Biologically variable ventilation increases arterial oxygenation over that seen with positive end-expiratory pressure alone in a porcine model of acute respiratory distress syndrome.

OBJECTIVES: We compared biologically variable ventilation (BVV) (as previously described) (1) with conventional control mode ventilation (CV) in a model of acute respiratory distress syndrome (ARDS) both at 10 cm H2O positive end-expiratory pressure. DESIGN: Randomized, controlled, prospective study. SETTING: University research laboratory. SUBJECTS: Farm-raised 3- to 4-month-old swine. INTERVENTIONS: Oleic acid (OA) was infused at 0.2 mL/kg/hr with FIO2 = 0.5 and 5 cm H2O positive end-expiratory pressure until PaO2 was < or =60 mm Hg; then all animals were placed on an additional 5 cm H2O positive end-expiratory pressure for the next 4 hrs. Animals were assigned randomly to continue CV (n = 9) or to have CV computer controlled to deliver BVV (variable respiratory rate and tidal volume; n = 8). Hemodynamic, expired gas, airway pressure, and volume data were obtained at baseline (before OA), immediately after OA, and then at 60-min intervals for 4 hrs. MEASUREMENTS AND MAIN RESULTS: At 4 hrs after OA injury, significantly higher PaO2 (213+/-17 vs. 123+/-47 mm Hg; mean+/-SD), lower shunt fraction (6%+/-1% vs. 18%+/-14%), and lower PaCO2 (50+/-8 vs. 65+/-11 mm Hg) were seen with BVV than with CV. Respiratory system compliance was greater by experiment completion with BVV (0.37+/-0.05 vs. 0.31+/-0.08 mL/cm H2O/kg). The improvements in oxygenation, CO2 elimination, and respiratory mechanics occurred without a significant increase in either mean airway pressure (14.3+/-0.9 vs. 14.9+/-1.1 cm H2O) or mean peak airway pressure (39.3+/-3.5 vs. 44.5+/-7.2 cm H2O) with BVV. The oxygen index increased five-fold with OA injury and decreased to significantly lower levels over time with BVV. CONCLUSIONS: In this model of ARDS, BVV with 10 cm H2O positive end-expiratory pressure improved arterial oxygenation over and above that seen with CV with positive end-expiratory pressure alone. Proposed mechanisms for BVV efficacy are discussed.

Biologically variable or naturally noisy mechanical ventilation recruits atelectatic lung.

Biologically variable mechanical ventilation (Vbv)-using a computer-controller to mimic the normal variability in spontaneous breathing-improves gas exchange in a model of severe lung injury (Lefevre, G. R., S. E. Kowalski, L. G. Girling, D. B. Thiessen, W. A. C. Mutch. Am. J. Respir. Crit. Care Med. 1996;154:1567-1572). Improved oxygenation with Vbv, in the face of alveolar collapse, is thought to be due to net volume recruitment secondary to the variability or increased noise in the peak inspiratory airway pressures (Ppaw). Biologically variable noise can be modeled as an inverse power law frequency distribution (y approximately 1/f(a)) (West, B. J., M. Shlesinger. Am. Sci. 1990;78:40-45). In a porcine model of atelectasis-right lung collapse with one-lung ventilation-we studied if Vbv (n = 7) better reinflates the collapsed lung compared with conventional monotonously regular control mode ventilation (Vc; n = 7) over a 5-h period. We also investigated the influence of sigh breaths with Vc (Vs; n = 8) with this model. Reinflation of the collapsed lung was significantly enhanced with Vbv-greater Pa(O(2)) (502 +/- 40 mm Hg with Vbv versus 381 +/- 40 mm Hg with Vc at 5 h; and 309 +/- 79 mm Hg with Vs; mean +/- SD), lower Pa(CO(2)) (35 +/- 4 mm Hg versus 48 +/- 8 mm Hg and 50 +/- 8 mm Hg), lower shunt fraction (9.7 +/- 2.7% versus 14.6 +/- 2.0% and 22.9 +/- 6.0%), and higher respiratory system compliance (Crs) (1.15 +/- 0.15 ml/cm H(2)O/kg versus 0.79 +/- 0.19 ml/cm H(2)O/kg and 0.77 +/- 0.13 ml/cm H(2)O/kg)-at lower mean Ppaw (15.7 +/- 1.4 cm H(2)O versus 18.8 +/- 2.3 cm H(2)O and 18.9 +/- 2.8 cm H(2)O). Vbv resulted in an 11% increase in measured tidal volume (VT(m)) over that seen with Vc by 5 h (14.7 +/- 1.2 ml/kg versus 13. 2 ml/kg). The respiratory rate variability programmed for Vbv demonstrated an inverse power law frequency distribution ( y approximately 1/f(a)) with a = 1.6 +/- 0.3. These findings provide strong support for the theoretical model of noisy end-inspiratory pressure better recruiting atelectatic lung. Our results suggest that using natural biologically variable noise has enhanced the performance of a mechanical ventilator in control mode.

