Vagal nerve stimulation preserves right ventricular function in a rat model of right ventricular pressure overload

Figure 1. Protocol. This study focused on the therapeutic effects of 2‐week vagal nerve stimulation (VNS) delivered by an implantable neurostimulator in free‐moving rats with pulmonary artery banding. VNS was initiated after randomization by echocardiography at Week 2. CTRL, control; PAB, pulmonary artery banding; SS, sham stimulation

Figure 2. Effects of vagal nerve stimulation (VNS) on power spectral density of heart rate. Representative traces of power spectral density of heart rate in a control rat without pulmonary artery banding (CTRL; a), a rat with pulmonary artery banding and sham stimulation (SS; b), and a rat with pulmonary artery banding and VNS (c). The high frequency (HF) component that represents parasympathetic nerve activity is lower in SS than in CTRL but is higher in VNS than in SS.

Figure 3. Effects of vagal nerve stimulation (VNS) on body weight and echocardiographic parameters. (a) RV diastolic dimension (RVDd), (b) RV systolic dimension (RVDs), (c) RV wall thickness (RVWT), and (d) tricuspid annular plane systolic excursion (TAPSE) is shown. Compared to SS, VNS significantly reduces RVDd and RVDs, and increases TAPSE. CTRL, control rats without pulmonary artery banding (n = 5); SS, rats with pulmonary artery banding and sham stimulation (n = 8); VNS, rats with pulmonary artery banding and VNS (n = 7). Data are expressed as mean ± SEM. Differences were tested by one‐way analysis of variance, followed by post hoc Tukey–Kramer test. *p < 0.05 and **p < 0.01 versus CTRL. † p < 0.05 and ‡ p < 0.01 versus SS.

Figure 4. Effects of vagal nerve stimulation (VNS) on hemodynamics and plasma brain natriuresis peptide (BNP). (a–g) Heart rate (HR), mean arterial pressure (AP), right ventricular (RV) systolic pressure (RVSP), RV end‐diastolic pressure (RVEDP), maximum first derivation of RV pressure (max + dP/dt), minimum first derivation of RV pressure (min − dP/dt), and cardiac index (CI) are shown. VNS significantly improves RV pump performance. (h) Plasma BNP level is shown. VNS significantly reduces plasma BNP levels compared to SS. CTRL, control rats without pulmonary artery banding (n = 5); SS, rats with pulmonary artery banding and sham stimulation (n = 8); VNS, rats with pulmonary artery banding and VNS (n = 7). Data are expressed as mean ± SEM. Differences were tested by one‐way analysis of variance, followed by a post hoc Tukey–Kramer test. *p < 0.05 and **p < 0.01 versus CTRL. † p < 0.05 and ‡ p < 0.01 versus SS.

Figure 5. Effects of vagal nerve stimulation (VNS) on pressure–volume loop analysis. Representative plots of pressure–volume loops in each group; CTRL, control rat without pulmonary artery banding (green); SS, a rat with pulmonary artery banding and sham stimulation (blue); VNS, a rat with pulmonary artery banding and VNS (red). Multiple loops are acquired by occlusion of the inferior vena cava. The slope of the loops was determined as the end‐systolic pressure–volume relationship (end‐systolic elastance; E es).

Figure 6. Effects of chronic vagal nerve stimulation (VNS) on histology of RV. Representative photomicrographs of (a) hematoxylin and eosin (HE) staining, (b) CD34 immunostaining, (c) Masson trichrome staining (MT), and (d) CD68‐positive cells are shown (n = 5 in each group). CTRL, control rats without pulmonary artery banding; SS, rats with pulmonary artery banding and sham stimulation; VNS, rats with pulmonary artery banding and VNS. Data are expressed as mean ± SEM. Differences were tested by one‐way analysis of variance, followed by post hoc Tukey–Kramer test. **p < 0.01 vs. CTRL. † p < 0.05 and ‡ p < 0.01 vs. SS.