Inflammation of Atrium After Cardiac Surgery Is Associated With Inhomogeneity of Atrial Conduction and Atrial Fibrillation

Abstract

Background— Atrial fibrillation (AF) is common after cardiac surgery. Abnormal conduction is an important substrate for AF. We hypothesized that atrial inflammation alters atrial conduction properties. Methods and Results— Normal mongrel canines (n=24) were divided into 4 groups consisting of anesthesia alone (control group); pericardiotomy (pericardiotomy group); lateral right atriotomy (atriotomy group); and lateral right atriotomy with antiinflammatory therapy (methylprednisolone 2 mg/kg per day) (antiinflammatory group). Right atrial activation was examined 3 days after surgery. Inhomogeneity of conduction was quantified by the variation of maximum local activation phase difference. To initiate AF, burst pacing was performed. Myeloperoxidase activity and neutrophil cell infiltration in the atrial myocardium were measured to quantify the degree of inflammation. The inhomogeneity of atrial conduction of the atriotomy and pericardiotomy groups was higher than that of the control group (2.02±0.10, 1.51±0.03 versus 0.96±0.08, respectively; P <0.005). Antiinflammatory therapy decreased the inhomogeneity of atrial conduction after atriotomy (1.16±0.10; P <0.001). AF duration was longer in the atriotomy and pericardiotomy groups than in the control and antiinflammatory groups ( P =0.012). There also were significant differences in myeloperoxidase activity between the atriotomy and pericardiotomy groups and the control group (0.72±0.09, 0.41±0.08 versus 0.18±0.03 ΔOD/min per milligram protein, respectively; P <0.001). Myeloperoxidase activity of the antiinflammatory group was lower than that of the atriotomy group (0.17±0.02; P <0.001). Inhomogeneity of conduction correlated with myeloperoxidase activity ( r =0.851, P <0.001). Conclusions— The degree of atrial inflammation was associated with a proportional increase in the inhomogeneity of atrial conduction and AF duration. This may be a factor in the pathogenesis of early postoperative AF. Antiinflammatory therapy has the potential to decrease the incidence of AF after cardiac surgery.

Ability to Induce Atrial Fibrillation in the Peri-operative Period Is Associated with Phosphorylation-dependent Inhibition of TWIK Protein-related Acid-sensitive Potassium Channel 1 (TASK-1)

“…Significant inflammation was quantified by comparing the presence of neutrophils as measured by the neutrophil-specific enzyme, myeloperoxidase, in the right atrium before and after induction of AF (1.0 Ϯ 0.2 unit/g in control tissue versus 36.8 Ϯ 4.8 units/g after AF; n ϭ 17; p Ͻ 0.001). These results are similar to those observed by Ishii et al (15). In tissue from failed AF animals, myeloperoxidase levels were intermediate (19.5 Ϯ 4.3 units/g; n ϭ 11), significantly greater than preoperative control tissue (p Ͻ 0.001) but significantly less than tissue from dogs in which AF induction was successful (p Ͻ 0.05).…”

“…First, we have not included dogs that underwent the surgical protocol but were not paced, nor have we included dogs that were paced in the absence of surgery. It is clear from the literature that atriotomy alone, in the absence of burst pacing, is insufficient to induce AF in the dog (15). Also, it is well established that burst pacing alone is insufficient to induce sustained AF in normal canine hearts (24,25) without some additional hormonal, neuronal, or surgical intervention.…”

“…Peri-operative AF Model-This study was performed under a protocol approved by the Institutional Animal Care and Use Committee of Columbia University, according to a modification of the method described by Ishii et al (15). Briefly, a thoracotomy was performed on anesthetized adult male mongrel canines (25-35 kg) treated with thiopental sodium (17 mg/kg i.v.)…”

Cardiomyocytes from phorbol myristate acetate-activated mesenchymal stem cells restore electromechanical function in infarcted rat hearts

“…However, remaining fibrosis in the MSCengrafted region may lead to continued electrical disturbances, which is supported by reports that dense fibrosis presents a for-midable physical barrier to cell regeneration (5) and acts as an electrical barrier that disturbs direct wave propagation, facilitating reentry (21,22). Moreover, excessive inflammation in the MSC-engrafted region might also cause inhomogenous conduction and delayed repolarization (23,24) as well as preventing the recruitment and survival of progenitor cells (25). Inexcitable properties of undifferentiated MSCs contribute to decreases in CV, increasing the susceptibility to ventricular arrhythmia and leading to sudden death.…”

Can We Predict the Occurrence of Atrial Fibrillation?

“…Systemic biomarkers of the acute phase response, inflammation, and oxidative stress are elevated in patients developing postoperative AF. 34,35 It has been suggested that there may be a genetic component to postoperative AF, as shown for the interleukin-6 promoter gene that appears to modulate the inflammatory response to surgery and susceptibility to postoperative AF. 36 Modern atrial tissue metabolomic and proteomic analyses support oxidative stress, acute phase, and apoptotic pathways to be involved.…”