Biologically variable ventilation prevents deterioration of gas exchange during prolonged anaesthesia.

We have studied the time course of changes in gas exchange and respiratory mechanics using two different modes of ventilation during 7 h of isoflurane anaesthesia in pigs. One group received conventional control mode ventilation (CV). The other group received biologically variable ventilation (BVV) which simulates the breath-to-breath variation in ventilatory frequency (f) that characterizes normal spontaneous ventilation. After baseline measurements with CV, animals were allocated randomly to either CV or BVV (FIO2 1.0 with 1.5% end-tidal isoflurane). With BVV, there were 376 changes in f and tidal volume (VT) over 25.1 min. Ventilation was continued over the next 7 h and blood gases and respiratory mechanics were measured every 60 min. The modulation file used to control the ventilator for BVV used an inverse power law frequency distribution (I/fa with a = 2.3 +/- 0.3). After 7 h, at a similar delivered minute ventilation, significantly greater PaO2 (mean 72.3 (SD 4.0) vs 63.5 (6.5) kPa) and respiratory system compliance (1.08 (0.08) vs 0.92 (0.16) ml cm H2O-1 kg-1) and lower PaCO2 (6.5 (0.7) vs 8.7 (1.5) kPa) and shunt fraction (7.2 (2.7)% vs 12.3 (6.2)%) were seen with BVV, with no significant difference in peak airway pressure (16.3 (1.2) vs 15.3 (3.7) cm H2O). A deterioration in gas exchange and respiratory mechanics was seen with conventional control mode ventilation but not with BVV in this experimental model of prolonged anaesthesia.

Improved arterial oxygenation after oleic acid lung injury in the pig using a computer-controlled mechanical ventilator.

We compared computer-controlled mechanical ventilation programmed for biologic variability of respiratory rate (RR) and tidal volume (VT) with conventional intermittent positive-pressure ventilation (IPPV) in an oleic acid (OA) lung injury model. Seventeen pigs were ventilated with an Ohio 7000 anesthesia ventilator. Minute ventilation (VE) was adjusted to maintain PaCO2 at 30 to 35 mm Hg at baseline and was not altered further. OA was infused at 0.2 ml/kg/h until PaO2 decreased to < 125 mm Hg (F(I)O2 = 0.5). Animals were randomly assigned to continue with conventional IPPV (control group; n = 8) or had IPPV computer-controlled (computer group; n = 9). Hemodynamic, respiratory gas, airway pressure, and volume data were obtained at baseline (before OA infusion), at Time 30 (after infusion), and at 30-min intervals for 240 min after OA. At experiment completion, the lungs were removed to determine the wet:dry weight ratios. The control group had RR fixed at 20 breaths/min. The computer group had a RR of 20 +/- 2.3 breaths/min (range, 15 to 27 breaths/min), comprising 369 different RR values with reciprocal changes in VT over 1,089 s before the program looped to repeat itself. There was no difference between groups in the volume of OA infused. By 120 min after lung injury, animals in the computer group had significantly greater PaO2, associated with a lower Qs/QT. Mean airway pressures and mean peak airway pressures were not different in the two groups. By 180 min, respiratory system compliance (Crs) was significantly lower in the control group. The wet:dry lung weight ratios were greater in the control group. Thus, in a porcine model of OA lung injury, computer-controlled mechanical ventilation, which is programmed for biologic variability, resulted in improved blood oxygenation without increasing mean airway pressures when compared with conventional IPPV.

Epinephrine decreases postoperative requirements for continuous thoracic epidural fentanyl infusions.

