Repeated exposure to transient obstructive sleep apnea–related conditions causes an atrial fibrillation substrate in a chronic rat model
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Repeated exposure to transient obstructive sleep apnea–related conditions causes an atrial fibrillation substrate in a chronic rat model. / Linz, Benedikt; Hohl, Mathias; Lang, Lisa; Wong, Dickson W.L.; Nickel, Alexander G.; De La Torre, Carolina; Sticht, Carsten; Wirth, Klaus; Boor, Peter; Maack, Christoph; Speer, Thimoteus; Jespersen, Thomas; Schotten, Ulrich; Sanders, Prashanthan; Böhm, Michael; Linz, Dominik.
In: Heart Rhythm, Vol. 18, No. 3, 2021, p. 455-464.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Repeated exposure to transient obstructive sleep apnea–related conditions causes an atrial fibrillation substrate in a chronic rat model
AU - Linz, Benedikt
AU - Hohl, Mathias
AU - Lang, Lisa
AU - Wong, Dickson W.L.
AU - Nickel, Alexander G.
AU - De La Torre, Carolina
AU - Sticht, Carsten
AU - Wirth, Klaus
AU - Boor, Peter
AU - Maack, Christoph
AU - Speer, Thimoteus
AU - Jespersen, Thomas
AU - Schotten, Ulrich
AU - Sanders, Prashanthan
AU - Böhm, Michael
AU - Linz, Dominik
N1 - Publisher Copyright: © 2020 Heart Rhythm Society
PY - 2021
Y1 - 2021
N2 - Background: High night-to-night variability in obstructive sleep apnea (OSA) is associated with atrial fibrillation (AF). Obstructive apneas are characterized by intermittent deoxygenation-reoxygenation and intrathoracic pressure swings during ineffective inspiration against occluded upper airways. Objective: We elucidated the effect of repeated exposure to transient OSA conditions simulated by intermittent negative upper airway pressure (INAP) on the development of an AF substrate. Methods: INAP (48 events/4 h; apnea-hypopnea index 12 events/h) was applied in sedated spontaneously breathing rats (2% isoflurane) to simulate mild-to-moderate OSA. Rats without INAP served as a control group (CTR). In an acute test series (ATS), rats were either killed immediately (n = 9 per group) or after 24 hours of recovery (ATS-REC: n = 5 per group). To simulate high night-to-night variability in OSA, INAP applications (n = 10; 24 events/4 h; apnea-hypopnea index 6/h) were repeated every second day for 3 weeks in a chronic test series (CTS). Results: INAP increased atrial oxidative stress acutely, represented in decreases of reduced to oxidized glutathione ratio (ATS: INAP: 0.33 ± 0.05 vs CTR: 1 ± 0.26; P = .016), which was reversible after 24 hours (ATS-REC: INAP vs CTR; P = .274). Although atrial oxidative stress did not accumulate in the CTS, atrial histological analysis revealed increased cardiomyocyte diameters, reduced connexin 43 expression, and increased interstitial fibrosis formation (CTS: INAP 7.0% ± 0.5% vs CTR 5.1% ± 0.3%; P = .013), which were associated with longer inducible AF episodes (CTS: INAP: 11.65 ± 4.43 seconds vs CTR: 0.7 ± 0.33 seconds; P = .033). Conclusion: Acute simulation of OSA was associated with reversible atrial oxidative stress. Cumulative exposure to these transient OSA-related conditions resulted in AF substrates and was associated with increased AF susceptibility. Mild-to-moderate OSA with high night-to-night variability may deserve intensive management to prevent atrial substrate development.
AB - Background: High night-to-night variability in obstructive sleep apnea (OSA) is associated with atrial fibrillation (AF). Obstructive apneas are characterized by intermittent deoxygenation-reoxygenation and intrathoracic pressure swings during ineffective inspiration against occluded upper airways. Objective: We elucidated the effect of repeated exposure to transient OSA conditions simulated by intermittent negative upper airway pressure (INAP) on the development of an AF substrate. Methods: INAP (48 events/4 h; apnea-hypopnea index 12 events/h) was applied in sedated spontaneously breathing rats (2% isoflurane) to simulate mild-to-moderate OSA. Rats without INAP served as a control group (CTR). In an acute test series (ATS), rats were either killed immediately (n = 9 per group) or after 24 hours of recovery (ATS-REC: n = 5 per group). To simulate high night-to-night variability in OSA, INAP applications (n = 10; 24 events/4 h; apnea-hypopnea index 6/h) were repeated every second day for 3 weeks in a chronic test series (CTS). Results: INAP increased atrial oxidative stress acutely, represented in decreases of reduced to oxidized glutathione ratio (ATS: INAP: 0.33 ± 0.05 vs CTR: 1 ± 0.26; P = .016), which was reversible after 24 hours (ATS-REC: INAP vs CTR; P = .274). Although atrial oxidative stress did not accumulate in the CTS, atrial histological analysis revealed increased cardiomyocyte diameters, reduced connexin 43 expression, and increased interstitial fibrosis formation (CTS: INAP 7.0% ± 0.5% vs CTR 5.1% ± 0.3%; P = .013), which were associated with longer inducible AF episodes (CTS: INAP: 11.65 ± 4.43 seconds vs CTR: 0.7 ± 0.33 seconds; P = .033). Conclusion: Acute simulation of OSA was associated with reversible atrial oxidative stress. Cumulative exposure to these transient OSA-related conditions resulted in AF substrates and was associated with increased AF susceptibility. Mild-to-moderate OSA with high night-to-night variability may deserve intensive management to prevent atrial substrate development.
KW - Atrial fibrillation
KW - Night-to-night variability
KW - Obstructive sleep apnea
KW - Rats
KW - Substrate
UR - http://www.scopus.com/inward/record.url?scp=85101126726&partnerID=8YFLogxK
U2 - 10.1016/j.hrthm.2020.10.011
DO - 10.1016/j.hrthm.2020.10.011
M3 - Journal article
C2 - 33080392
AN - SCOPUS:85101126726
VL - 18
SP - 455
EP - 464
JO - Heart Rhythm
JF - Heart Rhythm
SN - 1547-5271
IS - 3
ER -
ID: 279699921