Abstract
Myocardial A1 adenosine receptor (A1AR) overexpression protects hearts from ischemia-reperfusion injury; however, the effects during anoxia are unknown. We evaluated responses to anoxia-reoxygenation in wild-type (WT) and transgenic (Trans) hearts with ∼200-fold overexpression of A1ARs. Langendorff perfused hearts underwent 20 min anoxia followed by 30 min reoxygenation. In WT hearts peak diastolic contracture during anoxia was 45 ± 3 mmHg, diastolic pressure remained elevated at 18 ± 3 mmHg after reoxygenation, and developed pressure recovered to 52 ± 4 % of pre-anoxia. A1AR overexpression reduced hypoxic contracture to 29 ± 4 mmHg, and improved recovery of diastolic pressure to 8 ± 1 mmHg and developed pressure to 76 ± 3 % of pre-anoxia. Mitochondrial KATP blockade with 100 μM 5-hydroxydecanoate (5-HD) increased hypoxic contracture to 73 ± 6 mmHg in WT hearts, reduced post-hypoxic recoveries of both diastolic (40 ± 5 mmHg) and developed pressures (33 ± 3 %). In contrast, 5-HD had no effect on hypoxic contracture (24 ± 8 mmHg), or post-hypoxic diastolic (10 ± 2 mmHg) and developed pressures (74 ± 3 %) in Trans hearts. In summary, (i) A1AR overexpression improves myocardial tolerance to anoxia-reoxygenation, (ii) intrinsic mitochondrial KATP channel activation decreases hypoxic contracture and improves functional recovery in wild-type hearts, and (iii) mitochondrial KATP channels do not appear to play a major role in the functional protection from anoxia afforded by A1AR overexpression.
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Received: 5 February 2001, Returned for 1. revision: 21 February 2001, 1. Revision received: 20 August 2001, Returned for 2. revision: 3 September 2001, 2. Revision received: 24 October 2001, Accepted: 25 October 2001
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Cerniway, R., Morrison, R., Byford, A. et al. A1 adenosine receptor overexpression decreases stunning from anoxia-reoxygenation: role of the mitochondrial KATP channel. Basic Res Cardiol 97, 232–238 (2002). https://doi.org/10.1007/s003950200016
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DOI: https://doi.org/10.1007/s003950200016