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Biomedical subjects

C F Mackenzie

Publications and source records attributed to C F Mackenzie.

At least 37 records · Page 2Linked to original sources

Transfer of gas from the acinus during continuous flow and intermittent positive pressure ventilation.

We used a technique of measuring Xenon133 washout (XeW) from the alveolar space to evaluate transfer of gas from the acinus (Mackenzie et al., J. Appl. Physiol. 68: 2013-2018, 1990) during 2 min of apnea, 2 min of tracheal insufflation with oxygen (TRIO) and 90 sec of intermittent positive pressure ventilation (IPPV) in 6 anesthetized and paralyzed dogs. Xenon133 dissolved in saline was injected into an occluded acinar region through a pulmonary artery catheter, and XeW was measured by gamma scintillation scanning. With this technique, XeW during apnea represents the contribution of cardiogenic oscillations in regional flow. The XeW rate constant (min-1 +/- SE) was 0.37 +/- 0.03 during apnea. This was not different (P > 0.05) with TRIO (0.29 +/- 0.04). With IPPV, the rate constant increased to 3.49 +/- 0.39, faster than with either apnea or TRIO (P < 0.001). We conclude that: (1) TRIO does not increase convective gas transfer from the acini compared to apnea; and (2) transfer of gas out of the acini due to cardiogenic oscillations is a very small portion of the total gas eliminated during IPPV.

Animals↗

Effect of posture on lung and regional chest wall mechanics.

BACKGROUND: Little is known about the extent to which changes in postures in clinical situations affect respiratory mechanics, even in humans with healthy respiratory systems. This study tested the hypothesis that posture has only small effects on overall respiratory system mechanics in healthy subjects, despite changes in parts of the respiratory system in some postures. METHODS: Measurements were made of airway flow, airway and esophageal pressures, and rib cage and abdominal volume displacements (with inductance plethysmography) of awake, healthy subjects, relaxed at functional residual capacity, during external forcing at 0.2 Hz with a tidal volume of 8-10 ml/kg. From these measurements, discrete Fourier transform was used to calculate elastances (E) and resistances (R) of the total respiratory system, lungs, total chest wall, and compartments of the chest wall (rib cage, diaphragm-abdomen, and belly wall). Measurements were made while the subjects were in nine different postures: in six of these, the torso was straight; in three, the torso was bent or twisted. RESULTS: Although changes in mechanics of parts of the respiratory system were evident in certain postures, overall respiratory mechanics were not greatly affected by posture. Changing from sitting to supine decreased E and R of the diaphragm-abdomen about 50% (P < .05), but total chest wall E and R changed only slightly. Lung E increased 24% (P < .05), but total respiratory E did not change (P < .05). Lung and total respiratory R increased 40-50% (P < .05) with this same change in posture. As long as the torso was straight, however, changes in orientation of 30 degrees from the horizontal or a shift to lateral posture resulted in only minor changes in the variables measured. Postures in which the torso was twisted or bent increased E of the total chest wall 20-30% compared to supine (P < .05), due to increases in E of one or more compartments. Respiratory system E also increased, at most 14%. Although lung R decreased 30-45% (P < .05) in these postures compared to supine with a straight torso, chest wall and total respiratory R generally were unchanged. CONCLUSIONS: Changes in respiratory system mechanics over a wide range of postures that may be encountered clinically are relatively small in healthy awake subjects due to adaptability of total chest wall mechanical behavior.

Adult↗

Effect of lung volume on lung resistance and elastance in awake subjects measured during sinusoidal forcing.

