Effect of L-arginine or nitroglycerine during deep hypothermic circulatory arrest in neonatal lambs.
BACKGROUND
The role of nitric oxide (NO) in ischemia-reperfusion injury remains controversial. This study evaluated the effects of L-arginine (NO precursor) or nitroglycerine (NO donor) on cardiac and lung function after deep hypothermic circulatory arrest in neonatal lambs.


METHODS
Three groups of anesthetized lambs underwent cardiopulmonary bypass, deep hypothermic circulatory arrest (120 minutes at 18 degrees C), and rewarming (40 minutes). During reperfusion, L-arginine (5 mg/kg per minute), nitroglycerine (2 microg/kg per minute), or saline (control group) was infused for 100 minutes. All animals were separated from cardiopulmonary bypass and observed for 3 additional hours. Preload recruitable stroke work, cardiac index, pulmonary vascular resistance, alveolar-arterial oxygen difference, and lung compliance plasma nitrate/nitrite levels (NO metabolites) were measured before and after cardiopulmonary bypass. Malondialdehyde in heart tissue and lung tissue was measured 3 hours after cardiopulmonary bypass.


RESULTS
Recovery of preload recruitable stroke work and cardiac index were significantly higher in the L-arginine and nitroglycerine groups than in the control group (p < 0.05). Pulmonary vascular resistance was significantly lower in the L-arginine and nitroglycerine groups than in the control group (p < 0.05). Levels of NO metabolites and issue malondialdehyde did not differ among groups.


CONCLUSIONS
L-arginine and nitroglycerine improved recovery of left ventricular function and reduced pulmonary vascular resistance after deep hypothermic circulatory arrest. The mechanism of beneficial action could involve increased NO levels, but we did not find higher levels of NO metabolites compared with controls. Tissue malondialdehyde levels were not affected by L-arginine or nitroglycerine. These results show that, at these dosage levels, provision of substrate for NO production or provision of an NO donor were beneficial to the recovery of myocardial and pulmonary vascular function.
Hatsuoka
Shinichi
S
Department of Cardiovascular Surgery, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA.
Sakamoto
Takahiko
T
Stock
Ulrich A
UA
Nagashima
Mitsugi
M
Mayer
John E
JE
D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000494:pharmacology*; D006324:Heart Arrest, Induced; D007036:Hypothermia, Induced; D008170:Lung Compliance / Q000187:drug effects; D008315:Malondialdehyde / Q000032:analysis; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D005996:Nitroglycerin / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects; D012756:Sheep; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D009566:Nitrates; D009573:Nitrites; D008315:Malondialdehyde; D001120:Arginine; D005996:Nitroglycerin