TY - JOUR
T1 - Role of timing of administration in the cardioprotective effect of iloprost, a stable prostacyclln mimetic
AU - Cargnoni, Anna
AU - Boraso, Antonella
AU - Comini, Laura
AU - De Giuli, Federica
AU - Condorelli, Enrico
AU - Pasini, Evasio
AU - Ferrari, Roberta
PY - 1991/6/25
Y1 - 1991/6/25
N2 - We administered iloprost, a stable prostacyclin mimetic, 27 nM, to isolated and perfused rabbit hearts submitted, after 60 min of equilibration, to an ischaemic period (60 min at a coronary flow of 1 ml/min) followed by a period of reperfusion (30 min at a coronary flow of 25 ml/min). Iloprost was delivered at different times during the experimental protocol: 60 min before ischaemia, at the onset and after 30 min of ischaemia and only during reperfusion. The iloprost cardioprotective effect was evaluated in terms of recovery of left ventricular pressure developed during reperfusion, creatine phosphokinase (CPK) and noradrenaline release, mitochondrial function (expressed as yield, RCI (respiratory control index), QO2, ADP/O), ATP and creatine phosphate (CP) tissue contents, calcium homeostasis and by measuring several parameters of oxidative stress: reduced and oxidized glutathior e release and tissue contents, Mn and Cu-Zn Superoxide dismutase activities; glutathione reductase and peroxidase activities. Our data show that the cytoprotective action of iloprost is closely related to the time of administration. Optimal myocardial preservation was achieved when it was given before or at the onset of ischaemia. Iloprost administration 30 min after the onset of ischaemia was still beneficial, although to a lesser extent. Iloprost lost its protective effect when given only on reperfusion. The data suggest that the iloprost cardioprotective effect is related to maintainance of membrane integrity.
AB - We administered iloprost, a stable prostacyclin mimetic, 27 nM, to isolated and perfused rabbit hearts submitted, after 60 min of equilibration, to an ischaemic period (60 min at a coronary flow of 1 ml/min) followed by a period of reperfusion (30 min at a coronary flow of 25 ml/min). Iloprost was delivered at different times during the experimental protocol: 60 min before ischaemia, at the onset and after 30 min of ischaemia and only during reperfusion. The iloprost cardioprotective effect was evaluated in terms of recovery of left ventricular pressure developed during reperfusion, creatine phosphokinase (CPK) and noradrenaline release, mitochondrial function (expressed as yield, RCI (respiratory control index), QO2, ADP/O), ATP and creatine phosphate (CP) tissue contents, calcium homeostasis and by measuring several parameters of oxidative stress: reduced and oxidized glutathior e release and tissue contents, Mn and Cu-Zn Superoxide dismutase activities; glutathione reductase and peroxidase activities. Our data show that the cytoprotective action of iloprost is closely related to the time of administration. Optimal myocardial preservation was achieved when it was given before or at the onset of ischaemia. Iloprost administration 30 min after the onset of ischaemia was still beneficial, although to a lesser extent. Iloprost lost its protective effect when given only on reperfusion. The data suggest that the iloprost cardioprotective effect is related to maintainance of membrane integrity.
KW - Cardioprotection
KW - Iloprost
KW - Ischaemia (myocardial)
KW - Prostacyclin
KW - Reperfusion (myocardial)
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U2 - 10.1016/0014-2999(91)90454-X
DO - 10.1016/0014-2999(91)90454-X
M3 - Article
C2 - 1720098
AN - SCOPUS:0025765739
VL - 199
SP - 165
EP - 178
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 2
ER -