Pre-ischemic administration of landiolol prevents ischemia-reperfusion injury in the rat heart.
BACKGROUND
This study was designed to investigate whether administration of landiolol before or during ischemia protects the myocardium against ischemia-reperfusion (I/R) injury.


METHODS
Isolated rat hearts were perfused with Krebs-Henseleit buffer using Langendorff apparatus. Cardiac arrest was achieved using St. Thomas' Hospital cardioplegic solution for 3 min. Each heart was subjected to global ischemia at 37 degrees C for 45 min followed by reperfusion for 60 min. In protocol A, landiolol (5-200 microM) was administered before ischemia and in protocol B, landiolol (10-1000 microM) was administered during ischemia. Post-ischemic recovery of cardiac function after 60 min of reperfusion was expressed as a percentage of the pre-ischemic value. Creatinine kinase (CK) leakage during reperfusion for 20 min was also measured.


RESULTS
Post-ischemic recovery of cardiac function and CK leakage were significantly improved by administration of 100 microM landiolol in protocol A (left ventricular developed pressure, 54.5 +/- 10.5% vs 76.1 +/- 6.6%; dP/dtmax, 47.5 +/- 14.9% vs 71.4 +/- 6.9%; coronary flow, 68.5 +/- 7.1% vs 83.9 +/- 12.9%, and CK, 25.3 +/- 4.2 IU vs 20.3 +/- 7.4 IU). In protocol B, landiolol exerted no cardioprotective effect on cardiac function and CK leakage at each concentration.


CONCLUSIONS
Landiolol has a cardioprotective effect on I/R injury in the rat heart when administered before ischemia.
Takahashi
Yosuke
Y
Department of Cardiovascular Surgery, Osaka City University, Graduate School of Medicine, Japan. ysk@msic.med.osaka-cu.ac.jp
Shibata
Toshihiko
T
Sasaki
Yasuyuki
Y
Hirai
Hidekazu
H
Takemura
Shigekazu
S
Minamiyama
Yukiko
Y
Sakaguchi
Masanori
M
Suehiro
Shigefumi
S
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology
D000319:Adrenergic beta-Antagonists; D009025:Morpholines; C077049:landiolol; D014508:Urea