Optimizing Our Patients’ Entropy Production as Therapy? Hypotheses Originating from the Physics of Physiology

Understanding how nature drives entropy production offers novel insights regarding patient care. Whilst energy is always preserved and energy gradients irreversibly dissipate (thus producing entropy), increasing evidence suggests that they do so in the most optimal means possible. For living complex non-equilibrium systems to create a healthy internal emergent order, they must continuously produce entropy over time. The Maximum Entropy Production Principle (MEPP) highlights nature’s drive for non-equilibrium systems to augment their entropy production if possible. This physical drive is hypothesized to be responsible for the spontaneous formation of fractal structures in space (e.g., multi-scale self-similar tree-like vascular structures that optimize delivery to and clearance from an organ system) and time (e.g., complex heart and respiratory rate variability); both are ubiquitous and essential for physiology and health. Second, human entropy production, measured by heat production divided by temperature, is hypothesized to relate to both metabolism and consciousness, dissipating oxidative energy gradients and reducing information into meaning and memory, respectively. Third, both MEPP and natural selection are hypothesized to drive enhanced functioning and adaptability, selecting states with robust basilar entropy production, as well as the capacity to enhance entropy production in response to exercise, heat stress, and illness. Finally, a targeted focus on optimizing our patients’ entropy production has the potential to improve health and clinical outcomes. With the implications of developing a novel understanding of health, illness, and treatment strategies, further exploration of this uncharted ground will offer value.

Influence of nasal CPAP on cardiorespiratory control in healthy neonate

The present study aimed to further unravel the effects of nasal continuous positive airway pressure (nCPAP) on the cardiovascular and respiratory systems in the neonatal period. Six-hour polysomnographic recordings were first performed in seven healthy newborn lambs, aged 2–3 days, without and with nCPAP application at 6 cmH2O (nCPAP-6), in randomized order. The effects of nCPAP-6 on heart rate variability, respiratory rate variability, and cardiorespiratory interrelations were analyzed using a semiautomatic signal processing approach applied to ECG and respiration recordings. Thereafter, a cardiorespiratory mathematical model was adapted to the experimental conditions to gain further physiological interpretation and to simulate higher nCPAP levels (8 and 10 cmH2O). Results from the signal processing approach suggest that nCPAP-6 applied in newborns with healthy lungs: 1) increases heart rate and decreases the time and frequency domain indices of heart rate variability, especially those representing parasympathetic activity, while increasing the complexity of the RR-interval time series; 2) prolongs the respiratory cycle and expiration duration and decreases respiratory rate variability; and 3) slightly impairs cardiorespiratory interrelations. Model-based analysis revealed that nCPAP-6 increases the heart rate and decreases respiratory sinus arrhythmia amplitude, in association with a reduced parasympathetic efferent activity. These results were accentuated when simulating an increased CPAP level. Overall, our results provide a further understanding of the effects of nCPAP in neonates, in the absence of lung disease. NEW & NOTEWORTHY Application of nasal continuous positive airway pressure (CPAP) at 6 cmH2O, a level very frequently used in newborns, alters heart and respiratory rate variability, as well as cardiorespiratory interrelations in a full-term newborn model without lung disease. Moreover, whereas nasal CPAP at 6 cmH2O decreases parasympathetic efferent activity, there is no change in sympathetic efferent activity.

Influence of vigilance state on physiological consequences of seizures and seizure-induced death in mice

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. SUDEP occurs more commonly during nighttime sleep. The details of why SUDEP occurs at night are not well understood. Understanding why SUDEP occurs at night during sleep might help to better understand why SUDEP occurs at all and hasten development of preventive strategies. Here we aimed to understand circumstances causing seizures that occur during sleep to result in death. Groups of 12 adult male mice were instrumented for EEG, EMG, and EKG recording and subjected to seizure induction via maximal electroshock (MES) during wakefulness, nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Seizure inductions were performed with concomitant EEG, EMG, and EKG recording and breathing assessment via whole body plethysmography. Seizures induced via MES during sleep were associated with more profound respiratory suppression and were more likely to result in death. Despite REM sleep being a time when seizures do not typically occur spontaneously, when seizures were forced to occur during REM sleep, they were invariably fatal in this model. An examination of baseline breathing revealed that mice that died following a seizure had increased baseline respiratory rate variability compared with those that did not die. These data demonstrate that sleep, especially REM sleep, can be a dangerous time for a seizure to occur. These data also demonstrate that there may be baseline respiratory abnormalities that can predict which individuals have higher risk for seizure-induced death.

Expiratory activation of abdominal muscle is associated with improved respiratory stability and an increase in minute ventilation in REM epochs of adult rats

Breathing is more vulnerable to apneas and irregular breathing patterns during rapid eye movement (REM) sleep in both humans and rodents. We previously reported that robust and recurrent recruitment of expiratory abdominal (ABD) muscle activity is present in rats during REM epochs despite ongoing REM-induced muscle atonia in skeletal musculature. To develop a further understanding of the characteristics of ABD recruitment during REM epochs and their relationship with breathing patterns and irregularities, we sought to compare REM epochs that displayed ABD muscle recruitment with those that did not, within the same rats. Specifically, we investigated respiratory characteristics that preceded and followed recruitment. We hypothesized that ABD muscle recruitment would be likely to occur following respiratory irregularities and would subsequently contribute to respiratory stability and the maintenance of good ventilation following recruitment. Our data demonstrate that epochs of REM sleep containing ABD recruitments (REMABD+) were characterized by increased respiratory rate variability and increased presence of spontaneous brief central apneas. Within these epochs, respiratory events that displayed ABD muscle activation were preceded by periods of increased respiratory rate variability. Onset of ABD muscle activity increased tidal volume, amplitude of diaphragmatic contractions, and minute ventilation compared with the periods preceding ABD muscle activation. These results show that expiratory muscle activity is more likely recruited when respiration is irregular and its recruitment is subsequently associated with an increase in minute ventilation and a more regular respiratory rhythm.