Epidural thoracic fentanyl infusions provide effective preoperative analgesia after thoracotomy; however, side effects can limit the effectiveness of this technique. This study evaluates epinephrine as an adjunct to continuous thoracic epidural fentanyl infusions after thoracotomy. Thirty-eight patients were studied in a prospective, randomized, double-blind trial comparing fentanyl alone to fentanyl with epinephrine 1:300,000. Epidural infusion rates were titrated to equivalent pain relief using a visual analog scale. With the addition of epinephrine, there was a significant reduction in fentanyl requirements (0.82 +/- 0.07 vs 1.19 +/- 0.11 micrograms.kg-1.h-1, P = 0.005, repeated-measures analysis of variance) and in plasma fentanyl concentrations (steady state: 0.91 +/- 0.13 vs 1.65 +/- 0.23 ng/mL, P = 0.007, repeated-measures analysis of variance). There were no differences in pain scores, side effects, spirometry, patient satisfaction scores, or hemodynamic variables. This study demonstrates that adding epinephrine 1:300,000 to continuous thoracic epidural infusions decreases fentanyl requirements titrated for effective analgesia. The reduction in fentanyl requirements was associated with reduced fentanyl plasma concentrations.

Effects of interpleural bupivacaine (0.5%) on canine diaphragmatic function.

Several authors have questioned the potential for phrenic nerve paralysis with interpleural analgesia. This study was designed to examine the potential for phrenic nerve paralysis with the use of interpleural bupivacaine in dogs. Seven dogs were anesthetized, tracheally intubated, and allowed to breathe spontaneously with halothane/oxygen while in the supine position. After a midline laparotomy, two wires were inserted into the costal portion of each hemidiaphragm for measurement of electromyographic (EMG) signals. A balloon catheter was placed in the abdominal cavity to measure abdominal pressure. The abdomen was then closed. Airway pressure was measured through a side port in the endotracheal tube. Bilateral interpleural catheters were inserted with the loss-of-resistance technique. Each dog was used for two experiments, one on each side, except for one animal. To assess the contribution of the ipsilateral diaphragm to total respiratory effort, the airway was occluded at functional residual capacity for three consecutive breaths, and EMG, airway pressure, and abdominal pressure were measured. In five of nine experiments with bupivacaine, there was complete loss of EMG activity on the side of the injection. In two dogs, there was partial loss of diaphragmatic function, and in the remaining two, there was no change in EMG. In the normal saline solution group (n = 4), there was no change in the EMG. Two dogs that received bilateral bupivacaine injections developed paradoxical respiration with negative inspiratory intraabdominal pressures. Phrenic nerve paralysis or paresis can occur with interpleural blockade. The factors affecting the occurrence of this complication remain to be elucidated.

Valve morphogenesis and the microtubule center of the diatom Hantzschia amphioxys.

The siliceous valve of Hantzschia is briefly described, preparatory to following its morphogenesis. While Hantzschia is morphologically very different to Pinnularia, there are several subtle but important similarities in detail. Bundles of microfilaments, significant in generating the gliding motion of these cells, line the cytoplasmic fissure of the raphe. Valve morphogenesis in Hantzschia has been followed in live cells and by using transmission electron microscopy. Major re-organization and translocation of individual organelles, and also the nascent wall and its associated system of structural cytoplasmic components, are described. The spindle always forms on the concave side of the cell, opposite the raphes in the keels. A "polar complex" near each spindle pole consolidates into the "microtubule center" (MC) after cytokinesis. Each MC moves around its daughter nucleus to the center of the completed cleavage furrow and comes to rest on the narrow silicalemma running along the center of the cell. Microfilaments line first one and then both sides of the silicalemma before it grows outwards and begins to secrete the wall. Microtubules (MTs) extend along the silicalemma from the MC and directly over the future raphe; a compact row of mitochondria is organized along these MTs, flanking each MC. After about one hour in this central position, the whole assemblage of MC, MTs, mitochondria and silicalemma with its forming wall, move laterally across to the convex side of the parent valves. Now, the valve thickens steadily. The fibulae that hold the wall together where it is perforated by the raphe, grow out as flanges fusing with the transverse ribs across the keel. As in Pinnularia, the raphe fissure is occluded precisely adjacent to the MC, which also suppresses formation of the fibulae in this restricted region. The nascent wall structure suggests that silica is being precipitated on to a fibrous base. After valve formation, each MC migrates back to its interphase position at the concave side of the daughter cell. The MC undergoes characteristic morphological changes during these morphogenetic events and remains throughout tightly associated with a pronounced evagination of the nucleus. Ultrastructural comparisons suggest that the Hantzschia symmetry could have originally been derived from that of Pinnularia.