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- Gondalia, Jagdish Shivlal, 1959
(författare)
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Effect of Ischaemia-Reperfusion on Rabbit Kidney and Human Brain
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Free radicals are produced in various organs at ischaemia-reperfusion. The final stage in radical damage is lipid peroxidation. We have demonstrated previously that a lipid-soluble antioxidant improves restoration of bioenergetics in rabbit kidneys after ischaemia, as reflected in 31P spectrometry. Radical production in the brain during surgery for carotid artery stenosis can be measured using an ex vivo spin trap method. Aims of the present study: 1. To examine whether pretreatment with a combination of a lipidsoluble and a water-soluble antioxidant causes improved restoration of bioenergetics in rabbit kidneys after ischaemia compared to single treatment with a lipid soluble antioxidant. 2. To examine whether pretreatment with allopurinol or acetylcysteine influences radical production in conjunction with surgery for carotid artery stenosis. 3. To study the relationship between various markers for arteriosclerosis and the production of free radicals in conjunction with surgery for carotid artery stenosis. Methods: New Zealand white rabbits were used for the NMR experiments. Volume-selective 31P spectrometry was used to determine changes in bioenergetics during and after ischaemia following various pretreatments. An ex vivo spin trap method was used to measure radical production in the brain during carotid endarterectomy in control patients as well as patients pretreated with allopurinol or acetylcysteine. ICAM-1, MCP-9, MMP-1 and oxLDL serum levels were determined in the control patients. Results: Pretreatment with a combination of a lipid-soluble and a water-soluble antioxidant resulted in improved restoration in cell bioenergetics after ischaemia compared to single treatment with a lipid-soluble antioxidant. Production of radicals can be measured reproducibly using the ex vivo spin trap method. Pretreatment with allopurinol eliminated the strong correlation between e.g. degree of stenosis and leucocyte counts and radical production, which might indicate a beneficial effect of pretreatment with a xanthine oxidase inhibitor. Pretreatment with acetylcysteine on the other hand appeared to increase radical production. High levels of MMP-1 and low levels of ICAM-1 were associated with high radical production. Conclusion: A combination of a lipid-soluble and a water-soluble antioxidant is most effective in improving cell bioenergetics after ischaemia in rabbit kidneys. Allopurinol appears to have a beneficial effect in conjunction with carotid endarterectomy while acetylcysteine appears to increase radical production. MMP-1 is associated with increased radical production.
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| 2. |
- Gondalia, Jagdish Shivlal, 1959, et al.
(författare)
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Relationships between free radical levels during carotid endarterectomy and markers of arteriosclerotic disease
- 2007
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Ingår i: Int J Med Sci. - 1449-1907. ; 14:3, s. 124-130
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Tidskriftsartikel (refereegranskat)abstract
- Background: Free radical production is elevated in jugular venous blood emerging from the brain in conjunction with carotid endarterectomy. This study explores the relationships between markers for lesion progression in arteriosclerosis, production of radicals and clinical characteristics. Methods: The radical production during carotid endarterectomy was studied in 13 patients with an ex vivo spin trap method using OXANOH as a spin trap. MCP-1, ICAM-1, MMP-9 and oxLDL were determined in venous blood samples before, during and after clamping of the carotid artery. Principal component analysis (PCA) as well as partial least square regression analysis (PLS) was applied to interpret the data. Results: PCA and PLS analysis revealed that high values of MMP-9 and low values of ICAM-1 were associated with high radical production whereas MCP-1 and oxLDL were not correlated to radical production. MMP-9 was elevated at diabetes, high haemoglobin, high leucocyte counts and thrombocyte counts as well as at contralateral stenosis, whereas ICAM-1 showed reversed relationships to these clinical variables. MCP-1 increased during surgery. Conclusions: The main finding in our study is that MMP-9 in plasma is asscociated with radical production during carotid endarterectomy, suggesting that this enzyme might be involved in the pathogenesis of brain damage in conjunction with ischaemia-reperfusion.
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| 3. |
- Jonsson, Olof, 1941, et al.
(författare)
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Enhanced post-ischaemic recovery in rabbit kidney after pretreatment with an indeno-indole compound and ascorbate monitored in vivo by 31P magnetic resonance spectroscopy.
- 2003
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Ingår i: Scandinavian Journal of Urology and Nephrology. - 0036-5599. ; 37:6, s. 450-455
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate whether combined pretreatment with lipid- and water-soluble antioxidants gave better restoration of energy phosphates after ischaemia–reperfusion of rabbit kidneys than single pretreatment with a lipid-soluble antioxidant. Material and Methods: Thirteen New Zealand white rabbits were used for the study. Changes in energy phosphates were measured in vivo using volume-selective 31P magnetic resonance spectroscopy. The indeno–indole compound H290/51 was chosen as a lipid-soluble antioxidant and ascorbate as a water-soluble antioxidant. Results: The combined pretreatment led to significantly better restoration of the β-adenosine triphosphate:inorganic phosphate ratio after 60 min of ischaemia and 120 min of reperfusion compared with the single pretreatment. Analyses of blood pressure and blood gas changes showed that the beneficial effect of combined pretreatment was not caused by a better general condition of the animals in that group but by a direct effect on the kidneys. Conclusions: Combined pretreatment with lipid- and water-soluble antioxidants leads to better restoration of energy phosphates in rabbit kidneys subjected to ischaemia–reperfusion compared with single pretreatment with a lipid-soluble antioxidant.
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| 4. |
- Waters, S, et al.
(författare)
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Effects of pretreatment with a xanthine oxidase inhibitor on free radical levels during carotid endarterectomy.
- 2004
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Ingår i: Free Radic Res. - : Informa UK Limited. - 1071-5762 .- 1029-2470. ; 38:3, s. 283-293
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Free radicals contribute to the tissue damage caused by ischaemia-reperfusion. The aim of the present study was to investigate whether preoperative antioxidant therapy (allopurinol) affects free radical levels in cerebral venous blood in connection with surgery for carotid artery stenosis. Materials and methods: Twenty-five patients were randomised into the study. Thirteen were controls and 12 were pretreated with allopurinol the day before surgery. Before, during and after surgery, blood samples were drawn from the ipsilateral jugular vein. Radical levels were measured using the spin trap technique ex vivo using OXANOH as the spin trap. Multivariate statistics were used with Principal Component Analysis and Partial Least Square regression analysis. Results: Radical levels increased with diabetes, high leukocyte count, high creatinine and a high degree of contralateral stenosis. Radical levels decreased with high age, blood pressure, collateral circulation as well as operation for left-side carotid artery stenosis. After pretreatment with allopurinol, several of the relationships noted in the control group were eliminated, i.e. leukocyte count, side of operation, Betapred pretreatment and collateral circulation. Conclusions: Radical levels can be determined in connection with surgery for carotid artery stenosis using an ex vivo spin trap method. With preoperative antioxidant therapy the relationships between enhanced radical levels and clinical data, as seen in control subjects, disappeared. This might indicate a beneficial effect of preoperative pretreatment with antioxidants.
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