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At least 253 records · Page 14Linked to original sources
PubMed2002

Mechanical ventilation protects against diaphragm injury in sepsis: interaction of oxidative and mechanical stresses.

Overproduction of nitric oxide (NO) with attendant oxidative and nitrosative stress has been implicated in sepsis-induced diaphragm dysfunction. Here we determined the impact of controlled mechanical ventilation (MV) on rat diaphragm sarcolemmal injury, inducible NO synthase (iNOS) expression, and oxidative stress during endotoxemia. At 4 h after injection of endotoxin, impaired sarcolemmal integrity and decreased force production by the diaphragm were observed in spontaneously breathing rats. The use of MV during endotoxemia largely eliminated sarcolemmal damage and significantly improved diaphragm force production. These benefits were not associated with alterations in either iNOS expression or protein carbonyls (marker of oxidation), which remained abnormally elevated in septic diaphragms despite MV. Therefore, we hypothesized that the protection afforded by MV was due to its ability to decrease the level of mechanical stress placed on the sarcolemma, because the latter could be hyperfragile in the setting of increased oxidative stress. Using an in vitro system to independently modulate oxidative and mechanical stresses, we confirmed that these two factors act together in a synergistic fashion to favor sarcolemmal injury. Accordingly, our data suggest that MV protects the diaphragm during sepsis by abrogating an injurious interaction between oxidative and biomechanical stresses imposed on the sarcolemma.

Animals↗
PubMed1978

Vocal cord closure. A cause of upper airway obstruction during controlled ventilation.

Studies of vocal cord function were undertaken in a quadriplegic patient requiring ventilatory assistance, and in 2 normal subjects during controlled ventilation in a tank-type respirator. When the patient and the normal subjects relaxed and made no conscious effort to assist the respirator, the vocal cords were observed to close during inspiration and a large pressure gradient (12 to 19 cm H2O) developed across the cords. When the subjects made a slight inspiratory effort ("assist" mode), the cords opened widely during inspiration. There were large increases in flow and tidal volume in the "assist" mode compared with passive ventilation. Measurements of transdiaphragmatic pressure and esophageal pressure showed that these variables did not increase with the slight assist. Thus, increase in ventilation during the "assist" mode appeared to be due to alleviation of inspiratory obstruction at the level of the vocal cords. The same phenomenon was observed in the patient during phrenic nerve pacing. A pacemaker was designed to be triggered by the electromyographic impulse from an accessory muscle of respiration. In this manner, vocal cord opening could be coordinated with the mechanical assist given by the phrenic nerve pacer.

Adult↗
PubMed1979

Ventilation-perfusion imbalance after head trauma.

To investigate the role of ventilation-perfusion (VA/Q) imbalance in the hypoxemia observed after head injury, 5 male subjects (17 to 26 years of age) with isolated head trauma and subsequent hypoxemia were studied. Disturbances of ventilation and perfusion were assessed using the steady-state elimination of six inert gases of different solubilities. Paired studies were conducted during mechanical ventilation with a volume-cycled ventilator and during spontaneous ventilation. Distributions recovered from studies of spontaneous ventilation show a mode of ventilation and perfusion near a VA/Q of 1.0. In addition, 41% of the cardiac output was distributed to a second population of lung units with low VA/Q (less than 0.1) and shunt. During mechanical ventilation, perfusion to these regions of low VA/Q decreased to 21% of the cardiac output, whereas shunt fraction was unchanged. This was associated with a marked broadening of the VA/Q mode near 1.0, relative to the studies during spontaneous ventilation. Mean functional residual capacity during mechanical ventilation was not different from that during spontaneous ventilation. These results suggest that head injury can lead to hypoxemia through a failure of VA/Q regulatory mechanisms.

Adolescent↗
PubMed1982

The oxygen cost of breathing in patients with cardiorespiratory disease.

