Contribution of afferent pathway to vagal nerve stimulation-induced myocardial interstitial acetylcholine release in rats

2020 ◽  
Vol 319 (5) ◽  
pp. R517-R525
Author(s):  
Toru Kawada ◽  
Takashi Sonobe ◽  
Takuya Nishikawa ◽  
Yohsuke Hayama ◽  
Meihua Li ◽  
...  
Keyword(s):  
Nerve Stimulation ◽  
Low Voltage ◽  
Low Frequency ◽  
Left Ventricular ◽  
Vagal Nerve ◽  
Vagal Nerve Stimulation ◽  
Afferent Pathway ◽  
Ach Release ◽  
Vagal Afferent ◽  
Wistar Kyoto

Vagal nerve stimulation (VNS) has been explored as a potential therapy for chronic heart failure. The contribution of the afferent pathway to myocardial interstitial acetylcholine (ACh) release during VNS has yet to be clarified. In seven anesthetized Wistar-Kyoto rats, we implanted microdialysis probes in the left ventricular free wall and measured the myocardial interstitial ACh release during right VNS with the following combinations of stimulation frequency (F in Hz) and voltage readout (V in volts): F0V0 (no stimulation), F5V3, F20V3, F5V10, and F20V10. F5V3 did not affect the ACh level. F20V3, F5V10, and F20V10 increased the ACh level to 2.83 ± 0.47 ( P < 0.01), 4.31 ± 1.09 ( P < 0.001), and 4.33 ± 0.82 ( P < 0.001) nM, respectively, compared with F0V0 (1.76 ± 0.22 nM). After right vagal afferent transection (rVAX), F20V3 and F20V10 increased the ACh level to 2.90 ± 0.53 ( P < 0.001) and 3.48 ± 0.63 ( P < 0.001) nM, respectively, compared with F0V0 (1.61 ± 0.19 nM), but F5V10 did not (2.11 ± 0.24 nM). The ratio of the ACh levels after rVAX relative to before was significantly <100% in F5V10 (59.4 ± 8.7%) but not in F20V3 (102.0 ± 8.7%). These results suggest that high-frequency and low-voltage stimulation (F20V3) evoked the ACh release mainly via direct activation of the vagal efferent pathway. By contrast, low-frequency and high-voltage stimulation (F5V10) evoked the ACh release in a manner dependent on the vagal afferent pathway.

In vivo detection of endogenous acetylcholine release in cat ventricles

1994 ◽  
Vol 266 (3) ◽  
pp. H854-H860 ◽  
Author(s):  
T. Akiyama ◽  
T. Yamazaki ◽  
I. Ninomiya
Keyword(s):  
Nerve Stimulation ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Vagal Nerve ◽  
Vagal Nerve Stimulation ◽  
Left Ventricular Myocardium ◽  
Ach Release ◽  
Vagal Nerves ◽  
Dialysis Technique

To detect and monitor endogenous acetylcholine (ACh) release in the in vivo heart, we applied a dialysis technique to the hearts of anesthetized cats. Dialysis probes were implanted in the left ventricular myocardium and were perfused with Krebs-Henseleit solution containing Eserine (10(-4) M) at 3 microliters/min. Dialysate ACh concentration was measured with high-performance liquid chromatography. In four cats, the response to vagal stimulation was studied. Electrical stimulation of efferent vagal nerves (10 Hz) significantly increased dialysate ACh concentration from 596 +/- 118 (control) to 12,210 +/- 1,661 pM. After stimulation, dialysate ACh concentration significantly decreased to 382 +/- 80 pM below control. The influence of ganglionic blocker was determined in six cats. Control vagal nerve stimulation (10 Hz) increased dialysate ACh concentration from 582 +/- 136 to 9,102 +/- 754 pM. Local perfusion of hexamethonium (10(-4) M) did not affect this nerve stimulation-induced ACh increase (8,611 +/- 1,189 pM), and intravenous administration of hexamethonium (20 mg/kg) prevented this increase (340 +/- 88 pM). We examined the response to vagal nerve stimulation at different frequencies in three cats. Vagal nerve stimulation increased dialysate ACh concentration from a control of 588 +/- 211 to 1,227 +/- 195 pM at 2 Hz, 3,946 +/- 1,059 pM at 5 Hz, and 9,366 +/- 1,873 pM at 10 Hz. Dialysate ACh concentration reflects ACh release from postganglionic vagal nerves innervating the left ventricular myocardium; the dialysis technique permits estimation of relative changes in efferent cardiac vagal nerve activity.

