Effects of propentofylline on energy metabolism of the ischemic brain studied by in vivo 31P nuclear magnetic resonance spectroscopy.
The effects of 3-methyl-1-(5'-oxohexyl)-7-propylxanthine (propentofylline, HWA 285) on transient cerebral ischemia were studied in Mongolian gerbils by measuring the in vivo 31P nuclear magnetic resonance (NMR) spectra and cerebral water content. Transient ischemia was produced by bilateral common carotid artery occlusion for 30 min, which was followed by 60 min of reperfusion. Propentofylline (1, 2.5 or 30 mg/kg) or normal saline was administered intravenously at 2 min after the reperfusion. The 31P spectra during the occlusion showed a marked reduction in adenosine triphosphate (ATP) and phosphocreatine (PCr) with elevation of inorganic phosphate (Pi) in all groups. The intracellular pH (pHi) calculated from the chemical shift of Pi was markedly reduced in all groups. After the reperfusion, ATP, PCr, Pi and pHi gradually recovered towards the normal levels in the control group. In the 2.5 mg/kg propentofylline group, the energy recovery was significantly faster than in the controls. The cerebral water content measured at the end of reperfusion was significantly lower in the 2.5 mg/kg propentofylline group than in the controls. However, such cerebral protective effects were not observed in the 1 mg/kg and 30 mg/kg groups. The present results suggest that propentofylline may accelerate the energy recovery of the transiently ischemic brain and suppress the development of post-ischemic cerebral edema. The effects, however, were not dose-dependent in manner. The detailed mechanism of the effects requires further investigation.
Sasaki
M
M
Cerebral Circulation Laboratory, National Cardiovascular Center, Suita, Osaka, Japan.
Naritomi
H
H
Kanashiro
M
M
Nishimura
H
H
Sawada
T
T
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D001834:Body Water; D001923:Brain Chemistry / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D005849:Gerbillinae; D006863:Hydrogen-Ion Concentration; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010759:Phosphorus Isotopes; D014970:Xanthines / Q000494:pharmacology*
D010759:Phosphorus Isotopes; D014970:Xanthines; D002245:Carbon Dioxide; C032114:propentofylline; D000255:Adenosine Triphosphate