Effects of nicotinic acid and mepacrine on fatty acid accumulation and myocardial damage during ischemia and reperfusion.
To assess the nature of ischemia- and reperfusion-induced lipid changes and their consequences for myocardial function and integrity, Krebs-Henseleit perfused, isolated, working rat hearts were treated with nicotinic acid or mepacrine, putative inhibitors of triacylglycerol and phospholipid hydrolysis, respectively. In non-treated hearts 60 min ischemia resulted in a marked rise in myocardial fatty acid (FA) content. The FA content sharply increased further during 30 min reperfusion. Seven out of 16 (44%) hearts fibrillated continuously during reperfusion. Post-ischemic recovery of cardiac output (CO) of the non-fibrillating hearts amounted to 68 +/- 15% of the preischemic value. Nicotinic acid (10 microM) significantly reduced FA accumulation during ischemia (P less than 0.05), but not during reperfusion (0.05 less than P less than 0.10). Post-ischemic recovery of CO was improved (87 +/- 12%). This was neither associated with preservation of myocardial adenine nucleotide content, nor significant reduction of enzyme release. Mepacrine (1 microM) completely abolished reperfusion arrhythmias and improved recovery of CO (88 +/- 7% of pre-ischemic value). The reduction of FA content in ischemic and reperfused hearts did not reach the level of significance. Enzyme release was not attenuated. At 10 microM, mepacrine completely prevented accumulation of FAs during ischemia and reperfusion, abolished reperfusion-arrhythmias, and reduced enzyme release. No concomitant preservation of adenine nucleotides was observed. In conclusion, nicotinic acid and mepacrine are able to reduce ischemia- and reperfusion-induced changes in myocardial lipid metabolism. In addition, both drugs improve post-ischemic functional recovery. It remains to be established whether these effects are causally related.
van Bilsen
M
M
Department of Physiology, University of Limburg, Maastricht, The Netherlands.
van der Vusse
G J
GJ
Willemsen
P H
PH
Coumans
W A
WA
Roemen
T H
TH
Reneman
R S
RS
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control; D003327:Coronary Disease / Q000150:complications / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D009525:Niacin / Q000494:pharmacology*; D010740:Phospholipases / Q000037:antagonists & inhibitors; D011796:Quinacrine / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew
D005227:Fatty Acids; D009525:Niacin; D010740:Phospholipases; D011796:Quinacrine