E J Hide1, C Thiemermann. 1. William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, UK.
Abstract
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.
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 pentobarbitonerabbit. 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.