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• W1971966314 abstract "Helium induces preconditioning (He-PC) by mitochondrial calcium-sensitive potassium (mK(Ca)) channel-activation, but this effect is lost in the aged myocardium. Both, the upstream signalling pathway of He-PC and the underlying mechanisms for an age-related loss of preconditioning are unknown. A possible candidate as upstream regulator of mK(Ca) channels is protein kinase A (PKA). We investigated whether 1) regulation of PKA is involved in He-PC and 2) regulation of PKA is age-dependent. Young (2-3 months) and aged (22-24 months) Wistar rats were randomised to eight groups (each n=8). All animals underwent 25 min regional myocardial ischemia and 120 min reperfusion. Control (Con, Age Con) animals were not further treated. Young rats inhaled 70% helium for 3×5 min (He-PC). The PKA-blocker H-89 (10 μg/kg) was administered with and without helium (He-PC+H-89, H-89). Furthermore, we tested the effect of direct activation of mK(Ca) channels with NS1619. The adenylyl cyclase activator forskolin (For) was administered in young (300 μg/kg) and aged animals (300 and 1000 μg/kg). He-PC reduced infarct size from 60±4% (Con) to 37±10% (p<0.05). Infarct size reduction was completely abolished by H-89 (58±5%; p<0.05), but H-89 alone had no effect (57±2%). NS1619 reduced infarct size in the same concentration in both, young and aged rats (35±6%; p<0.05 vs. Con and 34±8%; p<0.05 vs. Age Con). Forskolin in a concentration of 300 μg/kg reduced infarct size in young (37±6%; p<0.05) but not in aged rats (48±13%; n.s.). In contrast, 1000 μg/kg Forskolin reduced infarct size also in aged rats (28±3%; p<0.05). He-PC is mediated by activation of PKA. Alterations in PKA regulation might be an underlying mechanism for the age-dependent loss of preconditioning." @default.
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• W1971966314 date "2012-01-01" @default.
• W1971966314 modified "2023-10-03" @default.
• W1971966314 title "Age-related loss of cardiac preconditioning: Impact of protein kinase A" @default.
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• W1971966314 doi "https://doi.org/10.1016/j.exger.2011.11.003" @default.
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