The safety of epidural spinal cord stimulation to restore function after spinal cord injury: post-surgical complications and incidence of cardiovascular events.

STUDY DESIGN: Cohort prospective study. OBJECTIVES: Epidural spinal cord stimulation (eSCS) improves volitional motor and autonomic function after spinal cord injury (SCI). While eSCS has an established history of safety for chronic pain, it remains unclear if eSCS in the SCI population presents the same risk profile. We aimed to assess safety and autonomic monitoring data for the first 14 participants in the E-STAND trial. SETTING: Hennepin County Medical Center, Minneapolis and Minneapolis Veterans Affairs Medical Center, Minnesota, USA. METHODS: Monthly follow-up visits assessed surgical and medical device-related safety outcomes as well as stimulation usage. Beat-by-beat blood pressure (BP) and continuous electrocardiogram data were collected during head-up tilt-table testing with and without eSCS. RESULTS: All participants had a motor-complete SCI. Mean (SD) age and time since injury were 38 (10) and 7 (5) years, respectively. There were no surgical complications but one device malfunction 4 months post implantation. Stimulation was applied for up to 23 h/day, across a broad range of parameters: frequency (18-700 Hz), pulse width (100-600 µs), and amplitude (0.4-17 mA), with no adverse events reported. Tilt-table testing with eSCS demonstrated no significant increases in the incidence of elevated systolic BP or a greater frequency of arrhythmias. CONCLUSIONS: eSCS to restore autonomic and volitional motor function following SCI has a similar safety profile as when used to treat chronic pain, despite the prevalence of significant comorbidities and the wide variety of stimulation parameters tested.

Cardiorespiratory hysteresis during incremental high-altitude ascent-descent quantifies the magnitude of ventilatory acclimatization.

NEW FINDINGS: What is the central question of this study? We assessed the utility of a new metric for quantifying ventilatory acclimatization to high altitude, derived from differential ascent and descent steady-state cardiorespiratory variables (i.e. hysteresis). Furthermore, we aimed to investigate whether the magnitude of cardiorespiratory hysteresis was associated with the development of acute mountain sickness. What is the main finding and its importance? Hysteresis in steady-state cardiorespiratory variables quantifies ventilatory acclimatization to high altitude. The magnitude of cardiorespiratory hysteresis during ascent to and descent from high altitude was significantly related to the development of symptoms of acute mountain sickness. Hysteresis in steady-state chemoreflex drive can provide a simple, non-invasive method of tracking ventilatory acclimatization to high altitude. ABSTRACT: Maintenance of arterial blood gases is achieved through sophisticated regulation of ventilation, mediated by central and peripheral chemoreflexes. Respiratory chemoreflexes are important during exposure to high altitude owing to the competing influence of hypoxia and hypoxic hyperventilation-mediated hypocapnia on steady-state ventilatory drive. Inter-individual variability exists in ventilatory acclimatization to high altitude, potentially affecting the development of acute mountain sickness (AMS). We aimed to quantify ventilatory acclimatization to high altitude by comparing differential ascent and descent values (i.e. hysteresis) in steady-state cardiorespiratory variables. We hypothesized that: (i) the hysteresis area formed by cardiorespiratory variables during ascent and descent would quantify the magnitude of ventilatory acclimatization; and (ii) larger hysteresis areas would be associated with lower AMS symptom scores during ascent. In 25 healthy, acetazolamide-free trekkers ascending to and descending from 5160 m, cardiorespiratory hysteresis was measured in the partial pressure of end-tidal CO2 , peripheral oxygen saturation, minute ventilation, chemoreceptor stimulus index (end-tidal CO2 /peripheral oxygen saturation) and the calculated steady-state chemoreflex drive (SS-CD; minute ventilation/chemoreceptor stimulus index) using portable devices (capnograph, peripheral pulse oximeter and respirometer, respectively). Symptoms of AMS were assessed daily using the Lake Louise questionnaire. We found that: (i) ascent-descent hysteresis was present in all cardiorespiratory variables; (ii) SS-CD is a valid metric for tracking ventilatory acclimatization to high altitude; and (iii) the highest AMS scores during ascent exhibited a significant, moderate and inverse correlation with the magnitude of SS-CD hysteresis (rs  = -0.408, P = 0.043). We propose that ascent-descent hysteresis is a new and feasible way to quantify ventilatory acclimatization in trekkers during high-altitude exposure.

The effects of high altitude ascent on splenic contraction and the diving response during voluntary apnoea.

NEW FINDINGS: What is the central question of this study? What is the relative contribution of a putative tonic splenic contraction to the haematological acclimatization process during high altitude ascent in native lowlanders? What is the main finding and its importance? Spleen volume decreased by -14.3% (-15.2 ml) per 1000 m ascent, with an attenuated apnoea-induced [Hb] increase, attesting to a tonic splenic contraction during high altitude ascent. The [Hb]-enhancing function of splenic contraction may contribute to restoring oxygen content early in the acclimatization process at high altitude. ABSTRACT: Voluntary apnoea causes splenic contraction and reductions in heart rate (HR; bradycardia), and subsequent transient increases in haemoglobin concentration ([Hb]). Ascent to high altitude (HA) induces systemic hypoxia and reductions in oxygen saturation ( SpO2 ), which may cause tonic splenic contraction, which may contribute to haematological acclimatization associated with HA ascent. We measured resting cardiorespiratory variables (HR, SpO2 , [Hb]) and resting splenic volume (via ultrasound) during incremental ascent from 1400 m (day 0) to 3440 m (day 3), 4240 m (day 7) and 5160 m (day 10) in non-acclimatized native lowlanders during assent to HA in the Nepal Himalaya. In addition, apnoea-induced responses in HR, SpO2 and splenic volume were measured before and after two separate voluntary maximal apnoeas (A1-A2) at 1400, 3440 and 4240 m. Resting spleen volume decreased -14.3% (-15.2 ml) per 1000 m with ascent, from 140 ± 41 ml (1400 m) to 108 ± 28 ml (3440 m; P > 0.99), 94 ± 22 ml (4240 m; P = 0.009) and 84 ± 28 ml (5160 m; P = 0.029), with concomitant increases in [Hb] from 125 ± 18.3 g l-1 (1400 m) to 128 ± 10.4 g l-1 (3440 m), 138.8 ± 12.7 g l-1 (4240 m) and 157.5 ± 8 g l-1 (5160 m; P = 0.021). Apnoea-induced splenic contraction was 50 ± 15 ml (1400 m), 44 ± 17 ml (3440 m; P > 0.99) and 26 ± 8 ml (4240 m; P = 0.002), but was not consistently associated with increases in [Hb]. The apnoea-induced bradycardia was more pronounced at 3440 m (A1: P = 0.04; A2: P = 0.094) and at 4240 m (A1: P = 0.037 A2: P = 0.006) compared to values at 1400 m. We conclude that hypoxia-induced splenic contraction at rest (a) may contribute to restoring arterial oxygen content through its [Hb]-enhancing contractile function and (b) eliminates further apnoea-induced [Hb] increases in hypoxia. We suggest that tonic splenic contraction may contribute to haematological acclimatization early in HA ascent in humans.