Limitation of myocardial infarct size in the rabbit by ischaemic preconditioning is abolished by sodium 5-hydroxydecanoate.

OBJECTIVE: To investigate the effect of the ATP-sensitive potassium (KATP) channel inhibitor sodium 5-hydroxydecanoate (5-HD) on the reduction in myocardial infarct size afforded by ischaemic preconditioning in the sodium pentobarbitone rabbit. METHODS: New Zealand white rabbits were anaesthetised with sodium pentobarbitone and subjected to 60 min occlusion of the first antero-lateral branch of the left coronary artery (LAL) followed by 120 min reperfusion. Ischaemic preconditioning was achieved by a single episode of 5 min LAL occlusion followed by 15 min reperfusion prior to the 60 min occlusion. 5-HD (5 mg kg-1), an ischaemia selective KATP channel inhibitor, was administered into the left ventricle as a bolus injection 10 min prior to the onset of ischaemic preconditioning. Injection of Evans blue dye was used to determine the area of the left ventricle at risk and infarct size was determined by incubation of the area at risk with nitro-blue tetrazolium. RESULTS: There were no significant differences between groups in haemodynamics or area at risk. Ischaemic preconditioning resulted in a significant reduction in infarct size (27 +/- 8%) when compared to control animals (55 +/- 3%; P < 0.05). Pretreatment of animals with 5-HD completely abolished the cardioprotection seen with ischaemic preconditioning (50 +/- 6%). CONCLUSION: 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.

Sulprostone-induced reduction of myocardial infarct size in the rabbit by activation of ATP-sensitive potassium 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 EP1/EP3 receptors were due to the activation of ATP-sensitive potassium (KATP) channels. 2. In anaesthetized rabbits pretreated with vehicle (5% ethanol in 0.9% saline; 0.05 ml min-1, 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 microgram kg-1 min-1 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 microgram kg-1 min-1) 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 micrograms kg-1; 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 EP1/EP3 prostanoid receptor agonist, sulprostone, reduces infarct size in the anaesthetized rabbit by a mechanism that involves the opening of KATP channels.

Endothelin-1-induced reduction of myocardial infarct size by activation of ATP-sensitive potassium channels in a rabbit model of myocardial ischaemia and reperfusion.

1. This study examined whether endothelin-1 (ET-1) reduces infarct size in a rabbit model of acute coronary artery occlusion (60 min) and reperfusion (120 min). In addition, we investigated whether the observed cardioprotective effect of ET-1 was due to the activation of ATP-sensitive potassium (KATP) channels by using two selective antagonists, glibenclamide and sodium 5-hydroxydecanoate (5-HD). 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 55 +/- 4% (n = 11). ET-1 (0.3 nmol kg-1), administered as a bolus injection into the left ventricle, had no effect on infarct size (62 +/- 2%, n = 4). A lower dose of ET-1 (0.03 nmol kg-1) resulted in a significant reduction in infarct size (infarct size 43 +/- 3%; P < 0.05, n = 16). The higher dose (0.3 nmol kg-1), but not the lower dose of ET-1 caused a significant rise in blood pressure, pressure rate index and hence, myocardial oxygen consumption. 3. The reduction in infarct size afforded by ET-1 (0.03 nmol kg-1) was abolished by pretreatment of rabbits with the KATP channel inhibitors, glibenclamide (0.3 mg kg-1) and 5-HD (5 mg kg-1), (infarct size 59 +/- 3 and 63 +/- 4% respectively; n = 4-9). 4. We propose that ET-1 reduces infarct size by opening KATP channels.

Reduction by prostaglandin E1 or prostaglandin E0 of myocardial infarct size in the rabbit by activation of ATP-sensitive potassium channels.

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.

The prevalence of F107 fimbriae and their association with Shiga-like toxin II in Escherichia coli strains from weaned Australian pigs.

A total of 480 haemolytic Escherichia coli (HEC) strains from weaned pigs were tested using an oligonucleotide probe to determine the prevalence of F107 fimbriae in Australia. Of these, 62% were positive. F107 was detected in serogroups O141, O138, O8, O45, O139, O157 and O98 but not in O149 nor O147. 81% of E. coli strains not producing other fimbriae (K88, 987P, K99 or F41) were positive for F107; 5% of strains with K88 fimbriae also had F107. Serological investigation of the expression of F107 fimbriae indicated that serogroups O141, O138, O8, O45 and O157 produced variant F107ac. Variant F107ab was found on O139 strains only. The F107 fimbrial subunits of both variants had a molecular weight of approximately 16 kDa. A total of 350 of the HEC strains were tested to determine the prevalence of the Shiga-like toxin II (SLT II) gene. 29.0% of these strains were positive. SLT II was detected in serogroups O141, O138, O149, O98, O45, O8 and O157 but not in O139. 25% of these strains were positive for both F107 and SLT II.