Pre-ischemic administration of landiolol prevents ischemia-reperfusion injury in the rat heart

Osaka City Med J. 2007 Jun;53(1):9-16.

Abstract

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.

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Dose-Response Relationship, Drug
  • Heart / drug effects
  • Heart / physiopathology
  • Ischemic Preconditioning, Myocardial / methods
  • Male
  • Morpholines / pharmacology*
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / physiopathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocardium / enzymology
  • Myocardium / pathology
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / pathology
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control*
  • Urea / analogs & derivatives*
  • Urea / pharmacology
  • Ventricular Dysfunction, Left / physiopathology

Substances

  • Adrenergic beta-Antagonists
  • Morpholines
  • landiolol
  • Urea