Application of tracheal gas insufflation to acute unilateral lung injury in an experimental model.

In unilateral lung injury, application of global positive end-expiratory pressure (PEEP) may cause overdistension of normal alveoli and redistribution of blood flow to diseased lung areas, thereby worsening oxygenation. We hypothesized that selective application of tracheal gas insufflation (TGI) will recruit the injured lung without causing overdistension of the normal lung. In eight anesthetized dogs, left lung saline lavage was performed until Pa(O(2))/FI(O(2)) fell below 100 mm Hg. Then, the dogs were reintubated with a Univent single lumen endotracheal tube that incorporates an internal catheter to provide TGI. After injury, increasing PEEP from 3 to 10 cm H(2)O did not change gas exchange, hemodynamics, or lung compliance. Selective TGI, while keeping end-expiratory lung volume (EELV) constant, improved Pa(O(2))/FI(O(2)) from 212 +/- 43 to 301 +/- 38 mm Hg (p < 0.01) while Pa(CO(2)) and airway pressures decreased (p < 0.01). During selective TGI, reducing tidal volume to 5.2 ml/kg while keeping EELV constant, normalized Pa(CO(2)), did not affect Pa(O(2))/FI(O(2)), and decreased end-inspiratory plateau pressure from 16.6 +/- 1.0 to 11.9 +/- 0.5 cm H(2)O (p < 0.01). In unilateral lung injury, we conclude that selective TGI (1) improves oxygenation at a lower pressure cost as compared with conventional mechanical ventilation, (2) allows reduction in tidal volume without a change in alveolar ventilation, and (3) may be a useful adjunct to limit ventilator-associated lung injury.

Selective tracheal gas insufflation during partial liquid ventilation improves lung function in an animal model of unilateral acute lung injury.

OBJECTIVE: During unilateral lung injury, we hypothesized that we can improve global lung function by applying selective tracheal gas insufflation (TGI) and partial liquid ventilation (PLV) to the injured lung. DESIGN: Prospective, interventional animal study. SETTING: Animal laboratory in a university hospital. SUBJECTS: Adult mixed-breed dogs. INTERVENTIONS: In six anesthetized dogs, left saline lung lavage was performed until PaO(2)/FiO(2) fell below 100 torr (13.3 kPa). The dogs were then reintubated with a Univent single-lumen endotracheal tube, which incorporates an internal catheter to provide TGI. In a consecutive manner, we studied 1) the application of 10 cm H(2)O of positive end-expiratory pressure (PEEP); 2) instillation of 10 mL/kg of perflubron (Liquivent) to the left lung at a PEEP level of 10 cm H(2)O (PLV+PEEP 10 initial); 3) application of selective TGI (PLV+TGI) while maintaining end-expiratory lung volume (EELV) constant; 4) PLV+TGI at reduced tidal volume (VT); and 5) PLV+PEEP 10 final. MEASUREMENTS AND MAIN RESULTS: Application of PLV+PEEP 10 initial did not change gas exchange, lung mechanics, or hemodynamics. PLV+TGI improved PaO(2)/FiO(2) from 189 +/- 13 torr (25.2 +/- 1.7 kPa) to 383 +/- 44 torr (51.1 +/- 5.9 kPa) (p <.01) and decreased PaCO(2) from 55 +/- 5 torr (7.3 +/- 0.7 kPa) to 30 +/- 2 torr (4.0 +/- 0.3 kPa) (p <.01). During ventilation with PLV+TGI, reducing VT from 15 mL/kg to 3.5 mL/kg while keeping EELV constant decreased PaO(2)/FiO(2) to 288 +/- 49 torr (38.4 +/- 6.5 kPa) (not significant) and normalized PaCO(2). At this stage, end-inspiratory plateau pressure decreased from 19.2 +/- 0.7 cm H(2)O to 13.6 +/- 0.7 cm H(2)O (p <.01). At PLV+PEEP 10 final, measurements returned to those observed at previous baseline stage (PLV+PEEP 10 initial). CONCLUSIONS: During unilateral lung injury, PLV with a moderate PEEP did not improve oxygenation, TGI superimposed on PLV improved gas exchange, and combination of TGI and PLV allowed a 77% reduction in VT without any adverse effect on PaCO(2).

Recruitment maneuvers in three experimental models of acute lung injury. Effect on lung volume and gas exchange.

Recruitment maneuvers (RM), consisting of sustained inflations at high airway pressures, have been advocated as an adjunct to mechanical ventilation in acute respiratory distress syndrome (ARDS). We studied the effect of baseline ventilatory strategy and RM on end-expiratory lung volume (EELV) and oxygenation in 18 dogs, using three models of acute lung injury (ALI; n = 6 in each group): saline lavage (LAV), oleic acid injury (OAI), and intratracheal instillation of Escherichia coli (pneumonia; PNM). All three models exhibited similar degrees of lung injury. The PNM model was less responsive to positive end-expiratory pressure (PEEP) than was the LAV or OAI model. Only the LAV model showed an oxygenation response to increasing tidal volume (VT). After RM, there were transient increases in Pa(O(2)) and EELV when ventilating with PEEP = 10 cm H(2)O. At PEEP = 20 cm H(2)O the lungs were probably fully recruited, since the plateau airway pressures were relatively high ( approximately 45 cm H(2)O) and the oxygenation was similar to preinjury values, thus making the system unresponsive to RM. Sustained improvement in oxygenation after RM was seen in the LAV model when ventilating with PEEP = 10 cm H(2)O and VT = 15 ml/kg. Changes in EELV correlated with changes in Pa(O(2)) only in the OAI model with PEEP = 10 cm H(2)O. We conclude that responses to PEEP, VT, and RM differ among these models of ALI. RM may have a role in some patients with ARDS who are ventilated with low PEEP and low VT.

Catecholamines, insulin and ACTH increase quantal size at the frog neuromuscular junction.

The size of miniature end-plate potentials (m.e.p.p.s) and miniature end-plate currents (m.e.p.c.s) at frog neuromuscular junctions was increased by a factor of two or more following treatment with norepinephrine, epinephrine, a cAMP derivative, insulin or ACTH. The increase in size was reversible. These agents do not appear to alter the ACh noise spectrum or the reversal potential of the end-plate. They do not alter the binding of alpha-bungarotoxin. Therefore they may increase the quantity of acetylcholine (ACh) in a quantum.

Activity increases quantal size at the frog neuromuscular junction.

Two h of nerve stimulation at 10 Hz or of elevated spontaneous release in hypertonic solution increased the size of miniature end-plate potentials (m.e.p.p.'s) and currents at the frog neuromuscular junction, probably by increasing the amount of acetylcholine in a quantum. Increases in quantal size may modulate synaptic transmission.