BACKGROUND: Although lung volume may be changed by certain procedures during anesthesia and mechanical ventilation, dependence of the dynamic mechanical properties of the lungs on lung volume are not clear. Based on studies in dogs, the authors hypothesized that changes in lung mechanics caused by anesthesia in healthy humans could be accounted for by immediate changes in lung volume and that lung resistance will not be decreased by positive end-expiratory airway pressure if tidal volume and respiratory frequency are in the normal ranges. METHODS: Lung resistance and dynamic lung elastance were measured in six healthy, relaxed, seated subjects during sinusoidal volume oscillations at the mouth (5 mL/kg; 0.4 Hz) delivered at mean airway pressure from -9 to +25 cmH2O. Changes in lung volume from functional residual capacity were measured with inductance plethysmographic belts. RESULTS: Decreases in mean mean airway pressure that caused decreases in lung volume from functional residual capacity comparable to those typically observed during anesthesia were associated with significant increases in both dynamic lung elastance and lung resistance. Increases in mean mean airway pressure that caused increases in lung volume from functional residual capacity did not increase lung resistance and increased dynamic lung elastance only above about 15 cmH2O. CONCLUSIONS: Increases in dynamic lung elastance and lung resistance with anesthesia can be explained by the accompanying, acute decreases in lung volume, although other factors may be involved. Increasing lung volume by increasing mean airway pressure with positive end-expiratory pressure will decrease lung resistance only if the original lung volume is low compared to awake, seated functional residual capacity.

Adult↗

Effects of cardiac oscillations on acinar gas mixing during pulmonary edema.

We used a previously reported technique (Mackenzie et al., J. Appl. Physiol. 68: 2013-2018, 1990) to measure the effects of severe pulmonary edema on acinar cardiogenic gas mixing in anesthetized dogs. We also tested how increases in lung volume affected gas mixing in healthy lungs and during pulmonary edema. Cardiogenic gas mixing was evaluated by measurement of the rate of washout of xenon133 injected into an occluded pulmonary artery during apnea. The rate constant of xenon133 washout was 0.40 min-1 (+/- 0.06 SE) in the healthy lung at functional residual capacity. It decreased (P < 0.05) to 0.08 min-1 (+/- 0.03) when lung volume was raised 500 ml. Pulmonary edema was induced by injection of oleic acid (0.06 mg.kg-1) into the right atrium over a 4-min period; clinical signs of severe pulmonary edema were present after 90 min. The rate constant for xenon133 washout (0.07 +/- 0.03 min-1) was less than in the healthy lung (P < 0.05), and was not changed after lung volume was increased (P > 0.05). We conclude that, in the presence of severe pulmonary edema: (1) acinar resistance is increased and/or magnitude of cardiogenic oscillations is decreased; and (2) salutary effects of increased lung volume are not due to enhancement of cardiogenic gas mixing.

Airway Resistance↗

Lung and chest wall impedances in the dog: effects of frequency and tidal volume.

Dependences of the mechanical properties of the respiratory system on frequency (f) and tidal volume (VT) in the normal ranges of breathing are not clear. We measured, simultaneously and in vivo, resistance and elastance of the total respiratory system (Rrs and Ers), lungs (RL and EL), and chest wall (Rcw and Ecw) of five healthy anesthetized paralyzed dogs during sinusoidal volume oscillations at the trachea (50-300 ml, 0.2-2 Hz) delivered at a constant mean lung volume. Each dog showed the same f and VT dependences. The Ers and Ecw increased with increasing f to 1 Hz and decreased with increasing VT up to 200 ml. Although EL increased slightly with increasing f, it was independent of VT. The Rcw decreased from 0.2 to 2 Hz at all VT and decreased with increasing VT. Although the RL decreased from 0.2 to 0.6 Hz and was independent of VT, at higher f RL tended to increase with increasing f and VT (i.e., as peak flow increased). Finally, the f and VT dependences of Rrs were similar to those of Rcw below 0.6 Hz but mirrored RL at higher f. These data capture the competing influences of airflow nonlinearities vs. tissue nonlinearities on f and VT dependence of the lung, chest wall, and total respiratory system. More specifically, we conclude that 1) VT dependences in Ers and Rrs below 0.6 Hz are due to nonlinearities in chest wall properties, 2) above 0.6 Hz, the flow dependence of airways resistance dominates RL and Rrs, and 3) lung tissue behavior is linear in the normal range of breathing.

