Respiratory Rate Effects Research Articles

The effects of respiratory rate and tidal volume on pulse pressure variation in healthy lungs–a generalized additive model approach may help overcome limitations

Pulse pressure variation (PPV) is a well-established method for predicting fluid responsiveness in mechanically ventilated patients. The predictive accuracy is, however, disputed for ventilation with low tidal volume (VT) or low heart-rate-to-respiratory-rate ratio (HR/RR). We investigated the effects of VT and RR on PPV and on PPV’s ability to predict fluid responsiveness. We included patients scheduled for open abdominal surgery. Prior to a 250 ml fluid bolus, we ventilated patients with combinations of VT from 4 to 10 ml kg−1 and RR from 10 to 31 min−1. For each of 10 RR-VT combinations, PPV was derived using both a classic approach and a generalized additive model (GAM) approach. The stroke volume (SV) response to fluid was evaluated using uncalibrated pulse contour analysis. An SV increase > 10% defined fluid responsiveness. Fifty of 52 included patients received a fluid bolus. Ten were fluid responders. For all ventilator settings, fluid responsiveness prediction with PPV was inconclusive with point estimates for the area under the receiver operating characteristics curve between 0.62 and 0.82. Both PPV measures were nearly proportional to VT. Higher RR was associated with lower PPV. Classically derived PPV was affected more by RR than GAM-derived PPV. Correcting PPV for VT could improve PPV’s predictive utility. Low HR/RR has limited effect on GAM-derived PPV, indicating that the low HR/RR limitation is related to how PPV is calculated. We did not demonstrate any benefit of GAM-derived PPV in predicting fluid responsiveness.Trial registration: ClinicalTrials.gov, reg. March 6, 2020, NCT04298931.

Effect of respiratory rate and size of cannula on pressure and dead-space clearance during nasal high flow in patients with COPD and acute respiratory failure

Nasal high flow (NHF) is an efficient oxygenation tool for the treatment of respiratory failure. The study investigated the effect of breathing pattern on positive airway pressure and dead-space clearance by NHF. The breathing cycle during NHF was characterized in 26 patients with acute respiratory failure (ARF) and stable COPD and after mechanical ventilation (post-MV) via tracheostomy where also pressure was measured in the trachea. Dead-space clearance was measured in airway models during different breathing patterns. NHF reduced the respiratory rate (RR) and TI/TE through prolonging the TE; the TI/TE ranged between ≤0.5 observed in the COPD patients and ∼1.0 in the ARF patients. NHF via a standard medium-sized cannula interface generated a low-level expiratory pressure proportional to NHF rate and breathing flow; the median generated positive end-expiratory pressure was only 1.71 cmH2O at NHF 45 L/min. The dilution and purging of expired gas from a nasal cavity model were observed to occur at the end of expiration as expiratory flow slowed and the dynamic pressure decreased. The higher RR with shorter end-expiratory period resulted in reduced dead-space clearance by NHF; 20 L/min cleared 43 ± 2 mL at RR 15 min-1 vs. 9 ± 5 mL at RR 45 min-1, P < 0.001, which was increased at higher NHF rate. At lower RR, the clearance was similar between NHF rates 20 and 60 L/min. Higher NHF rates elevate positive airway pressure, and at the increased RR can improve the clearance. This may enhance gas exchange and lead to a reduction in the work of breathing.NEW & NOTEWORTHY During nasal high flow (NHF) an increased breathing frequency, which is commonly observed in acute respiratory failure, can lead to decreased dead-space clearance. Higher NHF rates increase the clearance and reduce the rebreathing which may eventually lower the respiratory rate and the work of breathing. Monitoring of the respiratory rate could be an important indicator of not only the respiratory function but also the NHF rate selection and the therapy efficacy.

