Perfusing isolated rat hearts with hydrogen peroxide: an experimental model of cardiac dysfunction caused by reactive oxygen species.
A model of cardiac dysfunction induced by reactive oxygen species (ROS) was established by adding hydrogen peroxide (H2O2) to the perfusate of isolated, Langendorff-perfused rat hearts, and the mechanism of functional injury was investigated. The following groups were included: 1 (n = 7), control perfusion; 2 (n = 11), perfusion with H2O2 (180 mumol 1(-1) for 10 min followed by recovery for 50 min; 3 (n = 4), control perfusion with N-acetylcysteine (NAC, 100 mumol 1(-1); 4 (n = 7), perfusion with H2O2 and NAC; 5 (n = 4), control perfusion with thiourea (15 mmol 1(-1), 6 (n = 7), H2O2 and thiourea together; 7 (n = 4), control perfusion with catalase (150 U ml-1); 8 (n = 7), catalase and H2O2, 9 (n = 4), control perfusion with deferoxamine (5 mmol 1(-1); and 10 (n = 7), deferoxamine and H2O2. coronary flow (CF), left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and heart rate (HR) were measured. All values are mean +/- SEM. When given alone, catalase, thiourea, NAC and deferoxamine did not influence left ventricular pressures, but NAC, catalase and thiourea increased CF. H2O2 increased CF (maximum 146 +/- 6% of baseline value after 5 min, p < 0.001 compared to group 1), decreased LVDP (minimum 14 +/- 5% of baseline value after 10 min, p < 0.0004), and increased LVEDP (from 0 mmHg to a maximum of 54 +/- 7 mmHg after 5 min recovery, p < 0.0003). All these changes gradually reversed during recovery. Catalase and thiourea both inhibited the H2O2-induced effects, but catalase inhibition was more complete. Neither NAC nor deferoxamine had any effect on H2O2-induced cardiac dysfunction. In conclusion, H2O2 perfusion is a convenient and reversible model of ROS-induced functional injury to isolated rat hearts. H2O2, rather than the hydroxyl radical, seems to be the main injurious ROS in this model.
Skjelbakken
T
T
Division of Thoracic and Cardiovascular Surgery, University of Tromsø, Norway.
Valen
G
G
Vaage
J
J
D000818:Animals; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects*; D006331:Heart Diseases / Q000139:chemically induced*; D006861:Hydrogen Peroxide / Q000008:administration & dosage / Q000633:toxicity*; D066298:In Vitro Techniques; D008297:Male; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide