Role of ONO-3144, a new cardioplegic agent, in the reoxygenation injury in the anoxic myocardium.
We have investigated the effect of ONO-3144 (2-aminomethyl-4-tert-butyl-6-propionylphenol), which facilitates the conversion of prostaglandin G2 to H2 and acts as a scavenger of free radicals, on the reoxygenation injury in the anoxic heart. Rat hearts were perfused retrogradely with Krebs-Henseleit (KH) medium for 30 min (n = 8) in Group I. In Group II, the hearts which were perfused with anoxic KH medium for 40 min were reoxygenated for 30 min (n = 8). Group III hearts were similar to those in Group II except that 4 mg ONO-3144/liter was added to both anoxic and reoxygenation media (n = 8). Coronary effluent was collected for creatine kinase (CK) loss. Four rats hearts in each group were fixed for electron microscopic study and the remaining hearts were frozen in liquid nitrogen for measurement of adenosine triphosphate (ATP). A six-fold increase in CK leakage, observed after reoxygenation of anoxic heart, was prevented by ONO-3144. Tissue ATP was reduced from 22.2 +/- 0.9 mumol/g dry weight (Group I) to 5.5 +/- 1.1 mumol/g dry weight (Group II). A significant amount of ATP (9.05 +/- 1.22 mumol/g dry weight) was preserved in the treated Group III. The number of normal cells obtained by morphometrical analysis increased significantly from 56.7 +/- 7.8% (Group II) to 86.2 +/- 1.0% (Group III) and moderately injured cells were reduced to 3% in Group III as compared to 16% in the untreated Group I. Injury to the severely injured cells was not prevented by the drug treatment. At electron microscopic level, the cellular membranes, mitochondria and glycogen deposits were well preserved in Group III. Thus, ONO-3144 treatment provides a protection against reoxygenation injury in the anoxic myocardium by scavenging. .OH or other closely related species of free radicals. Therefore, free radicals generated through the conversion of prostaglandin G2 to H2 might play an important role in the reoxygenation injury of the anoxic myocardium.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D005609:Free Radicals; D006321:Heart / Q000187:drug effects*; D006324:Heart Arrest, Induced; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008854:Microscopy, Electron; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D010100:Oxygen / Q000633:toxicity*; D011427:Propiophenones / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains
D005609:Free Radicals; D011427:Propiophenones; C037467:2-aminomethyl-4-tert-butyl-6-propionylphenol; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D010100:Oxygen; D002118:Calcium