The ins and outs of breath holding: simple demonstrations of complex respiratory physiology

The physiology of breath holding is complex, and voluntary breath-hold duration is affected by many factors, including practice, psychology, respiratory chemoreflexes, and lung stretch. In this activity, we outline a number of simple laboratory activities or classroom demonstrations that illustrate the complexity of the integrative physiology behind breath-hold duration. These activities require minimal equipment and are easily adapted to small-group demonstrations or a larger-group inquiry format where students can design a protocol and collect and analyze data from their classmates. Specifically, breath-hold duration is measured during a number of maneuvers, including after end expiration, end inspiration, voluntary prior hyperventilation, and inspired hyperoxia. Further activities illustrate the potential contribution of chemoreflexes through rebreathing and repeated rebreathing after a maximum breath hold. The outcome measures resulting from each intervention are easily visualized and plotted and can comprise a comprehensive data set to illustrate and discuss complex and integrated cardiorespiratory physiology.

Impairment of autophagy decreases ventilator-induced lung injury by blockade of the NF-κB pathway

Excessive lung stretch triggers lung inflammation by activation of the NF-κB pathway. This route can be modulated by autophagy, an intracellular proteolytic system. Our objective was to study the impact of the absence of autophagy in a model of ventilator-induced lung injury. Mice lacking Autophagin-1/ATG4B ( Atg4b −/−), a critical protease in the autophagic pathway, and their wild-type counterparts were studied in baseline conditions and after mechanical ventilation. Lung injury, markers of autophagy, and activation of the inflammatory response were evaluated after ventilation. Mechanical ventilation increased autophagy and induced lung injury in wild-type mice. Atg4b −/− animals showed a decreased lung injury after ventilation, with less neutrophilic infiltration than their wild-type counterparts. As expected, autophagy was absent in mutant animals, resulting in the accumulation of p62 and ubiquitinated proteins. Activation of the canonical NF-κB pathway was present in ventilated wild-type, but not Atg4b-deficient, animals. Moreover, these mutant mice showed an accumulation of ubiquitinated IκB. High-pressure ventilation partially restored the autophagic response in Atg4b −/− mice and abolished the differences between genotypes. In conclusion, impairment of autophagy results in an ameliorated inflammatory response to mechanical ventilation and decreases lung injury. The accumulation of ubiquitinated IκB may be responsible for this effect.

Hypercapnia and Acidosis in Sepsis

Acute respiratory distress syndrome is a devastating disease that causes substantial morbidity and mortality. Mechanical ventilation can worsen lung injury, whereas ventilatory strategies that reduce lung stretch, resulting in a "permissive" hypercapnic acidosis (HCA), improve outcome. HCA directly reduces nonsepsis-induced lung injury in preclinical models and, therefore, has therapeutic potential in these patients. These beneficial effects are mediated via inhibition of the host immune response, particularly cytokine signaling, phagocyte function, and the adaptive immune response. Of concern, these immunosuppressive effects of HCA may hinder the host response to microbial infection. Recent studies suggest that HCA is protective in the earlier phases of bacterial pneumonia-induced sepsis but may worsen injury in the setting of prolonged lung sepsis. In contrast, HCA is protective in preclinical models of early and prolonged systemic sepsis. Buffering of the HCA is not beneficial and may worsen pneumonia-induced injury.

Respiratory control during postural changes in anesthetized cats

The effect of postural changes on respiration was investigated in ten anesthetized cats by applying body tilting during the inspiration phase while recording respiratory patterns, as given by the diaphragmatic EMG, together with either the lung volume or the air flow temperature. The results show that the head-up tilting during inspiration reduced the period of the inspiratory phase and increased the end-inspiratory lung volume. On the other hand, the head-down tilting during inspiration had opposite effects. These effects disappeared after transection of the vagus nerve. However, labyrinthectomy did not diminish the effects, probably because of functional suppression of the vestibular system due to the anesthetic. When correlating the activity of 15 vagal afferents presumably originating from the slowly adapting lung stretch receptors with lung volume changes during tilting, their maximum firing rate (87 ± 15.7 Hz) was increased with an increase in the lung inflation volume and was attained earlier on head-up tilting and it was reduced with a decrease of the lung volume on head-down tilting (63 ± 16.6 Hz) as compared with the value in the horizontal position (74 ± 14.2 Hz). These results suggest that respiratory modulation during head-up or head-down tilting is consistent with the Hering-Breuer reflexes and minimizes the externally induced lung volume changes during postural changes.