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

The Temperature of Inspired Air Influences Respiratory Water Loss in Young Lambs

The temperature of inspired air influences respiratory water loss (RWL) in young lambs. Water loss from the airways, oxygen consumption and carbon dioxide production were measured using an open flow-through system with a mass spectrometer, specially equipped with a water channel, for gas analysis. Measurements were made in 9 newborn lambs at 3 different inspired air temperatures keeping all other environmental factors stable, including the ambient air temperature. The water content of the inspired air was also kept constant. RWL was found to be 9.9 ± 3.9 (SD) mg/kg/min when the temperature of the inspired air was 30°C and its humidity 30%. At 40°C this loss increased to 11.5 ± 3.6 mg/kg/min, and at about 60°C it increased further to 26.0 ± 8.2 mg/kg/ min. The oxygen consumption was 10.0 ± 0.8(SD)ml/kg/min at 30°C and 10.4 ± 2.0 ml/kg/min at 60°C, a change which is not significant. Thus RWL is influenced by the temperature of the inspired air, with greater loss at higher temperatures.</jats:p

Respiratory Response to Adenosine in Newborn Lambs Is Modified by Hypoxemia and by Heat Stress

A study was made to determine whether adenosine is involved in the regulation of breathing and whether the respiratory response to injections of adenosine and its analogue &lt;i&gt;L&lt;/i&gt;-PIA (phenylisopropyl adenosine) is modified by moderate hypoxemia or by heat stress. Unanesthetized lambs with chronically implanted catheters were used for the investigation. Intravenous injections of adenosine caused an increase in the rate of breathing lasting for 5–30 s, except during heat stress, when the rate of breathing decreased. Injection of &lt;i&gt;L&lt;/i&gt;-PIA also increased the rate of breathing, but the effects lasted longer than after injection of adenosine. During heat stress the response to injection of &lt;i&gt;L&lt;/i&gt;-PIA varied. Both the arterial blood pressure and heart rate decreased transiently after intravenous injection of adenosine or &lt;i&gt;L&lt;/i&gt;-PIA, while the central venous pressure increased. Adenosine might thus be part of a positive feedback system that stimulates breathing under normal environmental conditions with or without moderate hypoxemia. The respiratory responses to injection of adenosine during heat stress are different, which might indicate that under this condition the effects of adenosine on breathing are modified by its influence on temperature control.</jats:p