We measured the oxygen cost of breathing (VO2resp) in 13 patients with cardiorespiratory disease requiring artificial ventilation as the difference between the oxygen consumption during spontaneous respiration (VO2tot) and that during artificial ventilation (VO2nonresp). Average VO2tot was 312 +/- 90 ml/min (mean +/- 1 SD), whereas VO2nonresp was 246 +/- 38 ml/min (p less than 0.01). Average VO2resp was 75 +/- 82 ml/min (range, 8 to 286), representing 24% of VO2tot or 8.7 +/- 8.9 ml O2/L ventilation. In normal resting adults, VO2resp in 5 to 10 ml/min, about 1 to 3% VO2tot, or 0.25 to 2.5 ml O2/L ventilation. The VO2resp had an exponential relationship with FEV1 (r = 0.97) in 6 patients who had had prior spirometry. Because minute ventilation was normal in our patients (8.8 +/- 2.2 L/min), the elevated VO2resp represented an increase in the work of breathing as well as a decrease in the efficiency of the respiratory muscles. These results suggest that, where O2 transport is compromised, artificial ventilation may release substantial quantities of oxygen for use by other body systems.

Adult↗
PubMed1984

Conditioning of the diaphragm with phrenic nerve stimulation after prolonged disuse.

We studied the effect of electrical stimulation of the phrenic nerve on the force frequency relationship of the disused diaphragm. A high quadriplegic who had been totally ventilator dependent for 6 months following a C2 fracture received bilateral phrenic nerve stimulators. During a 6-wk period of conditioning by electrical stimulation, the force of diaphragm contraction was assessed by measurement of transdiaphragmatic pressures during stimulation of each nerve over a range of frequencies. Tidal volume as well as rib cage and abdominal motion were studied. There was an upward shift of the force frequency relationship of the diaphragm over the 4-month period of phrenic nerve pacing using repetitive stimulus trains of 14 to 28 Hz. This improvement appeared to plateau at about 11 wk. The increase in contractility was accompanied by a progressive diminution in the stimulus frequency at which fusion of the contraction occurred. The disused diaphragm, like other skeletal muscle, may be conditioned with electrical stimulation.

Aminophylline↗
PubMed2003

Aerosol delivery and modern mechanical ventilation: in vitro/in vivo evaluation.

Aerosol delivery via a mechanical ventilator remains unregulated with no standards for drug delivery to intubated patients. Bench models predicting drug delivery have not been validated in vivo. For modern ventilator designs, we chose to identify, on the bench, the most important variables affecting aerosol delivery and to correlate in vitro predictions of aerosol delivery with in vivo end points independent of patient response. Test aerosols of albuterol and antibiotics were compared. Bench measurements of inhaled mass (percentage of nebulizer charge, mean +/- SEM) ranged from 5.7 +/- 0.5% to 37.4 +/- 1.6%, with breath-actuated nebulization and humidity identified as the most important factors determining aerosol delivery. In patients, sputum levels of deposited antibiotics varied from 1.10 to 19.6 microg/ml/mg. Variation in sputum levels correlated with predictions from the in vitro model. Aerosol delivery in ventilated patients can be efficient and reproducible only if defined ventilator parameters are tightly controlled. Key parameters can be determined via in vitro bench testing defining delivery standards for clinical trials of drugs with narrow therapeutic/toxicity ratios.

Administration, Inhalation↗
PubMed1997

Respiratory psychophysiology of panic disorder: three respiratory challenges in 98 subjects.

