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Postoperative atrial fibrillation: The role of the inflammatory response.

ABSTRACT: OBJECTIVE:Abnormal atrial conduction has been shown to be a substrate for postoperative atrial fibrillation (POAF). This study aimed to determine the relationship between the location of the atrial reentry responsible for POAF, and degree of atrial inflammation. METHODS:Normal mongrel dogs (n = 18) were divided into 3 groups: anesthesia alone (anesthesia), lateral right atriotomy (atriotomy), and lateral right atriotomy with anti-inflammatory therapy (steroid). Conduction properties of the right and left atria (RA and LA) were examined 3 days postoperatively by mapping. Activation was observed during burst pacing-induced AF. The RA and LA myeloperoxidase activity was measured to quantitate the degree of inflammation. RESULTS:Sustained AF (>2 minutes) was induced in 5 of 6 animals in the atriotomy group, but in none in the anesthesia or steroid groups. All sustained AF originated from around the RA incision. Three of these animals had an incisional reentrant tachycardia around the right atriotomy and 2 had a focal activation arising from the RA during AF. The LA activations in these animals were passive from the RA activation. The RA activation of the atriotomy group was more inhomogeneous than that of the anesthesia group (inhomogeneity index: 2.0 ± 0.2 vs 1.0 ± 0.1, P < .01). Steroid therapy significantly normalized the RA activation after the atriotomy (1.2 ± 0.1, P < .01). The inhomogeneity of the atrial conduction correlated with the myeloperoxidase activity (r = 0.774, P < .001). CONCLUSIONS:Reentrant circuits responsible for POAF are dependent on the degree of inflammation and rotate around the atriotomy. Anti-inflammatory therapy decreased the risk of postoperative AF.

SUBMITTER: Ishii Y

PROVIDER: S-EPMC5524456 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Postoperative atrial fibrillation: The role of the inflammatory response.

Ishii Yosuke Y Schuessler Richard B RB Gaynor Sydney L SL Hames Kiyomi K Damiano Ralph J RJ

The Journal of thoracic and cardiovascular surgery 20170209 6

<h4>Objective</h4>Abnormal atrial conduction has been shown to be a substrate for postoperative atrial fibrillation (POAF). This study aimed to determine the relationship between the location of the atrial reentry responsible for POAF, and degree of atrial inflammation.<h4>Methods</h4>Normal mongrel dogs (n = 18) were divided into 3 groups: anesthesia alone (anesthesia), lateral right atriotomy (atriotomy), and lateral right atriotomy with anti-inflammatory therapy (steroid). Conduction properti ...[more]

PMID: 28274566

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Project description:RationalePostoperative atrial fibrillation (POAF) is a common and troublesome complication of cardiac surgery. POAF is generally believed to occur when postoperative triggers act on a preexisting vulnerable substrate, but the underlying cellular and molecular mechanisms are largely unknown.ObjectiveTo identify cellular POAF mechanisms in right atrial samples from patients without a history of atrial fibrillation undergoing open-heart surgery.Methods and resultsMulticellular action potentials, membrane ion-currents (perforated patch-clamp), or simultaneous membrane-current (ruptured patch-clamp) and [Ca2+]i-recordings in atrial cardiomyocytes, along with protein-expression levels in tissue homogenates or cardiomyocytes, were assessed in 265 atrial samples from patients without or with POAF. No indices of electrical, profibrotic, or connexin remodeling were noted in POAF, but Ca2+-transient amplitude was smaller, although spontaneous sarcoplasmic reticulum (SR) Ca2+-release events and L-type Ca2+-current alternans occurred more frequently. CaMKII (Ca2+/calmodulin-dependent protein kinase-II) protein-expression, CaMKII-dependent phosphorylation of the cardiac RyR2 (ryanodine-receptor channel type-2), and RyR2 single-channel open-probability were significantly increased in POAF. SR Ca2+-content was unchanged in POAF despite greater SR Ca2+-leak, with a trend towards increased SR Ca2+-ATPase activity. Patients with POAF also showed stronger expression of activated components of the NLRP3 (NACHT, LRR, and PYD domains-containing protein-3)-inflammasome system in atrial whole-tissue homogenates and cardiomyocytes. Acute application of interleukin-1β caused NLRP3-signaling activation and CaMKII-dependent RyR2/phospholamban hyperphosphorylation in an immortalized mouse atrial cardiomyocyte cell-line (HL-1-cardiomyocytes) and enhanced spontaneous SR Ca2+-release events in both POAF cardiomyocytes and HL-1-cardiomyocytes. Computational modeling showed that RyR2 dysfunction and increased SR Ca2+-uptake are sufficient to reproduce the Ca2+-handling phenotype and indicated an increased risk of proarrhythmic delayed afterdepolarizations in POAF subjects in response to interleukin-1β.ConclusionsPreexisting Ca2+-handling abnormalities and activation of NLRP3-inflammasome/CaMKII signaling are evident in atrial cardiomyocytes from patients who subsequently develop POAF. These molecular substrates sensitize cardiomyocytes to spontaneous Ca2+-releases and arrhythmogenic afterdepolarizations, particularly upon exposure to inflammatory mediators. Our data reveal a potential cellular and molecular substrate for this important clinical problem.

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Postoperative atrial fibrillation: The role of the inflammatory response.

Publications

Postoperative atrial fibrillation: The role of the inflammatory response.

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