Peak Inflation Research Articles

Functional residual capacity measurement by heptafluoropropane in ventilated newborn lungs: In vitro and in vivo validation

Heptafluoropropane is an inert gas commercially used as propellant for inhalers. Since heptafluoropropane can be detected in low concentrations, it could also be used as a tracer gas to measure functional residual capacity and ventilation homogeneity. The aim of the present study was to validate functional residual capacity measurements by heptafluoropropane wash-in/wash-out (0.8%) during mechanical ventilation in small, surfactant-depleted lungs using a newborn piglet model. Prospective laboratory and animal trial. Animal laboratory in a university setting. Sixteen newborn piglets (age<12 hrs, median weight 1390 g [705-4200 g]) before and after surfactant depletion (Pao2<100 torr in Fio2=1.0) by lung lavage. Heptafluoropropane was measured with a new infrared mainstream sensor connected with the flow sensor of the Dräger Babylog 8000. Accuracy and precision of the measurement technique were tested in a mechanical lung model with a volume range from 11 to 35 mL. Reproducibility of the method and its sensitivity to detect changes of functional residual capacity were assessed in vivo by variation of ventilatory variables. In vitro the absolute error of functional residual capacity was <1 mL (relative errors<3%) with a coefficient of variation<4%. The coefficient of variation of consecutive in vivo measurements was only slightly higher (<5.1%). Measurement of heptafluoropropane concentrations in blood showed no significant accumulation for repeated functional residual capacity measurements within short time periods. After lung lavage, the functional residual capacity decreased from 20.9 mL/kg to 14.5 mL/kg (p<.05) despite increased ventilatory pressures, and lung clearance index (p<.001) and moment ratios (p<.01) increased significantly due to uneven alveolar ventilation. In healthy lungs, the increase in peak inflation pressure and positive end-expiratory pressure by 3-4 cm H2O had only a moderate effect on functional residual capacity (20.9+/-8.6 vs. 26.0+/-11.9 mL/kg, p=.17) and no effect on ventilatory homogeneity, whereas in surfactant-depleted lungs the functional residual capacity increased from 14.5+/-6.7 mL/kg to 29.9+/-12.6 mL/kg (p<.001) and lung clearance index and moment ratios decreased significantly (p < .01). Heptafluoropropane is a suitable tracer gas for precise functional residual capacity measurements tested in vitro and allows for reproducible measurements in ventilated small lungs without any adverse effects on mechanical ventilation. The sensitivity of the method is sufficiently high to demonstrate the effect of changes in ventilatory settings on the functional residual capacity and ventilation homogeneity.

Ventilator Y-Piece Pressure Compared with Intratracheal Airway Pressure in Healthy Intubated Children

Compare airway pressure measurements at the ventilator Y-piece of the breathing circuit (P( Y )) to intratracheal pressure measured at the distal end (P( T )) of the endotracheal tube (ETT) during mechanical ventilation and spontaneous breathing of intubated children. Thirty children (age range 29 days to 5 years) receiving general anesthesia were intubated with an ETT incorporating a lumen embedded in its sidewall that opened at the distal end to measure P( T ). Peak inflation pressure (PIP) was measured at P( Y ) and P( T ) during positive pressure ventilation. Just before extubation, all measurements were repeated and imposed resistive work of breathing (WOBi) was calculated at both sites while breathing spontaneously. Average PIP was approximately 25% greater at P( Y ) (19.7 +/- 3.4 cm H(2)O) vs. P( T ) (15.0 +/- 2.9 cm H(2)O), p < 0.01. During spontaneous inhalation P( T ) was 59% lower ({bond}8.5 +/- 4.0 cm H(2)O) vs. P( Y ) ({bond}3.5 +/- 2.0 cm H(2)O), p < 0.01. WOBi measured at P( Y ) (0.10 +/- 0.02 Joule/L) was 86% less than WOBi measured at P( T ) (0.70 +/- 0.40 Joule/L), p < 0.01. In healthy children P( Y ) significantly overestimates PIP in the trachea during positive pressure ventilation and underestimates the intratracheal airway pressure during spontaneous inhalation. During positive pressure ventilation P( T ) better assesses the pressure generated in the airways and lungs compared to P( Y ) because P( T ) also includes the difference in airway pressure across the ETT tube due to resistance. During spontaneous inhalation, P( T ) reflects the series resistance of the ETT and ventilator circuit, while P( Y ) reflects only the resistance of the ventilator circuit, accounting for the smaller decreases in pressure. Additionally, P( Y ) underestimates the total WOBi load on the respiratory muscles. Thus, P( T ) is a more accurate reflection of pulmonary airway pressures than P( Y ) and suggests that it should be incorporated into ventilator systems to more accurately trigger the ventilator and to reduce work of breathing.

