title: Superoxide dismutase restores contractile and metabolic dysfunction through augmentation of adenosine release in coronary microembolization.
abstract: BACKGROUND
  This study was undertaken to test the hypothesis that administration of superoxide dismutase (SOD) restores the contractile and metabolic dysfunction in coronary microembolization and that these beneficial effects of SOD are attributable to the restoration of 5'-nucleotidase activity and subsequent augmentation of adenosine release.
  
  
  RESULTS
  In 78 dogs before and after an injection of microspheres (15 microns in diameter) into the left anterior descending coronary artery, regional coronary blood flow (CBF), fractional shortening (FS), and lactate extraction ratio (LER) were measured with and without administration of recombinant human SOD (50 micrograms/kg/min i.c.). In the untreated dogs (n = 6), both FS and LER decreased after coronary microembolization (2.0 x 10(5) microspheres per ml CBF [mL/min]). FS and LER decreased from 24.2 +/- 1.3% to 5.1 +/- 1.2% and from 23.0 +/- 1.1% to -10.5 +/- 2.9%, respectively. These ischemic changes were associated with coronary hyperemic flow (141 +/- 8 versus 92 +/- 1 mL/100 g/min) and adenosine release (5.8 +/- 0.5 versus 0.4 +/- 0.1 nmol/100 g/min). Pretreatment with SOD augmented the hyperemic flow to 164 +/- 4 mL/100 g/min and enhanced the release of adenosine (9.6 +/- 0.6 nmol/100 g/min) associated with improvement of functional and metabolic dysfunction (FS, 14.8 +/- 2.3%; LER, 15.1 +/- 3.1%). Administration of SOD at 10 minutes (n = 5) and 30 minutes (n = 5) after coronary embolization restored the contractile function and lactate metabolism (at 10 minutes: FS, 16.7 +/- 2.2% and LER, 16.7 +/- 3.9%; at 30 minutes: FS, 11.1 +/- 1.3% and LER, 7.2 +/- 3.1%). However, administration of SOD 60 minutes after coronary embolization (n = 6) did not restore the contractile and metabolic dysfunction. The restoration of the contractile and metabolic dysfunction by SOD treatment was blunted by adenosine receptor blockade with 8-phenyltheophylline (n = 5). Myocardial 5'-nucleotidase activity at 2 hours after embolization was restored with SOD treatment at 10 minutes (n = 5) and 30 minutes (n = 5) after embolization. However, SOD treatment at 60 minutes after embolization (n = 6) did not restore 5'-nucleotidase activity compared with the SOD pretreatment group. Furthermore, coronary submaximal vasodilation induced by papaverine (n = 5) and adenosine (n = 5) abolished the beneficial effects of SOD.
  
  
  CONCLUSIONS
  We conclude that 1) in sustained myocardial ischemia, SOD treatment attenuates ischemic injury caused by coronary microembolization by restoration of 5'-nucleotidase activity and augmentation of adenosine release; 2) this beneficial effect of SOD is observed even after coronary microembolization; and 3) the beneficial effects of SOD are attributable to coronary vasodilation produced by augmented adenosine release.
authors.affiliation: First Department of Medicine, Osaka University School of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Takashima
authors.forename: M
authors.initials: M
authors.lastname: Hori
authors.forename: M
authors.initials: M
authors.lastname: Kitakaze
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: M
authors.initials: M
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Kamada
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004617:Embolism / Q000378:metabolism*; D007267:Injections; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008863:Microspheres; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D014664:Vasodilation / Q000502:physiology
chemical_list: D007773:Lactates; D019344:Lactic Acid; D013806:Theophylline; C028322:8-phenyltheophylline; D013482:Superoxide Dismutase; D015720:5'-Nucleotidase; D000241:Adenosine