Beneficial effects of befunolol on post-hypoxic recovery of cardiac contractility and myocardial metabolism.
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.
Department of Pharmacology, Tokyo College of Pharmacy, Japan.
Y
Y
Maruyama
K
K
Tanonaka
T
T
Niwa
S
S
Takeo
D000255:Adenosine Triphosphate / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D000860:Hypoxia / Q000188:drug therapy* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D011412:Propanolamines / Q000627:therapeutic use*; D011684:Purine Nucleosides / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011684:Purine Nucleosides; D010725:Phosphocreatine; C006034:befunolol; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D002118:Calcium