Comparison of N-methyl hexanoylhydroxamic acid, a novel antioxidant, with desferrioxamine and N-acetyl cysteine against reperfusion-induced dysfunctions in isolated rat heart.
The effects of a novel free radical scavenger, N-methyl hexanoylhydroxamic acid (NMHH) on ischaemia and reperfusion-induced dysfunction were compared with those of desferrioxamine (DFO) and N-acetyl cysteine (NAC) in isolated Langendorff-perfused rat heart. NMHH (150 microM) produced significant improvement in recovery of left ventricular developed pressure (LVDP) as compared with that of control hearts (35 +/- 8%) when included in the perfusate both before ischaemia and on reperfusion (68 +/- 6%) and on reperfusion alone (61 +/- 6%). In contrast, neither DFO (52 +/- 9%) nor NAC (54 +/- 12%), at the same concentration, produced a significant increase in recovery of LVDP when applied on reperfusion alone. Only DFO (77 +/- 5%), not NAC (54 +/- 12%), had a significant effect on recovery of LVDP when added to the perfusate before ischaemia and reperfusion. NAC applied before ischaemia produced significant improvement in recovery of heart rate (HR). The improved recovery of LVDP obtained with NMHH applied on reperfusion as compared with that obtained with controls and equimolar concentrations of DFO or NAC suggests that the novel hydroxamate NMHH is the more effective in attenuating reperfusion injury of contractile function in this model.
Collis
C S
CS
Division of Biochemistry, UMDS Guys Hospital, London, England.
Davies
M J
MJ
Rice-Evans
C
C
D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D003676:Deferoxamine / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D000975:Antioxidants; D002317:Cardiovascular Agents; D006877:Hydroxamic Acids; C082082:N-methyl hexanoylhydroxamic acid; D003676:Deferoxamine; D000111:Acetylcysteine