Effects of respiratory rate on venous-to-arterial CO2 tension difference in septic shock patients undergoing volume mechanical ventilation

BackgroundTo explore the effects of the respiratory rate (RR) on the venous-to-arterial CO2 tension difference (gapCO2) in septic shock patients undergoing volume mechanical ventilation.MethodsAdult patients with septic shock underwent volume mechanical ventilation between October 2015 and October 2016. RR was started at 10 breaths/min, and 2 breaths/min were added every 60 min until 16 breaths/min was reached. At every point, central venous and arterial blood gas measurements were obtained simultaneously.ResultsIn this study, gapCO2 induced by hyperventilation significantly increased, while the central venous carbon dioxide pressure (PvCO2) and the partial pressure of CO2 (PaCO2) in arteries decreased. The decreasing trend of the PaCO2 was more obvious than that of the PvCO2. HCO3− and ctCO2 were markedly decreased, when the RR was increased (P < 0.05). Central venous oxygen saturation (ScvO2) had a decreasing trend between 14 (77.1 ± 8.3%) and 16 (75.2 ± 8.7%) breaths/min; however, the difference was not significant.ConclusionsIn septic patients undergoing ventilation, respiratory alkalosis induced by hyperventilation caused an increase in the gapCO2. Clinicians should cautiously interpret the gapCO2 in hemodynamically stable ventilated septic shock patients and its relationship with low cardiac output and inadequate perfusion.

Effects of Respiratory Rate on Heart Rate Variability in Neurologic Outpatients with Epilepsies or Migraine: A Preliminary Study

Background: Variation of spontaneous respiratory rates and influences of spontaneous and paced breathing rates on heart rate variability (HRV) were assessed in patients with epilepsy or migraine, and HRV parameters were compared between the groups. Materials and Methods: Thirty neurologic outpatients, 16 diagnosed with epilepsies and 14 with migraine, were included. Autonomic testing consisted of short-term HRV, the deep breathing test (DBT), and measurement of HRV at systematically changed breathing rates (paced breathing, 5–18 breaths per minute, bpm). Results: Spontaneous respiratory rate during short-term HRV varied from 9 to 23 bpm in the epileptic group and from 5 to 21 bpm in migraine patients and was significantly and negatively correlated with SD of all normal RR intervals (SDNN) and total power (TP) in epileptic patients but not in migraine patients. Paced breathing rate had a significant effect on all HRV parameters assessed in both groups. HRV (SD1, SDNN, TP) and DBT (E-I, SD1, SDNN) parameters were significantly lower in the epileptic group. Group differences were significantly greater during slow compared to fast breathing. Conclusions: An important and new finding is the wide variation of spontaneous respiratory rate in both groups, along with the significant negative correlation with the assessed HRV parameters. The reduction of HRV during slow breathing in epileptic patients may indicate a diminished cardiorespiratory coupling caused by a probable loss of sensitivity within the cardiovagal brainstem circuitry.

Ultra-short heart rate variability recording reliability: The effect of controlled paced breathing.

Recent studies have reported that Heart Rate Variability (HRV) indices remain reliable even during recordings shorter than 5min, suggesting the ultra-short recording method as a valuable tool for autonomic assessment. However, the minimum time-epoch to obtain a reliable record for all HRV domains (time, frequency, and Poincare geometric measures), as well as the effect of respiratory rate on the reliability of these indices remains unknown. Twenty volunteers had their HRV recorded in a seated position during spontaneous and controlled respiratory rhythms. HRV intervals with 1, 2, and 3min were correlated with the gold standard period (6-min duration) and the mean values of all indices were compared in the two respiratory rhythm conditions. rMSSD and SD1 were more reliable for recordings with ultra-short duration at all time intervals (r values from 0.764 to 0.950, p<0.05) for spontaneous breathing condition, whereas the other indices require longer recording time to obtain reliable values. The controlled breathing rhythm evokes stronger r values for time domain indices (r values from 0.83 to 0.99, p<0.05 for rMSSD), but impairs the mean values replicability of domains across most time intervals. Although the use of standardized breathing increases the correlations coefficients, all HRV indices showed an increase in mean values (t values from 3.79 to 14.94, p<0.001) except the RR and HF that presented a decrease (t=4.14 and 5.96, p<0.0001). Our results indicate that proper ultra-short-term recording method can provide a quick and reliable source of cardiac autonomic nervous system assessment.

