The effect of a low molecular weight inhibitor of lipid peroxidation on ultrastructural alterations to ischemia-reperfusion in the isolated rat heart.
The effects of H290/51, a novel indenoindole derivative inhibitor of lipid peroxidation, on ultrastructural changes during cardiac ischemia-reperfusion injury were investigated. Langendorff-perfused rat hearts were exposed to 30 minutes of global ischemia followed by 20 minutes of reperfusion: Group A: Control hearts with standard buffer perfusion with vehicle added. Group B: H290/51 (10(-6) mol/l) added to buffer throughout stabilisation and reperfusion. In an additional Group C, where hearts were given H290/51, but not subjected to ischemia, the ultrastructure was preserved till the end of reperfusion. Absolute volumes and calculated volume fractions (Vv) of tissue and subcellular components were assessed with quantitative stereologic morphometry. After ischemia the increase in volume of extracellular interstitium was inhibited by H290/51 (247 +/- 80 vs. 159 +/- 50 microl, mean +/- SD, groups A and B, respectively, p<0.05). The Vv (interstitium/myocard) was higher in control hearts (0.318 +/- 0.062 vs. 0.206 +/- 0.067, p<0.05). Vv (cell edema/myocyte) was higher in the control group (0.144 +/- 0.07 vs. 0.083 +/- 0.033, p<0.05). Vv (myocyte/myocard) was higher in group B after ischemia than in the control group (0.622 +/- 0.071 vs. 0.707 +/- 0.052, p<0.05). The decreased Vv (capillary/myocard) after ischemia was inhibited by H290/51. After reperfusion there was no difference between groups. Treatment with H290/51 reduced edema and ensured better preserved sarcolemmal membrane structure during ischemia. The effect was no longer present after reperfusion.
Nagy
A
A
Crafoord Laboratory, Karolinska Institutet, Stockholm, Sweden. nagya@kmk.hu
Myklebust
R
R
Valen
G
G
Sjöquist
P O
PO
Vaage
J
J
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors*; D008297:Male; D008854:Microscopy, Electron; D008970:Molecular Weight; D017202:Myocardial Ischemia / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology*; D009206:Myocardium / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; C088233:H290-51; D007211:Indoles; D008054:Lipid Peroxides