Airway Resistance↗

Lung, chest wall, and total respiratory system resistances and elastances in the normal range of breathing.

We measured total respiratory system and lung and chest wall resistances (Rrs, Rl, and Rcw) and elastances (Ers, El, and Ecw) in awake, relaxed human subjects during sinusoidal volume forcing at the mouth from 0.2 to 0.6 Hz with tidal volumes (VT) of 6 to 18% VC at constant mean airway pressure. In addition, we repeated measurements with the lowest VT at a lower airway pressure and therefore at a lower mean lung volume (Vl). Rrs and Rcw decreased with increasing respiratory frequency (f) and VT, but Rl was independent of f and VT. All resistances were higher at the lower Vl. Ers and Ecw increased with increasing f and decreased with increasing VT. El increased slightly with increasing f but was not affected by VT. All elastances tended to increase at the lower Vl. We conclude that in the normal range of breathing amplitude and frequency, (1) lung properties are nearly constant if mean lung volume does not change, and (2) f and VT dependencies of total respiratory system properties are caused by the chest wall.

Adult↗

Effect of tidal volume on respiratory system elastance and resistance during anesthesia and paralysis.

Recent studies have shown that the mechanical properties of the respiratory system at normal breathing frequency in awake humans depend on tidal volume. Few measurements of respiratory system properties during anesthesia have accounted for this dependence. From measurements of airway pressure, flow and esophageal pressure, we calculated elastances and resistances of the total respiratory system (Ers and Rrs), chest wall (Ecw and Rcw), and lungs (El and Rl) in supine human volunteers during quasisinusoidal volume forcing in a normal range of breathing (250 to 800 ml) at normal breathing frequency (0.2 Hz). Measurements were made (1) with subjects awake and voluntarily relaxed; (2) after isoflurane-N2O anesthesia (end-tidal isoflurane concentration 0.3 to 0.5%); and (3) after complete muscle paralysis with vecuronium. In all conditions, Ers, Ecw, El, Rrs, and Rcw decreased at 800 ml tidal volume compared with 250 ml; Rl showed a similar decrease in awake measurements only. Compared with awake measurements, each elastance tended to increase after anesthesia, but only the increase in Ers was significant. Compared with anesthesia, there was no effect of paralysis on any measurement. We conclude that (1) tidal volume dependence of respiratory system properties in the normal range of breathing occurs in the absence of muscle activity; (2) anesthesia increases Ers and (3) respiratory muscle activity appears to be inhibited by isoflurane-N2O anesthesia at end-tidal isoflurane concentration of 0.3 to 0.5% during normocapnia.

Adult↗

Continuous endobronchial insufflation during internal mammary artery harvest.

Endobronchial insufflation of oxygen offers possible advantages over conventional ventilation modes in some clinical situations in which nonmovement of the chest may be desirable; however, endobronchial insufflation of oxygen has yet to be used during thoracic surgery in humans. Furthermore, the physiologic mechanisms underlying gas exchange during endobronchial insufflation of oxygen are unclear. This study assessed endobronchial insufflation of oxygen at 45 L/min in 11 patients with an open chest during internal mammary artery harvest. Cardiorespiratory function was measured at baseline during conventional mechanical ventilation and at 5-min intervals during the study period of 20-30 min. In all patients, clinically acceptable gas exchange was achieved, although PaCO2 increased from 32 +/- 3.2 to 44 +/- 7.5 mm Hg (mean +/- SD) at 5 min, but thereafter was unchanged (P greater than 0.1). Cardiac output, vascular pressures, and heart rate were unchanged, although pHa decreased. Surgical access for internal mammary artery harvesting was improved. No mucosal damage or complications occurred. During endobronchial insufflation of oxygen, efficacy of gas exchange and body weight were not correlated, but both subject height and age were correlated with high PaO2 and low PaCO2. We conclude that (a) endobronchial insufflation of oxygen can be used in patients with an open chest; (b) the efficacy of endobronchial insufflation of oxygen is probably improved by increased lung size and by collateral ventilation; and (c) cardiogenic gas mixing contributes little to gas exchange during endobronchial insufflation of oxygen.