Evaluation of Biocompatible Cardiopulmonary Bypass Circuit Use During Pediatric Open Heart Surgery

The contact of blood with nonbiological surfaces during cardiopulmonary bypass (CPB) induces a whole body inflammatory response and increases postoperative morbidity directly related to bleeding complications and end organ dysfunction. Methods to reduce these effects have included modification of extracorporeal circuits through biocompatible coating of disposables and the application of various pharmacological agents. Biocompatible coated surfaces are designed to mimic physiologic surfaces. This study was designed to ascertain the effects of using coated circuits during pediatric CPB. After Institutional Review Board approval and parent/guardian consent, patients undergoing CPB, weighing less than 15 kg, with target CPB temperatures more than 28°C, were enrolled into the Coated Circuit Group using an entirely biocompatible CPB circuit with poly(2methoxyethylacrylate) (PMEA) and a biocompatible coated oxygenator (n= 16). Those patients were retrospectively matched to control patients having the same congenital repair with respect to patient size, surgeon, anesthesiologist, bypass time, cross-clamp time, bypass temperature, and noncoated bypass disposables; (n= 16). CPB data collected included on-bypass platelet count, hematocrit (HCT), and CPB blood product use. Postprotamine data collected in the operating room included blood product use, time from initial protamine administration to chest closure, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and international normalized ratio (INR). Postoperative intensive care unit (ICU) data included blood product use, HCT, chest tube output, platelet count, PT, aPTT, INR, blood gases, lactate, and ventilator settings at 1, 2, 4, 6, 12, and 24 hours. Other data collected included intubation time, length of time to chest tube removal, and length of ICU stay. Statistical significance (p&lt; .05) was seen in units of platelets transfused postprotamine, ventilator peak inflation pressure (PIP) on admission to the ICU, postoperative day 0 packed red blood cells (PRBC) and fresh frozen plasma (FFP) transfused, and lactate at 1, 2, 4, 6, and 12 hours postoperative. Several parameters approached statistical significance, including PRBC transfused postprotamine, time from protamine administration to chest closure, postoperative day 0 platelets transfused, and ICU stay. The data suggest that PMEA biocompatible CPB circuits can be used safely during pediatric heart surgery, resulting in a decrease in postoperative blood product use, improved postoperative lung function, and a reduction in the time spent in the ICU.

