Unprovoked atrial tachyarrhythmias in aging spontaneously hypertensive rats: the role of the autonomic nervous system

Abstract

Experimental models of unprovoked atrial tachyarrhythmias (AT) in conscious, ambulatory animals are lacking. We hypothesized that the aging, spontaneously hypertensive rat (SHR) may provide such a model. Baseline ECG recordings were acquired with radiotelemetry in eight young (14-wk-old) and eight aging (55-wk-old) SHRs and in two groups of four age-matched Wistar-Kyoto (WKY) rats. Quantification of AT and heart rate variability (HRV) analysis were performed based on 24-h ECG recordings in unrestrained rats. All animals were submitted to an emotional stress protocol (air-jet). In SHRs, carbamylcholine injections were also performed. Spontaneous AT episodes were observed in all eight aging SHRs (median, 91.5; range, 4-444 episodes/24 h), but not in young SHRs or WKY rats. HRV analysis demonstrated significantly decreased low frequency components in aging SHRs compared with age-matched WKY rats (P < 0.01) and decreased low/high frequency ratios in both young (P < 0.01) and aging (P = 0.01) SHRs compared with normotensive controls. In aging SHRs, emotional stress significantly reduced the number of arrhythmic events, whereas carbamylcholine triggered AT and significantly increased atrial electrical instability. This study reports the occurrence of unprovoked episodes of atrial arrhythmia in hypertensive rats, and their increased incidence with aging. Our results suggest that autonomic imbalance with relative vagal hyperactivity may be responsible for the increased atrial arrhythmogenicity observed in this model. We also provide evidence that, in this model, the sympatho-vagal imbalance preceded the occurrence of arrhythmia. These results indicate that aging SHRs may provide valuable insight into the understanding of atrial arrhythmias.

Spontaneous atrial fibrillation after long-term transesophageal atrial burst pacing in rats. Technical and procedural approach to a new in vivo atrial fibrillation model

“…Given that during pacing waves are difficult, if not impossible, to recognize, AF duration is usually measured from the end of burst pacing to the first P wave detected after the irregular supraventricular rhythm. In accordance with previous studies (8), AF was defined in this study as rapid, irregular, supraventricular rhythm, with no visible P waves and irregular R-R intervals, lasting at least three beats. In other studies, a duration of at least 2 s was required to define AF (10).…”

“…Moreover, in the presence of substrate-modifying factors such as aging and hypertension, rat hearts develop spontaneous AF (8). Although it replicates well the human condition, AF occurrence in this latter model requires long-term (>12 months) follow-up (8).…”

“…All animals were housed individually in a climate-controlled room (21-24°C), with a 12/12-h light/dark cycle, and had free access to food and water. All rats were implanted at the beginning of the study with radiotelemetry ECG devices (TA11 CA-F40; Data Sciences International, St. Paul, MN), as described previously (8,12).…”

“…The protocol can easily be applied in other clinically-relevant models (e.g. models of diseases known to be associated with increased risk of AF, such as aging and hypertension, heart failure, or obesity [8,[13][14][15]), or in animals treated with drugs commonly used in AF patients.…”

Age-dependent myocardial transcriptomic changes in the rat. Novel insights into atrial and ventricular arrhythmias pathogenesis

“…Contrarily, based on the panel of studied genes, it appears that the ventricular myocardium is much less 'sensitive' to molecular aging, explaining the lower propensity to ventricular than atrial arrhythmias of the elderly. However, despite the pro-arrhythmic atrial molecular profile, we previously demonstrated using continuous electrocardiographic recordings that aging WKY rats do not develop significant atrial arrhythmic events, contrary to aging spontaneously hypertensive rats, which displayed high atrial arrhythmogenicity (28). Taken together, these observations suggest that atrial molecular aging is not a sufficient condition but more likely a facilitator of atrial arrhythmogenicity, and that the presence of other factors, such as arterial hypertension, is needed in order to initiate the arrhythmias.…”