Rehder, Kai

Abstract The sections in this article are: Effects of Anesthesia on the Chest Wall Anesthesia With Spontaneous Breathing Anesthesia‐Paralysis With Mechanical Ventilation of the Lungs Effects of Anesthesia on FRC Effects of Anesthesia on Pressure‐Volume Relationships Total Respiratory System Lungs Chest Wall Mechanisms for Changes in Pressure‐ Volume Relationships Effects of Anesthesia on Pressure‐Flow Relationships Effects of Anesthesia on Intrapulmonary Inspired‐Gas Distribution Anesthesia With Spontaneous Breathing Anesthesia‐Paralysis With Mechanical Ventilation of the Lungs Conclusions

Abstract The sections in this article are: Equation of Motion Application of Equation of Motion to a Model Determination of Resistance and Compliance Inertance and Reactance Impedance Time Constant Nonlinear Resistance and Hysteresis Application of Equation of Motion to the Respiratory System Applied Pressures Relationship to Lung Volume Tidal Breathing Opposing Pressures Flow Resistance Maximal Expiratory Flow Gas Compression and Measurement of Flow‐Volume Curves Dynamics of Breathing Breathing at Rest and During Exercise Factors Affecting Respiratory Dynamics

Halothane is a potent bronchodilator that attenuates vagally mediated constriction of canine airways, in part by a direct action on the smooth muscle cell. In tracheal smooth muscle, acetylcholine (ACh) produces a transient peak increase in cytosolic ionized calcium concentration ([Ca2+]i), which declines to a sustained plateau concentration that is higher than that of the unstimulated muscle, and a sustained increase in force. The transient peak [Ca2+]i is caused primarily by Ca2+ release from the sarcoplasmic reticulum (SR), whereas the plateau [Ca2+]i is caused primarily by influx of extracellular Ca2+ across the plasma membrane. This study was conducted to investigate the effects of halothane on the 1) transient peak [Ca2+]i during force development (i.e., developed force) and 2) plateau [Ca2+]i during force maintenance (i.e., sustained force) induced by ACh in isolated strips of canine tracheal smooth muscle. Changes in [Ca2+]i were measured with the photoprotein, aequorin. In muscle strips contracted after incubation with 1.1 (n = 5) or 1.5 (n = 5) minimum alveolar concentration (MAC) halothane, halothane significantly attenuated the transient peak aequorin luminescence (AL) and developed force and significantly prolonged the time necessary to reach peak AL and developed force; these effects were not dose dependent. In muscle strips (n = 3) contracted with ACh, addition of halothane caused a reduction in sustained force but no decrease in plateau AL.(ABSTRACT TRUNCATED AT 250 WORDS)

Prejunctional and postjunctional muscarinic receptor subtypes were characterized in canine trachealis muscle strips. In vitro contractile responses of muscle strips to acetylcholine or electric field stimulation were determined in the absence and the presence of gallamine, pirenzepine, and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP). Gallamine had no effect on the contractile response to acetylcholine but enhanced the contractile response to electric field stimulation. Pirenzepine and 4-DAMP reduced the contractile response to acetylcholine and electric field stimulation. The pA2 value for pirenzepine vs. acetylcholine [7.18 +/- 0.59 (SD)] was consistent with the affinity of pirenzepine for M2 or M3-receptors; whereas the pA2 value for 4-DAMP vs. acetylcholine (8.92 +/- 0.42) and the extremely low affinity of gallamine indicated postjunctional muscarinic receptors of the M3 subtype. The enhancement of the contractile response to electric field stimulation by gallamine suggested the presence of M2-prejunctional receptors.

To determine the cause of the difference in gas exchange between the prone and supine postures in dogs, gas exchange was assessed by the multiple inert gas elimination technique (MIGET) and distribution of pulmonary blood flow was determined using radioactively labeled microspheres in seven anesthetized paralyzed dogs. Each animal was studied in the prone and supine positions in random order while tidal volume and respiratory frequency were kept constant with mechanical ventilation. Mean arterial PO2 was significantly lower (P less than 0.01) in the supine [96 +/- 10 (SD) Torr] than in the prone (107 +/- 6 Torr) position, whereas arterial PCO2 was constant (38 Torr). The distribution of blood flow (Q) vs. ventilation-to-perfusion ratio obtained from MIGET was significantly wider (P less than 0.01) in the supine [ln SD(Q) = 0.75 +/- 0.26] than in the prone position [ln SD (Q) = 0.34 +/- 0.05]. Right-to-left pulmonary shunting was not significantly altered. The distribution of microspheres was more heterogeneous in the supine than in the prone position. The larger heterogeneity was due in part to dorsal-to-ventral gradients in Q in the supine position that were not present in the prone position (P less than 0.01). The decreased efficiency of oxygenation in the supine posture is caused by an increased ventilation-to-perfusion mismatch that accompanies an increase in the heterogeneity of Q distribution.

