Pretreatment with Tongxinluo protects porcine myocardium from ischaemia/reperfusion injury through a nitric oxide related mechanism.
BACKGROUND
The traditional Chinese medicine Tongxinluo can protect myocardium against ischaemia/reperfusion injury, but the mechanism of its action is not well documented. We examined the involvement of nitric oxide in the protective role of Tongxinluo.


METHODS
Miniswine were randomized to four groups of seven: sham, control, Tongxinluo and Tongxinluo coadministration with a nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (L-NNA, 10 mg/kg i.v.). Three hours after administration of Tongxinluo, the animals were anaesthetised and the left anterior descending coronary artery ligated and maintained in situ for 90 minutes followed by 3 hours of reperfusion before death. Area of no reflow and necrosis and risk region were determined pathologically by planimetry. The degree of neutrophil accumulation in myocardium was obtained by measuring myeloperoxidase activity and histological analysis. Myocardial endothelial nitric oxide synthase activity and vascular endothelial cadherin content were measured by colorimetric method and immunoblotting analysis respectively.


RESULTS
Tongxinluo significantly increased the local blood flow and limited the infarct and size of no reflow. Tongxinluo also attenuated myeloperoxidase activity and neutrophil accumulation in histological sections and maintained the level of vascular endothelial cadherin and endothelial nitric oxide synthase activity in the reflow region when compared with control group. The protection of Tongxinluo was counteracted by coadministration with L-NNA.


CONCLUSIONS
Tongxinluo may limit myocardial ischaemia and protect the heart against reperfusion injury. Tongxinluo regulates synthesis of nitric oxide by altering activity of endothelial nitric oxide synthase.
Cheng
Yu-tong
YT
Department of Cardiology, Peking Union Medical College, Fuwai Hospital and Cardiovascular Institute, and Chinese Academy of Medical Sciences, Beijing 100037, China.
Yang
Yue-jin
YJ
Zhang
Hai-tao
HT
Qian
Hai-yan
HY
Zhao
Jing-lin
JL
Meng
Xian-min
XM
Luo
Fu-liang
FL
Wu
Yi-ling
YL
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D015820:Cadherins / Q000032:analysis; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D008856:Microscopy, Fluorescence; D009203:Myocardial Infarction / Q000188:drug therapy / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D020556:Neutrophil Infiltration; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D013552:Swine; D013556:Swine, Miniature; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D004365:Drugs, Chinese Herbal; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D009195:Peroxidase; D000099152:Cadherin 5; C513941:tongxinluo