Prospective respiratory‐gated micro‐CT of free breathing rodents

Microcomputed tomography (Micro-CT) has the potential to noninvasively image the structure of organs in rodent models with high spatial resolution and relatively short image acquisition times. However, motion artifacts associated with the normal respiratory motion of the animal may arise when imaging the abdomen or thorax. To reduce these artifacts and the accompanying loss of spatial resolution, we propose a prospective respiratory gating technique for use with anaesthetized, free-breathing rodents. A custom-made bed with an embedded pressure chamber was connected to a pressure transducer. Anaesthetized animals were placed in the prone position on the bed with their abdomens located over the chamber. During inspiration, the motion of the diaphragm caused an increase in the chamber pressure, which was converted into a voltage signal by the transducer. An output voltage was used to trigger image acquisition at any desired time point in the respiratory cycle. Digital radiographic images were acquired of anaesthetized, free-breathing rats with a digital radiographic system to correlate the respiratory wave form with respiration-induced organ motion. The respiratory wave form was monitored and recorded simultaneously with the x-ray radiation pulses, and an imaging window was defined, beginning at end expiration. Phantom experiments were performed to verify that the respiratory gating apparatus was triggering the micro-CT system. Attached to the distensible phantom were 100 microm diameter copper wires and the measured full width at half maximum was used to assess differences in image quality between respiratory-gated and ungated imaging protocols. This experiment allowed us to quantify the improvement in the spatial resolution, and the reduction of motion artifacts caused by moving structures, in the images resulting from respiratory-gated image acquisitions. The measured wire diameters were 0.135 mm for the stationary phantom image, 0.137 mm for the image gated at end deflation, 0.213 mm for the image gated at peak inflation, and 0.406 mm for the ungated image. Micro-CT images of anaesthetized, free-breathing rats were acquired with a General Electric Healthcare eXplore RS in vivo micro-CT system. Images of the thorax were acquired using the respiratory cycle-based trigger for the respiratory-gated mode. Respiratory gated-images were acquired at inspiration and end expiration, during a period of minimal respiration-induced organ motion. Gated images were acquired with a nominal isotropic voxel spacing of 44 microm in 20-25 min (80 kVp, 113 mAs, 300 ms imaging window per projection). The equivalent ungated acquisitions were 11 min in length. We observed improved definition of the diaphragm boundary and increased conspicuity of small structures within the lungs in the gated images, when compared to the ungated acquisitions. In this work, we have characterized the externally monitored respiratory wave form of free-breathing, anaesthetized rats and correlated the respiration-induced organ motion to the respiratory cycle. We have shown that the respiratory pressure wave form is an excellent surrogate for the radiographic organ motion. This information facilitates the definition of an imaging window at any phase of the breathing cycle. This approach for prospectively gated micro-CT can provide high quality images of anaesthetized free-breathing rodents.

The inhibitory effect of ouabain on the response of slowly adapting pulmonary stretch receptors to hyperinflation in the rabbit

The combined effects of ouabain (Na +–K + ATPase inhibitor) and hyperinflation (inflation volume = three tidal volumes) on slowly adapting pulmonary stretch receptors (SARs) were studied before and after administration of nifedipine (an L-type Ca 2+ channel blocker) and KB-R7943 (a reverse-mode Na +–Ca 2+ exchanger blocker) in anesthetized, artificially ventilated rabbits after bilateral vagotomy. Before ouabain administration, hyperinflation stimulated SAR activity. After 20 min of ouabain administration (30 μg/kg) the SARs increased discharge rates in normal inflation. Under these conditions, hyperinflation initially stimulated SAR activity but subsequently inhibited the activity at peak inflation. Additional administration of 60 μg/kg ouabain (total dose = 90 μg/kg) caused a further stimulation of SAR activity, but 20 min later both normal inflation and hyperinflation resulted in a greater inhibition of the receptor activity. The hyperinflation-induced SAR inhibition in the presence of ouabain (30 μg/kg) was not significantly altered by administration of either nifedipine (2 and 4 mg/kg) or KB-R7943 (1 and 3 mg/kg). In another series of experiments, we further examined the combined effects of ouabain and hyperinflation in veratridine (a Na + channel opener, 40 μg/kg)-treated animals. After recovery from the veratridine effect on SAR activity, which vigorously stimulated the receptor activity, ouabain treatment (30 μg/kg) that silenced the receptor activity at peak inflation greatly inhibited hyperinflation-induced SAR stimulation. These results suggest that hyperinflation-induced SAR inhibition in the presence of ouabain may be related to a Na + overload, but not to a Ca 2+ influx via activation of L-type Ca 2+ channels, in the SAR endings.

Intratracheal pressure: A more accurate reflection of pulmonary airway pressure in pediatric patients with respiratory failure

