Abstract 16303: Autonomic Dysfunction Parallels the Progression of Pulmonary Arterial Hypertension in Monocrotaline Rats
Introduction: Although autonomic dysfunction in PAH has been increasingly attracting clinical interest as a potential therapeutic option (e.g. pulmonary artery denervation), its relationship with the progression of PAH remains poorly understood. Thus we investigated how PAH alters the autonomic balance and its regulatory system, baroreflex, in monocrotaline (MCT) induced PAH rats.
Methods/Results: In Sprague-Dawley rats (n=35), we subcutaneously injected MCT (60 mg/kg) or saline for control (CTL), and evaluated the autonomic function 3 and 3.5 week after the injection. MCT markedly increased right ventricular systolic pressure (RVSP) and induced right ventricular hypertrophy (RVH). Increases in plasma norepinephrine and 24-hour urinary norepinephrine excretion paralleled the progression of PAH (Fig. 1). MCT decreased the high frequency component of heart rate variability (HR) (0.81±0.17 vs. 2.72±0.52 msec2, p<0.05) and attenuated the HR response to atropine (2 mg/kg, intraperitoneally) (103.8±21.05 vs. 183.5±23.07 bpm, p=0.063) indicating underlying parasympathetic deactivation. To examine baroreflex function, we isolated bilateral carotid sinuses and controlled carotid sinus pressure (CSP). We evaluated the static responses of arterial pressure (AP) to CSP. MCT significantly lowered the static gain (-0.22±0.22 vs. -0.8±0.31, p<0.05, Fig. 2). We also evaluated the dynamic baroreflex function by estimating the transfer function in the frequency range of 0.01 to 1 Hz. Although MCT decreased the dynamic baroreflex gain (0.01Hz: 0.25±0.1 vs. 0.51±0.1, p<0.05, Fig. 3), the corner frequency which reflects how quickly the baroreflex can operate in stabilizing arterial pressure remained unchanged.
Conclusions: The sympatho-parasympathetic imbalance and baroreflex dysfunction parallel the progression of PAH. The autonomic dysfunction may contribute to worsen the prognosis of severe PAH, thereby could serve as a new therapeutic option in PAH.
Author Disclosures: M. Shinoda: None. K. Saku: None. Y. Oga: None. T. Tohyama: None. T. Nishikawa: None. K. Abe: None. T. Takehara: None. T. Kishi: None. H. Tsutsui: None. K. Sunagawa: None.
- © 2016 by American Heart Association, Inc.