Aged↗

Automated real-time data acquisition and analysis of cardiorespiratory function.

Microcomputer generation of an automated record without complexity or operator intervention is desirable in many circumstances. We developed a microcomputer system specifically designed for simplified automated collection of cardiorespiratory data in research and clinical environments. We tested the system during possible extreme clinical conditions by comparison with a patient simulator. Ranges used were heart rate of 35-182 beats per minute, systemic blood pressures of 65-147 mmHg and venous blood pressures of 14-37 mmHg, all with superimposed respiratory variation of 0-24 mmHg. We also tested multiple electrocardiographic dysrhythmias. The results showed that there were no clinically relevant differences in vascular pressures, heart rate, and other variables between computer processed and simulator values. Manually and computer recorded physiological variables were compared to simulator values and the results show that computer values were more accurate. The system was used routinely in 21 animal research experiments over a 4 month period employing a total of 270 collection periods. The file system integrity was tested and found to be satisfactory, even during power failures. Unlike other data collection systems this one (1) requires little or no operator intervention and training, (2) has been rigorously tested for accuracy using a wide variety of extreme patient conditions, (3) has had computer derived values measured against a standardized reference, (4) is reliable against external sources of computer failure, and (5) has screen and printout presentations with quick and easily understandable formats.

Computer Systems↗

Efficacy of tracheal insufflation of oxygen during oleic acid-induced pulmonary edema.

STUDY OBJECTIVES: To determine whether tracheal insufflation of oxygen (TRIO) might be useful in field resuscitation of casualties with lung dysfunction. DESIGN: Physiological measurements of cardiac and respiratory function were compared before and after oleic acid lung injury. SETTING AND PARTICIPANTS: Beagles were studied in a laboratory. INTERVENTIONS: Oleic acid (0.06 mL/kg) was injected over four minutes into the central venous port of a pulmonary artery catheter. Measurements were made during 30 minutes of TRIO before and after acute lung injury. MEASUREMENTS: Hemodynamic and respiratory measurements, including intravascular pressures, heart rate, cardiac output, blood gases, respiratory system compliance, and O2 consumption were recorded during conventional mechanical ventilation and TRIO. RESULTS: Before acute lung injury, PaO2 (mean +/- SD) increased (P less than .05) from 96 +/- 7.4 (13 +/- 1.0 kPa) during conventional mechanical ventilation to 360 +/- 123 mm Hg (48 +/- 16.4 kPa) after TRIO. PaCO2 (mean +/- SD) increased (P less than .05) from 39.5 +/- 1.1 (5.3 +/- 0.1 kPa) to 102 +/- 27.4 mm Hg (13.6 +/- 3.6 kPa). Arterial and mixed venous pH values decreased in proportion to PCO2. After acute lung injury, compliance decreased. PAO2 decreased (P less than .05) to 58 +/- 8.4 mm Hg (7.7 +/- 1.1 kPa) during conventional mechanical ventilation and increased (P less than .05) to 84 +/- 19.6 mm Hg (11.2 +/- 2.6 kPa) after 30 minutes of TRIO. CONCLUSION: Despite poor gas exchange after acute lung injury, TRIO maintained adequate oxygenation and may be useful for emergency ventilation even when pulmonary edema complicates resuscitation.

Animals↗

Dependencies of respiratory system resistance and elastance on amplitude and frequency in the normal range of breathing.