Peak inflation pressure (PIP) on many ventilators (P(vent)), measured distal to the exhalation limb or Y-piece of the breathing circuit, is assumed as the pressure applied to the airways and lungs. However, in vitro studies show P(vent) data are spurious. There are no studies evaluating the accuracy of P(vent) data for pediatric patients with acute respiratory failure. We hypothesized that intratracheal airway pressure (P(T)) is more accurate than P(vent) and that by using P(vent), abnormally increased imposed resistive work of breathing (WOBi) may go undetected. Prospective and descriptive study. A pediatric intensive care unit at a university hospital. Twenty-one pediatric patients with respiratory failure requiring mechanical ventilation. All patients were intubated with a commercially available endotracheal tube (ETT) with a pressure measuring the lumen opening at the distal end used for measuring P(T). Pressure/flow sensors positioned between the ETT and Y-piece measured tidal volume (V(T)) and flow rate. P(vent) data were recorded as displayed on the ventilator. WOBi was measured by integrating P(T) and V(T) data. PIP at P(vent) and P(T) were 26 +/- 8 cm H(2)O and 19 +/- 7 cm H(2)O, respectively (p < .05). P(T) measurements averaged 27% less than P(vent). The relationship between P(vent)-P(T) (pressure drop across the breathing circuit and ETT) and flow rate during spontaneous inhalation was highly correlated (r = .80, p < .002), indicating the greater the flow rate, the greater the pressure drop and WOBi. WOBi, ranging from 0.04-1.5 J/L, was measured in 52% of the patients. P(vent) significantly overestimates PIP. Moreover, P(vent) data does not allow for recognition of increased WOBi for many patients. Clinicians need to be aware of the limitations of P(vent) data and consider using ETTs that allow measurement of P(T), a more accurate reflection of pulmonary airway pressure.

Clara cell secretory protein and phospholipase A2activity modulate acute ventilator-induced lung injury in mice

Lung vascular permeability is acutely increased by high-pressure and high-volume ventilation. To determine the roles of mechanically activated cytosolic PLA2 (cPLA2)and Clara cell secretory protein (CCSP), a modulator of cPLA2 activity, we compared lung injury with and without a PLA2 inhibitor in wild-type mice and CCSP-null mice (CCSP-/-) ventilated with high and low peak inflation pressures (PIP) for 2- or 4-h periods. After ventilation with high PIP, we observed significant increases in the bronchoalveolar lavage albumin concentrations, lung wet-to-dry weight ratios, and lung myeloperoxidase in both genotypes compared with unventilated controls and low-PIP ventilated mice. All injury variables except myeloperoxidase were significantly greater in the CCSP-/- mice relative to wild-type mice. Inhibition of cPLA2 in wild-type and CCSP-/- mice ventilated at high PIP for 4 h significantly reduced bronchoalveolar lavage albumin and total protein and lung wet-to-dry weight ratios compared with vehicle-treated mice of the same genotype. Membrane phospho-cPLA2 and cPLA2 activities were significantly elevated in lung homogenates of high-PIP ventilated mice of both genotypes but were significantly higher in the CCSP-/- mice relative to the wild-type mice. Inhibition of cPLA2 significantly attenuated both the phospho-cPLA2 increase and increased cPLA2 activity due to high-PIP ventilation. We propose that mechanical activation of the cPLA2 pathway contributes to acute high PIP-induced lung injury and that CCSP may reduce this injury through inhibition of the cPLA2 pathway and reduction of proinflammatory products produced by this pathway.

Acute ventilator-induced vascular permeability and cytokine responses in isolated and in situ mouse lungs

To determine the influence of experimental model and strain differences on the relationship of vascular permeability to inflammatory cytokine production after high peak inflation pressure (PIP) ventilation, we used isolated perfused mouse lung and intact mouse preparations of Balb/c and B6/129 mice ventilated at high and low PIP. Filtration coefficients in isolated lungs and bronchoalveolar lavage (BAL) albumin in intact mice increased within 20-30 min after initiation of high PIP in isolated Balb/c lungs and intact Balb/c, B6/129 wild-type, and p55 and p75 tumor necrosis factor (TNF) dual-receptor null mice. In contrast, the cytokine response was delayed and variable compared with the permeability response. In isolated Balb/c lungs ventilated with 25-27 cmH(2)O PIP, TNF-alpha, interleukin (IL)-1 beta, IL-1 alpha, macrophage inflammatory protein (MIP)-2, and IL-6 concentrations in perfusate were markedly increased in perfusate at 2 and 4 h, but only MIP-2 was detectable in intact Balb/c mice using the same PIP. In intact wild-type and TNF dual-receptor null mice with ventilation at 45 cmH(2)O PIP, the MIP-2 and IL-6 levels in BAL were significantly increased after 2 h in both groups, but there were no differences between groups in the BAL albumin and cytokine concentrations or in lung wet-to-dry weight ratios. TNF-alpha was not be detected in BAL fluids in any group of intact mice. These results suggest that the alveolar hyperpermeability induced by high PIP ventilation occurs very rapidly and is initially independent of TNF-alpha participation and unlikely to depend on MIP-2 or IL-6.

