Entrainment of respiratory rhythm to respiratory oscillations of arterial PCO2 in vagotomized dogs.

The aim of this study was to demonstrate that the medullary respiratory rhythm generator is capable of entraining to respiratory oscillations of arterial PCO2 (CO2 oscillations). We used 10 anesthetized, paralyzed, vagotomized, and mechanically ventilated dogs. First, rate of mechanical ventilation was manually adjusted so that it matched the dog's spontaneous respiratory rate, which established a constant phase relationship between the mechanical ventilation and the burst of phrenic neurogram (initial phase). Then this phase relationship was temporally disturbed by a brief electrical stimulation of the superior laryngeal nerve (SLN). In the control group, the initial phase and the steady-state phase relationship after SLN stimulation were randomly distributed within the phase plane, implying no interaction between the respiratory center and mechanical ventilation. In contrast, when CO2 output from the lung was increased 2.6-fold above the control level by venous CO2 loading, the initial phase and the steady-state phase after SLN stimulation were locked in such a way that the onset of the burst of phrenic neurogram coincided with the peak of CO2 oscillations. This was not demonstrated when the dog was made hyperoxic. We therefore conclude that the respiratory center could entrain to phasic chemical afferent inputs originating from CO2 oscillations, provided they are considerably amplified.     

Effect of hypoxia on respiratory system impedance in dogs

Simon, B. A., P. B. Zanaboni, and D. P. Nyhan. Effectof hypoxia on respiratory system impedance in dogs. J. Appl. Physiol. 83(2): 451-458, 1997.The effects of hypoxia on lung and airwaymechanics remain controversial, possibly because of the confoundingeffects of competing reflexes caused by systemic hypoxemia. We comparedthe effects of systemic hypoxemia with those of unilateral alveolarhypoxia (with systemic normoxemia) on unilateral respiratory systemimpedance (Z) in intact, anesthetized dogs. Independent lungventilation was obtained with a Kottmeier endobronchial tube.Individual left and right respiratory system Z was measured duringsinusoidal forcing with 45 ml of volume at frequencies of 0.2-2.1Hz during control [100% inspiredO₂ fraction(FI_O2)], systemichypoxemia (10% FI_O2), andunilateral alveolar hypoxia (0%FI_O2 to left lung, 100%FI_O2 to right lung). Duringsystemic hypoxemia, there was a mean Z magnitude increase of 18%. Thischange was entirely attributable to a decrease in the imaginarycomponent of Z; there was no change in the real component of Z. Administration of atropine (0.2 mg/kg) did not block the increase in Zwith systemic hypoxemia. In contrast, there was no change in Z in thelung subjected to unilateral alveolar hypoxia. We conclude thatalveolar hypoxia has no direct effect on lung mechanical properties inintact dogs. In contrast, systemic hypoxemia does increase lungimpedance, apparently through a noncholinergic mechanism.

     

Modeling of respiratory system impedances in dogs

Mechanical impedances between 4 and 64 Hz of the respiratory system in dogs have been reported (A.C. Jackson et al. J. Appl. Physiol. 57: 34-39, 1984) previously by this laboratory. It was observed that resistance (the real part of impedance) decreased slightly with frequency between 4 and 22 Hz then increased considerably with frequency above 22 Hz. In the current study, these impedance data were analyzed using nonlinear regression analysis incorporating several different lumped linear element models. The five-element model of Eyles and Pimmel (IEEE Trans. Biomed. Eng. 28: 313-317, 1981) could only fit data where resistance decreased with frequency. However, when the model was applied to these data the returned parameter estimates were not physiologically realistic. Over the entire frequency range, a significantly improved fit was obtained with the six-element model of DuBois et al. (J. Appl. Physiol. 8: 587-594, 1956), since it could follow the predominate frequency-dependent characteristic that was the increase in resistance. The resulting parameter estimates suggested that the shunt compliance represents alveolar gas compressibility, the central branch represents airways, and the peripheral branch represents lung and chest wall tissues. This six-element model could not fit, with the same set of parameter values, both the frequency-dependent decrease in Rrs and the frequency-dependent increase in resistance. A nine-element model recently proposed by Peslin et al. (J. Appl. Physiol. 39: 523-534, 1975) was capable of fitting both the frequency-dependent decrease and the frequency-dependent increase in resistance. However, the data only between 4 and 64 Hz was not sufficient to consistently determine unique values for all nine parameters.     

pH dependence of the Coxiella burnetii glutamate transport system.

The transport of glutamate, apparently a primary energy source for Coxiella burnetii, has been examined. C. burnetii is shown to possess a pH-dependent active transport system for L-glutamate with an apparent Kt of 61.1 microM and Vmax of 8.33 pmol/s per mg at pH 3.5. Both L-glutamine and L-asparagine competitively inhibited transport of glutamate, but D-glutamate, L-aspartate, L-glutamate-gamma-methyl ester, methionine sulfoximine, or alpha-ketoglutarate did not compete. This transport system is both temperature and energy dependent. Uptake of glutamate is highly sensitive to uncouplers of oxidative phosphorylation such as 2,4-dinitrophenol and carbonyl cyanide-m-chlorophenyl hydrazone that decrease the proton motive force across the cytoplasmic membrane. ATPase inhibitors such as dicyclohexylcarbodiimide or metabolic poisons such as KCN, NaF, or arsenite were much less effective as inhibitors of glutamate transport. Uptake of glutamate did not appear to be coupled to Na+ symport as in Escherichia coli since no monovalent cation requirement could be demonstrated. Instead, the Vmax of glutamate transport showed good correlation with the transmembrane pH gradient (delta pH). From these results, we propose that L-glutamate transport by C. burnetii is energized via a proton motive force.     

