Compartmentation of energy metabolism in atrial myocardium of patients undergoing cardiac surgery

Abstract

The parameters of oxidative phosphorylation and its interaction with creatine kinase (CK)- and adenylate kinase (AK)-phosphotransfer networks in situ were studied in skinned atrial fibers from 59 patients undergoing coronary artery bypass surgery, valve replacement/correction and atrial septal defect correction. In atria, the mitochondrial CK and AK are effectively coupled to oxidative phosphorylation, the MM-CK is coupled to ATPases and there exists a direct transfer of adenine nucleotides between mitochondria and ATPases. Elimination of cytoplasmic ADP with exogenous pyruvate kinase was not associated with a blockade of the stimulatory effects of creatine and AMP on respiration, neither could it abolish the coupling of MM-CK to ATPases and direct transfer of adenine nucleotides. Thus, atrial energy metabolism is compartmentalized so that mitochondria form functional complexes with adjacent ATPases. These complexes isolate a part of cellular adenine nucleotides from their cytoplasmic pool for participating in energy transfer via CK- and AK-networks, and/or direct exchange. Compared to atria in sinus rhythm, the fibrillating atria were larger and exhibited increased succinate-dependent respiration relative to glutamate-dependent respiration and augmented proton leak. Thus, alterations in mitochondrial oxidative phosphorylation may contribute to pathogenesis of atrial fibrillation.

Selective downregulation of mitochondrial electron transport chain activity and increased oxidative stress in human atrial fibrillation

“…This is important because conditions that predispose to AF-such as aging, hypertension, coronary artery disease, heart failure, or ventricular or atrial dysfunction-can by themselves contribute to mitochondrial dysfunction and must be accounted for when estimating the impact of AF on mitochondrial function (5,11, 15,17). Moreover, it is not clear whether reported changes in myocardial energetics and mitochondrial function (1, 27, 56) are causative or the consequence of AF or associated conditions; nor is it clear whether the OXPHOS impairment reported in some (32) but not all (5a) animal studies also occurs in the human atria (12,37,50). Increasing evidence has accumulated that oxidative stress plays an important role in the pathogenesis of AF (47,17,62) and elevated oxidative stress markers are present in patients with AF (34,41,43,51).…”

Quantitative Proteomics of Changes in Energy Metabolism-Related Proteins in Atrial Tissue From Valvular Disease Patients With Permanent Atrial Fibrillation

“…12- 14 The understanding of the modification in cardiac energy metabolism during AF, however, remains relatively limited.…”

Energetic metabolism during acute stretch-related atrial fibrillation

“…Besides, direct and indirect evidence suggest that the activity of these two pumps might have been modified in our model. First, Barbey et al (12) have shown an increased activity of F 0 F 1 -ATPase but in absence of any change in Na,K-ATPase activity (7). On the other hand, the work by Songu-Mize et al (33) has shown increased Na pump activity by short term cyclic stretch in aortic smooth muscle cells.…”

“…While ionic remodeling (3)(4)(5) as well as changes in cellular and structural architecture (6) have been described, increasing evidence for a role of perturbations in energetic metabolism exists. In fact, various studies have shown modifications in energetic metabolism in both animal models (7)(8)(9)(10)(11) and humans (12)(13)(14) and after both chronic or short episodes of AF (9,10,(12)(13)(14). However, a variety of changes have been observed.…”

“…However, a variety of changes have been observed. Several works describe an increased demand in energy (7)(8)(9)11) while others have suggested impaired energy production or consumption (10,(12)(13)(14). In order to clarify the atrial energetic status during AF, we investigated the consequences of acute atrial stretch on atrial myocytes energetic metabolism.…”