Protective action of YM-12617, an alpha 1-adrenoceptor antagonist, on the hypoxic and reoxygenated myocardium.
The present study was designed to determine whether the 1-form of YM-12617, which was developed recently as an alpha 1-adrenoceptor blocker, is capable of protecting the myocardium from hypoxia-induced disturbances of cardiac function and metabolism. Isolated rabbit hearts were perfused for 25 min under hypoxic conditions in the absence or the presence of 28 microM YM-12617, followed by 45 min with oxygenated perfusion medium, and functional and metabolic changes of the heart were examined. Hypoxia induced several pathophysiological changes. Upon subsequent reoxygenation, there was less than 10% recovery of the contractile force and an approximately 40% recovery of the myocardial high-energy phosphates. Treatment with YM-12617 during the hypoxic periods resulted in approximately 90% recovery of the cardiac contractile function upon subsequent reoxygenation. Treatment with YM-12617 restored the myocardial high-energy phosphates, such as ATP and creatine phosphate, to approximately 90 and 80% of the initial value, respectively, during the subsequent reoxygenation. These results suggest that YM-12617 is capable of protecting the myocardium from hypoxia-induced disturbances of cardiac function and metabolism.
Tanonaka
K
K
Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuyama University, Japan.
Matsumoto
M
M
Miyake
K
K
Minematsu
R
R
Takeo
S
S
D000255:Adenosine Triphosphate / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001834:Body Water / Q000378:metabolism; D002118:Calcium / Q000097:blood / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003326:Coronary Circulation / Q000187:drug effects; D003402:Creatine Kinase / Q000097:blood / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology*; D010477:Perfusion; D011817:Rabbits; D013056:Spectrophotometry, Ultraviolet; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors; D000096926:Benzenesulfonamides
D000255:Adenosine Triphosphate; D000317:Adrenergic alpha-Antagonists; D002118:Calcium; D003402:Creatine Kinase; D010100:Oxygen; D013449:Sulfonamides; C044648:YM 12617; D000096926:Benzenesulfonamides