Continuous Positive Pressure Breathing Research Articles

Pharmacotherapy for female nocturia

Background: In 2018, nocturia and nocturnal lower urinary tract function definitions were updated in a clinically and practically based consensus report by the International Continence Society Standardization Steering Committee. Previous research has suggested that the pathophysiology of nocturia has a multifactorial etiology, including obstructive sleep apnea, overactive bladder syndrome, diabetes mellitus, sleep disturbance, congestive heart failure, primary polydipsia, and other factors.Current Concepts: Three main mechanisms have been identified: low functional bladder capacity, nocturnal polyuria, and diurnal polyuria (24-hour polyuria). Multifactorial pathophysiology implies multiple possible targets for therapeutic intervention, and suggests that it is unlikely that one treatment modality, including drugs, will be successful in all patients. The bladder diary is the most important diagnostic tool.Discussion and Conclusion: Strong evidence supports the efficacy of desmopressin and continuous positive pressure breathing. Antimuscarinic drugs for treating nocturia display limited usefulness because of their low efficacy for nocturnal polyuria. Management of nocturia may require a multidisciplinary approach to visualization and phenotyping of patients for diagnosis and therapy.

Deciphering the nitric oxide to carbon monoxide lung transfer ratio: physiological implications

Using simultaneous nitric oxide and carbon monoxide lung transfer measurements (T(LNO) and T(LCO)), the membrane transfer capacity (D(m)) and capillary lung volume (V(c)) as well as the dimensionless ratio T(LNO)/T(LCO) can be calculated. The significance of this ratio is yet unclear. Theoretically, the T(LNO)/T(LCO) ratio should be inversely related to the product of both lung alveolar capillary membrane (mu) and blood sheet thicknesses (K). NO and CO transfers were measured in healthy subjects in various conditions likely to be associated with changes in K and/or mu. Experimentally, deflation of the lung from 7.4 to 4.8 l decreased the T(LNO)/T(LCO) ratio from 4.9 to 4.2 (n=25) which was consistent mainly with a thickening of the blood sheet. Compared with continuous negative pressure breathing, continuous positive pressure breathing increased this ratio suggesting a thinning of the capillary sheet. It was also observed with 12 healthy subjects that slight haemodilution that may thicken the blood sheet decreased the T(LNO)/T(LCO) ratio from 4.85 to 4.52. In conclusion, the T(LNO)/T(LCO) ratio is related to the thickness of the alveolar blood barrier. This ratio provides novel information for the analysis of the diffusion properties.

From continuous positive-pressure breathing to ventilator-induced lung injury.

Continuous positive-pressure ventilation in acute respiratory failure. By Kumar A, Falke KJ, Geffin B, Aldredge CF, Laver MB, Lowentein E, Pontoppidan H. N Engl J Med 1970; 283:1430-6. Reprinted with permission. Continuous positive-pressure ventilation was used in eight patients with severe acute respiratory failure. Cardiac output and lung function were studied during continuous positive-pressure ventilation (mean end-expiratory pressure, 13 cm H2O) and a 30-min interval of intermittent positive-pressure ventilation. Although the mean cardiac index increased from 3.6 to 4.5 l/min per square meter of body surface area, the mean intrapulmonary shunt increased by 9% with changeover to intermittent positive-pressure ventilation. Satisfactory oxygenation was maintained in all patients during continuous positive-pressure ventilation with 50% inspired oxygen or less. With intermittent positive-pressure ventilation, arterial oxygen tension promptly fell by 161 mm of mercury, 79% occurring within 1 min. Prevention of air-space collapse during expiration and an increase in functional residual capacity probably explain improved oxygenation with continuous positive-pressure ventilation. In four patients, subcutaneous emphysema or pneumothorax developed. Weighed against the effects of prolonged hypoxemia, these complications were not severe enough to warrant cessation of continuous positive-pressure ventilation.

The introduction of positive endexpiratory pressure into mechanical ventilation: a retrospective.

