Age-related effects of compression rate and duration in cardiopulmonary resuscitation

The effects of various compression rate and duration combinations on chest geometry and cerebral perfusion pressure during cardiopulmonary resuscitation (CPR) were studied in immature swine. Pentobarbital-anesthetized 2- and 8-wk-old piglets received CPR after ventricular fibrillation. At compression rates of 40, 60, 80, 100, 120, and 150/min, duty cycle (compression duration/total cycle time) was increased from 10 to 80% by 10% increments. Mean aortic and sagittal sinus pressures, pulsatile displacement, and deformity of the anterior chest wall were measured. Increasing duty cycle increased cerebral perfusion pressure until chest relaxation time was compromised. Inadequate chest recoil, development of static chest deformation, and limitation of pulsatile chest wall movement occurred in both age groups when relaxation time was very short (150-200 ms in 2-wk-old piglets, 250-300 ms in 8-wk-old piglets). These changes in chest geometry correlated with deterioration of cerebral perfusion pressure only in 8-wk-old piglets. In the younger group, perfusion pressures plateaued but did not deteriorate. These data emphasize the importance of duty cycle in generating cerebral perfusion pressure and indicate that younger animals can tolerate high compression rates except at extremely long duty cycles.     

Vagal control of central and peripheral pulmonary resistance in developing piglets

To study the postnatal maturation of vagal control of airway muscle tone, we determined the effects of vagotomy and supramaximal vagal stimulation on the resistance of the respiratory system in eight newborn and seven 6-wk-old piglets. Because the lung periphery has distinctive responses to cholinergic agonists and a lower density of vagal fibers and cholinergic receptors than the central airways, we partitioned the respiratory resistance of the piglets between central airways (Rc) and peripheral airways and lung tissue (Rp) with bronchial catheters inserted in a retrograde manner. The piglets were anesthetized with alpha-chloralose and ventilated with positive airway pressure. Vagotomy did not change Rc or Rp in either the newborn or the 6-wk-old piglets. Vagal stimulation, on the other hand, increased both Rc (median increase 53% in the newborn and 72% in the 6-wk-old piglets) and Rp (54 and 42%, respectively). At all states of vagal tone, Rp increased as the lungs were inflated, suggesting a large contribution of tissue viscoelasticity to this resistance. Our results demonstrate that vagal bronchomotor tone is absent during mechanical ventilation with positive pressure in the developing piglet. However, vagal innervation of both central airways and tissue contractile elements is functionally competent at the time of birth in this species.     

Interrupter technique for measurement of respiratory mechanics in anesthetized cats

In six spontaneously breathing anesthetized cats (pentobarbital sodium, 35 mg/kg ip), airflow, changes in lung volume, and tracheal and esophageal pressures were measured. Airflow was interrupted by brief airway occlusions during relaxed expirations (elicited via the Breuer-Hering inflation reflex) and throughout spontaneous breaths. A plateau in tracheal pressure occurred throughout relaxed expirations and the latter part of spontaneous expirations indicating respiratory muscle relaxation. Measurement of tracheal pressure, immediately preceding airflow, and corresponding volume enabled determination of respiratory system elastance and flow resistance. These were partitioned into lung and chest wall components using esophageal pressure. Respiratory system elastance was constant over the tidal volume range, divided approximately equally between the lung and chest wall. While the passive pressure-flow relationship for the respiratory system was linear, those for the lung and chest wall were curvilinear. Volume dependence of chest wall flow resistance was demonstrated. During inspiratory interruptions, tracheal pressure increased progressively; initial tracheal pressure was estimated by backward extrapolation. Inspiratory flow resistance of the lung and total respiratory system were constant. Force-velocity properties of the contracting inspiratory muscles contributed little to overall active resistance.     

