Different effects of adenosine and calcium channel blockade on myocardial no-reflow after acute myocardial infarction and reperfusion.
BACKGROUND
Adenosine and calcium channel blockers have been used in the treatment of angiographic no-reflow directly after angioplasty for acute myocardial infarction (AMI). However, their effects on tissue perfusion after AMI and reperfusion are undefined. The present study was designed to compare the effect of adenosine with that of the calcium channel blockers diltiazem and verapamil on myocardial no-reflow.


METHODS
Coronary ligation area and area of no-reflow were determined with both myocardial contrast echocardiography in vivo and histopathological evaluation in 44 Yorkshire mini-swines randomized into five study groups: ten in control, eight in adenosine-treated, nine in diltiazem-treated, nine in verapamil-treated and eight in sham-operated. An acute myocardial infarction and reperfusion model was created with 3-h occlusion of the left anterior descending coronary artery followed by 1-h reperfusion.


RESULTS
Compared with the control group, adenosine significantly decreased the area of no-reflow measured with both methods from 78.5 and 82.3% to 20.7 and 21.5% of ligation area, respectively (both P < 0.01), reduced necrosis area, maintained VE-cadherin, beta-catenin and gamma-catenin levels in reflow myocardium (P < 0.05-0.01). Although diltiazem and verapamil also significantly decreased the area of no-reflow, they failed to significantly modify necrosis area, VE-cadherin, beta-catenin and gamma-catenin levels.


CONCLUSIONS
These findings support the concept that adenosine can reduce both structural and functional no-reflow, while calcium channel blockade can only reduce functional no-reflow.
Zhao
Jing-Lin
JL
Department of Cardiology, Cardiovascular Institute and Fu-Wai Heart Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Bei Li Shi Road 167, Xi-Cheng District, Beijing 100037, China.
Yang
Yue-Jin
YJ
Cui
Chuan-Jue
CJ
You
Shi-Jie
SJ
Wu
Yong-Jian
YJ
Gao
Run-Lin
RL
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics; D015820:Cadherins / Q000032:analysis / Q000235:genetics; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D013552:Swine; D013556:Swine, Miniature; D051176:beta Catenin / Q000032:analysis / Q000235:genetics; D051185:gamma Catenin / Q000032:analysis / Q000235:genetics; D000099152:Cadherin 5
D000241:Adenosine; D015703:Antigens, CD; D015820:Cadherins; D002121:Calcium Channel Blockers; D012333:RNA, Messenger; D051176:beta Catenin; D051185:gamma Catenin; D000099152:Cadherin 5