Continuous positive pressure breathing consisting of a pressure in the airways above the atmospheric level during spontaneous inspiration and expiration was used in the treatment of pulmonary edema and severe pneumonia even before World War II [1]. Positive endexpiratory airway pressure was also very commonly used in the experimental laboratory in any open chest preparation in order to prevent expiratory lung collapse. An important precondition for the introduction of positive endexpiratory pressure (PEEP) in conjunction with mechanical ventilation was established by the experiments of Cournand et al. in 1948 [2]. They found, however, that, compared to mechanical ventilation with ambient endexpiratory pressure, mechanical ventilation with PEEP was associated with a marked decrease in cardiac output due to reduced venous return of blood to the heart. Possible negative circulatory effects were the major concern in the early phase of clinical application of positive endexpiratory pressure.

Functional MRI (fMRI) detects decreased regional cerebral blood flow (rCBF) occipitally during continuous positive airway pressure (CPAP) breathing in human volunteers

Functional MRI (fMRI) detects decreased regional cerebral blood flow (rCBF) occipitally during continuous positive airway pressure (CPAP) breathing in human volunteers

Perfluorocarbon-associated gas exchange improves oxygenation, lung mechanics, and survival in a model of adult respiratory distress syndrome

To compare the effectiveness of perfluorocarbon-associated gas exchange to volume controlled positive pressure breathing in supporting gas exchange, lung mechanics, and survival in an acute lung injury model. A prospective, randomized study. A university medical school laboratory approved for animal research. Neonatal piglets. Eighteen piglets were randomized to receive perfluorcarbon-associated gas exchange with perflubron (n=10) or volume controlled continuous positive pressure breathing (n=8) after acute lung injury was induced by oleic acid infusion (0.15 mL/kg iv). Arterial and venous blood gases, hemodynamics, and lung mechanics were measured every 15 mins during a 3-hr study period. All animals developed a metabolic and a respiratory acidosis during the infusion of oleic acid. Following randomization, the volume controlled positive pressure breathing group developed a profound acidosis (p<.05), while pH did not change in the perfluorocarbon-associated gas exchange group. Within 15 mins of initiating perfluorocarbon-associated gas exchange, oxygenation increased from a PaO2 of 52 +/- 12 torr (6.92 +/- 1.60 kPa) to 151 +/- 93 torr (20.0 +/- 12.4 kPa) and continued to improve throughout the study (p<.05). Animals that received volume controlled positive pressure breathing remained hypoxic with no appreciable change in PaO2. Although both groups developed hypercarbia during oleic acid infusion, PaCO2, steadily increased over time in the control group (p<.01). Static lung compliance significantly increased postrandomization (60 mins) in the animals supported by perflurocarbon-associated gas exchange (p<.05), whereas it remained unchanged over time in the volume controlled positive pressure breathing group. However, survival was significantly higher in the perfluorocarbon-associated gas exchange group with eight (80%) of ten animals surviving the entire study period. Only two (25%) of the eight animals in the volume controlled positive pressure breathing group were alive at the end of the study period (log-rank statistic, p=.013). Perflurocarbon-associated gas exchange enhanced gas exchange, pulmonary mechanics, and survival in this model of acute lung injury.

Cardiorespiratory effects of perfluorocarbon-associated gas exchange at reduced oxygen concentrations