scholarly journals Electrophysiological effects of right and left vagal nerve stimulation on the ventricular myocardium

2014 ◽  
Vol 307 (5) ◽  
pp. H722-H731 ◽  
Author(s):  
Kentaro Yamakawa ◽  
Eileen L. So ◽  
Pradeep S. Rajendran ◽  
Jonathan D. Hoang ◽  
Nupur Makkar ◽  
...  
Keyword(s):  
Heart Rate ◽  
Nerve Stimulation ◽  
Regional Differences ◽  
Left Ventricular Pressure ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Vagal Nerve ◽  
Vagal Nerve Stimulation ◽  
Ventricular Pressure ◽  
Electrophysiological Effects

Vagal nerve stimulation (VNS) has been proposed as a cardioprotective intervention. However, regional ventricular electrophysiological effects of VNS are not well characterized. The purpose of this study was to evaluate effects of right and left VNS on electrophysiological properties of the ventricles and hemodynamic parameters. In Yorkshire pigs, a 56-electrode sock was used for epicardial ( n = 12) activation recovery interval (ARI) recordings and a 64-electrode catheter for endocardial ( n = 9) ARI recordings at baseline and during VNS. Hemodynamic recordings were obtained using a conductance catheter. Right and left VNS decreased heart rate (84 ± 5 to 71 ± 5 beats/min and 84 ± 4 to 73 ± 5 beats/min), left ventricular pressure (89 ± 9 to 77 ± 9 mmHg and 91 ± 9 to 83 ± 9 mmHg), and dP/d tmax (1,660 ± 154 to 1,490 ± 160 mmHg/s and 1,595 ± 155 to 1,416 ± 134 mmHg/s) and prolonged ARI (327 ± 18 to 350 ± 23 ms and 327 ± 16 to 347 ± 21 ms, P < 0.05 vs. baseline for all parameters and P = not significant for right VNS vs. left VNS). No anterior-posterior-lateral regional differences in the prolongation of ARI during right or left VNS were found. However, endocardial ARI prolonged more than epicardial ARI, and apical ARI prolonged more than basal ARI during both right and left VNS. Changes in dP/d tmax showed the strongest correlation with ventricular ARI effects ( R2 = 0.81, P < 0.0001) than either heart rate ( R2 = 0.58, P < 0.01) or left ventricular pressure ( R2 = 0.52, P < 0.05). Therefore, right and left VNS have similar effects on ventricular ARI, in contrast to sympathetic stimulation, which shows regional differences. The decrease in inotropy correlates best with ventricular electrophysiological effects.

scholarly journals Intravenous ivabradine augments the dynamic heart rate response to moderate vagal nerve stimulation in anesthetized rats

2019 ◽  
Vol 317 (3) ◽  
pp. H597-H606 ◽  
Author(s):  
Toru Kawada ◽  
Hiromi Yamamoto ◽  
Kazunori Uemura ◽  
Yohsuke Hayama ◽  
Takuya Nishikawa ◽  
...  
Keyword(s):  
Heart Rate ◽  
Nerve Stimulation ◽  
Heart Rate Response ◽  
Vagal Nerve ◽  
Vagal Nerve Stimulation ◽  
Corner Frequency ◽  
Moderate Intensity ◽  
Bradycardic Agent ◽  
Wistar Kyoto ◽  
White Noise Sequence

