Synergistic myoprotection of L-arginine and adenosine in a canine model of global myocardial ischaemic reperfusion injury.
BACKGROUND
Endogenous nitric oxide and adenosine increase simultaneously to keep the balance of energy demand and supply when the oxygen supply is insufficient, which suggests that nitric oxide and adenosine might exert a synergistic myoprotection during tissue hypoxia. In this study, we tested this hypothesis utilizing a canine model of prolonged global myocardial ischaemic reperfusion injury.


METHODS
In this double blind, controlled study, the hearts of 24 anaesthetized mongrel dogs were arrested for 2 hours with aortic cross clamping and blood cardioplegia. The treatment groups were those supplemented with 2 mmol/L L-arginine (ARG), supplemented with 1 mmol/L adenosine (ADO), ARG + ADO supplemented with both, and no supplementation (control) (n = 6 in each group). Haemodynamics, biochemical indices, adenosine triphosphate (ATP) content and myeloperoxidase activities of myocardium were determined to evaluate myocardial injury. Statistical comparison was performed by two way ANOVA.


RESULTS
Although the requirements for inotropic supports were higher, the cardiac outputs were lower in control group than in ARG, ADO and the combination groups. Plasma cardiac troponin I levels were higher and the areas of hydropic changes were larger in control group than in ARG and ADO groups. Combination of arginine and adenosine provided further myoprotection with respect to better cardiac performance, lower release of cardiac troponin I, and smaller areas of hydropic changes compared with ARG and ADO groups. ATP content was higher, but myeloperoxidase activities of myocardium were significantly lower in the combination group than in control, ARG and ADO groups (P < 0.05).


CONCLUSIONS
Combination of L-arginine and adenosine provides synergistic myoprotection in a canine model of global myocardial ischaemia. Thus, the combination is recommended when the heart is exposed to a prolonged ischaemia during cardiac surgery.
Du
Lei
L
Department of Anaesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China. dulei1972@yahoo.com.cn
Dian
Ke
K
Chen
Hui-jiao
HJ
An
Qi
Q
Jia
Meng-xing
MX
Yang
Ping-liang
PL
Wang
Wei
W
Deng
Shuo-zeng
SZ
Liu
Jin
J
D000241:Adenosine / Q000627:therapeutic use*; D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D001120:Arginine / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004285:Dogs; D004357:Drug Synergism; D004734:Energy Metabolism; D005260:Female; D006324:Heart Arrest, Induced; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism
D002316:Cardiotonic Agents; D000255:Adenosine Triphosphate; D001120:Arginine; D009195:Peroxidase; D000241:Adenosine