Prostaglandin I2 analogue and propranolol prevent ischaemia induced mitochondrial dysfunction through the stabilisation of lysosomal membranes.
Leakage of lysosomal enzymes is associated with irreversible cellular damage. To determine the effect of prostaglandin I2 analogue and propranolol on the ischaemic myocardium in relation to changes in lysosomal integrity 26 anaesthetised mongrel dogs were divided into three treatment groups and subjected to 2 h coronary occlusion. In the control group (n = 12) physiological saline was infused throughout the experiment. In the prostaglandin I2 analogue group (n = 7) the prostaglandin I2 analogue, OP-41483-alpha-CD;5(E)-6-Deoxa-6,9 alpha-methylene-15-cyclopentyl-16,17,18,19,20-pentanor-PGI2. alpha-cyclodextrin clathrate (5 ng.kg-1.min-1) was infused from 25 min before occlusion until the end of the experiment. In the propranolol group (n = 7) propranolol (0.3 mg.kg-1) was injected for 10 min 25 min before occlusion. Two hours after occlusion mitochondria were prepared from both ischaemic and non-ischaemic areas in each group and their function measured polarographically with succinate as substrate. Fractionation of myocardial tissue from both non-ischaemic and ischaemic areas was performed and the activities of lysosomal enzymes (N-acetyl-beta-glucosaminidase; beta-glucuronidase) were measured. In the control group, mitochondrial function in the ischaemic area was reduced compared with that from the non-ischaemic area. The activities of both lysosomal enzymes were increased significantly in the supernatant fraction obtained from the ischaemic area compared with those for the supernatant from the non-ischaemic area. The administration of prostaglandin I2 analogue or propranolol not only prevented the leakage of lysosomal enzymes but also maintained mitochondrial function.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology / Q000517:prevention & control*; D003505:Cyclodextrins / Q000627:therapeutic use*; D003912:Dextrins / Q000627:therapeutic use*; D004285:Dogs; D011464:Epoprostenol / Q000627:therapeutic use* / Q000031:analogs & derivatives; D006339:Heart Rate / Q000187:drug effects; D008247:Lysosomes / Q000187:drug effects* / Q000201:enzymology; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000502:physiology; D011433:Propranolol / Q000627:therapeutic use*; D013213:Starch / Q000627:therapeutic use*; D047391:alpha-Cyclodextrins
D003505:Cyclodextrins; D003912:Dextrins; D047391:alpha-Cyclodextrins; C051518:OP 41483-alpha-cyclodextrin; D013213:Starch; D011433:Propranolol; D011464:Epoprostenol