To determine whether reducing FIO2 during perfluorocarbon-associated gas exchange would cause deterioration of hemodynamics, lung mechanics, or gas exchange in normal piglets. A prospective, controlled animal trial. Experimental animal laboratory in a university setting. Twelve normal, anesthetized piglets, 7 to 14 days old, and weighing 3.31 +/- 0.75 kg. After the induction of anesthesia, tracheostomy and catheterization, piglets were stabilized. They were mechanically ventilated with a tidal volume of 15 mL/kg, inspiratory time of 25%, positive end-expiratory pressure of 4 cm H2O, and a respiratory rate of 20 to 28 breaths/min to obtain a baseline PaCO2 between 34 and 45 torr (4.7 and 6.0 kPa). Each animal was studied during continuous positive-pressure breathing, and during perfluorocarbon-associated gas exchange. They were ventilated at an FIO2 of 1.0 for 15 mins. FIO2 was randomly varied among 0.75, 0.5, and 0.3 every 15 mins, then returned to 1.0. At each FIO2, measurements of gas exchange, lung mechanics, and hemodynamics were made. After continuous positive-pressure breathing, perfluorocarbon-associated gas exchange was instituted by replacing the gaseous functional residual capacity of the lungs with perfluorooctylbromide. Animals were then ventilated and measurements were taken. At each FIO2, measurements of gas exchange (arterial blood gases and saturation), lung mechanics (mean airway pressure, static end-inspiratory pressure, and peak inspiratory pressure), and hemodynamics (heart rate, and mean arterial, right atrial, pulmonary artery occlusion, and pulmonary arterial pressures) were recorded. In six piglets, cardiac output was measured at each FIO2 by thermodilution. Cardiac index, indexed oxygen delivery and consumption, and indexed pulmonary vascular resistance were derived using standard formulas. Piglets were well saturated at all FIO2 settings during continuous positive-pressure breathing. However, during perfluorocarbon-associated gas exchange, arterial saturation decreased to 72% at an FIO2 of 0.3. Cardiac index and oxygen consumption were not affected by reducing FIO2 during perfluorocarbon-associated gas exchange, and were not significantly different than during continuous positive-pressure breathing. Oxygen delivery was reduced at an FIO2 of 0.3 during perfluorocarbon-associated gas exchange, but oxygen consumption remained in the flow independent portion of the curve despite arterial desaturation. Pulmonary arterial pressure was higher during perfluorocarbon-associated gas exchange than during continuous positive-pressure breathing. Pulmonary arterial pressure and indexed pulmonary vascular resistance were significantly higher during perfluorocarbon-associated gas exchange at an FIO2 of 0.3 than at any other FIO2 settings. Piglets showed no adverse effects on lung mechanics during perfluorocarbon-associated gas exchange. Hemodynamics were well supported at all FIO2 settings, and arterial blood was fully oxygenated during perfluorocarbon-associated gas exchange at an FIO2 of > or = 0.5.

Perfluorocarbon-associated gas exchange in gastric aspiration

To test whether perfluorocarbon-associated gas exchange (gas ventilation of the perfluorocarbon-liquid filled lung) could support oxygenation better than conventional positive pressure breathing in a piglet model of gastric aspiration-induced adult respiratory distress syndrome (ARDS). Prospective, randomized, blinded, controlled study. A critical care research laboratory in a university medical school. Fourteen healthy piglets. Under alpha-chloralose anesthesia and metocurine iodide neuromuscular blockade, 14 piglets underwent tracheostomy; central venous, systemic and pulmonary arterial catheterizations; and volume-regulated continuous positive-pressure breathing. Homogenized gastric aspirate (1 mL/kg) titrated to pH of 1.0 was instilled into the tracheostomy tube of each subject at 0 min to induce ARDS. Hemodynamics, lung mechanics, and gas exchange were evaluated every 30 mins for 6 hrs. Seven piglets were treated at 60 mins by tracheal instillation of perflubron, a volume selected to approximate normal functional residual capacity, and were supported by perfluorocarbon-associated gas exchange without modifying ventilatory settings. Perflubron was added to the trachea every hour to replace evaporative losses. There was a significant difference in oxygenation over time when tested by repeated-measures analysis of variance (F test = 8.78, p < .01). On further analysis, the differences were not significant from baseline to 2.5 hrs but became increasingly significant from 2.5 to 6 hrs after injury (p < .05) in the inflammatory phase of gastric aspiration-induced ARDS. Histologic evidence for ARDS in the treated group 6 hrs after injury was lacking. In the piglet model, perfluorocarbon-associated gas exchange with perflubron facilitates oxygenation in the acute phase of gastric aspiration-induced inflammatory ARDS when compared with conventional positive-pressure breathing. Histologic and physiologic data suggest that perfluorocarbon-associated gas exchange with perflubron might prevent ARDS if instituted after aspiration in the time window before the acute inflammatory process is manifest.

Changes in muscle sympathetic nerve activity and renal function during positive-pressure breathing in humans.

