Pretreatment with fosinopril or valsartan reduces myocardial no-reflow after acute myocardial infarction and reperfusion.
BACKGROUND
Both fosinopril and valsartan are effective in protecting endothelial function. We hypothesized that they may also reduce myocardial no-reflow. In addition, suppression of adenosine triphosphate-sensitive K (KATP) channel opening is an important mechanism for myocardial no-reflow. Therefore, this study sought to assess the effect of fosinopril and valsartan on myocardial no-reflow and explore the possible mechanism.


METHODS
Coronary ligation area and the area of no-reflow were determined with both myocardial contrast echocardiography in vivo and pathological means in 56 mini-swine randomized into seven study groups: eight in control, eight in fosinopril-pretreated (1 mg/kg/day) for 3 days, eight in fosinopril and glibenclamide (KATP channel blocker)-pretreated, eight in valsartan-pretreated (2 mg/kg/day) for 3 days, eight in valsartan and glibenclamide-pretreated, eight in glibenclamide-treated and eight in sham-operated. An acute myocardial infarction and reperfusion model was created with a 3-h occlusion of the coronary artery followed by a 2-h reperfusion. The levels of KATP channel proteins (SUR2, Kir6.1, and Kir6.2) in the reflow and no-reflow myocardium were quantified by Western blotting.


RESULTS
Compared with the control group, both fosinopril and valsartan significantly improved ventricular function, decreased area of no-reflow (myocardial contrast echocardiography: from 78.5+/-4.5 to 24.5+/-2.7 and 24.3+/-3.6%, pathological means: from 82.3+/-1.9 to 25.2+/-3.2 and 24.9+/-4.4% of ligation area, respectively; all P<0.01), reduced necrosis size from 98.5+/-1.3 to 88.9+/-3.6 and 89.1+/-3.1% of ligation area, respectively (both P<0.05). They also increased the levels of SUR2 and Kir6.2 (P<0.01), but had no effect on the level of Kir6.1 (P>0.05). A combination of fosinopril or valsartan with glibenclamide significantly increased area of no-reflow (P<0.05) and decreased the levels of SUR2 and Kir6.2 (P<0.01).


CONCLUSIONS
Pretreatment with fosinopril or valsartan can reduce myocardial no-reflow. This beneficial effect is due to activation of the KATP channel.
Zhao
Jing-lin
JL
Department of Cardiology, Cardiovascular Institute and Fu-Wai Heart Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Yang
Yue-jin
YJ
You
Shi-jie
SJ
Jing
Zhi-cheng
ZC
Wu
Yong-jian
YJ
Cheng
Ji-lin
JL
Gao
Run-lin
RL
D000208:Acute Disease; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001783:Blood Flow Velocity / Q000187:drug effects; D018890:Chemoprevention; D004727:Endothelium / Q000187:drug effects; D017328:Fosinopril / Q000494:pharmacology* / Q000627:therapeutic use; D017506:H(+)-K(+)-Exchanging ATPase / Q000187:drug effects*; D023421:Models, Animal; D009203:Myocardial Infarction / Q000517:prevention & control*; D015425:Myocardial Reperfusion; D009206:Myocardium; D013552:Swine; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan
D000959:Antihypertensive Agents; D013777:Tetrazoles; D000068756:Valsartan; D017506:H(+)-K(+)-Exchanging ATPase; D014633:Valine; D017328:Fosinopril