-arginine (1 mg/kg/min, n = 8) was initiated into the pulmonary circulation. Disaturated phosphatidylcholine, total phospholipids, and total proteins from tracheal aspirates were measured serially until the experiment ended (4 hours after rewarming). Various variables of pulmonary function were also monitored.


RESULTS
L-arginine led to less decrement of disaturated phosphatidylcholine/total phospholipids and disaturated phosphatidylcholine/total proteins after DHCA. At 4 hours after rewarming, L-arginine had significantly mitigated the deterioration of pulmonary static compliance (3.6 +/- 0.5 vs 3.3 +/- 0.3 mL/cm H2O) and partial pressure of arterial oxygen/fraction of inspired oxygen (330 +/- 48 vs 296 +/- 32 mm Hg). Pulmonary retention of water (6.2 +/- 1.0 vs 5.5 +/- 1.2) was significantly reduced. The L-arginine-treated group showed an increase in NO metabolites (NO2-/NO3-) from the pulmonary circulation, the extent of which is correlated to PS content.


CONCLUSIONS
Continuous L-arginine supplementation during DHCA attenuated PS depletion and, therefore, ameliorated postoperative pulmonary dysfunction.
Yang
Yanmin
Y
Department of Cardiovascular and Thoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. victor.yang@nrc-cnrc.gc.ca
Su
Zhaokang
Z
Cai
Jiming
J
Wang
Shunmin
S
Liu
Jinfen
J
Xu
Zhiwei
Z
Ding
Wenxiang
W
D000818:Animals; D001120:Arginine / Q000008:administration & dosage*; D006324:Heart Arrest, Induced; D007036:Hypothermia, Induced; D007552:Isotonic Solutions / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism*; D012129:Respiratory Function Tests; D000077325:Ringer's Lactate; D013552:Swine; D014132:Trachea / Q000737:chemistry
D007552:Isotonic Solutions; D010713:Phosphatidylcholines; D010743:Phospholipids; D011663:Pulmonary Surfactants; D000077325:Ringer's Lactate; D001120:Arginine; D009195:Peroxidase