Diastolic dysfunction of perfused rat hearts induced by hydrogen peroxide. Protective effect of selenium.
Oxidant substances such as hydrogen peroxide are postulated to cause cardiac dysfunction and injury in a number of pathological conditions. Selenium is an essential nutrient which serves as an oxidant defense through the selenoenzyme glutathione peroxidase. This enzyme metabolizes hydrogen peroxide; its activity in rat heart is reduced to 5% of control by selenium deficiency. Left ventricular function of selenium-deficient and control rat hearts was studied in a Langendorff preparation under isovolumic conditions. A stabilization period of 20 min was followed by a 70 min infusion of hydrogen peroxide at 375 or 1500 nmol/min. When no hydrogen peroxide was infused, perfusion for 90 min had no effect on systolic or diastolic function and no effect of selenium deficiency was detected. Hydrogen peroxide infusion into selenium-deficient hearts at 375 nmol/min led to impaired isovolumic relaxation and a substantial increase in end-diastolic pressure after 45 min which worsened progressively until the experiment was terminated. By contrast no effect was observed on systolic contractile function as assessed by peak pressure or developed pressure. Infusion of this dose of hydrogen peroxide into control hearts had no significant effect on diastolic or systolic function. However, infusion of 1500 nmol hydrogen peroxide/min into control hearts caused diastolic dysfunction after 30 min without affecting systolic function. These results indicate that hydrogen peroxide injury to the perfused rat heart is manifested by diastolic dysfunction before systolic dysfunction occurs. Selenium deficiency lowers the dose of hydrogen peroxide needed to cause diastolic dysfunction. This suggests that the selenoenzyme glutathione peroxidase protects the heart against hydrogen peroxide injury.
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
K H
KH
Konz
M
M
Haap
K E
KE
Hill
R F
RF
Burk
R A
RA
Walsh
D000818:Animals; D003971:Diastole / Q000187:drug effects*; D006321:Heart / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D064586:Selenic Acid; D012643:Selenium / Q000172:deficiency / Q000494:pharmacology*; D018036:Selenium Compounds
D018036:Selenium Compounds; D006861:Hydrogen Peroxide; D012643:Selenium; D064586:Selenic Acid