Low Distending Pressures Research Articles

Reabsorption atelectasis in a porcine model of ARDS: regional and temporal effects of airway closure, oxygen, and distending pressure

Little is known about the small airways dysfunction in acute respiratory distress syndrome (ARDS). By computed tomography (CT) imaging in a porcine experimental model of early ARDS, we aimed at studying the location and magnitude of peripheral airway closure and alveolar collapse under high and low distending pressures and high and low inspiratory oxygen fraction (FIO2). Six piglets were mechanically ventilated under anesthesia and muscle relaxation. Four animals underwent saline-washout lung injury, and two served as healthy controls. Beyond the site of assumed airway closure, gas was expected to be trapped in the injured lungs, promoting alveolar collapse. This was tested by ventilation with an FIO2 of 0.25 and 1 in sequence during low and high distending pressures. In the most dependent regions, the gas/tissue ratio of end-expiratory CT, after previous ventilation with FIO2 0.25 low-driving pressure, was significantly higher than after ventilation with FIO2 1; with high-driving pressure, this difference disappeared. Also, significant reduction in poorly aerated tissue and a correlated increase in nonaerated tissue in end-expiratory CT with FIO2 1 low-driving pressure were seen. When high-driving pressure was applied or after previous ventilation with FIO2 0.25 and low-driving pressure, this pattern disappeared. The findings suggest that low distending pressures produce widespread dependent airway closure and with high FIO2, subsequent absorption atelectasis. Low FIO2 prevented alveolar collapse during the study period because of slow absorption of gas behind closed airways.

Influence of the pattern of jejunal distension on mesenteric afferent sensitivity in the anaesthetized rat

Vagal, spinal and intestino-fugal fibres all potentially transmit mechanosensory afferent information from the gastrointestinal tract. We aimed to characterize the relative mechanosensitivity of these three different afferent populations supplying the rat jejunum. Afferent nerve discharge was recorded from pentobarbitone-anaesthetized rats during different distension protocols. Saline ramp distension (1 mL min(-1)) and barostat ramp distension (2 mmHg 4 s(-1)) each evoked biphasic responses but with the latter significantly attenuated especially at low distending pressures. Barostat controlled phasic distensions (10-50 mmHg, 25 s) evoked an afferent response with a peak at the onset of distension adapting to a plateau level that was maintained and comparable to the barostat ramp responses at the corresponding pressures. Chronic subdiaphragmatic vagotomy significantly attenuated the low pressure component of the response to balloon ramp distension and both peak and plateau responses to phasic distension. Single unit analysis showed an absence of low threshold afferent activity after vagotomy while the response to fibres with wide-dynamic range and high threshold sensitivity were preserved hexamethonium had no effect on the responses to either ramp or phasic distension. These findings suggest that the nature of the distension stimulus is critical in determining the pattern of response observed from the various subpopulations of afferents supplying the bowel wall.

Endothelin-A receptor antagonism during acute myocardial infarction in rats.

Endothelin levels are increased in rats with experimentally induced myocardial infarction. The purpose of this study was to determine whether endothelin-A (ET(A)) receptor antagonism alters ventricular remodeling and the development of heart failure after myocardial infarction (MI). We administered 10 mg/kg/day of A-127722 to rats post-MI for 6 weeks. A hemodynamic study was performed and passive pressure-volume curves obtained. In rats without infarcts, ET(A) receptor antagonist (n = 8; vehicle, n = 5) had no effect. However, in rats with infarcts ET(A) antagonism (n=14, MI = 35%; vehicle: n = 19, MI = 32%) reduced systemic arterial and LV systolic (but not end-diastolic) pressures and shifted the pressure-volume relationship to the right. Because LV mass was not changed, the volume-to-mass ratio was increased and was correlated inversely with the ability of the LV to maximally develop pressure. This increase in volume at low distending pressures was also coupled with a tendency (P < 0.06) for reduced scar thickness, suggesting that early initiation of an ET(A) receptor antagonism increased infarct expansion. The reduction in blood pressure offset the increase in volume such that wall stresses were unchanged, as was LV mass. The early use of ET(A) receptor antagonism in the rat model of myocardial infarction did not beneficially alter LV remodeling.