Evidence for the dependence of arterial haemostasis on ADP

The possible involvement of adenosine diphosphate (ADP) in haemostatic platelet aggregation was investigated by determining the duration of primary haemorrhage as standardized bleeding times from punctures of small mesenteric arteries in anaesthetized rats. The bleeding times were highly significantly increased by infusing into the mesenteric arterial blood flowing towards the punctures either the nucleotide-dephosphorylating enzyme apyrase or the ADP-receptor antagonists ATP, adenosine 5'-(beta,gamma-methylene)triphosphonate (AMP-PCP) or 2-methylthioadenosine 5'-(beta,gamma-methylene)triphosphonate (2-MeS-AMP-PCP). The increases in bleeding times could not be accounted for by local vasodilator effects of the agents. It is concluded that the presence of ADP through local release and/or formation at sites of vascular injury contributes significantly to haemostasis, presumably by accelerating platelet aggregation.     

Simulation of continuous blood O2 equilibrium curve over physiological pH, DPG, and Pco2 range

We analyzed 56 O2 equilibrium curves of fresh human blood, each from 0 to 150 Torr Po2. The data were collected over ranges of values for the 2,3-diphosphoglyceric acid-to-hemoglobin concentration ratio [DPG]/[Hb] of 0.2-2.7, for pH of 7.0-7.8, and for Pco2 of 7-70 Torr. Each curve was characterized according to the Adair scheme for the stepwise oxygenation of Hb, and the resulting constants (a1, a2, a3, a4) were analyzed to allow the simulation of the entire O2 equilibrium curve under any conditions of [DPG]/[Hb], pH, and Pco2 in the specified range. This analysis provides a powerful tool to study the affinity of Hb for O2 within the red blood cell and to predict the shape of the O2 equilibrium curve in various physiological and pathological states. Other attempts to predict blood O2 affinity have considered only P50 (the Po2 at one-half saturation with O2) or have provided too little data for continuous simulations.     

Physiological basis for resonant frequencies in respiratory system impedances in dogs

The lumped six-element model of the respiratory system proposed by DuBois et al. (J. Appl. Physiol. 8: 587-594, 1956) has often been used to analyze respiratory system impedance (Zrs) data. This model predicts a resonance (relative minimum in Zrs) at fr between 6 and 10 Hz and an antiresonance (relative maximum in Zrs) at far at higher frequencies (greater than 64 Hz). The far is due to the lumped tissue inertance (Iti) and the alveolar gas compression compliance (Cg). An fr and far have been recently reported in humans, but the far was shown to be not related to Iti and Cg, but instead it is the first acoustic antiresonance of the airways due to their axial dimensions). Zrs data to frequencies high enough to include the far have not been reported in dogs. In this study, we measured Zrs in dogs for frequencies between 5 and 320 Hz and found an fr at 7.5 +/- 1.6 Hz and two far at 97 +/- 13 and 231 +/- 27 Hz (far,1 and far,2, respectively). When breathing 80% He-20% O2, the fr shifted to 14 +/- 2 Hz, far,1 did not change (98 +/- 9 Hz), and far,2 increased to greater than 320 Hz. The behavior of fr and far,1 is consistent with the structure-function implied by the six-element model. However, the presence of an far,2 is not consistent with this model, because it is the airway acoustic antiresonance not represented in the model. These results indicate that, for frequencies that include the fr and far,1, the six-element model can be used to analyze Zrs data and reliable estimates of the model's parameters can be extracted by fitting the model to the data. However, more complex models must be used to analyze Zrs data that include far,2.     

Effects of acute pleural effusion on respiratory system mechanics in dogs

We determined regional (Vr) and overall lung volumes in six head-up anesthetized dogs before and after the stepwise introduction of saline into the right pleural space. Functional residual capacity (FRC), as determined by He dilution, and total lung capacity (TLC) decreased by one-third and chest wall volume increased by two-thirds the saline volume added. Pressure-volume curves showed an apparent increase in lung elastic recoil and a decrease in chest wall elastic recoil with added saline, but the validity of esophageal pressure measurements in these head-up dogs is questionable. Vr was determined from the positions of intraparenchymal markers. Lower lobe TLC and FRC decreased with added saline. The decrease in upper lobe volume was less than that of lower lobe volume at FRC and was minimal at TLC. Saline increased the normal Vr gradient at FRC and created a gradient at TLC. During deflation from TLC to FRC before saline was added, the decrease in lung volume was accompanied by a shape change of the lung, with greatest distortion in the transverse (ribs to mediastinum) direction. After saline additions, deflation was associated with deformation of the lung in the cephalocaudal and transverse directions. The deformation with saline may be a result of upward displacement of the lungs into a smaller cross-sectional area of the thoracic cavity.