Influence of angiotensin II type 1-receptor antagonist CV11974 on infarct size and adjacent regional function after ischemia-reperfusion in dogs.
The presence of nonischemic regional dysfunction at the adjacent region of the ischemic myocardium was demonstrated in clinical studies. Recent studies demonstrated an angiotensin II type 1 (AT1)-receptor antagonist reduced myocardial ischemia-reperfusion injury. We investigated the role of the adjacent region after reperfusion by studying the effects of AT1-receptor antagonist on myocardial function and infarct size. We investigated 12 open-chest anesthetized dogs undergoing 90 min of left anterior descending coronary artery occlusion followed by 4 h of reperfusion. Six dogs injected with an AT1-receptor antagonist (CV11974) immediately after reperfusion were compared with 6 control dogs. Percent systolic shortening (%SS) was measured by two sets of the pair sonomicrometer crystals implanted to adjacent and remote nonischemic myocardium. After 4 h of reperfusion, infarct size was measured. There were no significant differences of the %SS at baseline between two regions. In both groups, %SS at adjacent region after reperfusion was significantly decreased as compared with remote region. There were no significant differences between the two groups. Infarct size, as a percentage of the area at risk, was smaller in the AT, group than in control group (25.49+/-7.53% vs 68.58+/-26.88% P<0.01). AT1-receptor antagonist reduces infarct size. This effect is not related to the change of regional myocardial function at adjacent region after reperfusion.
Miyoshi
Hironori
H
The Second Department of Internal Medicine, Kansai Medical Univeristy, Moriguchi, Osaka, Japan. miyoshi@takii.kmu.ac.jp
Takayama
Yasuo
Y
Kitashiro
Shuji
S
Izuoka
Toshio
T
Saito
Daiki
D
Imuro
Yusuke
Y
Mimura
Jun
J
Yamamoto
Satoshi
S
Tokioka
Mari
M
Iwasaka
Toshiji
T
D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D004285:Dogs; D006439:Hemodynamics; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D011945:Receptors, Angiotensin / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013777:Tetrazoles / Q000494:pharmacology*; D016277:Ventricular Function, Left
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C081643:candesartan