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Chronic left atrial volume and pressure overload in the goat: A new model of sustained atrial fibrillation
Session 49 sured areas and in both groups. This increase was larger in the MR LA compared to controls. Sustained AF (⬎30 minutes) occurred only in the MR dogs. At 100 nM of ZP 123, duration of AF was markedly reduced for the MR group ( 96 ⫾ 3 % reduction, p ⬍0.001) and no sustained episodes could be induced; reducing the AF vulnerability in MR dogs to that of the controls. No ventricular arrhythmias were induced.
Conclusion: Improving gap junction conductance with ZP 123 increases atrial CV and reduces AF vulnerability in a model of AF due to chronic MR. These results suggest a role for this pharmacological approach in the prevention of AF in those substrates with altered conduction. AB48-5 FREQUENCY GRADIENTS DURING FOCALLY DRIVEN VS. SELFSUSTAINED ATRIAL FIBRILLATION IN THE CANINE ATRIA Joseph S. Ulphani, MD, Jason Ng, PhD, David Gordon, MD, PhD, Alexander R. Morris, Gregory Shade, BSc, Samer R. Dibs, MD, Rishi Arora, MD, Jeffery J. Goldberger, MD and Alan H. Kadish, MD. Northwestern University, Chicago, IL. Background: Left-to-right frequency gradients of atrial activation during atrial fibrillation (AF) have been observed both in animal models and in humans, suggesting the importance of the left atrium/pulmonary veins for the maintenance of AF. The objective of this study is to compare the frequency gradients between the two atria during focally driven versus self-sustained AF models in canine. Methods: Rectangular electrode arrays (8x14) were placed on the left (LA) and right (RA) atria of 14 anesthetized mongrel dogs. AF was induced using both burst pacing (PA) and aconitine (AC) administration. AC was administered in the RA for 8 dogs and in the LA in 6 dogs. Following QRS subtraction to remove ventricular artifacts, the peak frequency (PF) of each of the 224 4-second unipolar AF recordings was computed using the Fast Fourier Transform for each mode of induction. Results: Significant frequency gradients were seen during AF in 14 of 14 dogs following AC and 11 of 14 dogs following PA. Overall, the atria with AC application had higher mean PFs than the passively driven atria (11.2 ⫾ 2.2 vs. 8.8 ⫾ 1.0 Hz, p ⬍ 0.0005). The LA had higher mean PFs than the RA in the PA induced AF (9.2 ⫾ 0.9 vs. 8.8 ⫾ 1.0 Hz, p ⬍ 0.02). The frequency gradients were greater from AC than from PA (2.4 ⫾ 1.8 vs. 0.6 ⫾ 0.5 Hz, p ⬍ 0.003). AC applied in the LA produced larger frequency gradients than when applied to the RA (3.5 ⫾ 1.7 vs. 1.5 ⫾ 1.4 Hz, p ⬍ 0.05). Conclusions: Using AC and PA induction models, frequency gradients were shown to be dependent on mechanism and in focal AF the location of the driver. Significant left-to-right gradients were noted in the acute pacing model of AF suggesting the importance of the LA in sustaining AF. Understanding the frequency characteristics of AF may lead to improved identification of AF mechanisms in the clinical setting.
AB48-6 CHRONIC LEFT ATRIAL VOLUME AND PRESSURE OVERLOAD IN THE GOAT: A NEW MODEL OF SUSTAINED ATRIAL FIBRILLATION
S97 Jan Remes, MD, Thomas J. Van Brakel, MD, Guy Vaessen, K. Hamzeh, MD, Monique De Jong, Frederik Van der Veen, PhD and Jos G. Maessen, MD, PhD. Acad Ziekenhuis Maastricht, Maastricht, Netherlands. Background: Left atrial (LA) dilatation is associated with a high incidence of atrial fibrillation (AF) but the mechanisms are poorly understood. In the past, dilatation induced AF animal models have been developed, but the AF duration was limited. The aim of this study was to develop an animal model of long-lasting AF, induced by controlled chronic left atrial overload. Methods: In 12 goats, a left thoracotomy was performed to implant a 8mm vascular graft (gore-tex®) between the thoracic aorta and the LA. Intraoperative atrial overload was monitored by volume- and invasive pressure measurements. The LA was chronically instrumented with ultrasonic crystals and bipolar sensing/pacing electrodes. LA dilatation and electrophysiology were regularly evaluated in the conscious goats and compared with baseline and a control group of animals with a non-functional shunt. LA pressure was measured just prior to sacrifice. Results: Peroperatively, there was manifest LA overload with a volume augmentation of 59 ⫾ 42 % (p⬍0.01) and a mean LA pressure increase from 9 ⫾ 7 mmHg to 18 ⫾ 9 mmHg (p⬍0.05). At sacrifice (32 ⫾ 10 days), shunt patency was confirmed in 9 animals. In those, mean LA pressure at sacrifice was 20 ⫾ 8 mmHg and LA volume was further increased to 147 ⫾ 20 % (p⬍0.05). The AF duration increased significantly from 4.7 ⫾ 4.9 sec (day 0) to 113 ⫾ 82 hours (p⬍0.0001) after 16 ⫾ 7 days of open shunt. In six animals, sustained AF (⬎ 1 week) was present. In the animals with a closed shunt, the AF duration, LA pressure and volume did not change significantly. Conclusion: Chronic pressure/volume overload of the left atrium induces sustained atrial fibrillation in the goat. This model may provide new insights in the relation between atrial dilatation and atrial fibrillation, and may be of value to study novel treatments. ABSTRACT SESSION 49: DEVICES XV: Pacing in Sleep Apnea and in Special Heart Failure Populations Friday, May 6, 2005 4:45 p.m.