title: Reduction by prostaglandin E1 or prostaglandin E0 of myocardial infarct size in the rabbit by activation of ATP-sensitive potassium channels.
abstract: 1. This study examined whether pretreatment of rabbits with infusions of prostaglandin E1 (PGE1) or prostaglandin E0 (PGE0) (which were terminated prior to the onset of ischaemia) reduce myocardial infarct size arising from coronary artery occlusion (60 min) and reperfusion (120 min). In addition, we investigated whether the observed cardioprotective effects of these two prostaglandins were due to the activation of ATP-sensitive potassium (KATP) channels. 2. In the anaesthetized rabbit, infarct size (expressed as a percentage of the area at risk) after 60 min of coronary artery occlusion followed by 2 h of reperfusion was 59 +/- 4% (n = 10). PGE1 or PGE0 treatment (1.0 micrograms kg-1 min-1), administered as 1 h pretreatments (0.05 ml min-1, i.v.), significantly reduced infarct size to 44 +/- 6% (n = 6) or 42 +/- 1% (n = 6), respectively. PGE1 or PGE0 pretreatment resulted in a significant reduction in mean arterial blood pressure, which returned to baseline within 15 min of discontinuation of the infusion (i.e. prior to LAL ligation). 3. The reduction in infarct size afforded by PGE1 was abolished by pretreatment of rabbits with the KATP channel blockers, glibenclamide (60 +/- 4%; n = 8) or 5-hydroxydecanoate (58 +/- 6%; n = 6). Similarly, glibenclamide also largely attenuated the reduction in infarct size afforded by PGE0 (52 +/- 3%; n = 8). 4. We propose that a 1 h pretreatment of PGE1 or PGE0 reduces infarct size by activating protein kinase C resulting in the opening of KATP channels.
authors.affiliation: William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London.
authors.forename: E J
authors.initials: EJ
authors.lastname: Hide
authors.forename: P
authors.initials: P
authors.lastname: Ney
authors.forename: J
authors.initials: J
authors.lastname: Piper
authors.forename: C
authors.initials: C
authors.lastname: Thiemermann
authors.forename: J R
authors.initials: JR
authors.lastname: Vane
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000527:Alprostadil / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001711:Biotransformation / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003652:Decanoic Acids / Q000494:pharmacology; D004562:Electrocardiography / Q000187:drug effects; D005905:Glyburide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006880:Hydroxy Acids / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D000889:Anti-Arrhythmia Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D014665:Vasodilator Agents; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate; C086635:prostaglandin E0; D000527:Alprostadil; D005905:Glyburide