The possibility that the decreased urinary flow during continuous positive-pressure breathing (CPPB) may be a consequence of a reflex mediated via the cardiopulmonary baroreceptors to increase neurohumoral secretion or to change the sympathetic outflow was assessed. Muscle sympathetic nerve activity (MSNA) on the right peroneal nerve, vasoactive hormones, and renal and cardiovascular responses were measured during CPPB (+12 mmHg) in 10 male subjects (22.0 +/- 0.6 yr, 66.8 +/- 1.5 kg body wt). The experiments consisted of a 1-h control, 1 h with CPPB (experimental) or without CPPB (a time control), and a 1-h recovery period. Two blood samples were taken during each period for measurements of arginine vasopressin (AVP), plasma aldosterone (PAldo), plasma renin activity (PRA), norepinephrine, and atrial natriuretic peptide (ANP), and urine was collected hourly for the measurement of urine volume and electrolytes and clearances. MSNA rapidly increased (P < 0.05) at the onset of CPPB, continued to increase during exposure, and rapidly returned to the normal level at recovery. The MSNA changes coincided with increased plasma NE and were concurrent with a reduced (P < 0.05) urine output associated with a reduction of both free water and osmolal clearances, Na+ and osmolal excretions, and creatinine clearance (glomerular filtration rate). AVP and PRA increased (P < 0.05), whereas PAldo and ANP were unchanged. The results are consistent with the concept that increased sympathetic outflow may play a role in the reduction of urinary output and Na+ excretion during unloading of the cardiopulmonary receptors.

Positive end-expiratory pressure-induced, calcium-channel-mediated increases in pulmonary vascular resistance in neonatal lambs

a) To study the dose response of the calcium-channel-mediated increases in pulmonary vascular resistance with different levels of positive end-expiratory pressure; b) to study the reversibility of the calcium-channel mediated increases in pulmonary vascular resistance after discontinuation of positive end-expiratory pressure; and c) to study the effect of cyclooxygenase and lipoxygenase inhibition on the calcium-channel mediated increases in pulmonary vascular resistance. A prospective, multiexperimental, dose response study. Laboratory setting in a university hospital. Twenty-three 4- to 10-day-old neonatal lambs. Lungs of neonatal lambs were isolated in situ, and perfused at a constant flow rate, and ventilated at a fixed tidal volume and rate. Mean pulmonary arterial pressure responses to the application and discontinuation of four levels (3.7, 7.4, 11, and 14.7 mm Hg) of positive end-expiratory pressure were studied before and after calcium-channel blockade with verapamil (5 mg) (n = 12). In addition, the mean pulmonary arterial pressure response to 11 mm Hg of positive end-expiratory pressure was studied before and after inhibition of cyclooxygenase with indomethacin (10 mg/kg) (n = 6) and lipoxygenase with diethylcarbamazine (100 mg/kg) (n = 5). The magnitude of the calcium-channel-dependent mean pulmonary arterial pressure response 4 mins after the application of positive end-expiratory pressure was dose related (2.1, 3.0, 4.1, and 5.5 mm Hg with 3.7, 7.4, 11.0, and 14.7 mmHg positive end-expiratory pressure, respectively) and entirely reversible on discontinuation of positive end-expiratory pressure with a time course of 2 to 4 mins. Neither indomethacin nor diethylcarbamazine affected the pulmonary arterial pressure responses to positive end-expiratory pressure. Airway pressure changes with positive end-expiratory pressure were not affected by verapamil, indomethacin, or diethylcarbamazine. The calcium-channel-mediated pulmonary arterial pressure responses with positive end-expiratory pressure, applied during continuous positive pressure breathing, occur even at low levels of positive end-expiratory pressure, are dose dependent, and are not abolished by treatment with indomethacin or diethylcarbamazine.

Regulation of atrial natriuretic peptide release in normal humans

Atrial volume, pressure, and heart rate are considered the most important modulators of atrial natriuretic peptide (ANP) release, although their relative role is unknown. Continuous positive-pressure breathing in normal humans may cause atrial pressure and atrial volume to go in opposite directions (increase and decrease, respectively). We utilized this maneuver to differentially manipulate atrial volume and atrial pressure and evaluate the effect on ANP release. Effective filling pressure (atrial pressure minus pericardial pressure) was also monitored, because this variable has been proposed as another modulator of ANP secretion. We measured right atrial (RA) pressure, RA area, esophageal pressure (reflection of pericardial pressure), and RA and peripheral venous ANP in seven healthy adult males at rest and during continuous positive-pressure breathing (19 mmHg for 15 min). Continuous positive-pressure breathing decreased RA area (mean +/- SE, *P less than 0.05) 13.6 +/- 1.1 to 10.5 +/- 0.8* cm2, increased RA pressure 4 +/- 1 to 16 +/- 1* mmHg, increased esophageal pressure 2 +/- 1 to 12 +/- 1* mmHg, and increased effective filling pressure 2 +/- 0 to 4 +/- 1* mmHg. RA ANP increased from 67 +/- 17 to 91 +/- 18* pmol/l and peripheral venous ANP from 43 +/- 4 to 58 +/- 6* pmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous positive pressure breathing without and with inspiratory pressure support in acute respiratory failure when mean airway pressure is constant