– 6:15 p.m. AB49-1 TEMPORARY ATRIAL PACING IS INEFFECTIVE IN PREVENTING OBSTRUCTIVE SLEEP APNEA IN PATIENTS WITHOUT PERMANENT PACEMAKERS: A PROSPECTIVE, RANDOMIZED, CROSSOVER TRIAL *Andrew D. Krahn, MD, *Raymond Yee, MD, *George J. Klein, MD, Allan C. Skanes, MD, *Mark K. Erikson, BSc, *Toby Markowitz, BSc and Kathleen A. Ferguson, MD. University of Western Ontario, London, Ontario, Canada. Background: Apneic episodes during sleep are generally associated with profound bradycardia. Patients with permanent pacemakers may have reduced episodes of sleep apnea with their pacemaker rate set faster than their spontaneous nocturnal heart rate. We conducted a prospective, randomized, single blind crossover trial of temporary atrial pacing in obstructive sleep apnea to reduce the apnea hypopnea index (AHI, # apneas ⫹ hypopneas per hour of sleep). Methods: Fifteen patients (age 60⫾13 yrs, 12 male, BMI 31⫾5) with moderate to severe obstructive sleep apnea (AHI 34⫾14) underwent insertion of an externalized AAI permanent pacing system via the left subclavian vein. Patients underwent sleep studies, in hospital, during AAI pacing at 75 bpm, and OAO pacing. The order of pacing mode by night was randomized, with crossover the subsequent night. Patients were blinded to pacing mode, and analysis of sleep recordings was blinded to pacing mode. Results: Pacing was tolerated without complications in all patients. Pacing did not affect AHI, the frequency of desaturation or the minimum SaO2. There was a significant reduction in circulatory time with pacing (p⫽0.04). Conclusion: Temporary atrial pacing does not appear to benefit patients
Conclusion: Improving gap junction conductance with ZP 123 increases atrial CV and reduces AF vulnerability in a model of AF due to chronic MR. These results suggest a role for this pharmacological approach in the prevention of AF in those substrates with altered conduction. AB48-5 FREQUENCY GRADIENTS DURING FOCALLY DRIVEN VS. SELFSUSTAINED ATRIAL FIBRILLATION IN THE CANINE ATRIA Joseph S. Ulphani, MD, Jason Ng, PhD, David Gordon, MD, PhD, Alexander R. Morris, Gregory Shade, BSc, Samer R. Dibs, MD, Rishi Arora, MD, Jeffery J. Goldberger, MD and Alan H. Kadish, MD. Northwestern University, Chicago, IL. Background: Left-to-right frequency gradients of atrial activation during atrial fibrillation (AF) have been observed both in animal models and in humans, suggesting the importance of the left atrium/pulmonary veins for the maintenance of AF. The objective of this study is to compare the frequency gradients between the two atria during focally driven versus self-sustained AF models in canine. Methods: Rectangular electrode arrays (8x14) were placed on the left (LA) and right (RA) atria of 14 anesthetized mongrel dogs. AF was induced using both burst pacing (PA) and aconitine (AC) administration. AC was administered in the RA for 8 dogs and in the LA in 6 dogs. Following QRS subtraction to remove ventricular artifacts, the peak frequency (PF) of each of the 224 4-second unipolar AF recordings was computed using the Fast Fourier Transform for each mode of induction. Results: Significant frequency gradients were seen during AF in 14 of 14 dogs following AC and 11 of 14 dogs following PA. Overall, the atria with AC application had higher mean PFs than the passively driven atria (11.2 ⫾ 2.2 vs. 8.8 ⫾ 1.0 Hz, p ⬍ 0.0005). The LA had higher mean PFs than the RA in the PA induced AF (9.2 ⫾ 0.9 vs. 8.8 ⫾ 1.0 Hz, p ⬍ 0.02). The frequency gradients were greater from AC than from PA (2.4 ⫾ 1.8 vs. 0.6 ⫾ 0.5 Hz, p ⬍ 0.003). AC applied in the LA produced larger frequency gradients than when applied to the RA (3.5 ⫾ 1.7 vs. 1.5 ⫾ 1.4 Hz, p ⬍ 0.05). Conclusions: Using AC and PA induction models, frequency gradients were shown to be dependent on mechanism and in focal AF the location of the driver. Significant left-to-right gradients were noted in the acute pacing model of AF suggesting the importance of the LA in sustaining AF. Understanding the frequency characteristics of AF may lead to improved identification of AF mechanisms in the clinical setting.