Effects of vagotomy on respiratory mechanics in newborn and adult pigs

We have examined breathing patterns and respiratory mechanics in anesthetized tracheostomized newborn piglets and adult pigs and the changes determined by cervical bilateral vagotomy. Piglets had a respiratory system compliance and resistance, on a per kilogram basis, respectively, higher and smaller than the adults. After vagotomy neither variable changed in the newborn, but resistance dropped in the adult. This may suggest that efferent vagal control of bronchomotor tone is more pronounced in the adult. Respiratory system time constant was longer in newborns both before and after vagotomy. The distortion of the chest wall, examined as the ratio between the volume inhaled spontaneously and the passive volume for the same abdominal motion, was more marked in newborns, reflecting their higher chest wall compliance. The work per minute, computed from the pressure and volume changes, was larger in piglets. After vagotomy the external work per minute was not different; however, the larger tidal volumes were accompanied by a larger chest distortion. This may indicate that vagal control of the breathing pattern, by limiting the depth of inspiration and hence the amount of chest distortion, has implications on the energetics of breathing.     

Frequency-dependent effects of hypercapnia on respiratory mechanics of cats

The effect of increasing arterial partial pressure of CO2 (PaCO2) on respiratory mechanics was investigated in six anesthetized, paralyzed cats ventilated by constant-flow inflation. Respiratory mechanics were studied after end-inspiratory occlusions. Zero frequency resistance (Rmax), infinite frequency resistance (Rmin), and static elastance (Est) were calculated for the respiratory system, lung, and chest wall. Alveolar ventilation was manipulated by the addition of dead space to achieve a range of PaCO2 values of 29.3-87.3 mmHg. Cats did not become hypoxic during the experiment. Under control conditions marked frequency dependence in Rmax, Rmin, and Est of the respiratory system, lungs, and chest wall was demonstrated. The chest wall contributed 50% of the total resistance of the respiratory system. With increasing PaCO2 the only resistance observed to increase was Rmax of the lung (P less than 0.01). There were also no changes in the static elastic properties of either the lungs or the chest wall. These results suggest that hypercapnia increases resistance by changes in the lung periphery and not in the conducting airways.     

Diaphragmatic activity is a determinant of postnatal lung growth

To test the hypothesis that activity of respiratory muscles determines regional growth of lung parenchyma, we studied the effects of unilateral diaphragmatic paralysis on contralateral/ipsilateral lung growth in cats and piglets. Five 10- to 12-wk-old cats and five 8-wk-old piglets underwent unilateral diaphragmatic paralysis by thoracic and cervical phrenectomy, respectively. Five to seven weeks after surgery, when the cats were killed for studies of lung growth, gain in body weight was the same as in five sham-operated controls. At this time, mean pleural pressure ipsilateral to the paralyzed hemidiaphragm was the same as contralateral mean pleural pressure during tidal breathing, and values did not differ from controls. However overall functional residual capacity was lower in the phrenectomized cats (35 +/- 4 ml) than in the controls (55 +/- 11 ml, P less than 0.01). Growth of contralateral lungs relative to ipsilateral lungs was greater in the phrenectomized cats than in the controls, as shown by ratios of contralateral/ipsilateral wet lung weight (1.44 vs. 1.34, P less than 0.01), maximum inflation volume (1.53 vs. 1.33, P less than 0.05), and total protein content (1.45 vs. 1.26, P less than 0.05). Ratios of total protein to DNA and RNA to DNA were unchanged. One week after surgery in the piglets, the ratio of contralateral/ipsilateral wet lung weight was increased (1.61 vs. 1.29, P less than 0.01) and total weight of both lungs was reduced. We conclude that regional growth of lung parenchyma by cell proliferation depends in part on regional distribution of respiratory muscle activity.     

Chest wall and respiratory system mechanics in cats: effects of flow and volume

The effects of inspiratory flow rate and inflation volume on the resistive properties of the chest wall were investigated in six anesthetized paralyzed cats by use of the technique of rapid airway occlusion during constant flow inflation. This allowed measurement of the intrinsic resistance (Rw,min) and overall dynamic inspiratory impedance (Rw,max), which includes the additional pressure losses due to time constant inequalities within the chest wall tissues and/or stress adaptation. These results, together with our previous data pertaining to the lung (Kochi et al., J. Appl. Physiol. 64: 441-450, 1988), allowed us to determine Rmin and Rmax of the total respiratory system (rs). We observed that 1) Rw,max and Rrs,max exhibited marked frequency dependence; 2) Rw,min was independent of flow (V) and inspired volume (delta V), whereas Rrs,min increased linearly with V and decreased with increasing delta V; 3) Rw,max decreased with increasing V, whereas Rrs,max exhibited a minimum value at a flow rate substantially higher than the resting range of V; 4) both Rw,max and Rrs,max increased with increasing delta V. We conclude that during resting breathing, flow resistance of the chest wall and total respiratory system, as conventionally measured, includes a significant component reflecting time constant inequalities and/or stress adaptation phenomena.     

