Does hyperbaric oxygen therapy prevent airway anastomosis from breakdown?

Ischemia with subsequent necrosis of anastomoses, after central airway resection and reconstruction, remains a feared complication for thoracic surgeons and their patients. To date, there is no evidence to support the use of hyperbaric oxygen in the prevention of necrosis of airway reconstructions in humans. We present a patient who underwent central airway surgery with postoperative ischemia of an end-to-side anastomosis. Repeat visit to a hyperbaric oxygen chamber seemed to prevent the anastomosis from subsequent necrosis and dehiscence with complete healing as a result. In conclusion, hyperbaric oxygen treatment can be considered when ischemia or necrosis is observed in central airway anastomoses during postoperative bronchoscopic surveillance.

Effect of dopamine receptor agonists on sensory nerve activity: possible therapeutic targets for the treatment of asthma and COPD.

Sensory nerves regulate central and local reflexes such as airway plasma leakage, and cough and their function may be enhanced during inflammation. Evidence suggests that dopamine receptor agonists may inhibit sensory nerve-mediated responses. In this study dopamine inhibited vagal sensory nerve induced microvascular leakage in the rat. In order to characterize the receptor involved rat vagus preparations were utilized. Quinagolide (D(2/3) agonist), ropinirole (D(2/3/4) agonist), SKF 38393 (D(1/5) agonist), AR-C68397AA (Viozan) (dual D(2)/B(2) agonist) and dopamine inhibited hypertonic saline induced depolarization by approximately 50%. Data suggests that AR-C68397AA and quinagolide also inhibited depolarization of the human vagus. The quinagolide response was blocked by sulpiride (D(2/3) antagonist) but not SCH 23390 (D(1/5) antagonist); ropinirole was partially blocked by sulpiride, totally blocked by spiperone (at a concentration that blocks all dopamine receptors) but not by SCH 23390. The response to SKF 38393 was not blocked by sulpiride but was by SCH 23390. The inhibition evoked by AR-C68397AA was only partially blocked by SCH 23390 but not by sulpiride or spiperone whereas dopamine was blocked by spiperone. The effect of dopamine was not stimulus-specific as it inhibited capsaicin-induced depolarization of the rat vagus in a spiperone sensitive manner. In conclusion, dopamine receptor ligands inhibit depolarization of the rat and human vagus. These data suggest that dopamine receptor agonists may be of therapeutic benefit in the treatment of symptoms such as cough and mucus secretion which are evident in respiratory diseases such as asthma and chronic obstructive pulmonary disease.

Effects of the calcium ionophore A23187 on airway responsiveness to histamine and substance P in guinea pigs.

OBJECTIVE: We evaluated the mechanism of the airway hyperresponsiveness (AHR) induced by a calcium ionophore in guinea pigs. MATERIALS AND METHODS: Airway responsiveness to intravenous histamine (HS) and substance P (SP) was measured 24 h after a 1-h exposure to aerosolized A23187 (0.03 or 0.1 mg/ml) or its vehicle (10% DMSO). Changes were assessed by calculating -logPC350HS and logPC350SP. Neutral endopeptidase (NEP) activity in the airway tissues, as well as the nitrite (NO2) levels and the cell population in bronchoalveolar lavage fluid (BALF) was determined after measurement of pulmonary function. Changes in SP-induced vascular permeability 24 h after exposure to A23187 were measured by the Evans Blue dye extravasation technique. RESULTS: Exposure to A23187 caused a significant AHR to SP, along with a significant increase in the number of neutrophils and epithelial cells in the BALF. While there was no significant change in NEP activity in the airway tissues, the levels of nitrite in the BALF were significantly decreased in A23187-exposed animals. Significant correlations were found between the number of epithelial cells in the BALF and logPC350SP (r = 0.477, p < 0.05) and between nitrite levels in the BALF and -logPC350SP (r = 0.491, p < 0.05) A23187 exposure did not significantly change the SP-induced airway microvascular leakage. CONCLUSIONS: These data suggest that A23187 exposure induced AHR to SP possibly by reducing NO levels in the airway tissues. This may be due to damaged airway epithelium and/or NO breakdown by activated inflammatory cells in the airways of these guinea pigs.

Inhibitory actions of prostaglandin E1 on neurogenic plasma extravasation in rat airways.

To determine whether neurogenic inflammation can be inhibited by prostaglandin E1 (PGE1), that is suggested to have an inhibitory effect on neuropeptide release from airway sensory nerves, we examined plasma extravasation in the airways of anesthetized rats in vivo with Evans blue due as a marker. Neurogenic inflammation was produced by an i.v. injection of capsaicin (100 micrograms/kg) or by antidromic electrical stimulation of the right vagus nerve (4 Hz, 1 ms, 4 V for 1 min). Capsaicin injection significantly increased leakage of dye in the trachea and main bronchi. Similar increases in leakage were seen in the trachea and right bronchus on electrical stimulation of the right vagus nerve. PGE1 (1-1000 micrograms/kg) inhibited the leakage induced by capsaicin in the trachea and bronchi concentration dependently with complete inhibition at a concentration of 1000 micrograms/kg. Likewise, PGE1 (1000 micrograms/kg) significantly inhibited electrical stimulation-induced leakage in the trachea and right bronchus (P less than 0.01). I.v. substance P (SP; 1 microgram/kg) increased Evans blue dye extravasation in the same way as the leakage induced by capsaicin and electrical stimulation but PGE1 (1000 micrograms/kg) failed to inhibit SP-induced leakage in the trachea and main bronchi (P greater than 0.20). These results suggest that PGE1 inhibits neurogenic plasma leakage by presynaptic inhibition of the release of neuropeptides from sensory nerves.

