Fractal variability: an emergent property of complex dissipative systems.

The patterns of variation of physiologic parameters, such as heart and respiratory rate, and their alteration with age and illness have long been under investigation; however, the origin and significance of scale-invariant fractal temporal structures that characterize healthy biologic variability remain unknown. Quite independently, atmospheric and planetary scientists have led breakthroughs in the science of non-equilibrium thermodynamics. In this paper, we aim to provide two novel hypotheses regarding the origin and etiology of both the degree of variability and its fractal properties. In a complex dissipative system, we hypothesize that the degree of variability reflects the adaptability of the system and is proportional to maximum work output possible divided by resting work output. Reductions in maximal work output (and oxygen consumption) or elevation in resting work output (or oxygen consumption) will thus reduce overall degree of variability. Second, we hypothesize that the fractal nature of variability is a self-organizing emergent property of complex dissipative systems, precisely because it enables the system's ability to optimally dissipate energy gradients and maximize entropy production. In physiologic terms, fractal patterns in space (e.g., fractal vasculature) or time (e.g., cardiopulmonary variability) optimize the ability to deliver oxygen and clear carbon dioxide and waste. Examples of falsifiability are discussed, along with the need to further define necessary boundary conditions. Last, as our focus is bedside utility, potential clinical applications of this understanding are briefly discussed. The hypotheses are clinically relevant and have potential widespread scientific relevance.

Concomitant ventilatory and circulatory functions of the diaphragm and abdominal muscles.

Expulsive maneuvers (EMs) caused by simultaneous contraction of diaphragm and abdominal muscles shift substantial quantities of blood from the splanchnic circulation to the extremities. This suggests that the diaphragm assisted by abdominal muscles might accomplish ventilation and circulation simultaneously by repeated EMs. We tested this hypothesis in normal subjects by measuring changes (Δ) in body volume (Vb) by whole body plethysmography simultaneously with changes in trunk volume (Vtr) by optoelectronic plethysmography, which measures the same parameters as whole body plethysmography plus the volume of blood shifts (Vbs) between trunk and extremities: Vbs = ΔVtr-ΔVb. We also measured abdominal pressure, pleural pressure, the arterial pressure wave, and cardiac output (Qc). EMs with abdominal pressure ~100 cmH(2)O for 1 s, followed by 2-s relaxations, repeated over 90 s, produced a "stroke volume" from the splanchnic bed of 0.35 ± 0.07 (SD) liter, an output of 6.84 ± 0.75 l/min compared with a resting Qc of 5.59 ± 1.14 l/min. Refilling during relaxation was complete, and the splanchnic bed did not progressively empty. Diastolic pressure increased by 25 mmHg during each EM. Between EMs, Qc increased to 7.09 ± 1.14 l/min due to increased stroke volume and heart rate. The circulatory function of the diaphragm assisted by simultaneous contractions of abdominal muscles with appropriate pressure and duration at 20 min(-1) can produce a circulatory output as great as resting Qc, as well as ventilation. These combined functions of the diaphragm have potential for cardiopulmonary resuscitation. The abdominal circulatory pump can act as an auxiliary heart.

Towards a definition of life.

This article offers a new definition of life as a "self-contained, self-regulating, self-organizing, self-reproducing, interconnected, open thermodynamic network of component parts which performs work, existing in a complex regime which combines stability and adaptability in the phase transition between order and chaos, as a plant, animal, fungus, or microbe." Open thermodynamic networks, which create and maintain order and are used by all organisms to perform work, import energy from and export entropy into the environment. Intra- and extracellular interconnected networks also confer order. Although life obeys the laws of physics and chemistry, the design of living organisms is not determined by these laws, but by Darwinian selection of the fittest designs. Over a short range of normalized energy consumption, open thermodynamic systems change from deeply ordered to chaotic, and life is found in this phase transition, where a dynamic balance between stability and adaptability allows for homeokinesis. Organisms and cells move within the phase transition with changes in metabolic rate. Seeds, spores and cryo-preserved tissue are well within the ordered regime, while health probably cannot be maintained with displacements into the chaotic regime. Understanding life in these terms may provide new insights into what constitutes health and lead to new theories of disease.

Quantification of trapped gas with CT and 3 He MR imaging in a porcine model of isolated airway obstruction.

PURPOSE: To quantify regional gas trapping in the lung by using computed tomographic (CT)-determined specific gas volume and hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging in a porcine model of airway obstruction. MATERIALS AND METHODS: Four porcine lungs were removed after sacrifice for unrelated cardiac experiments, for which animal studies approval was obtained. Dynamic expiratory thin-section CT and (3)He MR imaging were performed during passive deflation from total lung capacity after obstructions were created with inverted one-way endobronchial exit valves in segmental or lobar bronchi to produce identifiable regions of trapped gas. Changes in specific gas volume were assessed from CT data for defined regions of interest within and outside of obstructed segments and for entire lobes. Helium 3 data were analyzed according to the corresponding regional signal reduction during expiration, compared with the total magnetic moment at each time point. RESULTS: In 4.5 seconds of free collapse, volume decreased by 6% +/- 2 (standard error) and 53% +/- 3, respectively, in trapped-gas lobes and in unobstructed regions (P < .0001). Specific gas volume changed by 6% +/- 2 in areas of trapped gas and decreased by 56% +/- 3 in unobstructed regions, from 3.4 mL/g +/- 0.2 to 1.5 mL/g +/- 0.1 (P < .0001). The (3)He signal intensity decreased by 25% +/- 6 and 71% +/- 3, respectively, in trapped-gas and normal regions (P = .0008). In unobstructed regions, the percentage decreases in specific gas volume and (3)He signal intensity were not statistically different from one another (P = .89). CONCLUSION: The results obtained from the model of gas trapping demonstrate that CT-determined specific gas volume and (3)He MR imaging can help identify and quantify the extent of regional trapped gas in explanted porcine lungs.