Mean airway pressure (Pawm) may be a major factor for PaO2, functional residual capacity, and cardiac output in acute respiratory failure (ARF). To clarify effects of inspiratory pressure support (IPS) as a ventilatory mode in ARF, we studied patients in ARF either using IPS or continuous positive pressure breathing (CPAP) at the same level of Pawm, measuring respiratory and circulatory parameters. After consent, 10 patients in ARF of moderate severity (PaO2:FiO2 205 +/- 108 at positive end expiratory pressure (PEEP) 8.7 +/- 3.1 cmH2O; mean +/- SD) were investigated. Measurements were on day 7.4 +/- 8.4 after onset of ARF. IPS was 13.5 +/- 3.9 cmH2O above PEEP. To result in constant Pawm, PEEP was reduced for IPS (Pawm IPS 11.1 +/- 3.6 vs. Pawm CPAP 9.9 +/- 3.3 cmH2O, ns; PEEP IPS 8.7 +/- 3.1 vs. PEEP CPAP 10.6 +/- 4.3 cmH2O, p = 0.04). Inspired concentration of oxygen (FiO2) and the ventilator (Siemens 900 C) were not changed for the individual patient. For IPS, tidal volume (VT) increased by +31% and respiratory frequency (RF) decreased by -19% (VT IPS 608 +/- 179 vs. VT CPAP 465 +/- 141 ml, p = 0.01; RF IPS 21.6 +/- 7.6 vs. RF CPAP 26.7 +/- 8.3 breaths per minute, p = 0.02). Also, PaCO2 showed a tendency to be lower for IPS, not reaching significance (PaCO2 IPS 44.3 +/- 5 vs. PaCO2 CPAP 47.4 +/- 4.9 mmHg, p = 0.1). All other parameters were unchanged (expiratory minute volume, PaO2, pH, intravascular pressures, cardiac index, stroke volume index (n = 6), systemic and pulmonary vascular resistances, venous admixture, deadspace (n = 3), oxygen consumption and oxygen delivery). WE CONCLUDE: When Pawm remained constant, IPS added to CPAP improved VT and RF without improving oxygenation or deteriorating circulation in patients with ARF of moderate severity. IPS mainly supports the ability to breathe spontaneously in ARF.

Electrical and mechanical output of the expiratory muscles in anesthetized dogs

In anesthetized intact and vagotomized dogs chest wall diameters, expiratory muscles' (EM) electrical activity, work, mean pressure and volume displacement contributed by EM contraction were assessed in the supine and upright posture during rebreathing, and during continuous positive pressure breathing (CPAP) in the supine posture. Corresponding inspiratory mechanical output variables were related to diaphragm activity. During resting breathing triangularis sterni and internal interosseous were more easily recruited than transversus abdominis and external oblique. EM activity increased with tilting, CPAP and rebreathing. Vagotomy depressed or abolished abdominal EM activity, with lesser effects on rib cage EM. Expiratory mechanical output grossly parallelled EM activity: it markedly depended on rib cage and abdominal EM coactivation, besides lung inflation and chest wall shape. Upper rib cage configuration at end-expiration never departed from the relaxation one, suggesting trivial effects of the triangularis sterni contraction. Lower chest wall distortion occurred almost regularly, so that much of EM activity was not converted into external work. In contrast with expiratory electromechanical relations, those for the diaphragm were always highly significant and independent of EM activation.

