N-acetylcysteine reduces lung reperfusion injury after deep hypothermia and total circulatory arrest.
OBJECTIVE
We hypothesized that the use of N-acetylcysteine would ameliorate the lung reperfusion injury observed after deep hypothermia and total circulatory arrest (DHTSA).


METHODS
Experiments were carried out on 12 adult mongrel dogs of either sex weighing 25 to 30 kg. The animals were randomly divided into two groups of six animals each. All animals were cooled to an esophageal temperature of 15 degrees C during 30 minutes and underwent 60 minutes of DHTSA, followed by the reinstitution of cardiopulmonary bypass (CPB) and rewarming. Before rewarming, while 100 mL physiologic saline solution was added into the pump in group I, 50 mg/kg N-acetylcysteine(NAC) was given in group II. Heart rate, mean arterial pressure, pulmonary arterial pressure, left atrial pressure, central venous pressure, and cardiac output were recorded. To measure lung tissue malondialdehyde (MDA), water content and polymorphonuclear leukocytes (PMNs) count, lung tissue samples were taken before CPB and after weaning CPB. In addition, alveolar-arterial oxygen difference (AaDO(2))()for tissue oxygenation was calculated by obtaining arterial blood gas samples. Dynamic lung compliance (DLC) was measured before CPB and after CPB.


RESULTS
MDA levels before CPB of 44.2 +/- 3.9 nmol/g tissue rose to 76.6 +/- 5.6 nmol/g tissue after weaning CPB in group I (p = 0.004). In group II also, the MDA levels increased from 43.5 +/- 4.2 to 57.4 +/- 5.6 nmol MDA/g tissue after weaning CPB (p = 0.006). The MDA increase in group II after CPB was found to be significantly lower than in group I (p = 0.006). The wet-to-dry lung weight ratio in the NAC group was 5.1 +/- 0.2, significantly less than in the control group (5.9 +/- 0.3), (p = 0.004). AaDO(2) significantly increased in the group I and II (p = 0.002 and p = 0.002, respectively); this elevation in group I was significant than in group II (p = 0.044). In histopathological examination, it was observed that neutrophil counts in the lung parenchyma rose significantly after CPB in both groups (p < 0.001). The increase in group I was significantly larger than group II (p < 0.001).


CONCLUSIONS
Results represented in our study indicate that addition of NAC into the pump after DHTSA can reduce lung reperfusion injury.
Cakir
Omer
O
Department of Cardiovascular Surgery, Dicle University, School of Medicine, Diyarbakir, Turkey. omercak@dicle.edu.tr
Oruc
Ahmet
A
Kaya
Sedat
S
Eren
Nesimi
N
Yildiz
Fetin
F
Erdinc
Levent
L
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002315:Cardiopulmonary Bypass; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006324:Heart Arrest, Induced; D006339:Heart Rate / Q000187:drug effects; D007036:Hypothermia, Induced; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D008170:Lung Compliance / Q000187:drug effects; D055370:Lung Injury; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008955:Models, Cardiovascular; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects; D015427:Reperfusion Injury / Q000628:therapy*; D014655:Vascular Resistance / Q000187:drug effects
D016166:Free Radical Scavengers; D008315:Malondialdehyde; D010100:Oxygen; D000111:Acetylcysteine