Cardioprotective effects of recombinant human extracellular-superoxide dismutase type C in rat isolated heart subjected to ischemia and reperfusion.
The cardioprotective effect of recombinant human extracellular-superoxide dismutase type C (rh-EC-SOD C) was studied in isolated perfused rat heart subjected to left coronary artery ligation for 30 or 60 min followed by 30-min reperfusion. A comparison was made with the effects of bovine CuZn-SOD. Reperfusion after 30-min coronary artery ligation was associated with a release of creatine kinase (CK) into the coronary effluent (71 +/- 5.2 IU/30 min), which was markedly reduced (39 +/- 5.5 IU/30 min) in hearts perfused with rh-EC-SOD C (28 mg/L). CuZn-SOD (4 or 20 mg/l) or a lower concentration of rh-EC-SOD C (5.6 mg/l) did not significantly attenuate CK outflow during reperfusion, however. In both vehicle- and SOD-treated hearts, the left ventricular developed pressure (LVDP) and the coronary flow recovered to 80-90% of baseline at the end of the reperfusion period. Increasing the ischemic period from 30 to 60 min caused a much more pronounced cardiac injury measured after 30-min reperfusion. In the hearts that received vehicle, recovery of LVDP (in percentage of baseline values) at the end of reperfusion was 58 +/- 2%, which was increased to 84 +/- 3 and 83 +/- 5% after treatment with rh-EC-SOD C (28 mg/L) and CuZn-SOD (20 mg/L), respectively. The corresponding values for recovery in coronary flow were 54 +/- 3% (vehicle), 69 +/- 4% (rh-EC-SOD C), and 74 +/- 3% (CuZn-SOD).(ABSTRACT TRUNCATED AT 250 WORDS)
Sjöquist
P O
PO
Department of Pharmacology, Hässle Research Laboratories, Mölndal, Sweden.
Carlsson
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L
Jonason
G
G
Marklund
S L
SL
Abrahamsson
T
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D003402:Creatine Kinase / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology*
D011994:Recombinant Proteins; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D003402:Creatine Kinase