Rebuttal from Jeremy R. Beitler, Rolf D. Hubmayr and Atul Malhotra

More than a decade after low tidal volume ventilation for acute respiratory distress syndrome (ARDS) first gained widespread acceptance, it is still unknown how best to manage its effects on minute ventilation. High respiratory rate, or permissive hypercapnia? Limiting respiratory rate has been shown in preclinical models to reduce lung injury even at a constant arterial CO2 tension (; Vaporidi et al. 2008). Curley and colleagues (2013) go one step further, making the case for additional benefit from hypercapnia during low tidal volume ventilation. As we find no great fault with the balanced case put forward by our Canadian colleagues, our rebuttal focuses on challenges in designing more definitive trials. First, how might the independent effects of respiratory rate, and pH each be considered? Tris-hydroxymethyl amino-methane (THAM) buffer might be used to identify the effects of hypercapnia independent of acidaemia. To isolate the effects of respiratory rate from , inspired CO2 could be administered during high respiratory rate to induce hypercapnia to a degree comparable to a low-rate strategy. Optimizing respiratory rate must also consider airflow dynamics since high rates may lead to auto-positive end-expiratory pressure (auto-PEEP). Second, what is the minimum acceptable pH, and how should severe acidaemia be managed? A minimum pH approaching 7.15 was well tolerated haemodynamically in a heterogeneous ARDS population (Carvalho et al. 1997), while other studies specified a pH nadir between 7.05 (Brochard et al. 1998) and 7.30 (Brower et al. 2000) before encouraging intervention. THAM has shown promise as an effective buffer during fixed minute ventilation (Kallet et al. 2000), although further study is warranted before its widespread adoption as a rescue therapy. Finally, how do we ensure the protection of patients at highest risk of harm from hypercapnia? Patients with intracranial hypertension may fare poorly from hypercapnia-induced cerebral vasodilatation, as may patients with pre-existent right ventricular compromise facing hypercapnic pulmonary vasoconstriction (Curley et al. 2010). Similarly, anti-inflammatory effects of hypercapnia may be deleterious in pulmonary or extra-pulmonary sepsis compared to other ARDS precipitants. Moreover, increased sedation or paralysis, with associated risk of iatrogenic injury, may be required during hypercapnia to maintain patient–ventilator synchrony and minimize large swings in transpulmonary pressures from spontaneous breathing efforts (Malhotra & Drazen, 2013). Only with carefully designed studies will the role be defined for optimizing respiratory rate, and pH in individual patients with varying comorbidities and ARDS severity. The range of preclinical findings and heterogeneity of current clinical practice indicate a great need for further research in this area.

New images, new insights for VILI

prioritization of high-volume vs. low-volume mechanisms of ventilator-induced lung injury (VILI) is an issue that is often discussed and debated in clinical ventilator management. Abundant laboratory studies ([7][1]), as well as several prominent clinical studies ([1][2], [3][3], [14][4], [19][5]),

Effects of Respiratory Rate and Tidal Volume on Gas Exchange in Total Liquid Ventilation

Using a rabbit model of total liquid ventilation (TLV), and in a corresponding theoretical model, we compared nine tidal volume-respiratory rate combinations to identify a ventilator strategy to maximize gas exchange, while avoiding choked flow, during TLV. Nine different ventilation strategies were tested in each animal (n = 12): low [LR = 2.5 breath/min (bpm)], medium (MR = 5 bpm), or high (HR = 7.5 bpm) respiratory rates were combined with a low (LV = 10 ml/kg), medium (MV = 15 ml/kg), or high (HV = 20 ml/kg) tidal volumes. Blood gases and partial pressures, perfluorocarbon gas content, and airway pressures were measured for each combination. Choked flow occurred in all high respiratory rate-high volume animals, 71% of high respiratory rate-medium volume (HRMV) animals, and 50% of medium respiratory rate-high volume (MRHV) animals but in no other combinations. Medium respiratory rate-medium volume (MRMV) resulted in the highest gas exchange of the combinations that did not induce choke. The HRMV and MRHV animals that did not choke had similar or higher gas exchange than MRMV. The theory predicted this behavior, along with spatial and temporal variations in alveolar gas partial pressures. Of the combinations that did not induce choked flow, MRMV provided the highest gas exchange. Alveolar gas transport is diffusion dominated and rapid during gas ventilation but is convection dominated and slow during TLV. Consequently, the usual alveolar gas equation is not applicable for TLV.