Airway blood flow modifies allergic airway smooth muscle contraction.

We tested the hypothesis that airway perfusion modifies the contractile response of airway smooth muscle to allergen challenge by influencing the clearance of locally released spasmogens. In six intact, lightly sedated, sheep allergic to Ascaris suum, we measured tracheal mucosal blood flow (Qtr) with a soluble gas uptake method and tracheal dead space (Vtr), an index of airway smooth muscle tone, by helium dilution before and serially after local aerosol challenge with A. suum extract or ragweed extract (control). The former challenge was repeated during continuous intravenous infusion of either vasopressin or nitroglycerin, which by themselves had no effect on Vtr and decreased and increased Qtr, respectively. Ragweed had no effect on Qtr and Vtr, whereas A. suum increased mean (+/- SE) Qtr by 111 +/- 31% (p less than 0.05) and decreased mean Vtr by 15 +/- 2% (p less than 0.05) immediately after challenge, with Qtr returning to baseline by 40 min and Vtr by 80 min. Vasopressin infusion prevented the A. suum-induced increase in Qtr and prolonged the decrease in mean Vtr (p less than 0.05). During nitroglycerin infusion, A. suum failed to alter Qtr or Vtr. Vasopressin and nitroglycerin had no effect on the contractile responses of tracheal smooth muscle to A. suum in vitro. These results indicate that the effects of vasopressin and nitroglycerin on antigen-induced airway smooth muscle contraction in vivo were due to alterations in airway blood flow rather than to alterations in the release of or airway smooth muscle responsiveness to chemical mediators.

Inflammatory mediators involved in antigen-induced airway microvascular leakage in guinea pigs.

Antigen challenge of ovalbumin (OA)-sensitized guinea pigs results in significant (p less than 0.05) increases in vascular permeability to Evans blue (EB) dye in the airways, esophagus, and bladder. Mean values +/- SEM in ng EB/mg wet weight tissue for unsensitized versus sensitized animals were: trachea, 23.6 +/- 6.6 versus 92.5 +/- 11.1; main bronchi, 31.1 +/- 12.2 versus 153.1 +/- 14.9; "central" intrapulmonary airways (ipa), 34.6 +/- 11.2 versus 101.3 +/- 6.2; and "peripheral" ipa, 26.2 +/- 6.8 versus 93.5 +/- 13.6. We investigated the involvement of several mediators of inflammation in this process. FPL 55712, a sulfidopeptide leukotriene receptor antagonist, caused significant inhibition of leakage in trachea (to 55.1 +/- 9.8) and main bronchi (91.7 +/- 15.8). Blockade of the cyclooxygenase and lipoxygenase pathways with BW 755C, but not of the cyclooxygenase pathway alone with indomethacin, also significantly reduced EB dye extravasation in trachea (55.1 +/- 18.0), main bronchi (71.7 +/- 23.0), and "central" ipa (62.7 +/- 16.4). The histamine antagonists, chlorpheniramine and cimetidine, only inhibited microvascular leakage in main bronchi (94.4 +/- 20.0). PAF-receptor blockade with the ginkgolide mixture BN 52063 had no effect. Nedocromil sodium, a mast cell stabilizer and an inhibitor of inflammatory cell activation, caused significant inhibition throughout the airways: trachea, 50.4 +/- 10.6; main bronchi, 72.0 +/- 15.3; "central" ipa 61.0 +/- 8.6; "peripheral" ipa 41.9 +/- 12.2. Thus, histamine and lipoxygenase products (in particular, leukotrienes), but not PAF, may mediate the antigen-induced increase in vascular permeability to different degrees in differing regions of the respiratory tract in guinea pigs.

Effect of acute haemorrhage and autotransfusion on respiration in the pig.

The effect of haemorrhage and transfusion of blood on minute ventilation, VE, in eight anaesthetized pigs was studied by bleeding the animals from the jugular vein and retransfusion of the same quantity of blood. Bleeding the pig from the jugular vein at approximately 50 ml/min, during 2 min, decreased V/ by 8.4 +/- 5.6 per cent of the pre-bleeding control valve (p = 0.0004) and when the same quantity of blood was retransfused the VE increased by 11.8 +/- 12.4 per cent (p=0.03). The possible mechanisms are discussed. We conclude that: a) mechanoreceptors localized in pulmonary circulation play an important role in the VE response during the first seconds of venous haemorrhage and venous transfusion, b) autotransfusion from moving legs and its effect on pulmonary mechanoreceptors may explain in part hyperpnoea at the onset of muscular exercise.