Response of large superficial dorsal hand veins to locally infused nitroglycerine in young, normal subjects

Nitroglycerine relaxes vascular smooth muscle and is routinely use to treat angina and congestive heart failure. However, in preliminary observations of severe heart failure patients, nitroglycerine did not dilate superficial veins, although the observations were made at the top of the distention-pressure relationship for superficial veins. Hence, the purpose of this study was to examine whether the venodilating effects of nitroglycerine could be demonstrated at lower distending pressures. Dorsal hand vein diameter was measured using a linear variable differential transformer in 14 normal, healthy subjects, 20-34 years old. The distention-pressure response was obtained by applying 10-mmHg (1 mmHg = 133.3 Pa) increments of distending pressure from 10 to 50 mmHg. Distention-pressure curves were constructed during randomized, single blind local intravenous infusions (constant rate of 0.1 mL/min) of dextrose or nitroglycerine (100 ng/min). No significant differences were observed during the study in heart rate or arterial pressure between dextrose and nitroglycerine. No difference in superficial dorsal venous distension at any of the five applied distending pressures was observed during infused dextrose compared with infused nitroglycerine (10 mmHg, 0.21 +/- 0.03 vs. 0.23 +/- 0.04 mm; 20 mmHg, 0.63 +/- 0.06 vs. 0.63 +/- 0.05 mm; 30 mmHg, 0.82 +/- 0.08 vs. 0.82 +/- 0.08 mm; 40 mmHg, 0.93 +/- 0.09 vs. 0.94 +/- 0.09 mm; 50 mmHg, 0.98 +/- 0.10 vs. 0.98 +/- 0.09 mm; p = ns). Thus, locally infused nitroglycerine, at very high local concentrations, was unable to significantly vasodilate large superficial dorsal hand veins of normals even at low distending pressures. Further investigation is required of the actions of nitroglycerine on different venous beds and the arterial circulation, in addition to possible difference in response of subject populations such as congestive heart failure in which there may be different basal levels of resting venomotor tone.

Beneficial effects of the "open lung approach" with low distending pressures in acute respiratory distress syndrome. A prospective randomized study on mechanical ventilation.

Alveolar overdistention and cyclic reopening of collapsed alveoli have been implicated in the lung damage found in animals submitted to artificial ventilation. To test whether these phenomena are impairing the recovery of patients with acute respiratory distress syndrome (ARDS) submitted to conventional mechanical ventilation (MV), we evaluated the impact of a new ventilatory strategy directed at minimizing "cyclic parenchymal stretch." After receiving pre-established levels of hemodynamic, infectious, and general care, 28 patients with early ARDS were randomly assigned to receive either MV based on a new approach (NA, consisting of maintenance of end-expiratory pressures above the lower inflection point of the P x V curve, VT < 6 ml/kg, peak pressures < 40 cm H2O, permissive hypercapnia, and stepwise utilization of pressure-limited modes) or a conventional approach (C = conventional volume-cycled ventilation, VT = 12 ml/kg, minimum PEEP guided by FIO2 and hemodynamics and normal PaCO2 levels). Fifteen patients were selected to receive NA, exhibiting a better evolution of the PaO2/FIO2 ratio (p < 0.0001) and of compliance (p = 0.0018), requiring shorter periods under FIO2 > 50% (p = 0.001) and a lower FIO2 at the day of death (p = 0.0002). After correcting for baseline imbalances in APACHE II, we observed a higher weaning rate in NA (p = 0.014) but not a significantly improved survival (overall mortality: 5/15 in NA versus 7/13 in C, p = 0.45). We concluded that the NA ventilatory strategy can markedly improve the lung function in patients with ARDS, increasing the chances of early weaning and lung recovery during mechanical ventilation.

Nitroprusside and regional vascular capacitance in patients with severe congestive heart failure.

