Morphological and biochemical evidence of protective effect by ONO-3144, a free radical scavenger, on the reoxygenation injury in the anoxic myocardium

M. Ashraf, H. Kobayashi, P. M. Rahamathylla

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

We have investigated the effect of ONO-3144 (2:aminomethyl-4-tert-butyl-propionylphenol), which accelerates the conversion of prostaglandin G2 to H2 and acts as a scavenger for free radicals, on the reoxygenation injury in the anoxic heart. Rat hearts were perfused retrogradely with Krebs-Henseleit (KH) medium for 30 minutes in Group I. In Group II, the hearts which were perfused with anoxic KH medium for 40 minutes were reoxygenated for 30 minutes. Group III was similar for Group II except that 4 mg ONO-3144/liter was added in anoxic medium. Group IV was similar to group III except ONO-3144 was present both during anoxia and reoxygenation. Coronary effluent was collected for the measurement of creatine phosphokinase (CPK). Tissue from each group was processed for electron microscopy, adenosine triphosphate (ATP), and tissue calcium. A six-fold increase in CPK leakage that was observed after reoxygenation of anoxic heart was prevented by ONO-3144. Tissue ATP was reduced from 21.65 ± 1.1 μmol/gm dry weight (Group I) to 4.83 ± 0.8 μmol/gm dry weight (Group II). A significant amount of ATP (9.05 ± 1.22 μmol/gm dry weight) was preserved in the treated Group IV. The number of normal cells obtained by morphological analysis increased significantly from 24.2 ± 8.4% (Group II) to 70.00 ± 4.0% (Group IV), and severely injured cells were also reduced to 19.8 ± 2.8% in the same group as compared to 54.8% in the untreated Group II. At the electron microscopic level, the cellular membranes, mitochondria, vascular endothelium, and glycogen deposits were well preserved in Group IV. The treatment during anoxia only did not minimize the reoxygenation damage (Group III). Thus, treatment with ONO-3144 provides a great protection against reoxygenation injury to the myocyte and vascular endothelium of the anoxic myocardium, perhaps by scavenging active oxygen species.

Original languageEnglish (US)
Pages (from-to)351-364
Number of pages14
JournalAmerican Journal of Cardiovascular Pathology
Volume2
Issue number4
Publication statusPublished - Jan 1 1989
Externally publishedYes

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ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pathology and Forensic Medicine

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