Maintenance of end-expiratory recruitment with increased respiratory rate after saline-lavage lung injury

LETTERS TO THE EDITORMaintenance of end-expiratory recruitment with increased respiratory rate after saline-lavage lung injuryE. Costa, and M. AmatoE. Costa, and M. AmatoPublished Online:01 Jun 2007https://doi.org/10.1152/japplphysiol.00154.2007MoreSectionsPDF (27 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat To the Editor: In the intriguing report by Syring et al. (3), the authors concluded that comparable reductions in tidal recruitment were obtained by either applying external positive end-expiratory pressure (PEEP) or by increasing respiratory rate. This latter conclusion deserves scrutiny, but their data seem not to support it. First, the reported time constant (0.47 s) of the oxygen probe used (1) is too long. By considering the short equilibrium time available in the high-rate group (inspiratory time = 1.66 s/expiratory time = 0.83 s), one could predict that this catheter measured only 82.5% of the actual arterial Po2 oscillations in these animals. In the best scenario, part of the decrease in arterial Po2 oscillations in the high-rate group should be ascribed to insufficient temporal resolution of the catheter. The same group, however, had previously shown that arterial Po2 changes following massive alveoli recruitment or derecruitment required 10–20 s to stabilize (1). By considering such longer time constants, the perceived swings in arterial Po2 would be just 13% of those in equilibrium. Therefore, respiratory rate should have a profound impact on the measured amplitude of arterial Po2 irrespective of the amount of tidal recruitment. Another important methodological limitation was the high plateau pressure used (28 cmH2O). Under low-PEEP conditions, such high inspiratory pressure in rabbits commonly exceeds the reopening pressure and results in tidal recruitment (2), which increases lung capillary Po2 each inspiration, resulting in a higher average arterial Po2 especially when inspiration is long (inspiratory time = 1.66 s). In this context, a high average arterial Po2 in the high-rate group was not enough to guarantee a permanently open-lung status. To prove that, the authors should demonstrate a high average arterial Po2 even after decreasing plateau pressures substantially.REFERENCES1 Baumgardner JE, Markstaller K, Pfeiffer B, Doebrich M, Otto CM. Effects of respiratory rate, plateau pressure, and positive end-expiratory pressure on PaO2 oscillations after saline lavage. Am J Respir Crit Care Med 166: 1556–1562, 2002.Crossref | ISI | Google Scholar2 Rotta AT, Gunnarsson B, Fuhrman BP, Hernan LJ, Steinhorn DM. Comparison of lung protective ventilation strategies in a rabbit model of acute lung injury. Crit Care Med 29: 2176–2184, 2001.Crossref | PubMed | ISI | Google Scholar3 Syring RS, Otto CM, Spivack RE, Markstaller K, Baumgardner JE. Maintenance of end-expiratory recruitment with increased respiratory rate after saline-lavage lung injury. J Appl Physiol 102: 331–339, 2007.Link | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: M. Amato, 455 Dr. Arnaldo Ave., Rm. 2206, Sao Paulo SP 01246903, Brazil (e-mail: [email protected]) Download PDF Previous Back to Top Next FiguresReferencesRelatedInformationCited ByA fibre optic oxygen sensor that detects rapid PO2 changes under simulated conditions of cyclical atelectasis in vitroRespiratory Physiology & Neurobiology, Vol. 191A Numerical Model of the Respiratory Modulation of Pulmonary Shunt and PaO2 Oscillations for Acute Lung Injury12 December 2009 | Annals of Biomedical Engineering, Vol. 38, No. 3Reply to Costa and AmatoJames E. Baumgardner, and Rebecca S. Syring1 June 2007 | Journal of Applied Physiology, Vol. 102, No. 6 More from this issue > Volume 102Issue 6June 2007Pages 2414-2414 Copyright & PermissionsCopyright © 2007 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.00154.2007PubMed17551113History Published online 1 June 2007 Published in print 1 June 2007 Metrics

SU‐DD‐A2‐06: The Effect of Respiratory Rate and Radiation Timing On Dose Coverage in Dynamic Breast IMRT

