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Atrial and Peripheral Indices of Platelet Activation and Endothelial Dysfunction in Patients with Lone Non-valvular Atrial Fibrillation
S100
Heart, Lung and Circulation 2012;21:S1–S142
CSANZ 2012 Abstracts
ABSTRACTS
242 Atrial and Peripheral Indices of Platelet Activation and Endothelial Dysfunction in Patients with Lone Nonvalvular Atrial Fibrillation
both AF per se and its associated comorbidities contribute to endothelial dysfunction and prothrombotic risk. http://dx.doi.org/10.1016/j.hlc.2012.05.252
H. Lim 1,2,∗ , S. Willoughby 1 , C. Schultz 1 , M. Alasady 1 , D. Lau 1 , D. Leong 1 , A. Brooks 1 , R. Mahajan 1 , A. Ganesan 1 , H. Abed 1 , K. Roberts-Thomson 1 , G. Young 1 , M. Worthley 1 , P. Sanders 1
243
1 Centre
W. Lim ∗ , M. Neo, P. Kuklik, A. Ganesan, D. Saint, P. Sanders
for Heart Rhythm Disorders, Royal Adelaide Hospital and The University of Adelaide, Adelaide, Australia 2 Austin and Northern Health, Melbourne, Australia Background: While atrial fibrillation (AF) is associated with increased left atrial (LA) thromboembolic risk it remains unclear whether this risk is due to AF per se or the accompanying comorbidities. Methods: Seventy patients undergoing catheter ablation for paroxysmal and persistent AF (32 lone AF, 38 AF with comorbidities) were recruited, compared with 15 patients with left-sided accessory pathways as controls. Blood samples were obtained from the LA, right atrium (RA) and femoral vein (FV) after transeptal puncture and before heparin administration. Platelet activation (platelet P-selectin) was measured by flow cytometry and asymmetric dimethylarginine (ADMA) was measured using enzyme-linked immunosorbent assay. Results: In patients with lone AF, platelet activation was significantly elevated in the LA compared to the FV (Ln P-selectin % 2.7 ± 0.1 vs. 2.5 ± 0.1; p < 0.05). There was no significant difference between sites in controls (p = 0.1). There was no significant difference in ADMA between sampling sites within lone AF patients (p = 0.2) and controls (p = 0.8). Comparing between groups, there was a significant stepwise increase in ADMA levels between controls, lone AF patients and patients with AF and comorbidities (p < 0.001).
Atrial Electrophysiological Remodelling in a Pre-obese Mouse Model of Type II Diabetes: Electrophysiological Mapping Studies
Centre for Heart Rhythm Disorders, University of Adelaide and Royal Adelaide Hospital, Adelaide, South Australia, Australia Introduction: Both diabetes mellitus (DM) and atrial fibrillation (AF) are burgeoning epidemics affecting millions worldwide. The relationship between DM and AF remains inconclusive, with equivocal results. Furthermore, the association between obesity in type 2 diabetic patients and the development of AF remains unknown. This study sought to characterise left atria electrophysiological properties in pre-obese NONcNZO10/LtJ (NON) mice, a mouse model of human obesity-induced type 2 diabetes. NON mice have been previously characterised to be pre-obese and hyperglycaemic by eight weeks of age and a moderately obese state with insulin resistance at 13 weeks. Methods: NON mice (n = 9) and SWR/J (control) mice (n = 7) aged 11 weeks were anaesthetised and the left atria excised and placed on a custom-made micro-electrode array (25 electrodes with 0.5 mm inter-electrode spacing). Effective refractory period (ERP) was measured using standard extra-stimulus pacing and conduction velocity (CV) and conduction heterogeneity index (CHI) were subsequently analysed offline. Results: NON mice body weights were significantly greater than controls (25 ± 0.8 vs. 23 ± 0.4 g respectively; p < 0.05). ERP distribution was significantly increased in NON mice (p < 0.001). Additionally, NON mice displayed increased CHI (2.953 ± 0.142 vs. 2.540 ± 0.125 respectively; p < 0.05) but average CV was not significantly reduced in NON mice comparing to controls (0.237 ± 0.014 vs. 0.248 ± 0.016 m s−1 respectively; p = 0.620). Conclusion: Pre-obese hyperglycaemic mice demonstrated increased refractoriness and conduction heterogeneity but normal conduction velocities in the left atria. http://dx.doi.org/10.1016/j.hlc.2012.05.253
Conclusion: Left atrial platelet activation is significantly elevated compared to the peripheral circulation in patients with lone non-valvular AF. A stepwise increase was observed for ADMA in controls, patients with lone AF and patients with AF and comorbidities, suggesting
