Effects of a novel, low-molecular weight inhibitor of lipid peroxidation on ischemia-reperfusion injury in isolated rat hearts and in cultured cardiomyocytes.

Abstract

We investigated the effect of H290/51, a novel, low-molecular-weight inhibitor of lipid peroxidation, on cardiac ischemia-reperfusion injury. Lactate dehydrogenase (LD) release from cultured cardiomyocytes exposed to 1 h hypoxia and 4 h reoxygenation was measured after pretreatment with different concentrations of H290/51. In another series, Langendorff-perfused rat hearts were exposed to 30 min global ischemia and 60 min reperfusion (n=minimum 10 in each group): 1. Control ischemia-reperfusion. 2. Vehicle throughout the experiment. 3. Vehicle during stabilization, and H290/51 (10(-6) mol/l) during reperfusion. 4. H290/51 throughout the experiments. During reoxygenation of isolated cardiomyocytes, H290/51 dose dependently inhibited LD release with an pIC50 value of 7.2+/-0.4 (mean+/-SEM), with 10(-6) mol/l as the lowest efficient concentration. In isolated hearts ischemia-reperfusion induced severe reperfusion arrhythmias, reduced left ventricular developed pressure (LVDP) and coronary flow (CF), and increased LV end-diastolic pressure (LVEDP). LD activity in the effluent increased. H290/51 throughout perfusion (group 4) reduced the occurrence of severe reperfusion arrhythmias (p < .0001), attenuated the decrease of LVDP (p < .008), and CF (p < .006), the increase of LVEDP (p < .008), and the release of LD (p < .002). Tissue contents of thiobarbituric acid-reactive substances did not increase during reperfusion in controls, but was reduced in group 4 (p < .004). H290/51 given only during reperfusion (group 3) tended to improve cardiac function, but significantly so only for increase of CF (p < .01). The lipid peroxidation inhibitor H290/51 attenuated cardiac injury induced by ischemia-reperfusion.

• Authors: A Nagy, G Valen, B Ek, P Sellei, P O Sjöquist, J Vaage
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 24 Issue 9 Pg. 1462-9 (Jun 1998) ISSN: 0891-5849 [Print] United States
• PMID: 9641264 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• H290-51
• Indoles
• Thiobarbituric Acid Reactive Substances
• L-Lactate Dehydrogenase

Topics

• Animals
• Animals, Newborn
• Antioxidants (pharmacology)
• Blood Pressure (drug effects)
• Cells, Cultured
• Coronary Circulation (drug effects)
• In Vitro Techniques
• Indoles (pharmacology)
• L-Lactate Dehydrogenase (metabolism)
• Lipid Peroxidation (drug effects)
• Male
• Myocardial Reperfusion Injury (enzymology, metabolism, physiopathology)
• Myocardium (chemistry, enzymology, metabolism)
• Rats
• Rats, Sprague-Dawley
• Thiobarbituric Acid Reactive Substances (analysis)
• Ventricular Function, Left (drug effects)