Perfluorocarbon-associated gas exchange

Liquid ventilation with oxygenated perfluorocarbon eliminates surface tension due to pulmonary air/fluid interfaces, and improves pulmonary function and gas exchange in surfactant deficiency. In liquid ventilation, perfluorocarbon is oxygenated, purged of CO2, and cycled into and out of the lungs using an investigational device. A new approach, perfluorocarbon-associated gas exchange, uses a conventional ventilator and combines features of liquid ventilation and continuous positive-pressure breathing. In 13 normal piglets, a volume of perfluorocarbon equivalent to the normal functional residual capacity (30 mL/kg) was instilled into the trachea, left in situ, and volume-regulated gas ventilation (FIO2 1.0) was resumed. For 1 hr, perfluorocarbon was continuously bubble-oxygenated within the lungs, where it directly participated in gas exchange. PaO2 and PaCO2 averaged 401 +/- 51 and 40 +/- 4 torr (53.6 +/- 6.8 and 5.3 +/- 0.5 kPa), respectively. Peak airway pressure during perfluorocarbon-associated gas exchange (22 +/- 2 cm H2O at 1 hr) and during continuous, positive-pressure breathing (23 +/- 4 cm H2O) were nearly identical. Venous oxygen saturation and pH were normal (73 +/- 8% and 7.43 +/- 0.05, respectively, at 1 hr). Perfluorocarbon-associated gas exchange was uniformly well tolerated, and its efficiency approached that of continuous positive-pressure breathing. Applications of perfluorocarbon technology to lung disease may not be limited by existing instrumentation.

Lung mechanics and airway pressure transmission in infants after open heart surgery

To evaluate the effects of positive airway pressure on lung mechanics and airway pressure transmission into the intrathoracic space, airway and intrathoracic pressure were recorded during stepwise lung inflation in 17 infants undergoing open heart surgery during the first year of life. Eleven of the 17 patients had cuffed tracheal tubes allowing calculation of lung and chest wall compliance. In 7 of these 11 patients, lung inflation to 2.5 ml/kg above functional residual capacity produced an improvement in initially low lung compliance. This volume increment required elevation of airway pressure by 4-11 cm H2O above ambient. Further lung inflation to 10 ml/kg did not effect an improvement in lung mechanics. In the remaining patients, initial lung compliance was high and remained unchanged throughout the range of lung inflation. Transmission of pressure into the intrathoracic space averaged 47 +/- 9% (mean +/- SD) and ranged from 33% to 61% when airway pressure was 10-15 cm H2O. The results indicate that the use of moderately elevated airway pressure is required to optimize lung distensibility in most infants immediately after open heart surgery. When evaluating circulatory effects of elevated airway pressure, assumption of a 50% pressure transmission is appropriate for clinical purposes. However, the observed wide range of pressure transmission warrants careful hemodynamic monitoring during continuous positive pressure breathing.

Proximal mean airway pressure

Although airway and alveolar pressures are not instantly equal during positive-pressure ventilation, proximal mean airway pressure (Paw) is the simplest available indirect gauge of mean alveolar pressure (Palv). To ascertain the relation of Paw to Palv and the limits of agreement between the two measures, real-time curves of proximal airway pressure (at the hub of the endotracheal tube) and alveolar pressure were generated by repeated airway occlusion at numerous PEEP levels in four groups of ventilated lambs or piglets: normal controls, oleic acid-injured and serotonin stimulated lambs, and preparations with mechanically induced air trapping. From these curves, Paw and Palv were determined. In all groups, Paw proved to be a precise estimator of Palv during volume-regulated, time-cycled, continuous positive-pressure breathing.

Pulmonary vascular resistance after cessation of positive end-expiratory pressure.