This study investigates the effects of sodium nitroprusside on regional vascular capacitance in eight patients with severe congestive heart failure (New York Heart Association class IV) and pulmonary hypertension. Regional relative blood volumes in the splanchnic and pulmonary region were determined by equilibrium blood pool scintigraphy. Hepatic venous wedge pressure and the mean of pulmonary artery and pulmonary capillary wedge pressure were used to represent the distending pressures of the splanchnic and pulmonary capacitance vessels, respectively. The dose of sodium nitroprusside was increased stepwise until systolic pulmonary artery pressure decreased below 50 mm Hg. This caused reductions in mean aortic pressure from 89 +/- 5 to 66 +/- 3 mm Hg (p less than 0.005), in pulmonary capillary wedge pressure from 31 +/- 1 to 16 +/- 2 mm Hg (p less than 0.001), and in hepatic venous wedge pressure from 10.0 +/- 1.0 to 5.9 +/- 0.6 mm Hg (p less than 0.005). Intestinal blood volume increased by 26 +/- 7% (p less than 0.005), whereas hepatic blood volume decreased by 9 +/- 3% (p less than 0.02). Pulmonary blood volume was unchanged. Analysis of intestinal and pulmonary vascular pressure-volume relations showed larger or equal blood volumes contained at lower distending pressures, indicating that sodium nitroprusside reduced smooth muscle tone of the capacitance vessels in these regions. The reduction of hepatic blood volume was compatible with passive expulsion of blood subsequent to reduced venous pressure. There was no change in the count rate from the spleen. Nitroprusside reduced venous pressure in patients with congestive heart failure by active relaxation of intestinal and pulmonary capacitance vessels. Hepatic vascular volume was probably reduced by a passive mechanism.

Gas exchange in low‐compression HFPPV is maintained at low distending pressures in the pig

The fact that collateral ventilation normally occurs in the human lung has led to the suggestion that it might contribute to the successful clinical effects of low-compression high-frequency positive-pressure ventilation (HFPPV). As the pig has poor collateral ventilation, pulmonary vasoconstriction has to be part of the regulatory mechanisms matching ventilation-perfusion. A study was made on nine pigs anesthetized with ketamine hydrochloride intravenously to elucidate the maintenance of ventilation-perfusion balance during mechanical ventilation. Comparisons were made between the ventilatory patterns provided by a conventional ventilator (Servo-Ventilator 900C) and an improved prototype of a low-compression system for volume-controlled ventilation (system H). A ventilatory frequency of 20 breaths per min (bpm) with SV-900C (SV-20) and system H (H-20) and of 60 bpm with system H (H-60) was used. The experimental conditions were otherwise identical. Positive end-expiratory pressures (PEEP) were applied to maintain the same mean airway pressure with the three systems. The tidal volume required for normoventilation differed significantly between the three ventilatory patterns, but there were no differences in circulatory and oxygen-transport variables. By measurements of airway pressure and intrapleural liquid surface pressure, it was demonstrated that the distending pressure (at end-inspiration) was significantly lower with a low-compression system (H-20 versus SV-20), especially at a high ventilatory frequency (H-60 versus H-20). Consequently, although the mean airway pressure was set at the same level for the three different ventilatory modalities, the distending pressures required for the same alveolar ventilation and arterial oxygenation differed significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Response of tracheal slowly adapting stretch receptors to longitudinal forces

During breathing and various respiratoru maneuvers the trachea sustains significant longitudinal stresses which could be sensed by its mechanoreceptors. In this study we have measured the longitudinal motion and elongation of the trachea in supine, anesthetized dogs during quiet breathing and with occlusion of the upper airways and recorded the response of tracheal stretch receptors in each of the two conditions. The respiratory modulation of intrathoracic tracheal stretch receptors is essentially absent during airway occlusion when the elongation of the trachea becomes greater than in a quiet breath. We have also measured the response of tracheal stretch receptors to transmural pressure at different tracheal length, both statically and dynamically. When the trachea is elongated the receptors decreased their activity at higher positive pressures and remained unaffected with lower distending pressures, at zero transmural pressure and with collapsing pressures. These results indicate that the longitudinal forces applied to the trachea are not capable of changing the transducing properties of its stretch receptors over most of its pressure-volume range, only toward its TLC position their response appear to become attenuated.

