Effect of neuromuscular blockade and assisted ventilation on breathing pattern, ventilation, and respiratory muscle function of anesthetized dogs

8 healthy dogs were anesthetized with a continuous infusion of pentobarbital (1 mg/kg/h) and were weakened but not paralyzed by intravenous succinylcholine (1 mg/kg/h). They were then studied during alternating periods of spontaneous breathing and assisted ventilation (IPPB). After succinylcholine, there was a significant increase in PaCO2, no significant change in respiratory frequency, a significant decrease in tidal volume, no significant change in P100 and a significant decrease in peak diaphragm EMG. Comparing periods of IPPB with periods of spontaneous breathing, there was a decrease in PaCO2 to a mean approximating that before succinylcholine, an increase in tidal volume, no change in frequency, and significant decreases in P100 and diaphragm EMG. In three experiments in which PaCO2 was maintained constant during IPPB, IPPB again resulted in a decrease in EMG and P100. Assisted mechanical ventilation of partially paralyzed dogs resulted in a fall in PaCO2 and a decrease in respiratory center output as measured by diaphragm EMG and P100. The fall in PaCO2 could be ascribed to decreasing the limited muscular work of breathing even in the presence of normal mechanics. A major part of the changes in EMG and P100 could be ascribed to chages in chemoreceptor drive but alteration of other inputs which were not specifically indentified, such as lung reflexes and/or chest wall reflexes, must also have had an effect.     

Abdominal muscle use during breathing in the anesthetized dog

The electromyograms of the rectus abdominis, external oblique, and transversus abdominis muscles were recorded in eight lightly anesthetized, spontaneously breathing dogs. During quiet breathing in the supine posture seven animals invariably had a phasic expiratory activity in the transversus, whereas only two animals had invariable expiratory activity in the external oblique. An intermittent expiratory activity in the rectus was recorded in only one animal. The degree of activation, expressed as a percentage of the activity detected during breathing with 25 cm H2O positive end-expiratory pressure (PEEP), was also significantly greater (P less than 0.05) for the transversus (mean +/- SEM: 29.4 +/- 8.6%) than the external oblique (5.5 +/- 2.3%). Head up tilting and progressive hypercapnia elicited substantial increases in transversus and external oblique expiratory activity in all animals, whereas head down tilting caused marked decreases in expiratory activity. In each posture and at any given end-tidal CO2, however, the amount of transversus activity was larger than the amount of external oblique activity. The rectus was usually silent in all the conditions. Bilateral cervical vagotomy suppressed external oblique activity in most supine animals, and the muscle was no longer recruited by PEEP, head up tilting, or hypercapnia. In contrast, there was residual transversus expiratory activity in all supine animals (11.1 +/- 3.1%), as well as some expiratory recruitment during PEEP, head up tilting, and hypercapnia. These results indicate that: (1) the transversus is the primary abdominal muscle of expiration in the anesthetized dog; and (2) its behavior resembles that of the triangularis sterni, although it is more dependent on vagal afferent pathways. The present findings also strengthen the important fact that spontaneous quiet expiration in the dog is an active rather than passive process.     

Levodropropizine does not affect P0.1 and breathing pattern in healthy volunteers and patients with chronic respiratory impairment

To evaluate whether the peripherally acting antitussive levodropropizine could affect the respiratory drive and the breathing pattern, we performed a double-blind, randomised, cross-over trial in 12 healthy volunteers and 12 patients with chronic respiratory impairment associated with chronic obstructive pulmonary disease.Levodropropizine 6% drops (at the recommended dose for adults) or placebo were administered orally t.i.d. for 10 consecutive administrations.Mouth occlusion pressure (P0.1), minute ventilation (V(e)), tidal volume (V(t)), respiratory rate (RR), mean inspiratory flow (V(t)/T(i)), end-tidal CO(2) (EtCO(2)), oxygen saturation (SaO(2)), forced expiratory volume in 1 s (FEV(1)), and the response to a hypercapnic stimulus were measured before and 1 h after the first and the last drug administration.Levodropropizine did not modify P0.1 in basal conditions and after a hypercapnic stimulus, either in healthy volunteers or in patients. In parallel, levodropropizine did not significantly affect V(t), RR, V(e), V(t)/T(i) and EtCO(2) in both the populations. Minor changes were induced by levodropropizine on SaO(2) in healthy volunteers, which despite a statistical difference, were too low to gain a clinical significance.These results confirmed the respiratory safety of levodropropizine 6% drops administered at the recommended dosage either in healthy volunteers or patients with chronic respiratory impairment.     

