Protection of the heart from ischemia by a new oligomeric derivative of prostaglandin E1.
A lipophilic oligomeric ester was synthesized from prostaglandin E1. The compound was found to protect a Langendorff perfused rat heart from ischemic insult. After 15 minutes cessation of perfusion, the flow was restarted, and the recovery of contraction was measured. In control experiments, the recovery was 16.1 +/- 7.3%. In the case of pre-ischemic addition of the compound (10 micrograms/ml at 10 minutes before ischemic insult), the recovery was 31 +/- 13.2% (n = 7; the difference was not significant). In post-ischemic addition (10 micrograms/ml), the recovery was 75.9 +/- 9.0% (n = 7; p less than 0.01). The compound was also effective in protecting rat heart myocytes against a 60 minutes anoxia/15 minutes reoxygenation injury as judged by the loss of "rod-shaped" intact myocytes. At a 10 micrograms/ml concentration, the compound protected against the loss of rod-shaped myocytes by 30% in pre-anoxia addition and 35% in post-anoxia addition. The levels of significance in these experiments were p less than 0.001. Possible mechanisms of action of this compound are discussed.
Ohnishi
S T
ST
Membrane Research Institute, University City Science Center, Philadelphia, PA 19104.
Katsuoka
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M
D000527:Alprostadil / Q000031:analogs & derivatives*; D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D008954:Models, Biological; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D010100:Oxygen / Q000378:metabolism; D010477:Perfusion; D011453:Prostaglandins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D015203:Reproducibility of Results
D011453:Prostaglandins; C060276:MR 356; D000527:Alprostadil; D010100:Oxygen