Properties of a lysophospholipase-transacylase from rat lung: its possible involvement in the synthesis of lung surfactant.

In 1961 Klaus et al. (1) first suggested that 1,2 dipalmitoyl-phosphatidylcholine (DPPC) comprised the functional constituent of the pulmanary surfactant, which prevents the lung alveoli from collapsing at low distending pressures. Ever since this discovery, there has been much interest in the synthesis and secretion of phospholipids, especially of DPPC, in lung. There are two routes for the de novo synthesis of phosphatidylcholine in lung, i.e. the classical CDP-choline pathway and the sequential N-methylation of phosphatidylethanolamine. Current knowledge indicates the former pathway to be by far the most important one (see refs. 2 and 3 for a review). Evidence from both in vitro and in vivo experiments suggests that the CDP-choline pathway produces primarily unsaturated species of phosphatidylcholine (4–7). Two auxiliary mechanisms, both involving lysophosphatidylcholine (lyso PC), are thought to play an important role in the conversion of unsaturated species into fully saturated species, mainly DPPC, of phosphatidylcholine. Firstly, acylation of 1-acyl lyso PC (8) with palmitoyl-CoA would lead to the formation of mainly DPPC, since the 1-position of the phosphatidylcholine precursor for the endogenous 1-acyl lyso PC is esterified for about 80% with palmitate (9–11). Secondly, a transacylation mechanism involving two molecules of 1-acyl lyso PC (12) would yield by the same argument mainly DPPC. Which of the two pathways contributes most to the synthesis of DPPC in vivo is still a matter of considerable debate and arguments in favour of both pathways can be provided. The specificity of acylCoA: lyso PC acyltransferases in lung microsomes is such that the incorporation of palmitate into the 2-position of 1-acyl lyso PC is higher than observed for liver microsomes, but no preferential esterification is observed when compared with unsaturated fatty acids (4,13,14). However, surfactant synthesis is generally believed to occur in alveolar type II cells (for a recent review see ref. 3) and the specificity of the acyltransferases of these cells may be masked in microsomes derived from total lung homogenate. Indeed, evidence has been provided which might indicate that the preference for palmitate in the acylation of 1-acyl lyso PC is higher in cells presumably derived from alveolar type II cells (15,16).

Studies on elastic recoil of the lung in a pediatric population.

Volume-pressure curves were determined in lungs excised postmortem in 27 subjects who ranged in age from premature newborns to 23 years. Volumes were expressed in milliliters per gram of lung tissue. Despite the considerable scatter of the curves, a trend toward larger values at full inflation and steeper curves near collapse volumes occurred with increasing age up to approximately eight years. When lung volumes were expressed as percentage of those obtained at 20 cm H2O of transpulmonary pressure, it was apparent that the volumes at lower distending pressures did not change with age or body length indicating that the over-all shape of the static pressure characteristics did not change. Discrepancies with previously published data on living human subjects allowed for speculation regarding the factors influencing autopsy determinations such as interstitial edema and variability of blood content.

Pulmonary Surfactant in Health and Disease

The airspaces of the lung may be compared to several hundred million bubbles blown on airways, and the surface tension necessary to prevent alveolar emptying can be estimated. If the alveolar surface were made of a transudate of plasma, we would expect the alveoli to be empty at the end of expiration. Instead, current evidence indicates that the surface tension of the lung varies widely and alveoli do not collapse because the surface tension can be very low. However, if the surface tension is high due to an abnormal surface, or if the distending pressure is maintained low, we would expect focal atelectasis. Although a very low surface tension must be necessary in the lung at low distending pressures, the lung extracts and apparently the lung, cannot maintain a low surface tension for a prolonged period. Occasional increase of the surface area, as normally occurs with a deep breath, may replenish the surface, but during shallow breathing with a low distending pressure, the lung surface area decreases with eventual atelectasis. This atelectasis is not due to airway collapse and does not need to follow the distribution of a bronchus.