Viscoplasticity of respiratory tissues

Low-frequency mechanical behavior of various respiratory tissues shows certain similarities. In this study we test the hypothesis that rate-independent plastic processes along with rate-dependent viscoelastic processes are responsible. We considered oscillatory responses of several respiratory tissues measured over prescribed ranges of frequency (up to 6 Hz) and amplitude of forcing. These included the excised cat lung, the human chest wall in vivo, and two components of the chest wall: the excised dog rib cage and the excised rabbit abdominal viscera; some data were previously reported and some are new. We analyzed these data using the viscoplastic model of Hildebrandt (J. Appl. Physiol. 28: 365-372, 1970). It consists of three compartments: a plastoelastic compartment mechanically in parallel with a viscoelastic compartment, both in series with a lumped inertia. We fitted oscillatory data of the above respiratory tissues to the model by a least-squares technique. The fit was qualitatively consistent with the observations and exhibited moderately good to very good quantitative correspondence. As an independent verification of this approach, we obtained the stress relaxation after a step-volume change. Based on the oscillatory response of cat lungs, the calculated stress relaxation function was found to be generally consistent with corresponding observations. This study indicates that both plasticity and viscoelasticity appear to be important determinants of mechanical behavior of respiratory tissues at low frequencies and that inertial effects are negligible.     

Effect of respiratory muscle tension on lung volume.

The chest wall is modeled as a linear system for which the displacements of points on the chest wall are proportional to the forces that act on the chest wall, namely, airway opening pressure and active tension in the respiratory muscles. A standard theorem of mechanics, the Maxwell reciprocity theorem, is invoked to show that the effect of active muscle tension on lung volume, or airway pressure if the airway is closed, is proportional to the change of muscle length in the relaxation maneuver. This relation was tested experimentally. The shortening of the cranial-caudal distance between a rib pair and the sternum was measured during a relaxation maneuver. These data were used to predict the respiratory effect of forces applied to the ribs and sternum. To test this prediction, a cranial force was applied to the rib pair and a caudal force was applied to the sternum, simulating the forces applied by active tension in the parasternal intercostal muscles. The change in airway pressure, with lung volume held constant, was measured. The measured change in airway pressure agreed well with the prediction. In some dogs, nonlinear deviations from the linear prediction occurred at higher loads. The model and the theorem offer the promise that existing data on the configuration of the chest wall during the relaxation maneuver can be used to compute the mechanical advantage of the respiratory muscles.     

Compliances of the liquid-filled lungs and chest wall during development in fetal sheep.

Our aim was to measure the compliance of the liquid-filled lungs (CL), and the compliance of the chest wall (CW) in fetal sheep in utero. CL and CW were measured in 6 fetuses. The compliance of the lungs and chest wall combined (respiratory system, Crs) was measured in 9 fetuses. Pressure differences across the lungs (PL), chest wall (PW) and respiratory system (Prs) were measured while the lungs were deflated and inflated with liquid from their resting lung liquid volume (V1). V1 was measured using an indicator dilution technique. Specific compliance values were obtained by normalizing the values of CL, CW and Crs with respect to values of V1. From values obtained during stepwise inflation from V1, specific compliances (ml/cm H2O/ml of lung liquid) were: lungs, 0.22 +/- 0.02; chest wall, 0.41 +/- 0.07; respiratory system, 0.13 +/- 0.01. Specific compliances of the lungs, chest wall and respiratory system did not change significantly with advancing gestational age from 120 to 143 days. Our baseline data will be valuable in assessing the in utero progress of the structural development of the lungs following manipulations known to cause altered lung growth.     