Purpose: IMRT has been shown to be capable of delivering plans with desirable homogeneous dose distribution for breast cancer treatment. However, the dose distribution may be influenced by interplay between dynamic MLC and respiratory motion. The purpose of this study was to investigate the impact of respiratory rate and radiation timing on the dose distribution of breast dynamic IMRT. Method and Materials: Using similar setup configuration, a helical CT and 4DCT image sets for six breast cancer patients were collected and contoured. Dynamic IMRT plans were designed using the helical CT images. The planned MLC sequence was segmented according to the respiratory phases with a series of respiratory rates (7.5–30/min) and radiation timing (evenly distributed in respiratory cycles). The segmented dynamic MLC sequences were applied to the radiation fields on the corresponding 4DCT phases. A program was developed to calculate the cumulative dose distribution from all the phases. Results: For normal breathing rates (15–20/min), the dose coverage didn't change significantly regardless of radiation starting time. The change of target V90 was less than 2%. However, for extremely slow respiratory rates (7.5–10/min), the dose distribution and V90 changed significantly depending on the radiation timing. The change of target V90 was more than 10%. There was no significant dose coverage change for the underlying heart regardless respiratory rate or radiation timing. Conclusions: For breast patients treated with dynamic IMRT, if the respiratory rate of the patient is within the “normal” range then the impact of such respiration on dose coverage of the target was found to be statistically insignificant. However, the dose distribution may change significantly when patient has a slow breathing rate. Respiratory gating may be required to obtain satisfactory dose coverage for such cases. There was no significant dose distribution change for heart regardless respiratory rate or radiation timing.

Effect of respiratory rate on airway deadspace ventilation during exercise in cystic fibrosis

Gas exchange during exercise in patients with cystic fibrosis (CF) is characterised by an elevated physiological deadspace to tidal volume ratio. While this has been attributed to alveolar ventilation–perfusion mismatch, there are other potential causes of the high proportion of wasted ventilation, including factors relating to the volume and the ventilation of the airway deadspace. CF ( n=6, F=1, FEV 1 26–63% pred) and control ( n=6, F=2) subjects completed steady-state exercise on a cycle ergometer. Gas exchange was measured breath-by-breath and the volume of the airway deadspace ( V D aw ) determined using the equal areas method. Exercise data were interpolated to a CO 2 output of 0.7 l/min. V D aw was similar in the two groups both at rest and during exercise. However, the airway deadspace ventilation ( V ̇ D aw ) (median (inter-quartile range)), patients, 6.8 (5.1–7.1) l/min; controls, 4.9 (3.5–5.6) l/min, P<0.05) was significantly greater in the CF group due to a greater respiratory frequency. These results indicate that in CF patients, abnormally increased V ̇ D aw is an important contributor to the total (physiological) deadspace ventilation. Exercise performance in CF might be enhanced by efforts directed at facilitating an increase in exercise tidal volume and therefore the adoption of a more efficient pattern of breathing.

Respiratory system mechanics in acute respiratory distress syndrome.

Respiratory mechanics research is important to the advancement of ARDS management. Twenty-eight years ago, research on the effects of PEEP and VT indicated that the lungs of ARDS patients did not behave in a manner consistent with homogenously distributed lung injury. Both Suter and colleagues] and Katz and colleagues reported that oxygenation continued to improve as PEEP increased (suggesting lung recruitment), even though static Crs decreased and dead-space ventilation increased (suggesting concurrent lung overdistension). This research strongly suggested that without VT reduction, the favorable effects of PEEP on lung recruitment are offset by lung overdistension at end-inspiration. The implications of these studies were not fully appreciated at that time, in part because the concept of ventilator-associated lung injury was in its nascent state. Ten years later. Gattinoni and colleagues compared measurements of static pressure-volume curves with FRC and CT scans of the chest in ARDS. They found that although PEEP recruits collapsed (primarily dorsal) lung segments, it simultaneously causes overdistension of non-dependent, inflated lung regions. Furthermore, the specific compliance of the aerated, residually healthy lung tissue is essentially normal. The main implication of these findings is that traditional mechanical ventilation practice was injecting excessive volumes of gas into functionally small lungs. Therefore, the emblematic low static Crs measured in ARDS reflects not only surface tension phenomena and recruitment of collapsed airspaces but also overdistension of the remaining healthy lung. The studies reviewed in this article support the concept that lung injury in ARDS is heterogeneously distributed, with resulting disparate mechanical stresses, and indicate the additional complexity from alterations in chest wall mechanics. Most of these studies, however, were published before lung-protective ventilation. Therefore, further studies are needed to refine the understanding of the mechanical effects of lung-protective ventilation. Although low-VT ventilation is becoming a standard of care for ARDS patients, many issues remain unresolved; among them are the role of PEEP and recruitment maneuvers in either preventing or promoting lung injury and the effects of respiratory rate and graded VT reduction on mechanical stress in the lungs. The authors believe that advances in mechanical ventilation that may further improve patient outcomes are likely to come from more sophisticated monitoring capabilities (ie, the ability to measure P1 or perhaps Cslice) than from the creation of new modes of ventilatory support.

