Browsing by Author "Greer-Short, Amara D."

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    Distinguishing between overdrive excited and suppressed ventricular beats in guinea pig ventricular myocardium
    Greer-Short, Amara D.; Poelzing, Steven (Frontiers, 2015-02-18)
    Rapid ventricular pacing rates induces two types of beats following pacing cessation: recovery cycle length (RCL) prolongation (overdrive suppression) and RCL shortening (overdrive excitation). The goals of this study were to compare common experimental protocols for studying triggered activity in whole-heart preparations and differentiate between recovery beats using a new methodology. Post-pacing recovery beat cycle length (RCL) and QRS were normalized to pre-paced R-R and QRS intervals and analyzed using a K-means clustering algorithm. Control hearts only produced suppressed beats: RCL ratio increased with rapid pacing (25 +/- 4.0%, n = 10) without changing QRS duration. Rapid pacing during hypercalcemia + hypothermia (5.5 mM and 34 degrees C) produced significantly earlier excited beats (53 +/- 14%, n = 5) with wider QRS durations (58 +/- 6.3%, n = 5) than suppressed beats. Digoxin + hypothermia (0.75 mu M) produced the most excited beats with significantly earlier RCL (44 +/- 3.2%, n = 6) and wider QRS (60 +/- 3.1%, n = 6) ratios relative to suppressed beats. Increasing pacing further shortened RCL (30 +/- 7.8%, n = 6). In a prospective study, TTX (100 nM) increased RCL ratio (15 +/- 6.0%, n = 10) without changing the QRS duration of excited beats. The algorithm was compared to a cross-correlation analysis with 93% sensitivity and 94% specificity. This ECG based algorithm distinguishes between triggered and automatic activity.
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    The Temporal Nature of Ectopic Activity in Guinea Pig Ventricular Myocardium
    Greer-Short, Amara D. (Virginia Tech, 2016-04-29)
    The temporal nature of ectopic activity is important to elucidating the mechanisms that can lead to arrhythmogenesis. However, challenges remain in distinguishing between ectopic and non-ectopic beats. A new methodology was developed and validated to distinguish between beat types. Rapid pacing was used to induce both ectopic and non-ectopic beats. Using an electrocardiogram, the post-pacing recovery beat cycle length (RCL) and QRS were normalized to pre-paced R-R and QRS intervals and analyzed using a K-means clustering algorithm. Control hearts only produced beats with RCL ratios that increased with rapid pacing, suggestive of non-ectopic activity. Hypercalcemia and digoxin both produced significantly earlier beats with wider QRS durations, suggestive of ectopic activity. Increasing pacing further shortened RCL during digoxin + hypothermia, a mechanistic identifier of ectopic activity. When tested against a previously validated analysis, our algorithm performed well. Therefore, this electrocardiogram based algorithm distinguishes between ectopic and non-ectopic beats. In a prospective study, tetrodotoxin increased RCL ratio without changing the QRS duration of excited beats, suggesting neuronal sodium channels play an important role in ectopic beat timing. The next goal was to create a consistent model of ectopic activity. Both sympathetic and parasympathetic stimulation independently potentiate arrhythmogenesis, and we investigated the effects of independent and simultaneous stimulation on the temporal nature of arrhythmogenesis. Isoproterenol (ISO), a sympathetic agonist, transiently produced ectopic activity and increased heart rate. Acetylcholine (ACh), a parasympathetic agonist, did not significantly produce ectopic activity but did slow heart rate. ACh added after ISO also transiently produced ectopic activity, while heart rate remained slowed. Importantly, ISO following ACh persistently increased ectopic activity and heart rate. Therefore, ISO following ACh is an ideal model for creating sustained ectopic activity. Mature animals exhibited sustained arrhythmogenesis while young animals did not. When ACh was removed and then followed by ISO, ectopic activity and heart rate transiently increased, similar to ISO alone. This suggests that maintained ACh perfusion can sustain ISO sensitivity, in contrast to ISO perfusion alone. The data in this dissertation provide an insight into the mechanisms that affect the ectopic beat timing and arrhythmia propensity.
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    Temporal response of ectopic activity in guinea pig ventricular myocardium in response to isoproterenol and acetylcholine
    Greer-Short, Amara D.; Poelzing, Steven (Frontiers, 2015-10-20)
    Both beta adrenergic and musoarinio receptor stimulation independently potentiate arrhy-thmogenesis. However, the effect of simultaneous stimulation on arrhy-thmogenesis is not well known. The purpose of this study was to determine the temporal response of arrhythmia risk to individual and combined autonomic agonists. Guinea pig hearts were excised and Langendorff-perfused. The beta adrenergic receptor and musoarinio receptor agonists were isoproterenol (ISO, 0.6 mu M) and acetylcholine (ACh, 10 mu M), respectively. All measurements with agonists occurred over 21 min. ISO induced ectopic activity for the first 8 min. ISO also transiently shortened and then prolonged R-R interval over a similar time course. ACh added after ISO transiently induced ectopic activity for 12 min, while R-R interval invariantly prolonged. ACh alone produced few ectopic beats, while invariantly prolonging R-R interval. In contrast to ISO alone, ISO following ACh significantly increased ectopic activity and shortened R-R interval for the duration of the experiment. Animals aged 17-19 months exhibited sustained arrhythmogenesis while those aged 11-14 did not. When ACh was removed in older hearts while ISO perfused, a transient increase in ectopic activity and decreased R-R interval was observed, similar to ISO alone. These data suggest that pre-treating with and maintaining ACh perfusion can sustain ISO sensitivity, in contrast to ISO perfusion alone.