Document Detail

Mepacrine protects the isolated rat heart during hypoxia and reoxygenation--but not by inhibition of phospholipase A2.
MedLine Citation:
PMID:  9062648     Owner:  NLM     Status:  MEDLINE    
Mepacrine (quinacrine) has in a number of studies been shown to protect the heart from ischemic injury, a protection commonly claimed to be due to inhibition of phospholipase A2. The aim of the present study was to investigate the effect of mepacrine 1 microM on isolated, buffer perfused rat hearts subjected to 60 min hypoxia and 30 min reoxygenation. We also wanted to clarify whether any cardioprotective effect was due to inhibition of phospholipase A2 or to other effects of the drug. Mepacrine led to a substantial fall in left ventricular developed pressure (LVDP) and coronary flow (CF) during normoxic perfusion. Treated hearts showed less increase in LVEDP and less fall in LVDP during the hypoxic period, and significantly fewer hearts stopped beating compared to untreated controls. Release of CK during hypoxia and reoxygenation was reduced in treated hearts compared to controls (19.9 +/- 3.8 vs. 73.1 +/- 13.3 IU, p < 0.05). Lipid analyses of the myocardium showed a significant increase in the total amount of non esterified fatty acids (NEFA) in both untreated and mepacrine treated hypoxic hearts compared to normoxic controls, but to a significantly lower level in the mepacrine treated hearts. However, contribution of polyunsaturated NEFAs to total NEFAs did not differ between the groups. Also, neither total amount of fatty acids nor amount of polyunsaturated fatty acids obtained from the 2-position of the phospholipid fraction differed between the treated and untreated groups. In an enzyme assay, mepacrine 1 microM did not inhibit phospholipase A2 activity. We conclude that in our model mepacrine protects the heart from hypoxic injury, but probably by another mechanism than inhibition of phospholipase A2 induced membrane damage.
E Bugge; T M Gamst; A C Hegstad; T Andreasen; K Ytrehus
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Basic research in cardiology     Volume:  92     ISSN:  0300-8428     ISO Abbreviation:  Basic Res. Cardiol.     Publication Date:  1997 Feb 
Date Detail:
Created Date:  1997-05-22     Completed Date:  1997-05-22     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0360342     Medline TA:  Basic Res Cardiol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  17-24     Citation Subset:  IM    
Department of Medical Physiology, University of Tromso, Norway.
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MeSH Terms
Anoxia / drug therapy*
Enzyme Inhibitors / pharmacology*
Fatty Acids, Nonesterified / analysis,  metabolism
Heart / drug effects*,  physiology
Hemodynamics / drug effects
Myocardium / chemistry
Phospholipases A / antagonists & inhibitors,  drug effects*,  metabolism
Phospholipases A2
Quinacrine / pharmacology*
Rats, Wistar
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Fatty Acids, Nonesterified; 83-89-6/Quinacrine; EC 3.1.1.-/Phospholipases A; EC A2

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