Diltiazem and verapamil reduce the loss of adenine nucleotide metabolites from hypoxic hearts.
The present study was undertaken to elucidate possible mechanisms for a protection of myocardial cells from hypoxia-induced derangements in cardiac function and metabolism by calcium antagonists. For this purpose, rabbit hearts were perfused for 20 min under hypoxic conditions in the presence of 312 ng/ml diltiazem or 125 ng/ml verapamil, and then for 45 min under reoxygenated conditions. Metabolic changes in the myocardium and the perfusate were examined throughout. Hypoxia induced a marked decline in myocardial high-energy phosphates and an immediate release of ATP metabolites, such as adenosine, inosine and hypoxanthine, from the perfused heart. These changes were effectively depressed by diltiazem and verapamil. Hypoxia and subsequent reoxygenation resulted in a release of creatine phosphokinase from the heart, which was completely inhibited by the treatment with either diltiazem or verapamil. Myocardial calcium contents were increased by 20 min-hypoxic perfusion. Both diltiazem and verapamil are capable of preventing hypoxia-induced increase in the transmembrane flux of cellular components, which may be beneficial for the preservation of substances necessary for the ATP regeneration after hypoxia and for the inhibition of calcium overload in cardiac cells.
Takeo
S
S
Department of Physiology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Japan.
Tanonaka
K
K
Tazuma
Y
Y
Fukao
N
N
Yoshikawa
C
C
Fukumoto
T
T
Tanaka
T
T
D000227:Adenine Nucleotides / Q000378:metabolism*; D000241:Adenosine / Q000378:metabolism; D000818:Animals; D001834:Body Water / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D007288:Inosine / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D011817:Rabbits; D012016:Reference Values; D014700:Verapamil / Q000494:pharmacology*
D000227:Adenine Nucleotides; D007042:Hypoxanthines; D019271:Hypoxanthine; D007288:Inosine; D014700:Verapamil; D003402:Creatine Kinase; D004110:Diltiazem; D000241:Adenosine; D002118:Calcium