Dynamic lung compliance in newborn and adult cats

Static (Cstat) and dynamic (Cdyn) lung compliance and lung stress relaxation were examined in isolated lungs of newborn kittens and adult cats. Cstat was determined by increasing volume in increments and recording the corresponding change in pressure; Cdyn was calculated as the ratio of the changes in volume to transpulmonary pressure between points of zero flow at ventilation frequencies between 10 and 110 cycles/min. Lung volume history, end-inflation volume, and end-deflation pressure were maintained constant. At the lowest frequency of ventilation, Cdyn was less than Cstat, the difference being greater in newborns. Between 20 and 100 cycles/min, Cdyn of the newborn lung remained constant, whereas Cdyn of the adult lung decreased after 60 cycles/min. At all frequencies, the rate of stress relaxation, measured as the decay in transpulmonary pressure during maintained inflation, was greater in newborns than in adults. The frequency response of Cdyn in kittens, together with the relatively greater rate of stress relaxation, suggests that viscoelasticity contributes more to the dynamic stiffening of the lung in newborns than in adults. A theoretical treatment of the data based on a linear model of viscoelasticity supports this conclusion.     

Effect of distortion on the mechanical properties of newborn piglet lung

During breathing the relatively high chest wall-to-lung compliance ratio of the newborn favors distortion of the respiratory system. In this study we have examined the effect of lung deformation, generated by a hydrostatic pleural surface pressure gradient, on the static (Cstat) and dynamic (Cdyn) compliance of the isolated newborn piglet lung. Seven lungs from piglets 2-7 days old have been studied in a saline-filled plethysmograph. Static pressure-volume (PV) curves were obtained by changing the volume a known amount and measuring the corresponding changes in transpulmonary pressure. Dynamic PV curves were obtained by ventilating the lung at a fixed pressure and at 20 cycles/min. These experiments were repeated in an air plethysmograph on the undeformed lung. Lung volume history was standardized prior to each maneuver by three inflations to 20-25 cmH2O. Lung collapse was avoided by applying an end-expiratory load equal to the transpulmonary pressure at functional residual capacity. Cstat was not significantly different between the deformed and undeformed lung (P greater than 0.05). Cdyn was less than Cstat in both cases (P less than 0.025) and was reduced further by deformation (P less than 0.05). We conclude that 1) peripheral airway obstruction or the viscoelastic properties of the piglet lung, or both, decrease Cdyn, and 2) deformation increases the external (PV) respiratory work by further decreasing Cdyn.     

Positive effort dependence of maximal expiratory flow

The maximal expiratory-flow volume (MEFV) curve in normal subjects is thought to be relatively effort independent over most of the vital capacity (VC). We studied seven normal males and found positive effort dependence of maximal expiratory flow between 50 and 80% VC in five of them, as demonstrated by standard isovolume pressure-flow (IVPF) curves. We then attempted to distinguish the effects of chest wall conformational changes from possible mechanisms intrinsic to the lungs as an explanation for positive effort dependence. IVPF curves were repeated in four of the subjects who had demonstrated positive effort dependence. Transpulmonary pressure was varied by introducing varied resistances at the mouth but effort, as defined by pleural pressure, was maintained constant. By this method, chest wall conformation at a given volume would be expected to remain the same despite changing transpulmonary pressures. When these four subjects were retested in this way, no increases in flow with increasing transpulmonary pressure were found. In further studies, voluntarily altering the chest wall pattern of emptying (as defined by respiratory inductive plethysmography) did however alter maximal expiratory flows, with transpulmonary pressure maintained constant. We conclude that maximal expiratory flow can increase with effort over a larger portion of the vital capacity than is commonly recognized, and this effort dependence may be the result of changes in central airway mechanical properties that occur in relation to changes in chest wall shape during forced expiration.     

