Effect of the ultrashort-acting beta-blocker Brevibloc on free-radical-mediated injuries during the early reperfusion state.
The left descending coronary artery (LAD) was ligated for 45 min or 90 min followed by 1-h reperfusion. During experiments the animals in Group I (15 dogs) received saline infusion, in Group II (20 dogs) they received the ultrashort-acting beta-blocker Brevibloc (esmolol HCl). The marker of lipid peroxidation the malondialdehyde (MDH) as well as endogen scavengers, the glutathione (GSH), and superoxide dismutase (SOD) were measured in the heart tissue homogenates. In blood and heart tissue samples the 6-keto-prostaglandin F1 alpha (PGF1 alpha) and thromboxane B2 (TXB2) were determined. Biochemical measurements revealed that esmolol HCl has beneficial effect on the free-radical-meduated-damage reducing the MDA content in the ischemic area. In Group I the value of MDA after 90 min of LAD ligature was 138 +/- 5.6%, in Group II the elevation was only 107.4 +/- 3.2%. After treatment with Brevibloc the GSH content of ischemic-reperfused areas decreased slightly (81.75 +/- 3.5% of the normal value), moreover, in Group I the depletion of GSH was considerable (64.5 +/- 4.2%). Coronary reperfusion caused the release of eicosanoids in both groups, mainly in the first 10 min. The highest value of thromboxane in blood samples could be measured in Group I after 90 min of LAD ligature (24.8 +/- 3.6 pmol/ml; the normal value 8-12 pmol/ml). In Group II during the same period of experiments the TXB2 in the blood was 14 +/- 3.7 pmol/ml. In heart tissue samples the amount of endoperoxides increased in ischemic and non-ischemic areas of Group I and II. Nevertheless, the calculated ratio of PGF1 alpha and TXB2 was near to the normal after Brevibloc treatment (0.85-0.9; the normal values were 1-1.2). These results indicate that esmolol HCl can modulate both the free-radical-mediated reaction and arachidonic acid metabolism.
Department of Experimental Surgery, University Medical School, Pécs, Hungary.
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Röth
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Török
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood / Q000378:metabolism; D000208:Acute Disease; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D003327:Coronary Disease / Q000097:blood / Q000473:pathology*; D004285:Dogs; D005260:Female; D005609:Free Radicals; D008297:Male; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D010100:Oxygen / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000097:blood / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D005609:Free Radicals; D011412:Propanolamines; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C036604:esmolol; D010100:Oxygen