AB48-6 CHRONIC LEFT ATRIAL VOLUME AND PRESSURE OVERLOAD IN THE GOAT: A NEW MODEL OF SUSTAINED ATRIAL FIBRILLATION
S97 Jan Remes, MD, Thomas J. Van Brakel, MD, Guy Vaessen, K. Hamzeh, MD, Monique De Jong, Frederik Van der Veen, PhD and Jos G. Maessen, MD, PhD. Acad Ziekenhuis Maastricht, Maastricht, Netherlands. Background: Left atrial (LA) dilatation is associated with a high incidence of atrial fibrillation (AF) but the mechanisms are poorly understood. In the past, dilatation induced AF animal models have been developed, but the AF duration was limited. The aim of this study was to develop an animal model of long-lasting AF, induced by controlled chronic left atrial overload. Methods: In 12 goats, a left thoracotomy was performed to implant a 8mm vascular graft (gore-tex®) between the thoracic aorta and the LA. Intraoperative atrial overload was monitored by volume- and invasive pressure measurements. The LA was chronically instrumented with ultrasonic crystals and bipolar sensing/pacing electrodes. LA dilatation and electrophysiology were regularly evaluated in the conscious goats and compared with baseline and a control group of animals with a non-functional shunt. LA pressure was measured just prior to sacrifice. Results: Peroperatively, there was manifest LA overload with a volume augmentation of 59 ⫾ 42 % (p⬍0.01) and a mean LA pressure increase from 9 ⫾ 7 mmHg to 18 ⫾ 9 mmHg (p⬍0.05). At sacrifice (32 ⫾ 10 days), shunt patency was confirmed in 9 animals. In those, mean LA pressure at sacrifice was 20 ⫾ 8 mmHg and LA volume was further increased to 147 ⫾ 20 % (p⬍0.05). The AF duration increased significantly from 4.7 ⫾ 4.9 sec (day 0) to 113 ⫾ 82 hours (p⬍0.0001) after 16 ⫾ 7 days of open shunt. In six animals, sustained AF (⬎ 1 week) was present. In the animals with a closed shunt, the AF duration, LA pressure and volume did not change significantly. Conclusion: Chronic pressure/volume overload of the left atrium induces sustained atrial fibrillation in the goat. This model may provide new insights in the relation between atrial dilatation and atrial fibrillation, and may be of value to study novel treatments. ABSTRACT SESSION 49: DEVICES XV: Pacing in Sleep Apnea and in Special Heart Failure Populations Friday, May 6, 2005 4:45 p.m.– 6:15 p.m. AB49-1 TEMPORARY ATRIAL PACING IS INEFFECTIVE IN PREVENTING OBSTRUCTIVE SLEEP APNEA IN PATIENTS WITHOUT PERMANENT PACEMAKERS: A PROSPECTIVE, RANDOMIZED, CROSSOVER TRIAL *Andrew D. Krahn, MD, *Raymond Yee, MD, *George J. Klein, MD, Allan C. Skanes, MD, *Mark K. Erikson, BSc, *Toby Markowitz, BSc and Kathleen A. Ferguson, MD. University of Western Ontario, London, Ontario, Canada. Background: Apneic episodes during sleep are generally associated with profound bradycardia. Patients with permanent pacemakers may have reduced episodes of sleep apnea with their pacemaker rate set faster than their spontaneous nocturnal heart rate. We conducted a prospective, randomized, single blind crossover trial of temporary atrial pacing in obstructive sleep apnea to reduce the apnea hypopnea index (AHI, # apneas ⫹ hypopneas per hour of sleep). Methods: Fifteen patients (age 60⫾13 yrs, 12 male, BMI 31⫾5) with moderate to severe obstructive sleep apnea (AHI 34⫾14) underwent insertion of an externalized AAI permanent pacing system via the left subclavian vein. Patients underwent sleep studies, in hospital, during AAI pacing at 75 bpm, and OAO pacing. The order of pacing mode by night was randomized, with crossover the subsequent night. Patients were blinded to pacing mode, and analysis of sleep recordings was blinded to pacing mode. Results: Pacing was tolerated without complications in all patients. Pacing did not affect AHI, the frequency of desaturation or the minimum SaO2. There was a significant reduction in circulatory time with pacing (p⫽0.04). Conclusion: Temporary atrial pacing does not appear to benefit patients