We calculated respiratory system resistance (Rrs) and elastance (Ers) from pressure and flow at the mouth in six seated subjects relaxed at FRC (cheeks tightly compressed) during sinusoidal volume forcing (250, 500, and 750 ml) at 0.2, 0.4, and 0.6 Hz. Dependencies of Rrs and Ers on frequency and tidal volume were generally the same in each subject; Rrs tended to decrease with frequency and tidal volume, whereas Ers tended to increase with frequency and decrease with tidal volume. Multiple linear regression of combined data indicated that the frequency and tidal volume effects on Rrs and Ers were significant (p less than 0.05), and that the effects on Rrs decreased at higher flows. Average Rrs was highest (4.43 cm H2O/L/s +/- 0.21 SE) at 0.2 Hz-250 ml, and lowest (3.07 cm H2O/L/s +/- 0.37) at 0.6 Hz-750 ml. Average Ers was highest (12.1 cm H2O/L +/- 1.1) at 0.6 Hz-250 ml, and lowest (7.1 cm H2O/L +/- 0.6) at 0.2 Hz-750 ml. We conclude that frequency and tidal volume dependencies in Rrs and Ers in the normal range of breathing should be considered when interpreting measurements of respiratory system impedance or developing models to describe the mechanical behavior of the respiratory system.

Airway Resistance↗

Effects of cardiac oscillations and lung volume on acinar gas mixing during apnea.

We evaluated the importance of cardiogenic gas mixing in the acini of 13 dogs during 2 min of apnea. 133Xe (1-2 mCi in 4 ml of saline) was injected into an alveolar region through an occluded pulmonary artery branch, and washout was measured by gamma scintillation scanning during continued occlusion or with blood flow reinstated. The monoexponential rate constant for Xe washout (XeW) was -0.4 +/- 0.08 (SE) min-1 at functional residual capacity (FRC) with no blood flow in the injected region. It decreased by more than half at lung volumes 500 ml above and 392 ml below FRC. With intact pulmonary blood flow, XeW was -1.0 +/- 0.08 (SE) min-1 at FRC, and it increased with decreasing lung volume. However, if calculated Xe uptake by the blood was subtracted from the XeW measured with blood flow intact, resulting values at FRC and at FRC + 500 ml were not different from XeW with no blood flow. Reasonable calculation of Xe blood uptake at 392 ml below FRC was not possible because airway closure, increased shunt, and other factors affect XeW. After death, no significant XeW could be measured, which suggests that XeW caused by molecular diffusion was small. We conclude that 1) the effect of heart motion on the lung parenchyma increases acinar gas mixing during apnea, 2) this effect diminishes above or below FRC, and 3) there is probably no direct effect of pulmonary vascular pulsatility on acinar gas mixing.

Animals↗

Low-flow endobronchial insufflation with air for 2 hours of apnea provides ventilation adequate for survival.

We tested the efficacy of low-flow endobronchial insufflation (EI) with air, as it may be useful in emergency situations in which positive-pressure mechanical ventilation is not possible. The only equipment required is a source of compressed air with flow controller and a specially designed insufflation catheter. The insufflation catheter has forked ends that can be positioned blindly in the mainstem bronchi. In six anesthetized, apneic dogs averaging 9.6 kg, we determined that the average air flow needed to maintain PaO2 above 45 mm Hg and PaCO2 below 65 mm Hg after 30 min was 2.5 L/min. At these flow rates, all dogs survived 2 h of endobronchial insufflation with no neurologic dysfunction. The small internal diameters (0.8 mm) of the catheter ends increase gas exit velocity and allow for adequate oxygenation and CO2 removal at low flow rates. Endobronchial insufflation could also be employed with cricothyroidotomy and a compressor for emergency situations in the field involving mass casualties, where oxygen supplies and equipment are limited.

Animals↗

Tracheal insufflation of oxygen at low flow: capabilities and limitations.

