Recognition and management of left atrial dissection during mitral repair.

BACKGROUND: Left atrial dissection (LAtD) is a rare but potentially life-threatening complication of mitral valve surgery. Its management is not well stablished in the literature. However, early recognition through intraoperative TEE and attention to changes in the left atrial free wall during saline leak testing can lead to avoidance of severe complications. CASE PRESENTATION: We report a case of LAtD detected by intraoperative transesophageal echocardiogram (TEE) following mitral valve repair for primary mitral valve regurgitation secondary to degenerative mitral valve disease with MAZE IV procedure for atrial fibrillation. LAtD was noted on TEE as an expanding double density along the wall of the left atrium with a jet originating at the posterior annulus flowing into the LAtD which was repaired. Separation from bypass following LAtD repair was complicated by severe biventricular dysfunction requiring significant inotropic support and placement of an intra-aortic balloon pump (IABP). Patient's post-operative course was further complicated by right sided heart failure requiring placement of a right sided impella which was subsequently removed on POD 4. Patient was discharged home on POD 17. Transthoracic echo at 1 month, 3 months demonstrated resolution of the LAtD. A follow up echo at 4 years showed complete resolution of the LAtD with an intact mitral repair, trace mitral regurgitation, and a mean gradient across the repair of 3 mm Hg. CONCLUSIONS: Left atrial dissection is a rare but serious complication of mitral valve surgery. We provide a review of the current literature regarding LAtD, emphasizing the need to consider this complication early during mitral surgery to allow for uncomplicated repair.

Miro1-mediated mitochondrial positioning supports subcellular redox status.

Mitochondria are strategically trafficked throughout the cell by the action of microtubule motors, the actin cytoskeleton and adapter proteins. The intracellular positioning of mitochondria supports subcellular levels of ATP, Ca2+ and reactive oxygen species (ROS, i.e. hydrogen peroxide, H2O2). Previous work from our group showed that deletion of the mitochondrial adapter protein Miro1 leads to perinuclear clustering of mitochondria, leaving the cell periphery devoid of mitochondria which compromises peripheral energy status. Herein, we report that deletion of Miro1 significantly restricts subcellular H2O2 levels to the perinuclear space which directly affects intracellular responses to elevated mitochondrial ROS. Using the genetically encoded H2O2-responsive fluorescent biosensor HyPer7, we show that the highest levels of subcellular H2O2 map to sites of increased mitochondrial density. Deletion of Miro1 or disruption of microtubule dynamics with Taxol significantly reduces peripheral H2O2 levels. Following inhibition of mitochondrial complex 1 with rotenone we observe elevated spikes of H2O2 in the cell periphery and complementary oxidation of mitochondrial peroxiredoxin 3 (PRX3) and cytosolic peroxiredoxin 2 (PRX2). Conversely, in cells lacking Miro1, rotenone did not increase peripheral H2O2 or PRX2 oxidation but rather lead to increased nuclear H2O2 and an elevated DNA-damage response. Lastly, local levels of HyPer7 oxidation correlate with the size and abundance of focal adhesions (FAs) in MEFs and cells lacking Miro1 have significantly smaller focal adhesions and reduced phosphorylation levels of vinculin and p130Cas compared to Miro1+/+ MEFs. Together, we present evidence that the intracellular distribution of mitochondria influences subcellular H2O2 levels and local cellular responses dependent on mitochondrial ROS.

Dynamic regulation of subcellular mitochondrial position for localized metabolite levels.

Mitochondria are not passive bystanders aimlessly floating throughout our cell's cytoplasm. Instead, mitochondria actively move, anchor, divide, fuse, self-destruct and transfer between cells in a coordinated fashion, all to ensure proper structure and position supporting cell function. The existence of the mitochondria in our cells has long been appreciated, but their dynamic nature and interaction with other subcellular compartments has only recently been fully realized with the advancement of high-resolution live-cell microscopy and improved fractionization techniques. The how and why that dictates positioning of mitochondria to specific subcellular sites is an ever-expanding research area. Furthermore, the advent of new and improved functional probes, sensitive to changes in subcellular metabolite levels has increased our understanding of local mitochondrial populations. In this review, we will address the evidence for intentional mitochondrial positioning in supporting subcellular mitochondrial metabolite levels, including calcium, adenosine triphosphate and reactive oxygen species and the role mitochondrial metabolites play in dictating cell outcomes.