On defining total lung capacity in the mouse.

Maximal lung volume or total lung capacity in experimental animals is dependent on the pressure to which the lungs are inflated. Although 25-30 cm H2O are nominally used for such inflations, mouse pressure-volume (P-V) curves show little flattening on inflation to those pressures. In the present study, we examined P-V relations and mean alveolar chord length in three strains (C3H/HeJ, A/J, and C57BL/6J) at multiple inflation pressures. Mice were anesthetized, and their lungs were degassed in vivo by absorption of 100% O2. P-V curves were then recorded in situ with increasing peak inflation pressure in 10-cm H2O increments up to 90 cm H2O. Lungs were quickly frozen at specific pressures for morphometric analysis. The inflation limbs never showed the appearance of a plateau, with lung volume increasing 40-60% as inflation pressure was increased from 30 to 60 cm H2O. In contrast, parallel flat deflation limbs were always observed, regardless of the inflation pressure, indicating that the presence of a flat deflation curve cannot be used to justify measurement of total lung capacity in mice. Alveolar size increased monotonically with increasing pressure in all strains, and there was no evidence of irreversible lung damage from these inflations to high pressures. These results suggest that the mouse lung never reaches a maximal volume, even up to nonphysiological pressures >80 cm H2O.

Time and pressure dependence of transvascular Clara cell protein, albumin, and IgG transport during ventilator-induced lung injury in mice.

We compared the transport of three proteins with different hydrodynamic radii with ultrastructural changes in lungs of intact mice ventilated at peak inflation pressures (PIP) of 15, 35, 45, and 55 cmH(2)O for 2 h and PIP of 55 cmH(2)O for 0.5 and 1 h. After 2 h of ventilation, significant increases were observed in plasma Clara cell secretory protein (1.9 nm radius) at 35 cmH(2)O PIP and in bronchoalveolar lavage fluid albumin (3.6 nm radius) at 45 cmH(2)O PIP and IgG (5.6 nm radius) at 55 cmH(2)O PIP. Increased concentrations of all three proteins and lung wet-to-dry weight ratios were significantly correlated with PIP and ventilation time. Clara cell secretory protein and albumin increased significantly after 0.5 h of 55 cmH(2)O PIP, but IgG increased only after 2 h. Separation of endothelium or epithelium to form blebs was apparent only in small vessels (15-30 microm diameter) at 45 cmH(2)O PIP and after 0.5 h at 55 cmH(2)O PIP but became extensive after 2 h of ventilation at 55 cmH(2)O PIP. Junctional gaps between cells were rarely observed. Ultrastructural lung injury and protein clearances across the air-blood barrier were related to ventilation time and PIP levels. Protein clearances increased in relation to molecular size, consistent with increasing dimensions and frequency of transmembrane aqueous pathways.

Historical Perspectives

Historical Perspectives

Vascular segmental permeabilities at high peak inflation pressure in isolated rat lungs.

The response of segmental filtration coefficients (Kf) to high peak inflation pressure (PIP) injury was determined in isolated perfused rat lungs. Total (K f,t ), arterial (K f,a ), and venous (K f,v ) filtration coefficients were measured under baseline conditions and after ventilation with 40-45 cmH(2)O PIP. K f,a and K f,v were measured under zone I conditions by increasing airway pressure to 25-27 cmH(2)O. The microvascular segment K f (K f,mv ) was then calculated by: K f,mv = K f,t - K f,a - K f,v. The baseline K f,t was 0.090 +/- 0.022 ml. min(-1). cm H2O(-1). 100 g(-1) and segmentally distributed 18% arterial, 41% venous, and 41% microvascular. After high PIP injury, K f,t increased by 680%, whereas K f,a, K f,v, and K f,mv increased by 398, 589, and 975%, respectively. Pretreatment with 50 microM gadolinium chloride prevented the high PIP-induced increase in K f in all vascular segments. These data imply a lower hydraulic conductance for microvascular endothelium due to its large surface area and a gadolinium-sensitive high-PIP injury, produced in both alveolar and extra-alveolar vessel segments.