Effects of tracheotomy on respiratory mechanics in spontaneously breathing patients.

Tracheotomy is a method of intubating the trachea, which is employed in several clinical settings, including the treatment of head and neck neoplasms. Tracheotomy is believed to facilitate weaning through changes in respiratory mechanics. Existing information concerning functional changes associated with tracheotomy are limited to comparisons with orotracheal intubation. In this study, respiratory mechanics were monitored in seven spontaneously breathing patients, before and after an elective tracheotomy was performed for surgical treatment of cancer. Campbell diagrams were constructed by plotting pressure, obtained with an oesophageal balloon catheter, against volume, obtained from a pneumotachograph placed at the airway opening. Work of breathing was calculated as the internal area of the Campbell diagram and was partitioned into its elastic and inspiratory and expiratory resistive components. Oesophageal pressure was also used to quantify intrinsic positive end-expiratory pressure (PEEPi) and the pressure-time product (PTP), which is considered to be proportional to the oxygen cost of breathing. PTP was divided into its resistive and elastic components. Inspiratory resistive work, PEEPi, inspiratory PTP, as well as its resistive and elastic components were significantly reduced by tracheotomy. Tracheotomy significantly reduces work of breathing and pressure-time product in spontaneously breathing patients.     

Desensitization of the cough reflex during limb muscle contraction in anesthetized rabbits

The ‘cough network’ exhibits plasticity at the sensor and integration levels leading to modulation of the strength or pattern of the cough reflex. Little is known about the interactions between cough and human activities, especially during exercise. The present study was designed to determine whether exercise, mimicked by electrically induced muscle contractions, can modify the incidence and/or strength of cough following mechanical stimulation of the trachea in anesthetized rabbits.Thirteen anesthetized, tracheotomized rabbits were studied by a total of 311 tracheal stimulations: 196 at rest and 115 during exercise.During muscle contractions, the incidence of the cough reflex (CR) decreased and the expiration reflex (ER) increased (p < 0.0001). The sensitivity of the CR and ER both decreased during exercise compared to the sensitivity of the CR at rest (p < 0.02), while the strength of the expulsive response remained unchanged.These results indicate that adjustments occurring during muscle contractions likely downregulate tracheal defensive reflexes in anesthetized rabbits.     

How does deep breathing affect office blood pressure and pulse rate?

Little is known about the relation between deep breathing (DB) and blood pressure (BP). We studied the relationship between DB and BP in a large Japanese population. The subjects were recruited from randomly selected clinics and hospitals that were members of a medical association, and divided into two groups. In one group, BP was measured before and after taking 6 DB over a period of 30 s, and in the other group BP was measured before and after a 30-s rest in a sitting position without DB. Before these measurements, all patients rested 10 min or more in the waiting room and another 2 min or more in the doctor's office. Analyses were performed on data collected from 21,563 subjects. In both groups, systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate (PR) were significantly reduced after DB or a 30-s rest compared with the baseline measurements (p < 0.001). SBP reductions were greater in the DB group than in the 30-s rest group (normotensives: -6.4 +/- 8.3 vs. -3.0 +/- 7.4 mmHg, p < 0.001; untreated hypertensives: -9.6 +/- 10.2 vs. -5.9 +/- 9.1 mmHg, p < 0.001; treated hypertensives: -8.3 +/- 9.6 vs. -4.4 +/- 8.3 mmHg, p < 0.001). Greater BP reductions were found in patients with a higher baseline BP in both the DB and 30-s rest groups. In conclusion, the present study showed a baseline BP-dependent BP reduction by DB, suggesting that BP measurement should be done without DB in the office because DB lowers BP.     