The abdominal circulatory pump.

Blood in the splanchnic vasculature can be transferred to the extremities. We quantified such blood shifts in normal subjects by measuring trunk volume by optoelectronic plethysmography, simultaneously with changes in body volume by whole body plethysmography during contractions of the diaphragm and abdominal muscles. Trunk volume changes with blood shifts, but body volume does not so that the blood volume shifted between trunk and extremities (Vbs) is the difference between changes in trunk and body volume. This is so because both trunk and body volume change identically with breathing and gas expansion or compression. During tidal breathing Vbs was 50-75 ml with an ejection fraction of 4-6% and an output of 750-1500 ml/min. Step increases in abdominal pressure resulted in rapid emptying presumably from the liver with a time constant of 0.61+/-0.1SE sec. followed by slower flow from non-hepatic viscera. The filling time constant was 0.57+/-0.09SE sec. Splanchnic emptying shifted up to 650 ml blood. With emptying, the increased hepatic vein flow increases the blood pressure at its entry into the inferior vena cava (IVC) and abolishes the pressure gradient producing flow between the femoral vein and the IVC inducing blood pooling in the legs. The findings are important for exercise because the larger the Vbs the greater the perfusion of locomotor muscles. During asystolic cardiac arrest we calculate that appropriate timing of abdominal compression could produce an output of 6 L/min. so that the abdominal circulatory pump might act as an auxiliary heart.

Airway bypass improves the mechanical properties of explanted emphysematous lungs.

RATIONALE: By creating artificial communications through bronchial walls into the parenchyma of explanted lungs (airway bypass), we expect to decrease the amount of gas trapped and to increase the rate and volume of air expelled during forced expirations. OBJECTIVES: To describe the mechanism by which airway bypass improves the mechanical properties of the emphysematous lung. METHODS: Lung compartments and mechanics were measured before and after airway bypass, which was created by placement of three or four stent-supported fenestrations in 10 emphysematous lungs removed at transplantation surgery. MEASUREMENTS AND MAIN RESULTS: Minimal volume after passive deflation decreased by a mean of 1.54 L (range, 0.7-2.5 L) or 60% (range, 37-86%). Explanted VC increased by 1.30 L or 132% (range, 78-318%). Maximal expiratory flows and volumes increased. Flow resistance decreased. CONCLUSIONS: Because these data show that airway bypass improves the mechanics of breathing in severely emphysematous lungs in vitro, there is now strong empirical support that this procedure can improve ventilatory function in patients by reducing gas trapping and flow resistance.

Chest wall dynamics and muscle recruitment during professional flute playing.

Respiratory parameters and sound were recorded during professional flute playing in order to assess what physiological processes were associated with the control of sound production that results in 'breath support' which in turn is associated with high quality playing. Four standing young professional flautists played flute excerpts with and without breath support. Recordings included optoelectronic plethysmographic measurements of chest wall volume (V(cw)) and its compartments, surface electromyography of the scalene, lateral abdominal, rectus abdominus, parasternal and sternocleidomastoid muscles, mouth pressure, and sound. Flow was estimated from differentiating V(cw) during playing. Results showed that flute support entails antagonistic contraction of non-diaphragmatic inspiratory muscles that tends to hold the rib cage at higher lung volume. This relieves the expiratory muscles from the task of producing the right mouth pressure, especially at the end of the phrases, so they can contribute more to the finer control of mouth pressure modulations required for high quality playing.

A human model of the pathophysiology of chronic obstructive pulmonary disease.

This short review summarizes a series of studies on the effects of expiratory flow limitation (EFL) at approximately 1 L/s during incremental exercise to maximal workload (Wmax) in normal subjects on exercise performance, respiratory muscle dynamics and control, and CO(2) elimination. Each subject served as his or her own control by performing the same protocol without EFL. Additionally, an index of cardiac output was measured before and after imposing EFL while the subjects exercised at Wmax, Wmax was reduced to 65% of control by severe dyspnoea. EFL forced a decrease in the shortening velocity of expiratory muscles, resulting in increased expiratory pressures which accounted for 66% of the variance in Borg scale ratings of dyspnoea. In spite of an increase in the shortening velocity of inspiratory muscles, inspiratory pressures and power increased, because EFL exercise induced hypercapnia, which increased the chemical drive to breathe. This was in part due to an increased alveolar dead space presumably resulting from a reduction in pulmonary capillary blood volume secondary to the high expiratory pressures. A vicious circle was established in which expiratory muscle pressures induced hypercapnia, which resulted in an even stronger expiratory muscle contraction. The imposition of EFL reduced cardiac output by 10% and decreased arterial O(2) saturation, reducing energy supplies to working locomotor and respiratory muscles. This model reproduces the most important clinical features of COPD, and these arise from ventilatory pump dysfunction rather than from the lung. It also leads to hypotheses that can be tested in patients with COPD.