[A new approach to the understanding of the mechanism of ischemia/reperfusion damage in the heart and the effects of anti-ischemic drugs].
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.
Abiko
Y
Y
Department of Pharmacology, Asahikawa Medical College, Japan.
Hashizume
H
H
Hara
A
A
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004109:Dilazep / Q000031:analogs & derivatives* / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D008244:Lysophosphatidylcholines / Q000378:metabolism; D017202:Myocardial Ischemia / Q000209:etiology* / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000209:etiology* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010172:Palmitoylcarnitine / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; C092019:K 7259; D008244:Lysophosphatidylcholines; D014665:Vasodilator Agents; D010172:Palmitoylcarnitine; D011433:Propranolol; D004110:Diltiazem; D004109:Dilazep