|
Pathophysiological Studies in Volunteers
Vassilakopoulos and colleagues studied the phenomenon of cytokine release during strenuous resistive breathing. Anesthetized, tracheostomized, spontaneously breathing rats were subjected to 1, 3, or 6 hours of inspiratory resistive loading, corresponding to 45 to 50% of the maximum inspiratory pressure. The diaphragm and the gastrocnemius muscles were excised at the end of the loading period, and mRNA expression for cytokines was studied. Unloaded sham-operated rats breathing spontaneously were used as control animals. mRNA for interleukin 6 (IL-6) and IL-1ß and, to a lesser extent, tumor necrosis factor ß, IL-10, IFN- , and IL-4 were significantly increased in a time-dependent fashion in the diaphragm, but not in the gastrocnemius muscle of loaded animals or in the diaphragm of control animals. The levels of IL-6 and IL-1ß protein in the diaphragm of loaded animals also were increased. Immune staining revealed IL-6 protein localized in diaphragmatic muscle fibers. The authors concluded that increased ventilatory muscle activity during resistive loading induces differential elevation of proinflammatory and antiinflammatory cytokine expression in the ventilatory muscles.
When mechanical ventilation is delivered under normocapnic conditions, its cessation is accompanied by central apneas. To determine whether increases in tidal volume or increases in respiratory rate are responsible for the change in respiratory rhythm, Rice and coworkers
increased tidal volume (to 135 to 220% of eucapnic volume) and respiratory rate (1 or 3 breaths above eucapnic rate) in 7 healthy subjects during NREM sleep. During controlled ventilation, an increase in tidal volume (by 65% or more of eucapnic volume) plus an increase in rate (of 1 breath per minute) eliminated transdiaphragmatic pressure. Cessation of controlled ventilation was accompanied by prolongation of expiratory time (by 2 to 4 times the control value); the increases in expiratory time were proportional to the increases in tidal volume during controlled ventilation but were independent of further increases in ventilator rate. During and after assist-control ventilation, increases in tidal volume (to 135 to 220% of eucapnic volume) were accompanied by decreases in transdiaphragmatic pressure in proportion to the increase in tidal volume; each ventilator inflation was actively triggered and the increase in expiratory time on cessation of mechanical ventilation was less than 20% of that seen after cessation of controlled ventilation. The authors conclude that both increases in ventilator rate and delivered volume during mechanical ventilation cause inhibition of respiratory motor output via nonchemical mechanisms (neuromechanical effects of repeated and augmented lung inflation), and that the resetting of respiratory rhythm is greater with additional increase in ventilator rate than with increase in delivered volume alone.
In 11 healthy men performing cycle exercise, Fukuoka and coworkers
investigated the contributions of hypoxic ventilatory responsiveness, hypercapnic ventilatory responsiveness, and other factors in the stimulus responsible for exercise hyperpnea during hypoxia. Exercise was performed at an oxygen concentration of 12% at three constant work rates (40%, 60%, and 80% of a subject's ventilatory threshold at hypoxia). Compared with normoxia, hypoxic ventilatory responsiveness was increased during hypoxia, and then increased in proportion with the increase in work rate. In contrast, hypercapnic ventilatory responsiveness was unaffected by the difference in work rate at hypoxia, but it did exceed the level of responsiveness during normoxia. The decrease in the half-time of hypoxic ventilation became significant with an increase in work rates and was lower than at normoxia. Hypoxic ventilatory responsiveness accounted for 63% of the variance of hypoxic ventilatory dynamics at the onset of exercise and hypercapnic ventilatory responsiveness accounted for 9%. On-kinetics and off-kinetics of oxygen uptake were slower under hypoxic conditions than under normoxic conditions, but were not altered by changing work rates during hypoxia. The authors conclude that the faster hypoxic ventilatory dynamics at the onset of exercise can be attributed mostly to augmentation of hypoxic ventilatory responsiveness with increases in work rates rather than to hypercapnic ventilatory responsiveness.
The ventilatory response to hypoxia in the presence of hypocapnia is controversial. Corne and coworkers
used volume-cycled ventilation to measure the ventilatory response to hypoxia during eucapnia and hypocapnia. The response of respiratory muscle pressure to hypoxia (expressed as cm H2O per percentage oxygen saturation) was 0.53 at eucapnia, 0.26 at end-tidal PCO2 of 6 mm Hg below eucapnia, and 0.003 at PCO2 of 12 mm Hg below eucapnia. Similar reductions were evident for respiratory rate (expressed as breaths per minute per percentage oxygen saturation): 0.17 at eucapnia, 0.11 at PCO2 of 6 mm Hg below eucapnia, and 0.01 at PCO2 of 12 mm Hg below eucapnia. The responses of respiratory muscle pressure and respiratory rate at a PCO2 of 12 mm Hg below eucapnia were not significantly different from zero. The authors conclude that regardless of the strength of the hypoxic ventilatory response at eucapnia, the responses are lost when PCO2 is reduced (in a stable manner) by 6 to 12 mm Hg below eucapnia.
Citations 1-4 of 4 total displayed.
Differential Cytokine Gene Expression in the Diaphragm in Response to Strenuous Resistive Breathing
- Theodoros Vassilakopoulos, Maziar Divangahi, George Rallis, Osama Kishta, Basil Petrof, Alain Comtois, and Sabah N. A. Hussain
Am. J. Respir. Crit. Care Med. 170: 154 -161. First published online as doi:10.1164/rccm.200308-1071OC
[Abstract]
[Full text]
Chemoreflex Drive and the Dynamics of Ventilation and Gas Exchange during Exercise at Hypoxia
- Yoshiyuki Fukuoka, Masako Endo, Yasuharu Oishi, and Haruo Ikegami
Am. J. Respir. Crit. Care Med. 168: 1115-1122.
[Abstract]
[Full text]
Controlled versus Assisted Mechanical Ventilation Effects on Respiratory Motor Output in Sleeping Humans
- Anthony J. Rice, Hideaki C. Nakayama, Hans C. Haverkamp, David F. Pegelow, James B. Skatrud, and Jerome A. Dempsey
Am. J. Respir. Crit. Care Med. 168: 92 -101. First published online as doi:10.1164/rccm.200207-675OC
[Abstract]
[Full text]
Hypoxic Respiratory Response during Acute Stable Hypocapnia
- Stephen Corne, Kim Webster, and Magdy Younes
Am. J. Respir. Crit. Care Med. 167: 1193-1199.
[Abstract]
[Full text]
|
|