Effects of respiratory rate, plateau pressure, and positive end-expiratory pressure on PaO2 oscillations after saline lavage.

One of the proposed mechanisms of ventilator-associated lung injury is cyclic recruitment of atelectasis. Collapse of dependent lung regions with every breath should lead to large oscillations in PaO2 as shunt varies throughout the respiratory cycle. We placed a fluorescence-quenching PO2 probe in the brachiocephalic artery of six anesthetized rabbits after saline lavage. Using pressure-controlled ventilation with oxygen, ventilator settings were varied in random order over three levels of positive end-expiratory pressure (PEEP), respiratory rate (RR), and plateau pressure minus PEEP (Delta). Dependence of the amplitude of PaO2 oscillations on PEEP, RR, and Delta was modeled by multiple linear regression. Before lavage, arterial PO2 oscillations varied from 3 to 22 mm Hg. After lavage, arterial PO2 oscillations varied from 5 to 439 mm Hg. Response surfaces showed markedly nonlinear dependence of amplitude on PEEP, RR, and Delta. The large PaO2 oscillations observed provide evidence for cyclic recruitment in this model of lung injury. The important effect of RR on the magnitude of PaO2 oscillations suggests that the static behavior of atelectasis cannot be accurately extrapolated to predict dynamic behavior at realistic breathing frequencies.

The proton pump of heme-copper oxidases.

Proton pumping heme-copper oxidases represent the terminal, energy-transfer enzymes of respiratory chains in prokaryotes and eukaryotes. The Cu B-heme a 3 (or heme o) binuclear center, associated with the largest subunit I of cytochrome c and quinol oxidases, is directly involved in the coupling between dioxygen reduction and proton pumping. The role of the other subunits is less clear. The following aspects will be covered in this paper:i) the efficiency of coupling in the mitochondrial aa 3 cytochrome c oxidase. In particular, the effect of respiratory rate and protonmotive force on the H +/e - stoichiometry and the role of subunit IV; ii) mutational analysis of the aa 3 quinol oxidase of Bacillus subtilis addressed to the role of subunit III, subunit IV and specific residues in subunit I; iii) possible models of the protonmotive catalytic cycle at the binuclear center. The observations available suggest that H +/e -coupling is based on the combination of protonmotive redox catalysis at the binuclear center and co-operative proton transfer in the protein.

Substantia nigra stimulation and blood pressure effects of locally applied kainic acid

Cardiovascular response to electrical stimulation of the substantia nigra were studied in awake, unrestrained cats. Significant increases in the arterial blood pressure, heart rate and respiratory rate appeared simultaneously with the somatomotor effects of stimulation. Twenty-four hours after local microinjection of kainic acid into the site of stimulation the blood pressure responses to stimulation were reduced by 70%, while the changes in heart rate and respiratory rate effects were not statistically significant. Intense somatomotor effects appeared about 30 min after the injection. However, the animal recovered much of its behavioural functions within five hours. It is concluded that the substantia nigra, besides its somatomotor functions, has a role in regulation of blood pressure.

Adverse Effect of Respiratory Rate on Volatile Anesthetic Reporting in Three Infrared Anesthetic Monitors

Adverse Effect of Respiratory Rate on Volatile Anesthetic Reporting in Three Infrared Anesthetic Monitors

Effect of respiratory rate, respiratory depth, and open versus closed mouth breathing on sublingual temperature

The effect of open mouth breathing, tachypnea, and hyperpnea, either alone or in combination, on sublingual and tympanic membrane temperature in healthy adults was investigated. Seventy-eight subjects maintained randomly assigned breathing patterns for 15 minutes. Temperatures were monitored immediately prior to and for 5 minutes following the breathing protocol. The only statistically significant finding (p less than .01) was a lower sublingual temperature with open mouth breathing. No significant changes in tympanic membrane temperature were seen.

