Preconditioning with hydrogen peroxide (H2O2) or ischemia in H2O2-induced cardiac dysfunction.
The possible cardioprotective effects of preconditioning by ischaemia (IPC) or a low dose of H2O2 (HPC) prior to a high dose of H2O2 was investigated. Langendorff-perfused rat hearts (n = 10 in each group) were subjected to 10 min of 140 micromol/L H2O2 and 30 min recovery after either (1) control perfusion, (2) 20 micromol/L H2O2 for 10 min, recovery 10 min, or (3) 2 x 2 min global ischaemia and 5 min reperfusion. 140 micromol/L H2O2 increased left ventricular end-diastolic pressure from 0 to 68+/-8 mmHg in controls (mean+/-SEM), which was attenuated by IPC (46+/-9 mmHg, p<0.001) and HPC (18+/-4 mmHg, p < 0.001 compared to controls, p < 0.01 compared to IPC). HPC, but not IPC, improved coronary flow (p < 0.02) and left ventricular developed pressure (p < 0.001) during recovery. Troponin T release was similar in all groups. Tissue thiobarbituric acid reactive substances, antioxidant capacity, catalase, and glutathione peroxidase were not influenced by 140 micromol/L H2O2. H2O2 decreased the level of tissue glutathione. This reduction was augmented by HPC (p <0.02) and attenuated by IPC (p < 0.02). H2O2 increased superoxide dismutase (p < 0.04). The increase was attenuated by IPC (p < 0.05), but not influenced by HPC. HPC efficiently protected cardiac function in H2O2-induced cardiac injury, while IPC had only a small protective effect. The functional protection cannot be explained by reduction of irreversible injury, attenuation of lipid peroxidation, or modification of tissue antioxidant parameters.
Valen
G
G
Department of Thoracic Surgery, Karolinska Hospital, Stockholm, Sweden. Guro.Valen@cmm.ki.se
Starkopf
J
J
Takeshima
S
S
Kullisaar
T
T
Vihalemm
T
T
Kengsepp
A T
AT
Löwbeer
C
C
Vaage
J
J
Zilmer
M
M
D000818:Animals; D000975:Antioxidants / Q000032:analysis / Q000378:metabolism*; D001794:Blood Pressure; D003326:Coronary Circulation; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000503:physiopathology; D006339:Heart Rate; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D015227:Lipid Peroxidation; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020107:Troponin T / Q000032:analysis / Q000378:metabolism; D016277:Ventricular Function, Left
D000975:Antioxidants; D017382:Reactive Oxygen Species; D020107:Troponin T; D006861:Hydrogen Peroxide