Ouabain, a Na(+)/K(+)-ATPase inhibitor, induces slowly adapting pulmonary stretch receptors (SARs) to discharge paradoxically. Paradoxical discharge is characterized by increased SAR activity during lung deflation coupled with silence during lung inflation. We hypothesized that over-excitation silences the SARs. Accordingly, if cyclic inflation pressure was reduced so as to lower SAR stimulation, paradoxical discharge would be prevented. In the present study, single-unit activity of SARs was recorded in anesthetized, open-chest and mechanically ventilated rabbits with positive-end-expiratory pressure (PEEP). After microinjection of ouabain into the receptive field, SAR activity initially increased and then gradually became paradoxical. During paradoxical cycling, SAR activity started and stopped abruptly, oscillating between high frequency discharge during lung deflation and silence during peak inflation. Removing PEEP reduced basal cyclic stimulation and returned the discharge pattern to normal, that is, SAR activity was highest at peak inflation pressure but silent during deflation. It is speculated that stretching SARs causes Na(+) influx, producing generator potential (GP). Normally, GP recovers by Na(+) extrusion via Na(+)/K(+)-ATPase. Ouabain inhibits the ATPase, which limits Na(+) extrusion, and thus sustains the GP. Therefore, after ouabain microinjection, lung inflation will further increase GP, causing over-excitation to silence the SARs.
Action Potentials ; physiology ; Adaptation, Physiological ; drug effects ; Animals ; Lung ; drug effects ; physiology ; Male ; Mechanoreceptors ; physiology ; Ouabain ; pharmacology ; Pulmonary Stretch Receptors ; drug effects ; physiology ; Pulmonary Ventilation ; drug effects ; physiology ; Rabbits ; Sodium-Potassium-Exchanging ATPase ; antagonists & inhibitors ; physiology ; Vagus Nerve ; physiology

Adult ; Female ; Humans ; Hydrocarbons ; adverse effects ; Male ; Middle Aged ; Occupational Exposure ; adverse effects ; Pulmonary Ventilation ; drug effects ; Radiography, Thoracic ; Smoke ; adverse effects ; X-Ray Film

This study was performed to compare the effect of intratesticular (IT) injection of xylazine/ketamine combination for canine castration with those of intramuscular (IM) or intravenous (IV) injection. Xylazine and ketamine was administered simultaneously via intratesticularly (IT group), intramuscularly (IM group) or intravenously (IV group) at doses of 2 and 10 mg/kg, respectively. Pain response at the time of injection, mean induction time, mean arousal time, mean walking time and cardiopulmonary function during anesthesia were monitored after the xylazine and ketamine administration. In IV and IM groups, heart rates were significantly decreased 30 and 45 min after xylazine and ketamine administration, respectively (p < 0.05). Respiratory rates were significantly decreased in the IV group (p < 0.05). In the IT group, there was no significant changes in heart and respiratory rates. The occurrence of cardiac arrhythmias was less severe in IT group compared with those in IM and IV groups. The route of administration did not affect rectal temperature. Mean induction time was significantly (p < 0.05) longer in IT group than in IM and IV groups. On the contrary, mean arousal time and mean walking time were shortened in IT group. Clinical signs related to pain response at the time of injection and vomiting were less observed in IT group than in IM group, and head shaking was less shown in IT group than in IM and IV groups during recovery period. These results indicated that intratesticular injection of xylazine/ketamine for castration has several advantages such as less inhibition of cardiopulmonary function and fast recovery from anesthesia without severe complications, and would be an effective anesthetic method for castration in small animal practice.
Anesthesia, Intravenous/veterinary ; Anesthetics, Combined/adverse effects/*therapeutic use ; Anesthetics, Dissociative/adverse effects/*therapeutic use ; Animals ; Body Temperature/drug effects ; Castration/*veterinary ; Dogs ; Drug Administration Routes/veterinary ; Electrocardiography/drug effects/veterinary ; Heart Rate/drug effects ; Injections/veterinary ; Injections, Intramuscular/veterinary ; Ketamine/adverse effects/*therapeutic use ; Male ; Pain, Postoperative/prevention&control/veterinary ; Pulmonary Ventilation/drug effects ; Testis/*drug effects ; Vomiting/chemically induced/veterinary ; Xylazine/adverse effects/*therapeutic use

OBJECTIVETo evaluate dose response of inhaled nitric oxide (iNO) for surfactant-treated rabbits with meconium aspiration-induced acute lung injury (ALI) and hypoxemic respiratory failure (HRF), and variation of measured iNO by continuous NO delivery in pressure support ventilation (PSV).