Heart, Lung and Circulation 2012;21:S1–S142
CSANZ 2012 Abstracts
ABSTRACTS
242 Atrial and Peripheral Indices of Platelet Activation and Endothelial Dysfunction in Patients with Lone Nonvalvular Atrial Fibrillation
both AF per se and its associated comorbidities contribute to endothelial dysfunction and prothrombotic risk. http://dx.doi.org/10.1016/j.hlc.2012.05.252
H. Lim 1,2,∗ , S. Willoughby 1 , C. Schultz 1 , M. Alasady 1 , D. Lau 1 , D. Leong 1 , A. Brooks 1 , R. Mahajan 1 , A. Ganesan 1 , H. Abed 1 , K. Roberts-Thomson 1 , G. Young 1 , M. Worthley 1 , P. Sanders 1
243
1 Centre
W. Lim ∗ , M. Neo, P. Kuklik, A. Ganesan, D. Saint, P. Sanders
for Heart Rhythm Disorders, Royal Adelaide Hospital and The University of Adelaide, Adelaide, Australia 2 Austin and Northern Health, Melbourne, Australia Background: While atrial fibrillation (AF) is associated with increased left atrial (LA) thromboembolic risk it remains unclear whether this risk is due to AF per se or the accompanying comorbidities. Methods: Seventy patients undergoing catheter ablation for paroxysmal and persistent AF (32 lone AF, 38 AF with comorbidities) were recruited, compared with 15 patients with left-sided accessory pathways as controls. Blood samples were obtained from the LA, right atrium (RA) and femoral vein (FV) after transeptal puncture and before heparin administration. Platelet activation (platelet P-selectin) was measured by flow cytometry and asymmetric dimethylarginine (ADMA) was measured using enzyme-linked immunosorbent assay. Results: In patients with lone AF, platelet activation was significantly elevated in the LA compared to the FV (Ln P-selectin % 2.7 ± 0.1 vs. 2.5 ± 0.1; p < 0.05). There was no significant difference between sites in controls (p = 0.1). There was no significant difference in ADMA between sampling sites within lone AF patients (p = 0.2) and controls (p = 0.8). Comparing between groups, there was a significant stepwise increase in ADMA levels between controls, lone AF patients and patients with AF and comorbidities (p < 0.001).
Atrial Electrophysiological Remodelling in a Pre-obese Mouse Model of Type II Diabetes: Electrophysiological Mapping Studies
Centre for Heart Rhythm Disorders, University of Adelaide and Royal Adelaide Hospital, Adelaide, South Australia, Australia Introduction: Both diabetes mellitus (DM) and atrial fibrillation (AF) are burgeoning epidemics affecting millions worldwide. The relationship between DM and AF remains inconclusive, with equivocal results. Furthermore, the association between obesity in type 2 diabetic patients and the development of AF remains unknown. This study sought to characterise left atria electrophysiological properties in pre-obese NONcNZO10/LtJ (NON) mice, a mouse model of human obesity-induced type 2 diabetes. NON mice have been previously characterised to be pre-obese and hyperglycaemic by eight weeks of age and a moderately obese state with insulin resistance at 13 weeks. Methods: NON mice (n = 9) and SWR/J (control) mice (n = 7) aged 11 weeks were anaesthetised and the left atria excised and placed on a custom-made micro-electrode array (25 electrodes with 0.5 mm inter-electrode spacing). Effective refractory period (ERP) was measured using standard extra-stimulus pacing and conduction velocity (CV) and conduction heterogeneity index (CHI) were subsequently analysed offline. Results: NON mice body weights were significantly greater than controls (25 ± 0.8 vs. 23 ± 0.4 g respectively; p < 0.05). ERP distribution was significantly increased in NON mice (p < 0.001). Additionally, NON mice displayed increased CHI (2.953 ± 0.142 vs. 2.540 ± 0.125 respectively; p < 0.05) but average CV was not significantly reduced in NON mice comparing to controls (0.237 ± 0.014 vs. 0.248 ± 0.016 m s−1 respectively; p = 0.620). Conclusion: Pre-obese hyperglycaemic mice demonstrated increased refractoriness and conduction heterogeneity but normal conduction velocities in the left atria. http://dx.doi.org/10.1016/j.hlc.2012.05.253
Conclusion: Left atrial platelet activation is significantly elevated compared to the peripheral circulation in patients with lone non-valvular AF. A stepwise increase was observed for ADMA in controls, patients with lone AF and patients with AF and comorbidities, suggesting