Cellular and isolated vessel experiments have shown that pulsatile and laminar shear stress to the endothelium produces significant release of mediators into the circulation. Periodic acceleration (pG_z) applied to the whole body in the direction of the spinal axis adds pulses to the circulation, thereby increasing pulsatile and shear stress to the endothelium that should also cause release of mediators into the circulation. The purpose of this study was to determine whether addition of pulses to the circulation through pG_zwould be sufficient to increase shear stress in whole animals and to acutely release mediators and how such a physical maneuver might affect coagulation factors. Randomized control experiments were performed on anesthetized, supine piglets. The treatment group (pG_z) ( n = 12) received pG_zwith a motion platform that moved them repetitively head to foot at ±0.4 g at 180 cpm for 60 min. The control group ( n = 6) was secured to the platform but remained on conventional ventilation throughout the 4-h protocol. Compared with control animals and baseline, pulsatile stress produced significant increases of serum nitrite, prostacyclin, PGE₂, and tissue plasminogen activator antigen and activity, as well as D-dimer. There were no significant changes in epinephrine, norepinephrine, cortisol, and coagulation factors between groups or from baseline values. Pulsatile and laminar shear stress to the endothelium induced by pG_zsafely produces increases of vasoactive and fibrinolytic activity. pG_zhas potential to achieve mediator-related benefits from the actions of nitric oxide and prostaglandins.

Diabetes has reached worldwide epidemic proportions, and threatens to be a significant economic burden to both patients and healthcare systems, and an important driver of cardiovascular mortality and morbidity. Improvement in lifestyle interventions (which includes increase in physical activity via exercise) can reduce diabetes and cardiovascular disease mortality and morbidity. Encouraging a population to increase physical activity and exercise is not a simple feat particularly in individuals with co-morbidities (obesity, heart disease, stroke, peripheral vascular disease, and those with cognitive and physical limitations). Translation of the physiological benefits of exercise within that vulnerable population would be an important step for improving physical activity goals and a stopgap measure to exercise. In large part many of the beneficial effects of exercise are due to the introduction of pulsatile shear stress (PSS) to the vascular endothelium. PSS is a well-known stimulus for endothelial homeostasis, and induction of a myriad of pathways which include vasoreactivity, paracrine/endocrine function, fibrinolysis, inflammation, barrier function, and vessel growth and formation. The endothelial cell mediates the balance between vasoconstriction and relaxation via the major vasodilator endothelial derived nitric oxide (eNO). eNO is critical for vasorelaxation, increasing blood flow, and an important signaling molecule that downregulates the inflammatory cascade. A salient feature of diabetes, is endothelial dysfunction which is characterized by a reduction of the bioavailability of vasodilators, particularly nitric oxide (NO). Cellular derangements in diabetes are also related to dysregulation in Ca²⁺ handling with increased intracellular Ca²⁺overload, and oxidative stress. PSS increases eNO bioavailability, reduces inflammatory phenotype, decreases intracellular Ca²⁺ overload, and increases antioxidant capacity. This narrative review and perspective will outline four methods to non-invasively increase PSS; Exercise (the prototype for increasing PSS), Enhanced External Counterpulsation (EECP), Whole Body Vibration (WBV), Passive Simulated Jogging and its predicate device Whole Body Periodic Acceleration, and will discuss current knowledge on their use in diabetes.

The hemodynamic effects of periodic acceleration (pG_z), induced in the spinal axis with noninvasive motion ventilation (NIMV), were studied in a piglet model of pulmonary hypertension associated with meconium aspiration. Animals ( n = 12) were anesthetized, paralyzed, intubated, and supported by conventional mechanical ventilation (CMV). Thirty minutes after tracheal instillation of meconium solution (6 ml/kg), either CMV ( n = 6) was continued or NIMV ( n = 6) was initiated. Changes in systemic and pulmonary hemodynamics and arterial blood gases were tracked for 2 h after aspiration. Thermodilution, cardiac output, and heart rate were not significantly different after meconium aspiration in the pG_zgroup relative to the CMV controls. Aortic pressure and systemic vascular resistance were significantly lower (∼30%) after meconium aspiration in NIMV animals relative to CMV animals. Pulmonary arterial pressure and pulmonary vascular resistance were also significantly lower, by 100%, after aspiration of meconium in the NIMV animals compared with the CMV controls. Meconium aspiration significantly decreased total respiratory compliance by ∼50% and increased total respiratory resistance by ∼100% in both CMV and NIMV animals, but such alterations did not differ between the two groups. Both CMV and NIMV satisfactorily supported ventilation in these paralyzed animals. In conclusion, NIMV through pG_zin the spinal axis decreased systemic and pulmonary vascular resistance in piglets after meconium aspiration.

A motion platform was developed that oscillates an animal in a foot-to-head direction ( z-plane). The platform varies the frequency and intensity of acceleration, imparting periodic sinusoidal inertial forces (pG_z) to the body. The aim of the study was to characterize ventilation produced by the noninvasive motion ventilator (NIMV) in animals with healthy and diseased lungs. Incremental increases in pG_z(acceleration) with the frequency held constant ( f = 4 Hz) produced almost linear increases in minute ventilation (V˙e). Frequencies of 2–4 Hz produced the greatest V˙eand tidal volume (Vt) for any given acceleration between ±0.2 and ±0.8 G. Increasing the force due to acceleration produced proportional increases in both transpulmonary and transdiaphragmatic pressures. Increasing transpulmonary pressure by increasing pG_zproduced linear increases in Vt, similar to spontaneous breathing. NIMV reversed deliberately induced hypoventilation and normalized the changes in arterial blood gases induced by meconium aspiration. In conclusion, a novel motion platform is described that imparts periodic sinusoidal acceleration forces at moderate frequencies (4 Hz) to the whole body in the z-plane. These forces, when properly adjusted, are capable of highly effective ventilation of normal and diseased lungs. Such noninvasive ventilation is accomplished at airway pressures equivalent to atmospheric or continuous positive airway pressure, with acceleration forces less than ±1 G_z.