Medroxyprogesterone acetate with acetazolamide stimulates breathing in cats

Both medroxyprogesterone acetate (MPA) and acetazolamide (ACET) increase ventilation. Combined administration of these agents could result in an additional improvement of blood gases, for example in patients with chronic obstructive pulmonary diseases. The aim of this study in anaesthetized female (ovariohysterectomized, pre-treated with 17-beta-estradiol) cats was to compare the effects on the CO2 response curve of MPA alone (4 microg kg(-1), i.v.) with those after MPA followed by ACET (4 mg kg(-1) i.v.). We performed dynamic end-tidal CO2 forcing and analysed the data with a two-compartment model comprising a fast peripheral and slow central compartment, characterized by CO2 sensitivities (Sp and Sc, respectively) and a single offset (the apnoeic threshold B). MPA reduced Sp from 0.22 +/- 0.09 (mean +/- S.D.) to 0.13 +/- 0.06 L min(-1) kPa(-1) (P < 0.01) and Sc from 1.01 +/- 0.38 to 0.88 +/- 0.32 L min(-1) kPa(-1) (P < 0.01). B decreased from 4.02 +/- 0.27 to 3.64 +/- 0.42 kPa (P < 0.01). Subsequent administration of ACET reduced Sp and Sc further to 0.09 +/- 0.06 and to 0.70 +/- 0.49 L min(-1) kPa(-1) (P < 0.01), respectively. The apnoeic threshold decreased further to 2.46 +/- 1.50 kPa (P < 0.01). Because both treatments reduced ventilatory CO2 sensitivity, we conclude that a simulating effect on ventilation is due to a decrease in the apnoeic threshold. Combined administration of MPA and ACET may lead to larger increases in ventilation than treatment with either drugs alone.     

Pulmonary rapidly adapting receptor stimulation does not increase airway resistance in anesthetized rabbits.

In open-chest artificially ventilated rabbits, removal followed by replacement of positive end-expiratory pressure (PEEP maneuver) favors stimulation of airway rapidly adapting receptors (RARs). The purpose of the present study was to determine whether activation of RARs can cause bronchoconstriction. We measured airway pressure, airflow, and tidal volume, and calculated dynamic lung compliance and total lung resistance. PEEP maneuver increased airway pressure swings (16.4 +/- 4% above control; p = 0.0016) and decreased compliance (to 84.8 +/- 2.8% of control; p = 0.0002) without changing resistance (108.0 +/- 4.4% of control; p = 0.85). On the other hand, the resistance increased greatly (93 +/- 13%, p < 0.01) after intravenous injection of acetylcholine or electrical stimulation of vagal efferents, indicating that our system could detect increases in the resistance. In a separate group, we stimulated RARs by stroking the trachea with a cotton tip (tickling), tickling produced cough, manifested by increased pressure and flow without resistance changing. These changes were abolished after paralysis with succinylcholine. Because we did not detect an increase in airflow resistance during activation of RARs by the PEEP maneuver and tickling, we conclude that increase in resistance may not be an important reflex component of airway RARs.     

nCPAP therapy does not affect respiratory mechanics of patients with sleep-related respiratory disturbances

We investigated in patients with sleep disordered breathing the influence of long-term nCPAP-therapy on airway mechanics and capillary blood gases. 109 patients (19 women, 90 men, age [mean +/- standard deviation] 59 +/- 10 years, apnea-hypopnea-index 34 +/- 24/h) were treated for 27 +/- 33 months, with a mean pressure of 7.7 +/- 2 mbar, mean usage 5.6 +/- 1.9 h/night. Vital capacity, FEV1, thoracic gas volume and capillary blood gases did not change during therapy, irrespective of the smoking history. However, in a subgroup of 6 patients who were hypoxemic before therapy, there was a significant increase of PaO2 from 63 +/- 4 to 70 +/- 6 mm Hg (p < 0.01). Neither the height of the pressure nor the duration of therapy did influence the course of lung function data.     

