Electrical Stimulation publications

Epidural electrical stimulation (EES) of the spinal cord restores locomotion in animal models of spinal cord injury but is less effective in humans. Here we hypothesized that this interspecies discrepancy is due to interference between EES and proprioceptive information in humans. Computational simulations and preclinical and clinical experiments reveal that EES blocks a significant amount of proprioceptive input in humans, but not in rats. This transient deafferentation prevents modulation of reciprocal inhibitory networks involved in locomotion and reduces or abolishes the conscious perception of leg position. Consequently, continuous EES can only facilitate locomotion within a narrow range of stimulation parameters and is unable to provide meaningful locomotor improvements in humans without rehabilitation. Simulations showed that burst stimulation and spatiotemporal stimulation profiles mitigate the cancellation of proprioceptive information, enabling robust control over motor neuron activity. This demonstrates the importance of stimulation protocols that preserve proprioceptive information to facilitate walking with EES.

Selective vagal nerve stimulation (sVNS) has been demonstrated to lower blood pressure (BP) in rats without causing major side effects. This method might be adapted for the treatment of therapy-resistant hypertension in patients. Converting enzyme inhibitors (CEIs) are among the first drugs that are administered for arterial hypertension and prominently reduce BP primarily by interacting with the renin-angiotensin system of the kidneys. Beyond the reduction of BP, CEI have a positive effect on the survival rate after myocardial infarction; they reduce the rates of stroke and improve the neurohormonal status in heart-failure patients. If sVNS might be introduced as a therapy against resistant hypertension, patients will at least partially stay on their CEI medication. It is therefore the aim of this study to investigate the influence of the CEI enalapril on the haemodynamic and respiratory effects of sVNS. In 10 male Wistar rats, a polyimide-based multichannel-cuff-electrode was placed around the vagal nerve bundle to selectively stimulate the aortic depressor nerve fibres. Stimulation parameters were adapted to the thresholds of the individual animals and included repetition frequencies between 30 and 50 Hz, amplitudes of 0.5 to 1.5 mA and pulse widths between 0.4 ms and 1.0 ms. BP responses were detected with a microtip transducer in the left carotid artery, and electrocardiography was recorded with subcutaneous electrodes. After intravenous administration of enalapril (2 mg/kg bodyweight), the animals' mean arterial blood pressures (MAPs) decreased significantly, while the heart rates (HRs) were not significantly influenced. The effects of sVNS on BP and HR were attenuated by enalapril but were still present. We conclude that sVNS can lower the MAP during enalapril treatment without relevant side effects.

Selective vagal nerve stimulation (sVNS) has been shown to reduce blood pressure without major side effects in rats. This technology might be the key to non-medical antihypertensive treatment in patients with therapy-resistant hypertension. β-blockers are the first-line therapy of hypertension and have in general a bradycardic effect. As VNS itself can also promote bradycardia, it was the aim of this study to investigate the influence of the β1-selective blocker Metoprolol on the effect of sVNS especially with respect to the heart rate. In 10 male Wistar rats, a polyimide multichannel-cuff electrode was placed around the vagal nerve bundle to selectively stimulate the aortic depressor nerve fibers. The stimulation parameters were adapted to the thresholds of individual animals and were in the following ranges: frequency 30-50 Hz, amplitude 0.3-1.8 mA and pulse width 0.3-1.3 ms. Blood pressure responses were detected with a microtip transducer in the carotid artery, and electrocardiography was recorded with s.c. chest electrodes. After IV administration of Metoprolol (2 mg kg(-1) body weight), the animals' mean arterial blood pressure (MAP) and heart rate (HR) decreased significantly. Although the selective electrical stimulation of the baroreceptive fibers reduced MAP and HR, both effects were significantly alleviated by Metoprolol. As a side effect, the rate of stimulation-induced apnea significantly increased after Metoprolol administration. sVNS can lower the MAP under Metoprolol without causing severe bradycardia.