Tracheal insufflation of oxygen (TRIO) may provide temporary oxygenation for patients or sustain life in apneic mass casualties when conventional ventilatory techniques are not available or feasible. Logistically, minimum flows of TRIO (Vmin) are desirable for field use and to reduce barotrauma should airway obstruction occur. We carried out a feasibility study to determine the efficacy of Vmin of TRIO delivered within 1 cm of the carina, in nine anesthetized and paralyzed dogs. Minimum flows of TRIO for these dogs of average weight (12 kg) was 91 mL/min. In six of the dogs Vmin TRIO was continued and provided oxygenation for an average of 1.5 h compatible with subsequent resuscitation with conventional ventilation. However, PaCO2 levels increased to mean values of 256 mm Hg in the 90 min. To determine what the effect of increased gas mixing was on gas exchange, we repeated Vmin TRIO for 10 min in six of the dogs with and without high frequency oscillations superimposed on the TRIO flow. The oscillations (60 mL at 16.3 Hz) increased carbon dioxide excretion but significantly impaired oxygenation. In completely apneic animals, TRIO at low flow delivered by cricothyroidotomy may be useful as an emergency procedure when upper airway obstruction limits the use of other airway management techniques. However, enhancement of gas mixing during low-flow TRIO impairs oxygenation, so that higher flows would be required when respiratory efforts occur.

Animals↗

Amplitude dependency of regional chest wall resistance and elastance at normal breathing frequencies.

Current methods for measurement of chest wall properties assume that resistance (R) and elastance (E) are independent of the volume breathed. In six healthy subjects relaxed at functional residual capacity, we measured total and regional R and E of the chest wall within the range of normal breathing frequencies (0.2 to 0.6 Hz) and tidal volumes (250 to 750 ml), using volume forcing at the mouth as previously described. With these methods, esophageal and gastric pressures are compared with surface displacements measured with inductance plethysmographic belts to calculate R and E of rib cage and diaphragm-abdomen "pathways." Rib cage R and E were 25 to 30% higher than that of the total chest wall at each frequency and volume, whereas diaphragm-abdomen R and E were at least five times higher. R of the chest wall and each of the pathways decreased by about 70% with increasing frequency and by about 30% with increasing tidal volume. E of the chest wall and each of the pathways also decreased by about 30% with increasing tidal volume but was independent of frequency in this range. These results are consistent with nonlinear, viscoplastic models presented elsewhere. We conclude that: (1) despite the great structural differences between the rib cage and diaphragm-abdomen, each exhibits nonlinear behavior similar to that of the total chest wall; (2) chest wall R and E depend importantly on frequency and tidal volume.

Adult↗

Experimental repair of ventricular septal defects using autologous right ventricular muscle flaps: preliminary report.

Survival after repair of postinfarction ventricular septal defects remains poor, often due to extensive loss of contractile muscle in the septum or left ventricle. We evaluated whether a contractile flap of right ventricular muscle could be used to repair a similar ventricular septal defect to augment left ventricular performance in 7 fully instrumented mongrel dogs (weight, 23 to 28 kg). By using hypothermic bypass and cold fibrillatory arrest, a trapezoidal right ventricle flap was fashioned from the free wall of the mid to lower right ventricle, basing its widest portion anteriorly on the septum and left ventricle. A large, 2-cm-diameter core of septum was excised beneath this flap to simulate a postinfarct ventricular septal defect. The right ventricular flap was then invaginated through the defect and sewn to the left ventricular side of the septum with pledgeted sutures taken full thickness through the flap and septum in a "vest-over-pants" fashion. Contraction of the right ventricular flap was confirmed visually and by postbypass multiple gated acquisition scans. The right ventricular defect was closed with fascia lata. All dogs were weaned from bypass without inotropes. Precardiac and postcardiac outputs of 2.5 +/- 0.5 versus 2.3 +/- 0.4 L/min and left ventricular end-diastolic pressures of 4 +/- 2 versus 4 +/- 3 mm Hg were identical. No shunts were detected by oxygen saturation. Autopsies confirmed the integrity of the repair. We conclude that septal defects can be repaired by using contractile right ventricular muscle, thus preserving left ventricular function. This technique offers promise for repair of postinfarction ventricular septal defects by using autologous, already conditioned to contract, cardiac muscle, but its application in humans must await long-term testing.

Animals↗