1 This study examined whether pretreatment of rabbits with infusions of prostaglandin El (PGEI) or prostaglandin Eo (PGEO) (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). PGEI or PGEo treatment (1.0 ,yg kg-' min-'), administered as 1 h pretreatments (0.05 ml min-', i.v.), significantly reduced infarct size to 44 + 6% (n = 6) or 42 + 1 % (n = 6), respectively. PGE, or PGEo 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 PGE, 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 PGEo (52 + 3%; n = 8).4 We propose that a 1 h pretreatment of PGEI or PGEO reduces infarct size by activating protein kinase C resulting in the opening of KATP channels.

1 This study examined whether (i) a 1 h pretreatment with or (ii) a continuous infusion of sulprostone reduces myocardial infarct size arising from coronary artery occlusion (60 min) and reperfusion (120 min) in the anaesthetized rabbit. In addition, we investigated whether the observed cardioprotective effect of this selective agonist of prostanoid EP,/EP3 receptors were due to the activation of ATPsensitive potassium (KATP) channels.2 In anaesthetized rabbits pretreated with vehicle (5% ethanol in 0.9% saline; 0.05 ml min-', i.v.) infarct size (expressed as a percentage of the area at risk) after 60 min of coronary artery occlusion followed by 120 min of reperfusion was 59 + 4% (n = 10). Pretreatment of rabbits with sulprostone (1.0 ug kg-' min-' for 1 h, discontinued immediately prior to coronary artery occlusion) did not reduce infarct size (60 + 4%; n = 4). In contrast, a continuous infusion of sulprostone (1.0 ig kg-' min-') starting 10 min prior to the onset of LAL occlusion and continued throughout the experiment, significantly reduced infarct size (41 + 5%, n = 6) when compared to the respective vehicle-treated controls (57 + 4%, n = 10; P <0.05). Sulprostone (pretreatment or continuous infusion) had no effect on any of the haemodynamic parameters measured. 3 The reduction in infarct size afforded by continuous infusion of sulprostone was abolished by pretreatment of rabbits with the KATP channel blocker 5-hydroxydecanoate (5-HD 5 pg kg-'; 63+4%; n =6). When administered alone, 5-HD had no effect on infarct size when compared to control (52+6, n=10). 4 We propose that a continuous infusion of the selective EP,/EP3 prostanoid receptor agonist, sulprostone, reduces infarct size in the anaesthetized rabbit by a mechanism that involves the opening of KATP channels.

These results support the hypothesis that the cardioprotection afforded by ischaemic preconditioning in the pentabarbitone anaesthetised rabbit is dependent on the opening of KATP channels.