Development of Fine Time Controller of a Transtracheal Jet Ventilator and Its Experimental Application

Background: Transtracheal jet ventilation (TTJV) with a large-bore angiocath that is inserted through the cricothyroid membrane can provide immediate oxygenation from a high pressure-oxygen wall outlet, as well as ventilation by means of manual triggering. However, there is widespread agreement that TTJV with a high pressure oxygen system may induce numerous complications including tracheal hemorrhage/ulceration, subcutaneous/mediastinal emphysema, and barotrauma resulting in a pneumothorax. The goal of this study was to highlight the potential effectiveness of a TTJ-ventilator with an oxygen supply pressure lower than 50 psig for proper oxygenation and ventilaton avoiding the possibility of complications from a high pressure oxygen supply system. Methods: Five mongrel dogs were intubated, paralyzed with vecuronium,and mechanically ventilated with enflurane in air maintaining the at 35-40 mmHg. A 16 G IV catheter was inserted percutaneously into the trachea below the tip of the endotrachealtube. We measured the injection volumes, entrained air volumes, and peak inflation pressures according d the changes of oxygen supply pressure (10 to 50 psig) with a fixed injection time (1 second). In addition, we evaluated the oxygenation effects of TTJV at 15 breaths per minute and an I: E 1 : 3 on 20 psig of oxygen supply pressure in hypoxic dogs. Results: A 16 G angiocath provided the injected volumes from 139 ml to 595 ml according to the changes of oxygen pressure from 10 to 50 psig. The entrained if volumes were 6.7-48% of total inspirated volumes. The was elevated over 300 mmHg and the was reduced to 45 mmHg within 1 minute of TTJV in hypoxic dogs. Conclusions: A TTJV system equipped with a time-controller and pressure-regulator can provide enough tidal volume to maintain oxygenation, and could minimize the volu/barotrauma of a conventional TTJV.

The Development of an Inspiratory Time Adjustable Transtracheal Jet Ventilator and Evaluation in a Human Adult Trachea-Lung Model

Background: Transtracheal jet ventilation (TTJV) has been used for ‘Cannot Ventilate/Cannot Intubate’ situation, lefe-saving situations, by simply introducing an IV catheter (angiocatheter) through the cricothyroid membrane. To decrease the occurrence of barotrauma caused by a continuous high pressure oxygen supply while applying TTJV, it would be ideal to have a TTJV system equipped with an inspiration time adjustable function which any currently commercially available TTJV does not have. Methods: Recently, we made a prototype of an inspiration time adjustable TTJV and measured the corresponding injection volumes and peak inflation pressures according to the changes of oxygen supply pressure and inspiration time using catheters ranging from 14 to 20 G in a simulated human adult trachea-lung model. Results: A 16 G angiocatheter provided 465 ± 5 ml of injected volume with a peak inflation pressure of 25 cmH2O under a 50 psi oxygen supply at 1 second of inspiration, which would be adequate for an adult tidal volume. When a 14 G catheter was used under the same conditions as above, the injected volume was 1128 ± 9 ml. All injected volumes were under 310 ml when 18 and 20 G angiocathers were used at various driving pressures (10-50 psi) and inspiration time (0.5, 0.75, and 1 s). Conclusions: An inspiration time adjustable TTJV can easily provide enough tidal volume to maintain oxygenation, and could be expected to prevent or reduce barotraumatic complications such as pneumothorax. (Korean J Anesthesiol 2001; 40: 211∼219) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ

Inhibitors of myosin light chain kinase and phosphodiesterase reduce ventilator-induced lung injury

Alveolar overdistension due to high peak inflation pressures (PIP) is associated with an increased capillary filtration coefficient (K(fc)). To determine which signal pathways contribute to this injury, we perfused isolated rat lungs with 5% bovine albumin in Krebs solution and measured K(fc) after successive 30-min periods of ventilation with peak inflation pressures (PIP) of 7, 20, 30, and 35 cmH(2)O. In a high-PIP control group, K(fc) increased significantly after ventilation with 30 and 35 cmH(2)O PIP, but significant increases were prevented by treatment with 100 microM trifluoperazine, an inhibitor of Ca(2+)/calmodulin, 500 nM ML-7, an inhibitor of myosin light chain kinase (MLCK), a combination of isoproterenol (20 microM) and rolipram (10 microM) to enhance intracellular cAMP levels, and a dose of KT-5720 (2 microM), which inhibits MLCK and protein kinase C. These studies suggest that the Ca(2+)/calmodulin-MLCK pathway augments capillary fluid leak after a modest high-PIP injury and that this is attenuated by kinase inhibition and increased intracellular cAMP.