Although the pentobarbital-anesthetized dog is often used as a model in studies of respiratory muscle activity during spontaneous breathing, there is no information regarding the stability of the pattern of breathing of this model over time. The electromyograms of several inspiratory and expiratory muscle groups were measured in six dogs over a 4-h period by use of chronically implanted electrodes. Anesthesia was induced with pentobarbital sodium (25 mg/kg iv), with supplemental doses to maintain constant plasma pentobarbital concentrations. Phasic electrical activity increased over time in the triangularis sterni, transversus abdominis, and external oblique muscles (expiratory muscles). The electrical activity of the costal diaphragm, crural diaphragm, and parasternal intercostal muscles (inspiratory muscles) was unchanged. These changes in electrical activity occurred despite stable plasma levels of pentobarbital and arterial PCO2. They were associated with changes in chest wall motion and an increased tidal volume with unchanged breathing frequency. We conclude that expiratory muscle groups are selectively activated with time in pentobarbital-anesthetized dogs lying supine. Therefore the duration of anesthesia is an important variable in studies using this model.

To determine the relative contribution of rib cage and abdominal muscles to expiratory muscle activity during quiet breathing, we used lumbar epidural anesthesia in six pentobarbital sodium-anesthetized dogs lying supine to paralyze the abdominal muscles while leaving rib cage muscle motor function substantially intact. A high-speed X-ray scanner (Dynamic Spatial Reconstructor) provided three-dimensional images of the thorax. The contribution of expiratory muscle activity to tidal breathing was assessed by a comparison of chest wall configuration during relaxed apnea with that at end expiration. We found that expiratory muscle activity was responsible for approximately half of the changes in thoracic volume during inspiration. Paralysis of the abdominal muscles had little effect on the pattern of breathing, including the contribution of expiratory muscle activity to tidal breathing, in most dogs. We conclude that, although there is consistent phasic expiratory electrical activity in both the rib cage and the abdominal muscles of pentobarbital-anesthetized dogs lying supine, the muscles of the rib cage are mechanically the most important expiratory muscles during quiet breathing.

The distribution of tidal air and nonshunted blood flow to each lung, the elimination of CO2 from each lung, and Paco2 were measured in ten anesthetized and paralyzed dogs during intermittent positive-pressure breathing in the supine position and before and after thoracotomy in the lateral decubitus position. Ventilation via a divided tracheal airway (Wright-Lategola) at a constant rate and a constant volume (±5%) with 65% oxygen in nitrogen was provided by a Bird ventilator. Reduction of total CO2 elimination and increase of ratio of total physiologic dead space to tidal volume were observed after thoracotomy. Mean percentages of total ventilation and blood flow to, and CO2 elimination from, the right lung were about 58% in the supine position. When the right or left lung became dependent in the lateral decubitus position, its proportional ventilation and CO2 elimination decreased. After thoracotomy was made on the superior nondependent side, further reductions were noted and blood flow to the dependent lung also decreased. Proportional CO2 elimination was more dependent on alveolar ventilation than on the ratio of ventilation to perfusion.

Both interregional and intraregional mechanisms may cause changes in N2 concentration of expired gas during the phases of the single-breath O2 test (SBO2) that follow dead-space washout. To evaluate the possible importance of each mechanism, we performed the SBO2 in excised canine lungs that were first suspended in air and then immersed in stable foams that simulated the vertical gradient of pleural pressure. The lungs were deflated at constant submaximal flows. The slope of phase III diminished with increasing expiratory flow and increased with foam immersion. The onset of phase IV depended on flow, and a terminal decrease in N2 concentration (phase V) was often observed. Simultaneously measured estimates of regional flows and volumes (J. Appl. Physiol. 65: 1764-1774, 1988) were used to further interpret these results. The onset of phase IV at flows greater than quasi-static signified the onset of flow limitation of dependent regions. The onset of phase V corresponded to flow limitation of nondependent regions.

We have previously demonstrated appreciable inhomogeneity of alveolar pressures measured by a capsule technique in excised canine lobes deflated at submaximal flows (J. Appl. Physiol. 65: 1757-1765, 1988). We further analyzed the results of these experiments by estimating alveolar volumes (VA) and regional flows from regional transpulmonary pressures, assuming that regional pressure-volume relationships were homogeneous. Deflation at submaximal flows of lungs suspended in air caused significant flow-dependent inhomogeneity of VA that increased as lung volume decreased. Immersion of lungs in stable foams that simulated the gradient of pleural pressure modified the pattern of emptying, but not always to a gravity-dependent sequence. Limitation of regional expiratory flow was often asynchronous during both air suspension and foam immersion. There was no evidence of a common regional flow-volume curve. Submaximal deflation is a complex heterogeneous process, with the interregional pattern of emptying determined by the interaction of factors that are both intrinsic and extrinsic to the lungs.