Effects of supplementation with iloprost on the cardioprotection by BW755C (a dual inhibitor of cyclooxygenase and lipoxygenase enzymes) in myocardial reperfusion injury.
The effect of BW755C (a dual inhibitor of cyclo- and lipoxygenase enzymes) alone and in combination with iloprost (a PGI2 analogue) on myocardial reperfusion injury was investigated in anaesthetised open-chest dogs. The left anterior descending coronary artery was occluded for a period of 40 min followed by reperfusion for 3 h. Dogs were administered either saline, BW755C (10 mg kg-1 slow bolus) or BW755C plus iloprost (100 ng kg-1 min-1 for 75 min) just prior to reperfusion. The haemodynamic data showed significant reduction in MAP and both LV peak-positive and peak-negative dP/dt following reperfusion in the saline-treated group, along with a delayed recovery of LVEDP. These changes were accompanied by significant depletion of myocardial ATP and glycogen stores. Administration of BW755C prevented the haemodynamic changes and replenished the HEP stores. Although coadministration of iloprost with BW755C afforded early normalisation of LVEDP and LV peak positive dP/dt, but MAP and LV peak negative dP/dt remained significantly depressed. Therefore, it might be concluded from this study that supplementation of BW755C with iloprost may have deleterious haemodynamic effects on the reperfused myocardium, particularly in the doses used.
Maulik
M
M
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, 110029, India.
Seth
S D
SD
Maulik
S K
SK
Manchanda
S C
SC
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004285:Dogs; D004336:Drug Antagonism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D016285:Iloprost / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000627:therapeutic use*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D014665:Vasodilator Agents / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D014665:Vasodilator Agents; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D016285:Iloprost