Effects of propranolol and diltiazem on the rate of high-energy phosphate metabolism in reperfused rat hearts--31P-NMR saturation transfer study.
The relationships between pressure rate product (PRP) and flux (PCr-->ATP) or flux (Pi-->ATP) were studied in isolated perfused rat hearts by the saturation transfer method using 31P-NMR. The effects of propranolol and diltiazem on phosphate metabolism were also studied. After a 40 min preischemic period, the hearts were subjected to a 15 min period of ischemia, followed by 60 min of reperfusion. Propranolol (0.4-1.2 microM) or diltiazem (3.0-6.0 microM) was infused for 30 min before ischemia and reinfused after reperfusion for 60 min. The flux (PCr-->ATP)/PRP ratio at reperfusion did not differ from that at preischemia. This value was also not affected by propranolol or diltiazem treatment. However, the flux (Pi-->ATP)/PRP ratio at reperfusion was significantly less than that at preischemia. Moreover, this value was significantly improved by propranolol or diltiazem treatment. This study demonstrates that 1) flux (PCr-->ATP) has a good correlation with cardiac performance, 2) stunned myocardium needs less ATP turnover for survival of its depressed contractile activity, and 3) flux (Pi-->ATP) can limit recovery of postischemic performance. Protective effects of propranolol and diltiazem are exerted on the flux (Pi-->ATP), i.e. ATP derived from glycolytic flux, in the reperfused heart.
Okayama
Y
Y
Third Department of Internal Medicine, Hamamatsu University School of Medicine, Japan.
Kobayashi
A
A
Fujise
Y
Y
Yamazaki
N
N
D000818:Animals; D004110:Diltiazem / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008962:Models, Theoretical; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion
D010710:Phosphates; D010761:Phosphorus Radioisotopes; D011433:Propranolol; D004110:Diltiazem