Efficacy of intracoronary administration of a short-acting β-blocker landiolol during reperfusion in pigs.
BACKGROUND
Although β-blockers are used to prevent myocardial ischemia/reperfusion injury, the risk of heart failure has limited β-blocker therapy in patients with acute myocardial infarction. This study evaluated efficacy of intracoronary administration of the short-acting β-blocker, landiolol, during reperfusion in pigs with acute myocardial ischemia.


RESULTS
In the non-ischemic model landiolol administered into the left anterior descending coronary artery (LAD) inhibited in a dose-dependent fashion segmental wall thickening (SWT) in the anterior LV wall without altering SWT in the posterior LV wall and without prolonged depression of global LV function except for the highest dose. In the ischemic model with 60 min LAD occlusion followed by reperfusion the medium dose landiolol administered into the LAD 1 min before and for 10 min during reperfusion inhibited initial recovery of SWT in the anterior LV wall but improved SWT in this region and global LV function late after reperfusion. Ultrastructural studies showed inhibition of sub-sarcolemmal bleb formation by treatment with landiolol 10 min after reperfusion associated with the inhibition of CK-MB release and the reduction of infarct size. There was no significant difference in CK-MB release and infarct size between landiolol treatment for 10 min and 180 min during reperfusion.


CONCLUSIONS
Selective and brief intracoronary administration of landiolol during reperfusion enhances myocardial salvage without causing deterioration of global LV function.
Park
Haengnam
H
Second Department of Internal Medicine, Division of Cardiology, Kansai Medical University, Moriguchi City, Japan.
Otani
Hajime
H
Oishi
Chihiro
C
Fujikawa
Mie
M
Yamashita
Koji
K
Okazaki
Toru
T
Sato
Daisuke
D
Ueyama
Takanao
T
Iwasaka
Junji
J
Yamamoto
Yoshihiro
Y
Iwasaka
Toshiji
T
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000818:Animals; D003331:Coronary Vessels; D004305:Dose-Response Relationship, Drug; D007269:Injections, Intra-Arterial; D009025:Morpholines / Q000008:administration & dosage*; D009203:Myocardial Infarction / Q000188:drug therapy*; D015427:Reperfusion Injury / Q000517:prevention & control*; D013552:Swine; D013997:Time Factors; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives*
D000319:Adrenergic beta-Antagonists; D009025:Morpholines; C077049:landiolol; D014508:Urea