Acute inhalation toxicity of 3-methylfuran in the mouse: Pathology, cell kinetics, and respiratory rate effects

The acute inhalation toxicity of 3-methylfuran (3MF) was investigated in male BALB c mice by morphologic examination of animals killed at varying timepoints following a 1-hr exposure to an initial chamber concentration of 14 to 37 μmol/liter (343 to 906 ppm). In addition, respiratory rate measurements and cell kinetics were used to assess quantitatively pulmonary damage and repair. Necrosis of nonciliated bronchiolar epithelial (Clara) cells was seen 1 day following exposure and was followed by regeneration, which was virtually complete, within 21 days. Cell kinetic studies showed peak bronchiolar cell proliferation at 3 days with a labeling index (LI) of 5.0% compared to 0.4% in controls. An increase in parenchymal cell proliferation was also noted coincident with a mild interstitial pneumonitis. This parenchymal proliferation, peaking at 10 days with an LI of 1.4% compared to 0.2% in controls, consisted primarily of type II epithelial and endothelial cell proliferation indicating possible delayed damage and repair of type I epithelial and endothelial cells. The respiratory rate showed an initial transient increase followed by a more prolonged decrease with eventual return to control levels. 3MF toxicity was also evidenced by a necrotizing suppurative rhinitis, centrilobular hepatic necrosis, lymphocyte necrosis in the thymus and spleen, sialoadenitis, and otitis media.

Anaesthetic uptake by the goldfish: effect of respiratory rate.

In order to assess the uptake of halothane by the goldfish, the respiratory rate of six fish was studied when water temperature was varied with and without changes in oxygen or carbon dioxide tension. The effective dose 50 of halothane (ED-50-H) and the time taken to reach it (T-ED-50-H) at an FIO2 of 0.35 in nitrogen, were studied when temperature and CO2 tension were varied. Nomograms were drawn to predict respiratory rate as a function of water CO2 tension, when CO2 was bubbled in air or in oxygen, and with changes in water temperature. At low temperatures (5 degrees C to 7.5 degrees C), respiratory rate remained below 10 per min, irrespective of CO2 partial pressure. At 28 degrees C, a CO2 partial pressure of 8 +/- 0.2 kPa produced a respiratory rate of 125 +/- 3/min in air, and in oxygen unexpectedly 140 +/- 3/min. Halothane ED-50 varied with temperature (0.8% at 10 degrees C and 1.6% at 23 degrees C). Time to reach ED-50-H decreased with increases in respiratory rate, but increased as water temperature was elevated.

The effects of respiratory rate on the mechanical work of breathing during muscular exercise

1. The mechanical work of breathing was measured from simultaneous records of endoesophageal pressure and tidal volume on three normal young subjects exercising on a bicycle-ergometer. The subjects were allowed to increase their ventilation with respiratory rate either spontaneous or regulated by a metronome (f ranging from 20 to 60 cycles per min). 2. At spontaneous respiratory rates the mechanical work of breathing (\(\dot W\)) was found to increase with increasing ventilation (\(\dot V\)) according to the equation proposed byOtis et al. (1950): $$\dot W = K_1 \dot V^2 + K_2 \dot V^3 .$$ 3. The values of the constantsK1 andK2 of equation 1 were found to be inversely proportional to the total lung capacity values of the subjects. 4. When tidal volume was within the range of the resting inspiratory capacity (i. e. when the end-expiratory level during exercise was equal to or above the resting end-expiratory level), the mechanical work of breathing was not affected appreciably by variations in respiratory rate or depth. When, on the other hand, the tidal volume became excessively large (i. e. when lung volumes below the resting end-expiratory level had to be utilized) the mechanical work of breathing was greatly increased. Since at a constant respiratory rate the subjects increased pulmonary ventilation by increasing the tidal volume alone, the lower the value off, the sooner were the subjects obliged to mobilize lung volumes below the resting end-expiratory level. Accordingly, mechanical work versus ventilation curves rise more steeply the lower is f. 5. When allowed to increase ventilation without any control of respiratory rate, the subjects chose spontaneously respiratory rates and levels in the range where pulmonary ventilation involved minimal effort.