Inhibition of breathing after surfactant depletion is achieved at a higher arterial PCO(2 )during ventilation with liquid than with gas

BACKGROUND: Inhibition of phrenic nerve activity (PNA) can be achieved when alveolar ventilation is adequate and when stretching of lung tissue stimulates mechanoreceptors to inhibit inspiratory activity. During mechanical ventilation under different lung conditions, inhibition of PNA can provide a physiological setting at which ventilatory parameters can be compared and related to arterial blood gases and pH. OBJECTIVE: To study lung mechanics and gas exchange at inhibition of PNA during controlled gas ventilation (GV) and during partial liquid ventilation (PLV) before and after lung lavage. METHODS: Nine anaesthetised, mechanically ventilated young cats (age 3.8 ± 0.5 months, weight 2.3 ± 0.1 kg) (mean ± SD) were studied with stepwise increases in peak inspiratory pressure (PIP) until total inhibition of PNA was attained before lavage (with GV) and after lavage (GV and PLV). Tidal volume (V(t)), PIP, oesophageal pressure and arterial blood gases were measured at inhibition of PNA. One way repeated measures analysis of variance and Student Newman Keuls-tests were used for statistical analysis. RESULTS: During GV, inhibition of PNA occurred at lower PIP, transpulmonary pressure (Ptp) and Vt before than after lung lavage. After lavage, inhibition of inspiratory activity was achieved at the same PIP, Ptp and Vt during GV and PLV, but occurred at a higher PaCO(2 )during PLV. After lavage compliance at inhibition was almost the same during GV and PLV and resistance was lower during GV than during PLV. CONCLUSION: Inhibition of inspiratory activity occurs at a higher PaCO(2 )during PLV than during GV in cats with surfactant-depleted lungs. This could indicate that PLV induces better recruitment of mechanoreceptors than GV

In Vivo Gene Knockdown in Rat Dorsal Root Ganglia Mediated by Self-Complementary Adeno-Associated Virus Serotype 5 Following Intrathecal Delivery

We report here in adult rat viral vector mediate-gene knockdown in the primary sensory neurons and the associated cellular and behavior consequences. Self-complementary adeno-associated virus serotype 5 (AAV5) was constructed to express green fluorescent protein (GFP) and a small interfering RNA (siRNA) targeting mammalian target of rapamycin (mTOR). The AAV vectors were injected via an intrathecal catheter. We observed profound GFP expression in lumbar DRG neurons beginning at 2-week post-injection. Of those neurons, over 85% were large to medium-diameter and co-labeled with NF200, a marker for myelinated fibers. Western blotting of mTOR revealed an 80% reduction in the lumbar DRGs (L4–L6) of rats treated with the active siRNA vectors compared to the control siRNA vector. Gene knockdown became apparent as early as 7-day post-injection and lasted for at least 5 weeks. Importantly, mTOR knockdown occurred in large (NF200) and small-diameter neurons (nociceptors). The viral administration induced an increase of Iba1 immunoreactivity in the DRGs, which was likely attributed to the expression of GFP but not siRNA. Rats with mTOR knockdown in DRG neurons showed normal general behavior and unaltered responses to noxious stimuli. In conclusion, intrathecal AAV5 is a highly efficient vehicle to deliver siRNA and generate gene knockdown in DRG neurons. This will be valuable for both basic research and clinic intervention of diseases involving primary sensory neurons

Maintained inspiratory activity during proportional assist ventilation in surfactant-depleted cats early after surfactant instillation: phrenic nerve and pulmonary stretch receptor activity

<p>Abstract</p> <p>Background</p> <p>Inspiratory activity is a prerequisite for successful application of patient triggered ventilation such as proportional assist ventilation (PAV). It has recently been reported that surfactant instillation increases the activity of slowly adapting pulmonary stretch receptors (PSRs) followed by a shorter inspiratory time (Sindelar et al, J Appl Physiol, 2005 [Epub ahead of print]). Changes in lung mechanics, as observed in preterm infants with respiratory distress syndrome and after surfactant treatment, might therefore influence the inspiratory activity when applying PAV early after surfactant treatment.</p> <p>Objective</p> <p>To investigate the regulation of breathing and ventilatory response in surfactant-depleted young cats during PAV and during continuous positive airway pressure (CPAP) early after surfactant instillation in relation to phrenic nerve activity (PNA) and the activity of PSRs.</p> <p>Methods</p> <p>Seven anesthetized, endotracheally intubated young cats were exposed to periods of CPAP and PAV with the same end-expiratory pressure (0.2–0.5 kPa) before and after lung lavage and after surfactant instillation. PAV was set to compensate for 75% of the lung elastic recoil.</p> <p>Results</p> <p>Tidal volume and respiratory rate were higher with lower PaCO₂and higher PaO₂during PAV than during CPAP both before and after surfactant instillation (p < 0.05; both conditions). As an indicator of breathing effort, esophageal deflection pressure and PNA were lower during PAV than during CPAP in both conditions (p < 0.02). Peak PSR activity was higher and occurred earlier during PAV than during CPAP (p < 0.01), and correlated linearly with PNA duration in all conditions studied (p < 0.001). The inspiratory time decreased as tidal volume increased when CPAP was changed to PAV, with the highest correlation observed after surfactant instillation (r = -0.769). No apneic periods could be observed.</p> <p>Conclusion</p> <p>PSR activity and the control of breathing are maintained during PAV in surfactant-depleted cats early after surfactant instillation, with a higher ventilatory response and a lower breathing effort than during CPAP.</p