Atrial high energy phosphate content and mitochondrial enzyme activity during chronic atrial fibrillation

Objective: Prolonged atrial fibrillation (AF) results in (ultra)structural remodelling of atrial cardiomyocytes resembling alterations seen in ischemi a-induced ventricular hibernation. The mechanisms underlying these changes are incompletely understood. In the present study we explored the hypothesi s that a profound imbalance in energy status during chronic AF acts as a st imulus for structural remodelling. Methods and Results: The content of high energy-phosphates and related compounds together with a selected number of mitochondrial enzymes, known to be altered under ischemic conditions, were determined in tissue samples taken from atria of goats in sinus rhythm (SR ) and after 1, 2, 4, 8 and 16 weeks of AF maintained by burst pacing. Atria l remodelling was quantified by counting the percentage of cells with >10% myolysis. During AF structural remodelling developed progressively, after 8 weeks about 40% of the atrial myocytes were affected. The concentration of adenine nucleotides and their degradation products did not change signific antly during AF. Also the activity of mitochondrial cytochrome c oxidase ac tivity was similar during AF and SR. Mitochondrial NADH-oxidase and proton- translocating ATPase activities were not induced by AF. The tissue content of phosphocreatine decreased during the first week by 60%, but completely r ecovered between 8 and 16 weeks of AF. Conclusions: The analysis of adenine nucleotides during AF provided no indication for the development of severe atrial ischemia. This notion is supported by enzyme cytochemical findings. However, AF-induced atrial remodelling was associated with a transient low ering of phosphocreatine content, suggesting an increase in energy demand d uring the early phase of AF. The subsequent recovery of the phosphocreatine pool indicates restoration of the balance between energy demand and supply in chronically fibrillating atria. (C) 2000 Elsevier Science B.V. All righ ts reserved.