Expiratory pattern of newborn mammals

The passive mechanical time constant (tau pass) of the respiratory system is relatively similar among newborn mammalian species, approximately 0.15-0.2 s. However, breathing rate (f) is higher in smaller species than larger species in order to accommodate the relatively larger metabolic demands. Since tidal volume per kilogram is an interspecies constant, in the fastest breathing species the short expiratory time should determine a substantial dynamic elevation of the functional residual capacity (FRC). We examined the possibility of a difference in expiratory time constant between dynamic and passive conditions by analyzing the expiratory flow pattern of nine newborn unanesthetized species during resting breathing. In most newborns the late portion of the expiratory flow-volume curve was linear, suggesting muscle relaxation. The slope of the curve, which represents the dynamic expiratory time constant of the respiratory system (tau exp), varied considerably among animals (from 0.1 to 0.7 s), being directly related to the inspiratory time and inversely proportional to f. In relatively slow-breathing newborns, such as infants and piglets, tau exp is longer than tau pass most likely due to an increase in the expiratory laryngeal resistance and FRC is substantially elevated. On the contrary, in the fastest breathing newborns (such as rats and mice) tau exp is similar or even less than tau pass, because at these high rates dynamic lung compliance is lower than its passive value and the dynamic elevation of FRC is small. In dynamic conditions, therefore, the product of tau exp and f is maintained within narrow limits.(ABSTRACT TRUNCATED AT 250 WORDS)     

Elastic moduli of lungs during postnatal development in the piglet

Several manifestations of lung disease during infancy suggest that mechanical interdependence can be relatively high in newborn lungs. To test this possibility, we measured elastic moduli and pleural membrane tension in lungs excised from piglets ranging in age from less than 12 h to 85 days. Near maximum inflation, newborn lungs (less than 12 h, n = 6) had no detectable pleural membrane tension, although 3- to 5-day-old lungs (n = 6) had tension greater than 5,000 dyn/cm. In contrast, parenchymal recoil was greater in the newborn lungs [19.3 +/- 3.0 (SD) vs. 14.3 +/- 2.4 cmH2O at 90% of maximum inflation volume, P less than 0.01]. Shear moduli were higher (13.5 +/- 4.6 vs. 9.2 +/- 1.5 cmH2O at 15 cmH2O transpulmonary pressure, P less than 0.05) and Poisson ratios were lower in the newborn lungs as compared with the 3- to 5-day-old lungs. Postnatal lung growth between 3 and 85 days was characterized by 1) a constant shear modulus (0.6 times transpulmonary pressure); 2) decrease in the bulk modulus (from 6.8 to 5.1 times transpulmonary pressure, P less than 0.005); and 3) evidence of gas trapping at progressively higher transpulmonary pressures. Therefore, growth of parenchyma in the piglet lung is associated with reduced stiffness to volume change but with no effect on overall stiffness to shape change. Nevertheless, a relatively great stiffness to shape change occurs transiently in newborn piglet lungs.     

Influence of phasic afferent information on phrenic neural output during hypercapnia

We measured the moving time average (MTA) of the phrenic neurogram before and after removal of phasic afferent information from the lungs, chest wall, and oscillations in blood gases by using constant-flow ventilation (CFV). Anesthetized dogs were studied at various levels of steady-state and progressive hypercapnia during spontaneous breathing and during CFV. When steady-state and progressive hypercapnia were compared, the frequency and height of the MTA phrenic neurogram were independent of the rate of induction of hypercapnia during each mode of ventilation. During spontaneous ventilation, the response to hypercapnia comprised mainly an increase in frequency with only a slight increase in the amplitude of the MTA phrenic waveform. During muscular paralysis and CFV, the responses were similar to those observed after vagotomy with mainly an increase in the amplitude and only a small increase in frequency. For both spontaneous breathing and CFV, increases in frequency were achieved mainly by a shortening in expiratory time with the inspiratory time remaining relatively constant. Our data support the concept of a centrally patterned respiratory generator, whose inherent pattern is modified by phasic feedback from peripheral receptors mainly of vagal origin.     

Compliance of chest wall in obese subjects

Whereas studies in awake subjects have demonstrated that chest wall compliance (Ccw) is low in obese subjects, the one study performed on paralyzed obese subject found Ccw to be normal. The purpose of this study was to measure Ccw in awake obese subjects with the pulse-flow technique, a method which appears to detect respiratory muscle relaxation. Seven normal males, 14 obese males, and 8 obese females [body mass index (BMI) varied from 20 to 83 kg/m2] were studied in the seated position. Ccw was measured by blowing air at a constant flow into the mouth and lungs for approximately 2 s and calculated by dividing airflow in liters per second by the change in esophageal minus body surface pressure in centimeters of water per second. In normal and obese subjects we found no correlation between BMI and Ccw. We conclude that obesity does not decrease Ccw.     

