Reduction of experimental myocardial infarct size by infusion of lactosylphenyl Trolox.
OBJECTIVE
The aim was to determine if lactosylphenyl Trolox could improve myocardial resistance to ischaemia and reperfusion. Lactosylphenyl Trolox is derived by coupling p-aminophenyl-beta-D-lactopyranoside to Trolox. Trolox, a polar analogue of vitamin E, has been found to protect human cardiomyocytes against oxyradicals and to reduce myocardial damage by 66% in a canine ischaemia-reperfusion model.


METHODS
New Zealand white rabbits (weighing approximately 3.5 kg) were subjected to 1 h ischaemia by ligation of the main branch of the anterior ventricular coronary artery. Approximately 1-2 min before release of ischaemia, a 30 ml bolus of saline (placebo control) or saline containing lactosylphenyl Trolox was injected into the right external jugular vein, followed by 3 h reperfusion. The area at risk was identified by staining with Evans Blue. Area of necrosis was indicated by tetrazolium red staining, confirmed by histopathology and quantified by planimetry.


RESULTS
The control group (n = 6) had 46.6(SD 10.0)% necrosis of the area at risk but the lactosylphenyl Trolox treated groups (n = 6 per group) had reduced necrosis: 34.0(6.5)%, 17.4(8.2)%, and 6.9(3.6)% at doses of 2.5, 5.0, and 10 mumol.kg-1, respectively (each with p < 0.05 v control value). These translated to 48.6(14.0)%, 62.7(17.6)%, and 85.3(7.8)% myocardial salvage, respectively. In contrast, the salvages achieved with 2.5 and 10 mumol.kg-1 of Trolox were 31.0(11.0)% and 62.1(18.9)% respectively (both p < 0.05 v lactosylphenyl Trolox).


CONCLUSIONS
Lactosylphenyl Trolox reduces myocardial infarct size more effectively than Trolox in a rabbit model of ischaemia-reperfusion.
Wu
T W
TW
Department of Clinical Biochemistry, University of Toronto Faculty of Medicine, Toronto General Hospital, Ontario, Canada.
Wu
J
J
Zeng
L H
LH
Sugiyama
H
H
Mickle
D A
DA
Au
J X
JX
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002839:Chromans / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006027:Glycosides / Q000627:therapeutic use*; D006651:Histocytochemistry; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D011817:Rabbits; D013778:Tetrazolium Salts
D002839:Chromans; D006027:Glycosides; D013778:Tetrazolium Salts; C073455:lactosylphenyl-trolox