Transcutaneous vagal nerve stimulation during lower body negative pressure.

BACKGROUND: Para-sympathetic vagal activation has profound influence on heart rate and other cardiovascular parameters. We tested the hypothesis that transcutaneous Vagal Nerve Stimulation (tVNS) through the auricular branch of the vagus nerve would attenuate the normal sympathetic response to central blood volume reduction by lower body negative pressure (LBNP). METHOD: 10 healthy volunteers (6 female; age 21 ± 2 years; weight 62 ± 13 kg; height 167 ± 12 cm) were included in this cross-over design trial. After 15 min rest in supine position, subjects underwent three 15-min periods of 30 mmHg LBNP intervention with and without cyclic tVNS stimulation. Continuous cardiovascular parameters (Nexfin) were recorded. RESULTS: Overall tVNS did not convincingly attenuate sympathetic response to central hypovolemia. Deactivation of the tVNS during LBNP resulted in increased MAP at 2.3 ± 0.5 mmHg (P < 0.001). Comparing the cyclic actual active stimulation periods to periods with pause during tVNS intervention showed a decrease in HR by 72.9 ± 11.2 to 70.2 ± 11.6 bpm (mean ± SD; P < 0.05), and concomitant increases in SV (86.0 ± 12.1 to 87.2 ± 12.6 mL; P < 0.05), MAP (82.9 ± 6.3 to 84.0 ± 6.2 mmHg; P < 0.05) and TPR (1116.0 ± 111.1 to 1153 ± 104.8 dyn*s/cm5; P < 0.05). CONCLUSION: tVNS in 30 s cycles during LBNP can selectively attenuate HR, prompting a compensatory augmented sympathetic response. It would appear the method used in this study at least, has an isolated cardiac inhibitory effect probably mediated by augmented vagal activity on the sinoatrial or atrio-ventricular node, possibly in combination with reduced activity in the sympathetic cardiac nerve.

Gravitational effects on intraocular pressure and ocular perfusion pressure.

Changes in the gravitational vector by postural changes or weightlessness induce fluid shifts, impacting ocular hemodynamics and regional pressures. This investigation explores the impact of changes in the direction of the gravitational vector on intraocular pressure (IOP), mean arterial pressure at eye level (MAPeye), and ocular perfusion pressure (OPP), which is critical for ocular health. Thirteen subjects underwent 360° of tilt (including both prone and supine positions) at 15° increments. At each angle, steady-state IOP and MAPeye were measured, and OPP calculated as MAPeye - IOP. Experimental data were also compared to a six-compartment lumped-parameter model of the eye. Mean IOP, MAPeye, and OPP significantly increased from 0° supine to 90° head-down tilt (HDT) by 20.7 ± 1.7 mmHg (P < 0.001), 38.5 ± 4.1 mmHg (P < 0.001), and 17.4 ± 3.2 mmHg (P < 0.001), respectively. Head-up tilt (HUT) significantly decreased OPP by 16.5 ± 2.5 mmHg (P < 0.001). IOP was significantly higher in prone versus supine position for much of the tilt range. Our study indicates that OPP is highly gravitationally dependent. Specifically, data show that MAPeye is more gravitationally dependent than IOP, thus causing OPP to increase during HDT and to decrease during HUT. In addition, IOP was elevated in prone position compared with supine position due to the additional hydrostatic column between the base of the rostral globe to the mid-coronal plane, supporting the notion that hydrostatic forces play an important role in ocular hemodynamics. Changes in OPP as a function of changes in gravitational stress and/or weightlessness may play a role in the pathogenesis of spaceflight-associated neuro-ocular syndrome.NEW & NOTEWORTHY Maintaining appropriate ocular perfusion pressure (OPP) is critical for ocular health. We measured the relative changes in intraocular and mean arterial pressures during 360° tilt and calculated OPP, which was elevated during head-down tilt and decreased during head-up tilt. Experimental data are also explained by our computational model. We demonstrate that OPP is more gravitationally dependent than previously recognized and may be a factor in the overall patho-etiology behind the weightlessness-induced spaceflight-associated neuro-ocular syndrome.

