Induction of endogenous tissue antioxidant enzyme activity attenuates myocardial reperfusion injury.
Efforts to reduce reperfusion injury have focused on exogenous therapies; however, endogenous attenuation of reperfusion injury can be induced by a single sublethal dose of endotoxin (ETX) prior to ischemia. The purposes of this study were to investigate (i) the early neutrophil-endothelial (PMN-EC) adherence, (ii) the associated myocardial oxidant stress, (iii) the relationship of oxidant stress to antioxidant enzyme activity, and (iv) the correlation of increased antioxidant enzyme activity to myocardial recovery following ischemia/reperfusion (I-R) injury at 36 hr. Rats were administered a sublethal dose (2% of LD50) of endotoxin (500 micrograms/kg, ip, Salmonella typhimurium). At 6 hr, myocardial neutrophil accumulation (histology), hydrogen peroxide (H2O2) levels, and myocardial tissue glutathione (glutathione and oxidized glutathione) levels were determined. At 24 hr myocardial tissue glutathione levels and catalase (CAT) activity were assayed. At 36 hr, myocardial tissue superoxide dismutase, glutathione peroxidase, glutathione reductase, catalase, and glucose-6-phosphate dehydrogenase (G-6-PD) were assayed. At 36 hr, hearts were subjected to a standard (20 min, global, 37 degrees C) ischemic insult followed by reperfusion. At 40 min of reperfusion, ventricular function was assessed (ventricular balloon; ventricular developed pressure +dP/dt, and -dP/dt).(ABSTRACT TRUNCATED AT 250 WORDS)
Bensard
D D
DD
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262.
Brown
J M
JM
Anderson
B O
BO
Banerjee
A
A
Shanley
P F
PF
Grosso
M A
MA
Whitman
G J
GJ
Harken
A H
AH
D000818:Animals; D000975:Antioxidants; D004731:Endotoxins / Q000494:pharmacology; D004790:Enzyme Induction; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D010084:Oxidation-Reduction; D010100:Oxygen / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium
D000975:Antioxidants; D004731:Endotoxins; D006861:Hydrogen Peroxide; D005978:Glutathione; D010100:Oxygen