OBJECTIVE: Respiratory abnormalities may play a central role in the pathophysiology of panic disorder. The current study was undertaken to examine the respiratory response in the largest series of subjects to date during three respiratory challenges that used improved methodology. METHOD: Fifty-nine patients with DSM-III-R panic disorder and 39 normal volunteers were challenged with 5% and 7% CO2 inhalation and room air hyperventilation separated by room air breathing with continuous spirometry. RESULTS: Patients with panic disorder were more sensitive to the anxiogenic effects of CO2 than were normal subjects, and CO2 was a more potent stimulus to panic than hyperventilation. Patients increased their respiratory rate more quickly during CO2 inhalation than did comparison subjects, and this increase preceded the panic attacks. Patients who panicked in response to 5% CO2 demonstrated continued rise in end-tidal CO2, while the end-tidal CO2 of the comparison groups stabilized. Low end-tidal CO2 and high variance in minute ventilation at baseline predicted panic attacks during CO2 inhalation. Following CO2 or hyperventilation challenges, respiratory rate dropped sharply, while tidal volume remained elevated longer in patients than in comparison subjects. CONCLUSIONS: The findings confirm the greater behavioral and physiological sensitivity of patients with panic disorder to CO2 inhalation and identify a series of respiratory abnormalities. Panic attacks in panic disorder may be explained by inefficient compensatory mechanisms, primarily of respiratory rate.

Administration, Inhalation↗
PubMed1999

History of Joubert syndrome and a 30-year follow-up of the original proband.

The 1960s were a period of great flowering in the recognition of neurologic disorders in children. The so-called ataxic cerebral palsies were an especially fertile field waiting for clarification. Congenital ataxia coupled with hyperpnea-apnea, abnormal eye movements, and retardation was identified as an autosomal-recessive syndrome eponimically associated with the senior author, Marie Joubert. The disorder, though rare, is increasingly recognized and a lay society dedicated to family support and research has been formed. In preparation for a recent symposium the original proband was re-examined 30 years later and the manifestations in adults clarified. Severe dysarthria was the most striking feature in this man, the hyperpnea-apnea had diminished, and the abnormal eye movements were less striking. Ataxia was still present but not severe. Poor judgment and borderline intelligence rounded out the clinical picture. Modern imaging has clarified, in part, the anatomic basis of this syndrome.

Adult↗
PubMed1999

Cerebellar and brainstem development: an overview in relation to Joubert syndrome.

An overview of cerebellar and brainstem development is provided as a foundation for suggesting hypotheses about developmental defects in Joubert syndrome. Although neuropathologic studies of Joubert syndrome are rare, and the spectrum of brain pathology is not yet known, consistent findings include agenesis of the cerebellar vermis and hypoplasia or fragmentation of several brainstem nuclei (including dentate nuclei, inferior olives, and basis pontis), nuclei and tracts of cranial nerve V, solitary nuclei and tracts, and nuclei gracilis and cuneatus. Two aspects of cerebellar development might be important in the pathogenesis of Joubert syndrome: First, cerebellar development is regulated by a critical region of the embryo called the "midbrain-hindbrain organizer," and both mesencephalic and metencephalic elements take part in normal cerebellar development. While the metencephalon gives rise to the cerebellar hemispheres, the vermis is derived almost exclusively from the mesencephalon. This suggests that Joubert syndrome could involve an abnormality in formation of the pontomesencephalic junction (rhombomere 1). Second, the histogenesis of cranial nerve nuclei and brainstem structures derived from the embryonic rhombic lip (such as the inferior olives, neurons of the basis pontis, and arcuate nuclei) involves the formation, migration, and reorganization of nuclei and tracts during a critical period of development (6 to 8 weeks' gestation). Because these structures are abnormal in Joubert syndrome, an understanding of factors that regulate the proper formation and migration of cells that give rise to them could provide important clues about the pathogenesis of this disorder.

Animals↗
PubMed1999

Cognition, behavior, and development in Joubert syndrome.

This article reports on a series of studies of children with Joubert syndrome who were examined in three investigations from 1994 through 1998. Neuropsychologic screening of 10 of 40 children showed a variety of deficits in cognition, verbal memory, visuomotor, motor, and language-related tasks. Parent report of developmental attainments revealed only 3 of 40 children functioning in the borderline range, with the rest scoring in the severely impaired range. Parent reports of behaviors revealed problems in temperament, hyperactivity, aggressiveness, and dependency, as well as problems in physical development and care that were felt to be related to their neurologic handicaps. Future directions of research with this rare disorder are suggested.

Adolescent↗