MADVent: A low-cost ventilator for patients with COVID-19.

The COVID-19 pandemic has produced critical shortages of ventilators worldwide. There is an unmet need for rapidly deployable, emergency-use ventilators with sufficient functionality to manage COVID-19 patients with severe acute respiratory distress syndrome. Here, we show the development and validation of a simple, portable and low-cost ventilator that may be rapidly manufactured with minimal susceptibility to supply chain disruptions. This single-mode continuous, mandatory, closed-loop, pressure-controlled, time-terminated emergency ventilator offers robust safety and functionality absent in existing solutions to the ventilator shortage. Validated using certified test lungs over a wide range of compliances, pressures, volumes and resistances to meet U.S. Food and Drug Administration standards of safety and efficacy, an Emergency Use Authorization is in review for this system. This emergency ventilator could eliminate controversial ventilator rationing or splitting to serve multiple patients. All design and validation information is provided to facilitate ventilator production even in resource-limited settings.

Mobile Lower Body Negative Pressure Suit as an Integrative Countermeasure for Spaceflight.

BACKGROUND: Persistent headward fluid shift and mechanical unloading cause neuro-ocular, cardiovascular, and musculoskeletal deconditioning during long-term spaceflight. Lower body negative pressure (LBNP) reintroduces footward fluid shift and mechanical loading.METHODS: We designed, built, and tested a wearable, mobile, and flexible LBNP device (GravitySuit) consisting of pressurized trousers with built-in shoes to support ground reaction forces (GRF) and a thoracic vest to distribute load to the entire axial length of the body. In eight healthy subjects we recorded GRF under the feet and over the shoulders (Tekscan) while assessing cardiovascular response (Nexfin) and footward fluid shift from internal jugular venous cross-sectional area (IJVa) using ultrasound (Terason).RESULTS: Relative to normal bodyweight (BW) when standing upright, increments of 10 mmHg LBNP from 0 to 40 mmHg while supine induced axial loading corresponding to 0%, 13 ± 3%, 41 ± 5%, 75 ± 11%, and 125 ± 22% BW, respectively. Furthermore, LBNP reduced IJVa from 1.12 ± 0.3 cm² to 0.67 ± 0.2, 0.50 ± 0.1, 0.35 ± 0.1, and 0.31 ± 0.1 cm², respectively. LBNP of 30 and 40 mmHg reduced cardiac stroke volume and increased heart rate while cardiac output and mean arterial pressure were unaffected. During 2 h of supine rest at 20 mmHg LBNP, temperature and humidity inside the suit were unchanged (23 ± 1°C; 47 ± 3%, respectively).DISCUSSION: The flexible GravitySuit at 20 mmHg LBNP comfortably induced mechanical loading and desired fluid displacement while maintaining the mobility of hips and knee joints. The GravitySuit may provide a feasible method to apply low-level, long-term LBNP without interfering with daily activity during spaceflight to provide an integrative countermeasure.Petersen LG, Hargens A, Bird EM, Ashari N, Saalfeld J, Petersen JCG. Mobile lower body negative pressure suit as an integrative countermeasure for spaceflight. Aerosp Med Hum Perform. 2019; 90(12):993-999.

Lower body negative pressure to safely reduce intracranial pressure.

