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  • 1
    ISSN: 1432-2013
    Keywords: Key words Free radicals ; Ischaemia ; Reperfusion ; Myocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This study addressed the question of whether the sarcolemmal fragility of cardiomyocytes after anoxia and subsequent reoxygenation can be altered by modulation of the cellular glutathione state. Isolated ventricular cardiomyocytes (from adult rats) were exposed to 120 min anoxia and subsequently to 30 min reoxygenation. Osmotic stress was generated by reduction of medium osmolarity from 270 to 80 mosmol/l and sarcolemmal fragility assessed by the leakage of lactate dehydrogenase (LDH). Under normoxic conditions 6.7±1.0 % of total LDH activity was found extracellularly. Hyposmolar reoxygenation, but not hypoosmolar anoxia, increased LDH release (17.9±2.7% of total, P〈0.05). Increasing cellular glutathione content by pretreatment with N-acetylcysteine (1 mM) reduced LDH release following hyposmolar reoxygenation (12.3±1.9% vs. 18.2±2.9% of LDH in medium, P〈0.05). Depletion of glutathione content by pretreatment with buthionine sulphoximine (BSO, 200 µM), increased LDH release following osmotic stress already in normoxia (10.5±1.8% of LDH in medium; P〈0.05 vs. no BSO), and even further after reoxygenation (21.8±3.2%, P〈0.05 vs. normoxia). We conclude that the increased sarcolemmal fragility in reoxygenated cardiomyocytes is due to reoxygenation in the presence of reduced antioxidant defence.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1435-2451
    Keywords: Erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA) S-(p-nitrobenzyl)-6-thioinosine (NBMPR) Bretschneider's cardioplegic solution Ischemia–reperfusion injury Working-heart model for rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Background and aims: This study assessed the cardioprotective effects of inhibitors of adenosine metabolism in an isolated perfused rat heart model. Specifically, we studied the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)-adenine and the selective nucleoside transport inhibitor S-(p-nitrobenzyl)-6-thioinosine, in terms of their potential to enhance protection when added to Bretschneider's cardioplegic solution. Methods: Rat hearts were infused for 5 min with Krebs–Henseleit buffer solution (group 1), Bretschneider's cardioplegic solution (group 2), Bretschneider's cardioplegic solution with the addition of 25 µM erythro-9-(2-hydroxy-3-nonyl)-adenine and 5 µM S-(p-nitrobenzyl)-6-thioinosine (group 3), and Bretschneider's cardioplegic solution with the addtion of 25 µM erythro-9-(2-hydroxy-3-nonyl)-adenine only (group 4). After cardioplegic arrest and 45 min of ischemic storage at 25°C, the functional recovery of the hearts was tested during 15 min of Langendorff reperfusion and then 45 min of working heart reperfusion. Results: In relation to the cardioprotective effects of Bretschneider's cardioplegic solution alone, we observed an improved recovery of hemodynamic function of the hearts with the addition of both erythro-9-(2-hydroxy-3-nonyl)-adenine and S-(p-nitrobenzyl)-6-thioinosine. However, the myocardial adenosine triphosphate (ATP) concentration remained unchanged. Bradycardia observed under the addition of erythro-9-(2-hydroxy-3-nonyl)-adenine alone was prevented by the addition of S-(p-nitrobenzyl)-6-thioinosine. Conclusion: A combination of both substances may be tested further for cardiac preservation, as it might improve the recovery from ischemia at moderate temperatures.
    Type of Medium: Electronic Resource
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