Effects of paralysis with pancuronium on chest wall statics in awake humans

The influence of tonic inspiratory muscle activity on the relaxation characteristics of the chest wall, rib cage (RC), and abdominal wall (ABW) has been investigated in four highly trained subjects. Chest wall shape and volume were estimated with magnetometers. Pleural pressure (Pes) and abdominal pressure were measured with esophageal and gastric balloons, respectively. Subjects were seated reclining 30 degrees from upright, and respiratory muscle weakness was produced by pancuronium bromide until RC inspiratory capacity was decreased to 60% of control. Only minor changes were observed for Konno-Mead relaxation characteristics (RC vs. ABW) between control and paralysis. Similarly, although RC relaxation curves (RC vs. Pes) during paralysis were significantly different from control (P less than 0.05), the changes were small and not consistent. The differences between paralysis-induced changes in resting end-expiratory position of the chest wall and helium-dilution functional residual capacity (FRC) suggested changes in volume of blood within the chest wall. We conclude that 1) although tonic inspiratory activity of chest wall muscles exists, it does not significantly affect the chest wall relaxation characteristics in trained subjects; 2) submaximal paralysis produced by pancuronium bromide is likely to modify either spinal attitude or the distribution of blood between extremities and the thorax; these effects may account for the changes in FRC in other studies.     

Pulmonary venous pressure increases during alveolar hypoxia in isolated lungs of newborn pigs.

The purpose of this study was to determine whether pulmonary venous pressure increases during alveolar hypoxia in lungs of newborn pigs. We isolated and perfused with blood the lungs from seven newborn pigs, 6-7 days old. We maintained blood flow constant at 50 ml.min-1.kg-1 and continuously monitored pulmonary arterial and left atrial pressures. Using the micropuncture technique, we measured pressures in 10 to 60-microns-diam venules during inflation with normoxic (21% O2-69-74% N2-5-10% CO2) and hypoxic (90-95% N2-5-10% CO2) gas mixtures. PO2 was 142 +/- 21 Torr during normoxia and 20 +/- 4 Torr during hypoxia. During micropuncture we inflated the lungs to a constant airway pressure of 5 cmH2O and kept left atrial pressure greater than airway pressure (zone 3). During hypoxia, pulmonary arterial pressure increased by 69 +/- 24% and pressure in small venules increased by 40 +/- 23%. These results are similar to those obtained with newborn lambs and ferrets but differ from results with newborn rabbits. The site of hypoxic vasoconstriction in newborn lungs is species dependent.     

Pulmonary arterial and venous constriction during hypoxia in 3- to 5-wk-old and adult ferrets

We have determined the sites of hypoxic vasoconstriction in ferret lungs. Lungs of five 3- to 5-wk-old and five adult ferrets were isolated and perfused with blood. Blood flow was adjusted initially to keep pulmonary arterial pressure at 20 cmH2O and left atrial and airway pressures at 6 and 8 cmH2O, respectively (zone 3). Once adjusted, flow was kept constant throughout the experiment. In each lung, pressures were measured in subpleural 20- to 50-microns-diam arterioles and venules with the micropipette servo-nulling method during normoxia (PO2 approximately 100 Torr) and hypoxia (PO2 less than 50 Torr). In normoxic adult ferret lungs, approximately 40% of total vascular resistance was in arteries, approximately 40% was in microvessels, and approximately 20% was in veins. With hypoxia, the total arteriovenous pressure drop increased by 68%. Arterial and venous pressure drops increased by 92 and 132%, respectively, with no change in microvascular pressure drop. In 3- to 5-wk-old ferret lungs, the vascular pressure profile during normoxia and the response to hypoxia were similar to those in adult lungs. We conclude that, in ferret lungs, arterial and venous resistances increase equally during hypoxia, resulting in increased microvascular pressures for fluid filtration.