The present study was undertaken to determine whether
befunolol (
BFE 60, CAS 39543-79-8) a beta-
adrenoceptor blocking agent, improves post-hypoxic contractile and metabolic recovery of perfused hearts. Isolated rat hearts were perfused for 20 min under hypoxic conditions, followed by 45-min reoxygenation.
Hypoxia/reoxygenation induced less than 5% post-hypoxic recovery of cardiac contractile force, incomplete return of resting tension of hearts, accumulation of tissue
calcium, and release of
purine nucleosides and bases, and
creatine kinase from the heart. When hypoxic hearts were treated with 500 mumol/l
befunolol from 0 to 10 min of hypoxic perfusion, marked recovery of contractile force (more than 50% of the pre-hypoxic value), complete suppression of the tissue
calcium accumulation and significant suppression of the increase in
creatine kinase activity of the perfusate were seen after reoxygenation. This treatment also significantly prevented the release of
purine nucleosides and bases during
hypoxia. These results suggest that treatment with
befunolol during hypoxic perfusion is beneficial for post-hypoxic recovery of cardiac function and myocardial metabolism, probably through a mechanism of suppression of transmembrane flux of substrates,
ions and
enzymes. Cardiac contractile force upon the onset of
hypoxia declined more rapidly and myocardial high-energy
phosphate content after 10 min of
hypoxia was significantly higher in
befunolol-treated hearts than in hearts without treatment. Thus, energy-sparing effects may also contribute to the beneficial post-hypoxic recovery of cardiac function and metabolism.