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- Fu, Michael, 1963, et al.
(författare)
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Free radical scavenging enzymes and G protein mediated receptor signalling systems in ischaemically preconditioned porcine myocardium.
- 1993
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Ingår i: Cardiovascular research. - 0008-6363. ; 27:4, s. 612-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Increased antioxidant defence and altered G protein mediated receptor signalling systems could be expected in myocardial preconditioning. The myocardial antioxidant defence and the integrity of the G protein mediated receptor signalling systems were therefore examined in normal and preconditioned myocardium. METHODS: Preconditioning in the porcine heart was induced by two occlusions of the mid left anterior descending coronary artery for 10 min, with a 30 min reperfusion interval. Left ventricular biopsies were obtained from control and preconditioned regions 30 min after the last occlusion. RESULTS: In biopsies from the preconditioning region, neither the activities of superoxide dismutase of glutathione peroxidase, nor the content of malondialdehyde were changed. There were no alterations in either the number of receptors (beta adrenergic, muscarinic and endothelin receptors) or the amount of G proteins. Furthermore, the activity of adenylyl cyclase remained unchanged. CONCLUSIONS: No change in the antioxidant defence was demonstrated in preconditioned myocardium. This finding does not support the hypothesis that increased antioxidant defence could contribute to the cardioprotection of preconditioning. Additionally, an intact G protein mediated receptor signalling system was found in preconditioned myocardium with regard to beta adrenergic, muscarinic, and endothelin receptors.
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- Fu, Michael, 1963, et al.
(författare)
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Gi-mediated muscarinic adenylyl cyclase inhibition in timolol-treated stunned porcine myocardium.
- 1994
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Ingår i: Acta physiologica Scandinavica. - 0001-6772. ; 151:3, s. 291-9
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Tidskriftsartikel (refereegranskat)abstract
- The Gi-mediated muscarinic receptor-adenylyl cyclase system was examined in stunned myocardium induced by either three or five brief ischaemic periods after beta-adrenoceptor blockade by timolol (0.1 mg kg-1). The mid-left anterior descending coronary artery was occluded for 2, 10 and 2 min in four pigs, and for 2, 2, 5, 10 and 2 min in four other pigs. All the ischaemic periods were separated by 30 min of reperfusion and the biopsies were obtained 60 min after the last ischaemic period. Segment length function was measured in the ischaemic region and in the control region supplied by the left circumflex artery. In the two groups, the percentage systolic shortening was reduced equally, to 59 +/- 9 and 58 +/- 10% of control in the region subjected to ischaemia and only minimally in the control region. The biopsies from the stunned region from both groups showed: (1) no change in either the affinity for carbachol or the number of binding sites of the muscarinic receptors; (2) no alterations in messenger RNA encoding for the alpha subunit-2 of the inhibitory guanine nucleotide binding protein, as demonstrated by northern blot and solution hybridization; (3) no change in membrane-bound inhibitory guanine nucleotide binding protein, as shown by enzyme immunoassay utilizing a specific anti-peptide antibody, and (4) unchanged inhibition of stimulated adenylyl cyclase activity. These results suggest that there is an intact inhibitory guanine nucleotide binding protein-mediated muscarinic receptor adenylyl cyclase system in the stunned porcine myocardium.
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- Fu, Michael, 1963, et al.
(författare)
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Oxygen free radical injury and Gs mediated signal transduction in the stunned porcine myocardium.
- 1992
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Ingår i: Cardiovascular research. - 0008-6363. ; 26:5, s. 449-55
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim was to investigate involvement of oxygen free radicals and any changes in the Gs mediated beta adrenergic signalling system of stunned porcine myocardium. METHODS: Myocardial stunning was induced in eight pentobarbitone anaesthetised pigs by brief occlusions of the distal left anterior descending coronary artery for periods of up to 10 min. Segment length function was measured in the ischaemic region and in a control region supplied by the circumflex artery. Left ventricular biopsies were obtained from the two regions 1 h after the last occlusion for ultrastructural and biochemical studies. Timolol has been used to prevent arrhythmia during ischaemia. RESULTS: At the time when biopsies were obtained, percent systolic shortening was reduced to 58% in the region subjected to ischaemia and was only minimally reduced in the control region. In the biopsies from the stunned region: (1) electron microscopy showed mild and reversible intracellular changes in the stunned myocardium; (2) the activities of superoxide dismutase and glutathione peroxidase were decreased by 66% and 52%, respectively; (3) the content of malondialdehyde was increased by 49%; (4) neither density nor affinity of beta adrenoceptors showed any changes; (5) there were no alterations in messenger RNA encoding for the alpha subunit of the stimulatory guanine nucleotide binding protein (Gs), demonstrated by northern and dot-blot hybridisations; (6) ELISA technique utilising a specific antipeptide antibody showed no quantitative change in Gs; (7) the activity of adenyl cyclase was unchanged. CONCLUSIONS: Even though the stunned porcine myocardium showed substantial evidence of free radical injury, the beta adrenergic signalling system was intact.
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