Lung isolation for the prevention of air embolism in penetrating lung trauma. A case report

To illustrate a new airway and ventilatory management strategy for patients with unilateral penetrating lung injury. Emphasis is placed on avoiding positive pressure ventilation (PPV)-induced systemic air/gas embolism (SAE) through traumatic bronchiole-pulmonary venous fistulas. A 14-yr-old male, stabbed in the left chest, presented with hypovolemia, left hemopneumothorax, an equivocal acute abdomen, and no cardiac or neurological injury. In view of the risk of SAE, we did not ventilate the left lung until any fistulas, if present, had been excised. After pre-oxygenation, general anesthesia was induced and a left-sided double-lumen tube (DLT) was placed to allow right-lung ventilation. Bronchoscopy was performed. The surgeons performed a thorascopic wedge resection of the lacerated lingula. Upon completion of the repair, two-lung ventilation was instituted while the ECG, pulse oximetry, PETCO2, and blood pressure were monitored. Peak inflation pressure was increased slowly and was well tolerated up to 50 cm H2O. The patient's intravascular status was maintained normal. Patients with lung trauma are at risk of developing SAE when their lungs are ventilated with PPV. In a unilateral case, expectant non-ventilation of the injured lung until after repair is recommended.

QRS prolongation: a sensitive marker of ischemia during percutaneous transluminal coronary angioplasty.

The purpose of this study is to measure QRS duration changes in the human model of ischemia during percutaneous transluminal coronary angioplasty (PTCA) and compare these results to the commonly used ischemia markers, chest pain, and classical ST-T changes. Using a computerized method, QRS duration was measured in 51 patients undergoing elective PTCA. Three milliseconds (msec) or more prolongation of the QRS at peak inflation was considered to be an ischemic response. The results were compared to chest pain and ST-T changes and were analyzed for inflation site within individual coronary arteries. Forty-two patients had a pathological prolongation of the QRS during PTCA. Thirty-two patients developed chest pain, while 19 had ischemic ST-T changes. QRS duration was more prolonged in PTCA to proximal or middle segments of major arteries or their large branches, while it was less prolonged in distal segments or smaller branches. Using our method, QRS prolongation was an ischemia marker in most patients during PTCA and was more sensitive than chest pain or ST-T changes. QRS duration was more prolonged with occlusion of proximal and middle segments of major arteries. Cathet. Cardiovasc. Intervent. 50:177-183, 2000.

The High-Pressure Characteristics of the Cuff of the Intubating Laryngeal Mask Endotracheal Tube

