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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Basic research in cardiology 91 (1996), S. 35-37 
    ISSN: 1435-1803
    Keywords: Ischemic preconditioning ; adenosine ; ST segment ; protein kinase C
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Basic research in cardiology 91 (1996), S. 374-381 
    ISSN: 1435-1803
    Keywords: Glycogen ; preconditioning ; adenosine ; SPT ; bradykinin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Depletion of gycogen has been proposed as the mechanism of protection from ischemic preconditioning. The hypothesis was tested by seeing whether pharmacological manipublation of preconditioning causes parallel changes in cardiac glycogen content. Five groups of isolated rabbit hearts were studied. Group 1 experienced 30 min of ischemia only. Group 2 (PC) was preconditioned with 5 min of global ischemia followed by 10 min of reperfusion. Group 3 was preconditioned with 5 min exposure to 400 nM bradykinin followed by a 10 min washout period. Group 4 experienced exposure to 10 μM adenosine followed by a 10 min washout period, and the fifth group was also preconditioned with 5 min ischemia and 10 min reperfusion but 100 μM8-(p-sulfophenyl) theophylline (SPT), which blocks adenosine receptors, was included in the buffer to block preconditioning's protection. Transmural biopsies were taken before treatment, just prior to the 30 min period of global ischemia, and after 30 min of global ischemia. Glycogen in the samples was digested with amyloglucosidase and the resulting glucose was assayed. Baseline glycogen averaged 17.3±0.6 μmol glucose/g wet weight. After preconditioning glycogen decreased to 13.3±1.3 μmol glucose/g wet weight (p〈0.005 vs. baseline). Glycogen was similarly depleted after pharmacological preconditioning with adenosine (14.0±1.0 μmol glucose/g wet weight, p〈0.05 vs. baseline) suggesting a correlation. However, when proconditioning was performed in the pressence of SPT, which blocks protection, glycogen was also depleted by the same amount (13.3±0.7 μmol glucose/g wet weight, p=ns vs. PC). Bradykinin, which also mimics preconditioning, caused no depletion of glycogen (16.3±0.8 μmol glucoseig wet weight, p=ns vs. baseline). Because preconditioning with bradykinin did not deplete glycogen and because glycogen continued to be low when protection from preconditioning was blocked with SPT, we conclude that loss of glycogen per se does not cause the protection of preconditioning.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1435-1803
    Keywords: Ischemic preconditioning ; Na+/H+ exchange ; 5-(N-ethyl-N-isopropyl)amiloride (EIPA) ; protein kinase C
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We investigated the effects of 5-(N-ethyl-N-isopropyl)amiloride (EIPA) on infarction in isolated rabbit hearts and cardiomyocytes. Thirty min of regional ischemia caused 29.6±2.8% of the risk zone to infarct in untreated Krebs buffer-perfused hearts. Treatment with EIPA (1 μM) for 20 min starting either 15 min before ischemia or 15 min after the onset of ischemia significantly reduced infarction to 5.4±2.0% and 7.0±1.0%, respectively (p〈0.01 versus untreated hearts). In both cases salvage was very similar to that seen with ischemic preconditioning (PC) (7.1±1.5% infarction). Unlike the case with ischemic preconditioning, however, protection from EIPA was not blocked by 50μM polymyxin B, a PKC inhibitor, or 1μM glibenclamide, a KATP channel blocker. Forty-five min of regional ischemia caused 51.0±2.9% infarction in untreated hearts. Ischemic preconditioning reduced infarction to 23.4±3.1% (p〈0.001 versus untreated hearts). In these hearts with longer periods of ischemia pretreatment with EIPA reduced infarction similarly to 28.8±2.1% (p〈0.01 versus untreated hearts). However, when EIPA was combined with ischemic PC, no further reduction in infarction was seen (23.8±3.5% infarction). To further elucidate the mechanism of EIPA's cardioprotective effect, this agent was also examined in isolated rabbit cardiomyocytes. Preconditioning caused a delay of about 30 min in the progressive increase in osmotic fragility that occurs during simulated ischemia. In contrast, EIPA had no effect on the time course of ischemia-induced osmotic fragility. Furthermore, EIPA treatment did not alter the salutary effect of ischemic preconditioning when the two were combined in this model. We conclude that Na+/H+ exchange inhibition limits myocardial infarction in the isolated rabbit heart by a mechanism which is quite different from that of ischemic preconditioning. Despite the apparently divergent mechanisms, EIPA's cardioprotective effect could not be added to that of ischemic or metabolic preconditioning in these models.
    Type of Medium: Electronic Resource
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