Protective effects of the SOD-mimetic SC-52608 against ischemia/reperfusion damage in the rabbit isolated heart.
An experimental model of myocardial ischemia/reperfusion injury was used to assess the cardioprotective effects of SC-52608, a low molecular weight superoxide dismutase mimetic. Langendorff perfused rabbit isolated hearts were subjected to 30 min of global ischemia followed by 45 min of reperfusion. Hearts perfused in the presence of 20 microM SC-52608 exhibited a decrease in the release of creatine kinase and intracellular potassium compared to hearts receiving vehicle (control). A progressive increase in left ventricular end-diastolic pressure developed upon reperfusion in all hearts, but was significantly greater in control hearts when compared to hearts treated with SC-52608 (P < 0.05). In addition, results obtained with a radiolabeled monoclonal antibody to the intracellular protein myosin, indicate an increased degree of irreversible damage in vehicle-treated hearts. Myocardial protection was not significant in an additional group of hearts treated with 10 microM SC-52608. The hemodynamic, biochemical, morphological, as well as the antimyosin binding data, demonstrate that pretreatment with SC-52608 protects the myocardium from damage associated with global ischemia and reperfusion. The mechanism by which SC-52608 mediates the observed protective effect is most likely related to its ability to scavenge superoxide.
Kilgore
K S
KS
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0626.
Friedrichs
G S
GS
Johnson
C R
CR
Schasteen
C S
CS
Riley
D P
DP
Weiss
R H
RH
Ryan
U
U
Lucchesi
B R
BR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003326:Coronary Circulation / Q000187:drug effects; D003402:Creatine Kinase / Q000032:analysis; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use; D007424:Intracellular Fluid / Q000737:chemistry; D007527:Isoenzymes; D008297:Male; D008854:Microscopy, Electron; D017202:Myocardial Ischemia / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D009218:Myosins / Q000032:analysis / Q000276:immunology; D009942:Organometallic Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D010477:Perfusion; D011188:Potassium / Q000032:analysis; D011817:Rabbits; D013482:Superoxide Dismutase / Q000494:pharmacology / Q000627:therapeutic use; D013481:Superoxides / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000975:Antioxidants; D002317:Cardiovascular Agents; D016166:Free Radical Scavengers; D007527:Isoenzymes; D009942:Organometallic Compounds; D013481:Superoxides; C089774:SC 52608; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D009218:Myosins; D011188:Potassium