Ivabradine is a selective bradycardic agent that reduces the heart rate (HR) by inhibiting the hyperpolarization-activated cyclic nucleotide-gated channels. Although its cardiovascular effect is thought to be minimal except for inducing bradycardia, ivabradine could interact with cardiovascular regulation by the autonomic nervous system. We tested whether ivabradine modifies dynamic characteristics of peripheral vagal HR control. In anesthetized Wistar-Kyoto rats ( n = 7), the right vagal nerve was sectioned and stimulated for 10 min according to a binary white noise sequence with a switching interval of 500 ms. The efferent vagal nerve stimulation (VNS) trials were performed using three different rates (10, 20, and 40 Hz), and were designated as V0–10, V0–20, and V0–40, respectively. The transfer function from the VNS to the HR was estimated before and after the intravenous administration of ivabradine (2 mg/kg). Ivabradine increased the asymptotic dynamic gain in V0–20 [from 3.88 (1.78–5.79) to 6.62 (3.12–8.31) beats·min−1·Hz−1, P < 0.01, median (range)] but not in V0–10 or V0–40. Ivabradine increased the corner frequency in V0–10 [from 0.032 (0.026–0.041) to 0.064 (0.029–0.090) Hz, P < 0.01] and V0–20 [from 0.040 (0.037–0.056) to 0.068 (0.051–0.100) Hz, P < 0.01] but not in V0–40. In conclusion, ivabradine augmented the dynamic HR response to moderate VNS. At high VNS, however, ivabradine did not significantly augment the dynamic HR response, possibly because ivabradine reduced the baseline HR and limited the range for the bradycardic response to high VNS. NEW & NOTEWORTHY Ivabradine is considered to be a pure bradycardic agent that has little effect on cardiovascular function except inducing bradycardia. The present study demonstrated that ivabradine interacts with the dynamic vagal heart rate control in a manner that augments the heart rate response to moderate-intensity efferent vagal nerve stimulation.

scholarly journals Sub‐diaphragmatic vagal nerve stimulation alleviates rodent hypertension associated with gut dysbiosis and reduced serotonergic vagal afferent signaling

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Tao Yang ◽  
Basak Donertas Ayaz ◽  
Alan Araujo ◽  
Elliott W. Dirr ◽  
David M. Baekey ◽  
...  
Keyword(s):  
Nerve Stimulation ◽  
Vagal Nerve ◽  
Vagal Nerve Stimulation ◽  
Gut Dysbiosis ◽  
Vagal Afferent ◽  
Afferent Signaling

scholarly journals Closed-Loop Transcutaneous Auricular Vagal Nerve Stimulation: Current Situation and Future Possibilities

2022 ◽  
Vol 15 ◽  
Author(s):  
Yutian Yu ◽  
Jing Ling ◽  
Lingling Yu ◽  
Pengfei Liu ◽  
Min Jiang
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Closed Loop ◽  
Vagal Nerve ◽  
Vagal Nerve Stimulation ◽  
Afferent Nerve ◽  
Technical Issues ◽  
Vagal Afferent ◽  
Stimulation Current

Closed-loop (CL) transcutaneous auricular vagal nerve stimulation (taVNS) was officially proposed in 2020. This work firstly reviewed two existing CL-taVNS forms: motor-activated auricular vagus nerve stimulation (MAAVNS) and respiratory-gated auricular vagal afferent nerve stimulation (RAVANS), and then proposed three future CL-taVNS systems: electroencephalography (EEG)-gated CL-taVNS, electrocardiography (ECG)-gated CL-taVNS, and subcutaneous humoral signals (SHS)-gated CL-taVNS. We also highlighted the mechanisms, targets, technical issues, and patterns of CL-taVNS. By reviewing, proposing, and highlighting, this work might draw a preliminary blueprint for the development of CL-taVNS.

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