Early and late administration of a PGI2-analogue, ZK 36 374 (iloprost): effects on myocardial preservation, collateral blood flow and infarct size.
A number of investigations have reported that prostacyclin or prostacyclin analogues protect the ischaemic myocardium when administered early after myocardial ischaemia. Thus far, there are no reports describing whether these substances exert a cardioprotective effect when administered later than 0.5 h after coronary artery occlusion. Adult cats were subjected to acute coronary artery ligation for 5 h and administered the vehicle or ZK 36 374 (iloprost) (1.19 micrograms X kg-1 X min-1), a prostacyclin analogue, beginning at 0.5, 2 or 4 h. Compared with the MI-vehicle cats, ZK 36 374 prevented a decrease in myocardial creatine kinase specific activity, the loss of free amino nitrogen and the fall in percentage bound cathepsin D in the ischaemic area when infusion was started at 0.5 or 2 h (P less than 0.05). In addition ZK 36 374 started at 4 h still showed a significant protective effect against myocardial creatine kinase specific activity and amino nitrogen concentrations but not against cathepsin D. In a separate group of animals, regional myocardial blood flow and late coronary resistance were determined with radioactive labelled 15 +/- 1 micron microspheres. ZK 36 374 consistently reduced late diastolic coronary vascular resistance and increased coronary blood flow in nonischaemic regions of the myocardium (P less than 0.05) but only attenuated the further increase in late coronary resistance in the ischaemic myocardial regions. The infarcted area (NTB-staining) amounted to 9% of the total left ventricle after 5 h and was not reduced by ZK 36 374 (P greater than 0.05). In conclusion, ZK 36 374 exerted a significant biochemical cardioprotective effect when administered to 0.5, 2 or 4 h. The mechanism of cardioprotection does not appear to be due to increased myocardial perfusion but rather to some direct cellular action whose exact nature has yet to be elucidated.
D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002415:Cats; D003097:Collateral Circulation / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004334:Drug Administration Schedule; D011464:Epoprostenol / Q000008:administration & dosage / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D016285:Iloprost; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010976:Platelet Count
D002317:Cardiovascular Agents; D011464:Epoprostenol; D016285:Iloprost