KEY POINTS: During long-term missions, some astronauts experience structural and functional changes of the eyes and brain which resemble signs/symptoms experienced by patients with intracranial hypertension. Weightlessness prevents the normal cerebral volume and pressure 'unloading' associated with upright postures on Earth, which may be part of the cerebral and ocular pathophysiology. By placing the lower body in a negative pressure device (LBNP) that pulls fluid away from cranial compartments, we simulated effects of gravity and significantly lowered pressure within the brain parenchyma and ventricle compartments. Application of incremental LBNP demonstrated a non-linear dose-response curve, suggesting 20 mmHg LBNP as the optimal level for reducing pressure in the brain without impairing cerebral perfusion pressure. This non-invasive method of reducing pressure in the brain holds potential as a countermeasure in space as well as having treatment potential for patients on Earth with traumatic brain injury or other pathology leading to intracranial hypertension. ABSTRACT: Patients with elevated intracranial pressure (ICP) exhibit neuro-ocular symptoms including headache, papilloedema and loss of vision. Some of these symptoms are also present in astronauts during and after prolonged space-flight where lack of gravitational stress prevents daily lowering of ICP associated with upright posture. Lower body negative pressure (LBNP) simulates the effects of gravity by displacing fluid caudally and we hypothesized that LBNP would lower ICP without compromising cerebral perfusion. Ten cerebrally intact volunteers were included: six ambulatory neurosurgical patients with parenchymal ICP-sensors and four former cancer patients with Ommaya-reservoirs to the frontal horn of a lateral ventricle. We applied LBNP while recording ICP and blood pressure while supine, and during simulated intracranial hypertension by 15° head-down tilt. LBNP from 0 to 50 mmHg at increments of 10 mmHg lowered ICP in a non-linear dose-dependent fashion; when supine (n = 10), ICP was decreased from 15 ± 2 mmHg to 14 ± 4, 12 ± 5, 11 ± 4, 10 ± 3 and 9 ± 4 mmHg, respectively (P < 0.0001). Cerebral perfusion pressure (CPP), calculated as mean arterial blood pressure at midbrain level minus ICP, was unchanged (from 70 ± 12 mmHg to 67 ± 9, 69 ± 10, 70 ± 12, 72 ± 13 and 74 ± 15 mmHg; P = 0.02). A 15° head-down tilt (n = 6) increased ICP to 26 ± 4 mmHg, while application of LBNP lowered ICP (to 21 ± 4, 20 ± 4, 18 ± 4, 17 ± 4 and 17 ± 4 mmHg; P < 0.0001) and increased CPP (P < 0.01). An LBNP of 20 mmHg may be the optimal level to lower ICP without impairing CPP to counteract spaceflight-associated neuro-ocular syndrome in astronauts. Furthermore, LBNP holds clinical potential as a safe, non-invasive method for lowering ICP and improving CPP for patients with pathologically elevated ICP on Earth.

Mechanisms of increase in cardiac output during acute weightlessness in humans.

Based on previous water immersion results, we tested the hypothesis that the acute 0-G-induced increase in cardiac output (CO) is primarily caused by redistribution of blood from the vasculature above the legs to the cardiopulmonary circulation. In seated subjects (n = 8), 20 s of 0 G induced by parabolic flight increased CO by 1.7 ± 0.4 l/min (P < 0.001). This increase was diminished to 0.8 ± 0.4 l/min (P = 0.028), when venous return from the legs was prevented by bilateral venous thigh-cuff inflation (CI) of 60 mmHg. Because the increase in stroke volume during 0 G was unaffected by CI, the lesser increase in CO during 0 G + CI was entirely caused by a lower heart rate (HR). Thus blood from vascular beds above the legs in seated subjects can alone account for some 50% of the increase in CO during acute 0 G. The remaining increase in CO is caused by a higher HR, of which the origin of blood is unresolved. In supine subjects, CO increased from 7.1 ± 0.7 to 7.9 ± 0.8 l/min (P = 0.037) when entering 0 G, which was solely caused by an increase in HR, because stroke volume was unaffected. In conclusion, blood originating from vascular beds above the legs can alone account for one-half of the increase in CO during acute 0 G in seated humans. A Bainbridge-like reflex could be the mechanism for the HR-induced increase in CO during 0 G in particular in supine subjects.