[A new approach to the understanding of the mechanism of ischemia/reperfusion damage in the heart and the effects of anti-ischemic drugs].

Abstract

The classical understanding of the mechanism of anti-anginal or anti-ischemic drugs is an increase in blood supply to the heart and/or a decrease in oxygen consumption of the heart, maintaining energy balance in the heart between supply and demand and hence maintaining the tissue levels of high-energy phosphates. This scheme is reasonable. During reperfusion following ischemia, however, there is more serious damage to the heart, although the tissue levels of high-energy phosphates increase. This is probably because toxic substances are generated in the heart during ischemia/reperfusion. We propose that both lysophosphatidylcholine and palmitoyl-L-carnitine that accumulate in the myocardium during ischemia/reperfusion are candidates for the toxic substances that accelerate ischemia/reperfusion damage to the heart. Therefore, drugs that have anti-lysophosphatidylcholine and/or anti-palmitoyl-L-carnitine effects are promising for the treatment of ischemic heart diseases. We found that K-7259, a novel derivative of dilazep having a minimal effect on the normal heart, is a drug that attenuates the deleterious effects of both lysophosphatidylcholine and palmitoyl-L-carnitine on the heart, and therefore attenuates the ischemia/reperfusion damage.

• Authors: Y Abiko, H Hashizume, A Hara
• Journal: Nihon yakurigaku zasshi. Folia pharmacologica Japonica (Nihon Yakurigaku Zasshi) Vol. 108 Issue 4 Pg. 195-202 (Oct 1996) ISSN: 0015-5691 [Print] Japan
• PMID: 8940701 (Publication Type: English Abstract, Journal Article, Review)

Chemical References

• Adrenergic beta-Antagonists
• Calcium Channel Blockers
• K 7259
• Lysophosphatidylcholines
• Vasodilator Agents
• Palmitoylcarnitine
• Propranolol
• Diltiazem
• Dilazep

Topics

• Adrenergic beta-Antagonists (pharmacology)
• Calcium Channel Blockers (pharmacology)
• Coronary Circulation (drug effects)
• Dilazep (analogs & derivatives, pharmacology)
• Diltiazem (pharmacology)
• Energy Metabolism (drug effects)
• Humans
• Lysophosphatidylcholines (metabolism)
• Myocardial Ischemia (etiology, metabolism)
• Myocardial Reperfusion Injury (etiology, metabolism)
• Myocardium (metabolism)
• Oxygen Consumption (drug effects)
• Palmitoylcarnitine (metabolism)
• Propranolol (pharmacology)
• Vasodilator Agents (pharmacology)