This report describes the pulmonary vascular response of infant lamb lung to abrupt cessation of positive end-expiratory pressure (PEEP) during volume-regulated continuous positive-pressure breathing (CPPB). In an intact, endobronchially ventilated preparation, the increase in left lung blood flow (QL) after abrupt cessation of 11 Torr left lung PEEP was found to be gradual, although peak airway pressure (Pmax) fell promptly from 36 to 14 Torr; 49% of the increase in QL occurred greater than 10 s after cessation of PEEP. Recruitment of zone I vasculature that had been created by balloon occlusion of the left pulmonary artery was found to occur promptly after balloon deflation. Isolated neonatal lamb lungs, perfused at constant flow rate, showed similar persistent elevation of pulmonary vascular resistance after cessation of 15 Torr PEEP, although Pmax fell abruptly from 39 to 12 Torr. This hysteresis was eliminated by calcium channel blockade with verapamil, and the magnitude of the change in pulmonary arterial pressure after either application or cessation of PEEP was reduced (25 and 26%, respectively). These observations suggest that, during CPPB, lung stretch alters neonatal pulmonary vascular tone or, by causing calcium channel-dependent lung volume hysteresis, modulates pulmonary vascular resistance. This interaction exaggerates the effect of airway pressure changes on pulmonary vascular resistance during mechanical ventilation.

179 PROXIMAL AIRWAY AND AVEOLAR PRESSURES DURING MECHANICAL VENTILATION

During continuous positive pressure breathing(CPPB), proximal airway pressure(AP) and its mean value(MAP) reflect lung distending pressure, although their relationships to alveolar pressure (ALP) and its mean value(MALP) await definition. 10 infant lambs, under chloralose anesthesia and pancuronium bromide, were subjected to volume regulated, time cycled CPPB under conditions of constant inspiratory airflow. To estimate ALP, static recoil pressure was determined by interruption of airflow once every 10th breath, at a time in the respiratory cycle that was varied from trial to trial. From determinations of occlusion time, AP and ALP, real time AP and ALP curves were generated representing one respiratory cycle; MAP and MALP were calculated by integration; and the contribution to MALP of airway resistance(MALPr) was estimated from inspiratory(I) time, positive end-expiratory pressure(PEEP), peak ALP and MALP. Curves were generated at 25 and 50%, I, and at levels of PEEP between 0 and 11 mmHg. Due to airway resistance, AP exceeded ALP in inspiration and ALP exceeded AP over much of expiration(E). Yet airway resistance contributed little to MALP. Over the range of PEEP applied, and at both %I, proximal mean airway pressure was an accurate and precise estimator of mean alveolar pressure.

Effect of transrespiratory pressure on PETCO2-PaCO2 and ventilatory reflexes in humans.

Inspiratory muscle activity increases when lung volume is increased by continuous positive-pressure breathing in conscious human subjects (Green et al., Respir. Physiol. 35: 283-300, 1978). Because end-tidal CO2 pressure (PETCO2) does not change, these increases have not been attributed to chemoreflexes. However, continuous positive-pressure breathing at 20 cmH2O influences the end-tidal to arterial CO2 pressure differences (Folkow and Pappenheimer, J. Appl. Physiol. 8: 102-110, 1955). We have compared PETCO2 with arterial CO2 pressure (PaCO2). We have compared PETCO2 with arterial CO2 pressure (PaCO2) in healthy human subjects exposed to continuous positive airway pressure (10 cmH2O) or continuous negative pressure around the torso (-15 cmH2O) sufficient to increase mean lung volume by about 650 ml. The difference between PETCO2 and PaCO2 was not decreased, and we conclude that PETCO2 is a valid measure of chemical drive to ventilation in such circumstances. We observed substantial increases in respiratory muscle electromyograms during pressure breathing as seen previously and conclude this response must originate by proprioception. On average, the compensation of tidal volume thus afforded was complete, but the wide variability of individual responses suggests that there was a large cerebral cortical component in the responses seen here.

The effects of sustained lung inflation on the pattern of breathing in man.

1. Continuous positive-pressure breathing (CPPB) at airway pressures of 0.65-1.00 kPa above ambient pressure has been used to produce a sustained inflation of the lungs of approximately 1 litre in six normal male subjects. 2. Lung inflation produced a reduction in the ventilatory response to carbon dioxide inhalation by slow rebreathing in oxygen over approximately 45 min, with a reduction in the slope of the VE/Pet,CO2 and VT/Pet,CO2 relations (Pet,CO2, = end-tidal PCO2). 3. The pattern of breathing is altered, so that for any given expired minute ventilation (VE), tidal volume (VT) is reduced with a fall in breath duration (Tt) resulting from a decrease in inspiratory time (Ti) with no change in expiratory time (Te). 4. The break point on the VT/Ti relation is lowered.