Tests of respiratory muscle function

Respiratory muscle strength and endurance should be assessed when dyspnea, respiratory failure, or poor performance on routine pulmonary function tests are unexplained. Respiratory muscle strength can be measured non-invasively from maximal mouth pressures, but measurement of transdiaphragmatic pressure refines the assessment. The maximal voluntary ventilation test is the only simple index of ventilatory or respiratory muscle endurance. Other tests for endurance and fatigue are more difficult, but some newer techniques may be applicable to the clinical laboratory. Some patients who exhibit tachypnea, marked use of neck inspiratory muscles, and chest-abdomen asynchrony may be developing respiratory muscle fatigue.     

Pattern of breathing in a case of generalized respiratory muscle weakness

A patient with motor neuron disease is described. He had signs and laboratory data indicating generalized, symmetrical weakness, involving both inspiratory and expiratory muscle groups. The pattern of breathing involving recruitment of accessory muscles and expiratory contraction of abdominal muscles is similar to that seen in normal people at high minute ventilation, and suggests the compensating mechanism for increasing motor discharge to weak respiratory muscles is mediated centrally. Observation of this sort of respiratory activity gives a clinical clue to generalized respiratory muscle weakness.     

The pattern of respiratory muscle recruitment during pursed-lip breathing.

Data from the present study indicate a change in the pattern of chest wall muscle recruitment and improved ventilation with pursed-lip breathing (PLB) in COPD. Pursed lip breathing led to increased rib cage and accessory muscle recruitment during inspiration and expiration, increased abdominal muscle recruitment during expiration, decreased duty cycle of the inspiratory muscles and respiratory rate, and improved SaO2. In addition, PLB resulted in no change in pressure across the diaphragm and a less fatiguing breathing pattern of the diaphragm. Changes in chest wall muscle recruitment and respiratory temporal parameters concomitant with the increased SaO2 indicate a mechanism of improving ventilation with PLB while protecting the diaphragm from fatigue in COPD. Alterations in the pattern of respiratory muscle recruitment with PLB may be associated also with the amelioration of dyspnea. Further investigation is necessary to explore the relationship between the pattern of respiratory muscle recruitment during PLB and dyspnea.     

Low-dose streptozotocin-induced diabetes in the spontaneously hypertensive rat

Streptozotocin (STZ, 35 mg/kg body weight) was injected into spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, and plasma glucose and triglyceride concentrations measured 10 days later. Neither mean (+/- SEM) plasma glucose (130 +/- 3 v 136 +/- 3 mg/dL) nor triglyceride (93 +/- 6 v 108 +/- 7 mg/dL) concentrations increased in WKY rats. In contrast, both plasma glucose (141 +/- 3 v 262 +/- 36) and triglyceride (121 +/- 8 v 196 +/- 7 mg/dL) concentrations increased significantly (P less than .01) following administration of STZ in SHR. Furthermore, when SHR previously injected with STZ were fed a diet enriched in fructose, they had a further increase (P less than .01) in both plasma glucose (343 +/- 38 mg/dL) and triglyceride (774 +/- 57 mg/dL) concentrations. Plasma triglyceride concentration also increased significantly (P less than .05) when STZ-injected WKY rats ingested the fructose-enriched diet, but plasma glucose levels still remained within the normal range (152 +/- 5 mg/dL). These results indicate that SHR were more sensitive to the effects of a decrease in pancreatic beta-cell function (STZ) and an increase in insulin resistance (fructose feeding) than WKY rats.     

