71 research outputs found
Spontaneous obliteration of a dural arteriovenous fistula after treatment of polycythemia in a patient with Factor V Leiden mutation: case report
Role of genetic polymorphisms of ion channels in the pathophysiology of coronary microvascular dysfunction and ischemic heart disease
Glenoid morphology in light of anatomical and reverse total shoulder arthroplasty: a dissection- and 3D-CT-based study in male and female body donors
Effect on ex vivo platelet aggregation and in vivo cyclic flow with Na+/H+ exchange inhibition
Pharmacology and clinical assessment of cariporide for the treatment coronary artery diseases
Effect of Sodium/Hydrogen Exchange Inhibition on Myocardial Infarct Size after Coronary Artery Thrombosis and Thrombolysis
Adenylate kinase AK1 knockout heart: energetics and functional performance under ischemia-reperfusion
Deletion of the major adenylate kinase AK1 isoform, which catalyzes adenine nucleotide exchange, disrupts cellular energetic economy and compromises metabolic signal transduction. However, the consequences of deleting the AK1 gene on cardiac energetic dynamics and performance in the setting of ischemia-reperfusion have not been determined. Here, at the onset of ischemia, AK1 knockout mice hearts displayed accelerated loss of contractile force compared with wild-type controls, indicating reduced tolerance to ischemic stress. On reperfusion, AK1 knockout hearts demonstrated reduced nucleotide salvage, resulting in lower ATP, GTP, ADP, and GDP levels and an altered metabolic steady state associated with diminished ATP-to-P(i) and creatine phosphate-to-P(i) ratios. Postischemic AK1 knockout hearts maintained approximately 40% of beta-phosphoryl turnover, suggesting increased phosphotransfer flux through remaining adenylate kinase isoforms. This was associated with sustained creatine kinase flux and elevated cellular glucose-6-phosphate levels as the cellular energetic system adapted to deletion of AK1. Such metabolic rearrangements, along with sustained ATP-to-ADP ratio and total ATP turnover rate, maintained postischemic contractile recovery of AK1 knockout hearts at wild-type levels. Thus deletion of the AK1 gene reveals that adenylate kinase phosphotransfer supports myocardial function on initiation of ischemic stress and safeguards intracellular nucleotide pools in postischemic recovery.status: publishe
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