The human sinoatrial node (SAN) efficiently maintains heart rhythm even under adverse conditions. However, the specific mechanisms involved in the human SAN’s ability to prevent rhythm failure, also referred to as its robustness, are unknown. Challenges exist because the three-dimensional (3D) intramural structure of the human SAN differs from well-studied animal models, and clinical electrode recordings are limited to only surface atrial activation. Hence, to innovate the translational study of human SAN structural and functional robustness, we integrated intramural optical mapping, 3D histology reconstruction, and molecular mapping of the ex vivo human heart. When challenged with adenosine or atrial pacing, redundant intranodal pacemakers within the human SAN maintained automaticity and delivered electrical impulses to the atria through sinoatrial conduction pathways (SACPs), thereby ensuring a fail-safe mechanism for robust maintenance of sinus rhythm. During adenosine perturbation, the primary central SAN pacemaker was suppressed, whereas previously inactive superior or inferior intra-nodal pacemakers took over automaticity maintenance. Sinus rhythm was also rescued by activation of another SACP when the preferential SACP was suppressed, suggesting two independent fail-safe mechanisms for automaticity and conduction. The fail-safe mechanism in response to adenosine challenge is orchestrated by heterogeneous differences in adenosine A1 receptors and downstream GIRK4 channel protein expressions across the SAN complex. Only failure of all pacemakers and/or SACPs resulted in SAN arrest or conduction block. Our results unmasked reserve mechanisms that protect the human SAN pacemaker and conduction complex from rhythm failure, which may contribute to treatment of SAN arrhythmias.
This is the first study to visualize the 3D human SAN fibrotic structure in vivo using LGE-CMR. Identification of the 3D SAN location and its high fibrotic content by LGE-CMR may provide a new tool to avoid or target SAN structure during ablation.
Background: Recent studies have suggested that femoral tunnel drilling during anterior cruciate ligament (ACL) reconstruction (ACLR) with the use of a flexible reaming system through a standard anteromedial portal (AM-FR) may result in a different tunnel geometry compared with a rigid reamer through an accessory anteromedial portal with hyperflexion (AM-RR). Purpose: To summarize radiologic, anatomic, and clinical outcomes from available studies that directly compared the use of AM-FR versus AM-RR for independent femoral tunnel creation during ACLR. Study Design: Systematic review; Level of evidence, 4. Methods: A literature search was performed using the MEDLINE (PubMed) and Web of Science databases to identify all studies that directly compared radiologic, anatomic, and clinical outcomes between the use of AM-FR and AM-RR. The literature search, data recording, and methodological quality assessment was performed by 2 independent reviewers. The outcomes analyzed included resultant ACL graft positioning and graft bending angle; femoral tunnel positioning, aperture morphology, length, and widening; posterior wall breakage; and distance from various posterolateral knee structures. Results: A total of 13 studies met the eligibility criteria for inclusion. There was no difference in femoral tunnel aperture location between techniques. There were conflicting findings among studies regarding which technique resulted in a more acute graft bending angle. One study reported greater femoral tunnel widening upon follow-up with the use of AM-FR. AM-FR produced longer and more anteverted femoral tunnels than did AM-RR. The difference in tunnel length was significant and more prominent in lesser degrees of knee flexion. With AM-FR, femoral tunnels were farther from the lateral collateral ligament and peroneal nerve, and 1 of 5 studies had fewer reports of posterior wall breakage. There has been no literature comparing the clinical or functional outcomes of these techniques. Conclusion: Although no clinical studies exist comparing AM-FR and AM-RR for femoral tunnel creation during ACLR, both systems allow for reproducible positioning of an anatomic femoral tunnel aperture. The use of AM-FR results in longer and more anteverted femoral tunnels than using AM-RR, with exit points on the lateral femur that are different but safe. Surgeons should be aware of the technical differences with each method; however, further study is needed to identify any clinically important difference that results.
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