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AMP kinase mutation exacerbates electrocardiographic ST segment elevation in Ossabaw miniature swine during myocardial ischemia
Author(s) -
Chawla Aarti Rajeev,
Spencer Stephen Meredith,
Alloosh Mouhamad,
Byrd James Patrick,
Sturek Michael
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1099.6
Subject(s) - ischemia , ampk , medicine , cardiology , st segment , protein kinase a , endocrinology , kinase , chemistry , myocardial infarction , biochemistry
Myocardial ischemia results in ATP deprivation and impaired excitation‐contraction coupling. AMP‐activated protein kinase (AMPK) is quiescent during normal cardiac function, but as AMP/ATP rises during ischemia, AMPK is activated and increases glucose uptake and glycolysis. Ossabaw swine have a spontaneous point mutation of valine199 to isoleucine in the AMPK gamma subunit that impairs AMPK function. We hypothesized that ischemia would elicit greater ST segment elevation in AMPK mutant compared to non‐mutant swine. Ischemia was induced by balloon occlusion of the circumflex artery and verified by angiography, intravascular pressure, and flow. Ischemia‐induced ST segment elevation was quantified as the ratio of ST segment elevation over T wave amplitude prior to ischemia. AMPK mutants showed significant ST segment elevation of >1.0 within 3 minutes of ischemia, whereas non‐mutant swine showed only a 0.4 ST segment elevation during 15 minutes of ischemia. Intracoronary infusion of the AMPK activator aminoimidazole carboxamide ribonucleotide (AICAR, 0.1 mM) for 10 minutes before coronary occlusion did not alter the profound ST segment elevation in AMPK‐mutant swine. In contrast, AICAR completely prevented ST segment elevation in non‐mutant swine. These data indicate that fully functional cardiac AMPK plays a role in attenuating ischemia‐induced ST segment elevation. (Support: NIH HL062552)