The modern polyvinylchloride endotracheal tube (ET) has a large cuff that conforms to the shape of the trachea and can seal it with a low pressure. This large-volume, low-pressure cuffed ET design has, therefore, largely replaced the older red rubber ET which has a small-volume, high-pressure cuff that predisposes to tracheal ischemic complications, particularly during long-term use (1). The new intubating laryngeal mask endotracheal tube (ILM-ET) is an ET used in conjunction with the LMA-Fastrach™ Laryngeal Mask (Euromedical) for blind and fiberoptic-guided tracheal intubation. No specific information is currently available regarding the compliance characteristics of the ILM-ET cuff, which appears to be relatively small. Therefore, this study was designed to measure the compliance of the cuff of the ILM-ET and to compare it with that of the cuff of the polyvinylchloride and red rubber ET. Four size 7.5-mm (inside diameter) of each ET type was tested. The cuff of each tube was incrementally inflated in air, and the corresponding cuff pressure was measured using a calibrated pressure manometer. The ILM-ET cuff clearly exhibited high-pressure characteristics (Figure 1). At cuff volumes used during routine clinical practice, cuff pressure approached 100 mm Hg. Figure 1: The compliance curves of the cuff of three types of size 7.5-mm (inside diameter) endotracheal tubes (ET). Values are mean ± SD. Mallinckrodt, St. Louis, MO; Rüsch, High Wycombe, England; Euromedical, San Diego, CA.During inflation of a low-volume, high-pressure cuff, part of the cuff pressure is consumed in stretching the cuff wall itself. The pressure inside such a cuff is, therefore, higher than the pressure exerted on the tracheal mucosa (CT pressure) by the amount of pressure needed to maintain cuff inflation (2). Nonetheless, when using a low-volume, high-pressure cuffed ET, such as the ILM-ET, it is prudent to attempt to limit the CT pressure. Knowlson and Bassett (3) demonstrated that this could be achieved by inflating the cuff to the minimal volume that sealed the trachea (minimal occlusion volume [MOV]). The authors performed in vivo measurements of CT pressure in patients undergoing anesthesia with a low-volume, high-pressure cuff in place. The CT pressure ranged between 25 and 40 mm Hg at MOV, with a peak inflation pressure of 15 mm Hg and rose rapidly to very high levels with further increments in cuff volume. They concluded from their findings that low-volume, high-pressure cuffs were capable of sealing the trachea with reasonably low CT pressures as long as the cuff was maintained at MOV. The high-pressure characteristics of the cuff of the ILM-ET can be used as an argument against its long term use. Other problems which can be encountered during the long term use of the ILM-ET are the susceptibility to biting and the potential for accumulation of secretions at the reduced-caliber tube tip. In conclusion, the cuff of the ILM-ET is a low-volume, high-pressure cuff. It is, therefore, important when using this ET to maintain its cuff volume at MOV. Esme Riley MD Kerry DeGroot MD Medhat Hannallah MD, FFARCS

Capillary filtration coefficient, vascular resistance, and compliance in isolated mouse lungs.

Although many recently produced transgenic mice possess gene alterations affecting pulmonary vascular function, there are few baseline measurements of vascular resistance and permeability. Therefore, we excised the lungs of C57/BL6 mice and perfused them with 5% bovine serum albumin in RPMI-1640 culture medium at a nominal flow of 0.5 ml/min and ventilated them with 20% O(2)-5% CO(2)-75% N(2). The capillary filtration coefficient, a sensitive measurement of hydraulic conductivity, was unchanged over 2 h (0.33 +/- 0.03 ml. min(-1). cmH(2)O(-1). 100 g(-1)) in a control group ventilated with low peak inflation pressures (PIP) but increased 4. 3-fold after high PIP injury. Baseline pulmonary vascular resistance was 6.1 +/- 0.4 cmH(2)O. ml(-1). min. 100 g(-1) and was distributed 34% in large arteries, 18% in small arteries, 14% in small veins, and 34% in large veins on the basis of vascular occlusion pressures. Baseline vascular compliance was 5.4 +/- 0.3 ml. cmH(2)O(-1). 100 g(-1) and decreased significantly with increased vascular pressures. Baseline pulmonary vascular resistance was inversely related to both perfusate flow and microvascular pressure and increased to 202% of baseline after infusion of 10(-4) M phenylephrine due to constriction of large arterial and venous segments. Thus isolated mouse lung vascular permeability, vascular resistance, and the longitudinal distribution of vascular resistance are similar to those in other species and respond in a predictable manner to microvascular injury and a vasoconstrictor agent.

Ventilatory characteristics in mechanically ventilated patients during manual hyperventilation for chest physiotherapy.

We measured the tidal volumes and peak inflation pressures generated during manual hyperventilation for chest physiotherapy in 25 adult ventilated patients. The average tidal volume ranged from 711 to 1511 ml, with a mean (SD) of 1120 (274) ml. There was a negative correlation (p < 0.05) between the average tidal volume and the lung injury, as measured by the Murray lung injury score. The average peak inflation pressure ranged from 37 to 74 cmH2O with a mean (SD) of 51.5 (7.6) cmH2O. There was a positive correlation (p < 0.05) between average peak inflation pressure and the lung injury score. Mean (SD) PaO2 improved by 18.3 (14.3) kPa from baseline after physiotherapy (p < 0.05). Mean (SD) PaCO2 decreased by 0.1 (0.4) kPa. As the lung score increases higher inflation pressures and smaller tidal volumes are used suggesting an increased potential for barotrauma or volutrauma in susceptible lungs.