Tracheal gas insufflation-augmented continuous positive airway pressure in a spontaneously breathing model of neonatal respiratory distress

Respiratory distress syndrome (RDS) in neonates is characterized by labored breathing and poor gas exchange, often requiring ventilatory support. Continuous positive airway pressure (CPAP) is a preferred intervention to support spontaneous ventilatory efforts by sustaining lung volume recruitment, while it prevents derecruitment during exhalation by maintaining end-expiratory pressure. However, CO2 retention during CPAP often results in the need for mechanical ventilation. Since tracheal gas insufflation (TGI) promotes CO2 elimination by reducing prosthetic dead space, we hypothesized that TGI used with CPAP may reduce the need for more invasive therapies. The objective of this study was to evaluate the physiologic effect of TGI with CPAP in a spontaneously breathing model of acute lung injury with respect to gas exchange and pulmonary mechanics. Nineteen spontaneously breathing neonatal pigs (2.4 +/- 0.4 kg) were anesthetized, sedated, instrumented, and placed on CPAP at 5 cmH2O. All piglets were injured with intravenous oleic acid (0.08 ml/kg), and then randomized to receive CPAP with TGI (TGI; n = 9) or CPAP alone (control; n = 10). FiO2 was titrated at 0.05 every 15 min during the protocol to maintain SaO2 > 93%. Vital signs, arterial blood gases, pulmonary mechanics, and thoracoabdominal motion (TAM) were evaluated 30 min after injury and at 1-hr intervals for 4 hr. Following the 4-hr measurement, the piglets were sacrificed and the lungs were grossly examined. After initiation of treatment, we found that the PaCO2 was lower (33.1 +/- 5.0 vs. 47.0 +/- 10.3 mmHg; P < 0.01), while the oxygenation indices were greater (PaO2, SaO2, a/A ratio; P < 0.01) in the TGI group than with control animals. Subsequently, the pH was greater (7.45 +/- 0.08 vs. 7.36 +/- 0.08; P < 0.01) and closer to baseline values with TGI. By 4 hr, the FiO2 was titrated lower (0.37 +/- 0.06 vs. 0.49 +/- 0.15; P < 0.05) and ventilation was accomplished with a lower minute ventilation (MV) in the TGI group than in the control group (445 +/- 113 vs. 581 +/- 223 ml/kg/min; P < 0.01). Respiratory compliance was greater with TGI than control (0.76 +/- 0.13 vs. 0.63 +/- 0.11 ml/cmH2O/kg; P < 0.01), whereas resistance and TAM were similar between groups. We conclude that the use of TGI with CPAP in the treatment of RDS results in improved gas exchange and pulmonary mechanics. As such, TGI-augmented CPAP may prevent infants from requiring more invasive ventilation by reducing CO2 retention.     

Effect of respiratory muscle fatigue on breathing pattern during incremental exercise

We examined the breathing pattern during incremental exercise before and after induction of inspiratory muscle fatigue. Our aim was to determine whether induction of fatigue alters the ventilatory response to exercise and in particular whether such changes are most apparent at high levels of exercise when minute ventilation and thus inspiratory load are greatest. A group of 10 healthy subjects was studied on a cycle ergometer. Fatigue was achieved by having the subject breathe against an inspiratory threshold load that required the subject to generate 80% of the predetermined maximal mouth pressure to initiate airflow. Breathing pattern, oxygen consumption (VO2), mouth occlusion pressure (P0.1), and a visual analog scale (VAS) for respiratory effort were obtained for 3 min at rest and at 25, 50, 75, and 100% of the subject's maximal work load (Wmax) as determined by preliminary testing. Exercise was performed on two separate occasions, once immediately after induction of fatigue and the other as a control. Induction of fatigue had no effect on resting breathing and only minimal effects at the lower work loads (25 and 50% Wmax). At the higher work loads (75 and 100% Wmax) induction of fatigue significantly altered the pattern of breathing during exercise. At 75% of Wmax the respiratory frequency (f) increased from 22.5 +/- 4.4 (SD) during control to 27.0 +/- 6.7 breaths/min (p less than 0.02) following induction of fatigue; tidal volume was not significantly altered, 2.15 +/- 0.65 versus 2.24 +/- 0.74 L during control. The increase in f was due to reductions in both inspiratory and expiratory time because fractional inspiratory time remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)