The effects of N-methyl butyrohydroxamic acid and other monohydroxamates on reperfusion-induced damage to contractile function in the isolated rat heart.
The effects of three novel methyl substituted monohydroxamates N-methyl butyrohydroxamic acid (NMBH), N-methyl acetohydroxamic acid (NMAH) and N-methyl benzohydroxamic acid (NMBzH) against reperfusion induced contractile dysfunction were investigated in the isolated Langendorff-perfused rat heart. All these drugs produced an improved recovery of left ventricular developed pressure (LVDP) compared to control hearts in the order NMBH* (65 +/- 8%) > NMAH (59 +/- 8%) > NMBzH (48 +/- 3%) > control (35 +/- 3%) (mean +/- s.e.), however only the recovery obtained in NMBH treated hearts was significantly different from control hearts (*p > 0.05, Dunnett's test). Both NMAH (98 +/- 10%) and NMBH (84% +/- 8) produced a significant improvement in the recovery of heart rate (control 48 +/- 13%). There was no significant improvement of coronary flow, and NMBzH-treated hearts showed a significant reduction in recovery. The improved recovery in both LVDP and heart rate obtained with NMBH suggests this drug may be effective in attenuating reperfusion-induced contractile dysfunction in the isolated rat heart. Further, a comparison of the structures of the hydroxamates described in this study with the results obtained with desferrioxamine, (a trihydroxamate), and N-methyl hexanoylhydroxamic acid (NMHH) in other studies suggests that the nature of the alkyl chain attached to the carbonyl group of the hydroxamate may contribute to the efficacy of monohydroxamates in attenuating this type of myocardial injury in this model.
Collis
C S
CS
Division of Biochemistry, UMDS Guy's Hospital, London, UK.
Davies
M J
MJ
Rice-Evans
C
C
D000818:Animals; D005609:Free Radicals; D006352:Heart Ventricles / Q000503:physiopathology; D006877:Hydroxamic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology*; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar
D005609:Free Radicals; D006877:Hydroxamic Acids; C082751:N-methyl butyrohydroxamic acid