METHODSAdult rabbits (2.0 - 3.5 kg, n = 33) were randomized to receive intratracheal meconium instillation for 30 min and subjected to following treatment (n = 6 - 8). There were 4 groups: Control (C); NO, iNO at 1, 10, 20 and 40 x 10(-6) each for 60 min at 30 min interval of disconnection; Surf, intratracheal instillation of porcine lung surfactant phospholipids (100 mg/kg); SNO, both iNO and surfactant as in the NO and Surf groups; and a normal group (N), which did not undergo meconium aspiration but received sham deliveries of normal saline. All the animals were treated with PSV for 6 h. iNO levels at different input and sampling sites in the NO and SNO groups were detected by on-line chemiluminescent technique. The blood gas and lung mechanics were measured during the experiments every 2 h.

RESULTS(1) Meconium aspiration induced ALI and severe HRF (PaO(2)/FiO(2) < 200 mmHg) and depressed dynamic compliance of respiratory system (Cdyn) and airway resistance (Raw). In both Surf and NO groups modestly improved oxygenation was observed. In the SNO, values for PaO(2)/FiO(2) were improved from (185 +/- 39) mmHg at baseline to (301 +/- 123) mmHg at 6 h, while moderate or transient improvement was observed in both Surf and NO groups. Cdyn and Raw were only improved for short time in the Surf, NO and SNO groups. iNO had a mild response at 1 x 10(-6) to good response at 10 and 20 x 10(-6), but no further improvement occurred at 40 x 10(-6). The response of iNO in NO group was relatively transient compared to the SNO group. (2) When iNO was connected to the ventilator circuit, the connected site should be placed before humidifier to minimize fluctuation of iNO concentration, and sampling site for iNO monitoring should be placed adequately to eliminate artifact.

CONCLUSIONSiNO synergistically improved surfactant effects on oxygenation and lung mechanics. Continuous supply of iNO with non-continuous flow ventilator provided stable NO within accepted target range with least variation.

Administration, Inhalation ; Animals ; Drug Therapy, Combination ; Female ; Humans ; Infant, Newborn ; Lung ; drug effects ; pathology ; physiopathology ; Male ; Meconium ; Meconium Aspiration Syndrome ; complications ; Nitric Oxide ; administration & dosage ; therapeutic use ; Phospholipids ; therapeutic use ; Pulmonary Surfactants ; therapeutic use ; Pulmonary Ventilation ; Rabbits ; Random Allocation ; Respiratory Distress Syndrome, Adult ; etiology ; therapy ; Treatment Outcome

The aim of this study was to determine the effect of partial liquid ventilation (PLV) using a perfluorocarbon (PFC) on gas exchange and lung inflammatory response in a canine acute lung injury model. After inducing severe lung injury by oleic acid infusion, beagle dogs were randomized to receive either gas ventilation only (control group, n = 6) or PLV (PLV group, n = 7) by sequential instillation of 10 mL/kg of perfluorodecalin (PFC) at 30 min intervals till functional residual capacity was attained. Measurements were made every 30 min till 210 min. Then the lungs were removed and bronchoalveolar lavage (BAL) (35 mL/kg) was performed on the right lung and the left lung was submitted for histologic analysis. There was significant improvement in PaO2 and PaCO2 in the PLV group compared to the control group (p < 0.05) which was associated with a significant decrease in shunt (p < 0.05). There was no significant difference in parameters of lung mechanics and hemodynamics. There was a significant decrease in cell count and neutrophil percentage in BAL fluid and significantly less inflammation and exudate scores in histology in the PLV group (p < 0.05). We conclude that PLV with perfluorodecalin improves gas exchange and decreases inflammatory response in the acutely-injured lung.
Animal ; Blood Cell Count ; Bronchoalveolar Lavage Fluid ; Carbon Dioxide/analysis ; Disease Models, Animal ; Dogs ; Female ; Fluorocarbons/pharmacology* ; Hemodynamics ; Histocytochemistry ; Inflammation/prevention & control ; Lung Diseases/physiopathology* ; Lung Diseases/chemically induced ; Male ; Oleic Acid ; Oxygen/analysis ; Pulmonary Gas Exchange/drug effects* ; Pulmonary Ventilation/physiology* ; Respiratory Function Tests ; Ventilators, Mechanical