Osmolality alters tracheal blood flow and tracer uptake in anesthetized sheep

Wells, U.; Hanafi, Z.; Jg, Widdicombe

doi:10.1152/jappl.1994.77.5.2400

Cited by 18 publications

(17 citation statements)

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“…Luminal histamine caused a decrease in venous 99m Tc-DTPA concentration and output, as well as an increase in blood flow. A negative relationship between blood flow and 99m Tc-DTPA uptake has been observed in response to a variety of stimuli in this model, including histamine and other drugs given intravascularly, and luminal hyperosmolarity [5,10]. The cause is unknown, but may reflect changes in capillary fluid flux.…”

Section: Histamine-induced Changes In 99m Tc-dtpa Permeabilitymentioning

confidence: 75%

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Tracheal epithelial damage alters the effects of luminal histamine on blood flow and tracer flux in anaesthetized sheep

Wells¹,

Hanafi²,

Jg³

1996

Eur Respir J

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Epithelial damage greatly increases the flux of a low molecular weight tracer 99m technetium-diethylenetriamine penta-acetic acid ( 99m Tc-DTPA) from tracheal lumen to venous-blood in anaesthetized sheep. We have now investigated whether epithelial damage induced by the detergent, Triton X-100, alters the effects of luminal histamine on blood flow and 99m Tc-DTPA flux.The cervical trachea was filled with Krebs-Henseleit solution containing 99m Tc-DTPA. Tracheal arterial flow was measured and tracheal venous blood collected. The lumen was exposed to 100 µM histamine on two occasions (Hist 1 and Hist 2) for 15 min. In six out of 11 sheep, the lumen was also exposed to 0.2% Triton X-100 between Hist 1 and Hist 2.Triton X-100 increased the baseline 99m Tc-DTPA permeability coefficient from -5.3×10 -7 to -400±130×10 -7 cm·s -1 . After epithelial damage, Hist 2 produced significantly greater changes in arterial and venous flows than Hist 1 (n=5) (0-5 min: Hist 1 Q'a=+6.4±0.8%, Q'v=+6.2±6.2%; Hist 2 Q'a=+36.7±12.2%, Q'v=+35.4±8.8%). Similar changes did not occur in the controls. Venous 99m Tc-DTPA concentration during Hist 2 after epithelial damage (0-5 min -37.7±6.9%) was significantly different from Hist 1 (+5.2±7.0%).Thus, after epithelial damage, luminal histamine produces more rapid and larger changes in blood flow and a greater reduction in venous 99m Tc-DTPA concentration. Eur Respir J., 1996, 9, 78- It has been established by in vitro studies [1][2][3] that the airway epithelium is a barrier to the movement of low molecular weight hydrophilic compounds. However, recent studies in vivo measuring the movement of 99m technetium-diethylenetriamine penta-acetic acid ( 99m Tc-DTPA, a low molecular weight hydrophilic tracer of similar size to many drugs given by inhalation) from the tracheal lumen to venous blood suggest that the relevance of in vitro studies on permeability may be limited, for two reasons.Firstly, damage to the sheep tracheal epithelium in vivo increased the permeability coefficient of 99m Tc-DTPA (PDTPA) by a factor of 120 [4], a much greater change than that found in vitro using this tracer or other solutes of similar molecular weight [1][2][3]. This may be because the presence of a functional subepithelial capillary bed results in the sweeping away of the tracer in the bloodstream, thus altering both the flux and the concentration gradient of the tracer between tracheal lumen and the mucosa. Secondly, PDTPA is also greatly affected by changes in blood flow [5]. A negative relationship exists between venous 99 Tc-DTPA uptake and blood flow. The reason is unknown but may be related to changes in capillary fluid flux.Bronchoconstrictor agents, such as methacholine and histamine, cause vasodilatation, and when injected into the tracheal circulation markedly decrease PDTPA [5]. These drugs are often given by inhalation in provocation testing; asthmatics show an increased sensitivity, as measured by lung function tests [6,7]. This may be due, at least in part, to an increase in drug penetratio...

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Section: Histamine-induced Changes In 99m Tc-dtpa Permeabilitymentioning

confidence: 75%

“…Experimental preparation has been described previously [5,10]. Female sheep (25-30 kg) were anaesthetized with sodium pentobarbitone (initially 20 mg·kg -1 i.v.)…”

Section: Experimental Preparationmentioning

confidence: 99%

Tracheal epithelial damage alters the effects of luminal histamine on blood flow and tracer flux in anaesthetized sheep

Wells¹,

Hanafi²,

Jg³

1996

Eur Respir J

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“…The tracheae of the eight sheep used in preliminary experiments to test the effects of 1 and 20 mM MBS had first been exposed to hyperosmolar and hyposmolar Krebs-Henseleit solution (KH) in the same experiment [21] (see Protocol…”

Section: Methodsmentioning

confidence: 99%

“…The experimental preparation has been described previously [21,22]. Female sheep (25-30 kg) were anaesthetized with sodium pentobarbitone (initially 20 mg·kg -1 , i.v.).…”

Section: Experimental Preparationmentioning

confidence: 99%

Sodium metabisulphite causes epithelial damage and increases sheep tracheal blood flow and permeability

Wells

Hanafi²,

Jg³

1996

Eur Respir J

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Inhaled sodium metabisulphite (MBS) causes bronchoconstriction, cough and microvascular leakage. We have studied its effects on tracheal blood flow, potential difference (PD) and the permeability from tracheal lumen to venous blood of a low molecular weight hydrophilic tracer, 99m technetium-labelled diethylenetriamine penta-acetic acid ( 99m Tc-DTPA) in anaesthetized sheep.Flow was measured in a tracheal artery and blood from a cannulated tracheal vein collected for 5 min periods. The tracheal lumen was filled with Krebs-Henseleit solution (KH) containing 99m Tc-DTPA for six to eight 15 min periods. During the third or fourth period, MBS (1, 20 or 100 mM) was washed into the tracheal lumen for 15 min.MBS increased tracheal blood flow (venous flow (Q'v), 5-10 min MBS exposure period: 1 mM -9±18% (n=3); 20 mM +16±5% (n=5; p<0.05); 100 mM + 43±13% (n=5; p<0.05). It decreased PD in a concentration-dependent way. Venous 99m Tc-DTPA concentration increased progressively to +266±176 and + 958±321% 25-30 min after exposure to 20 and 100 mM MBS, respectively (p<0.05 for both). These effects were not blocked by luminal frusemide (3-7 mM) or flurbiprofen (100-500 µM). Histological sections showed changes to the epithelial cells and large intercellular spaces.Thus, luminal sodium metabisulphite increases tracheal blood flow, reduces transmural potential difference and causes tracheal epithelial damage, leading to an increase in 99m Tc-labelled diethylenetriamine penta-acetic acid permeability. Eur Respir J., 1996, 9, 976- Sodium metabisulphite (MBS) is a widely-used food preservative which, when ingested, causes bronchoconstriction in some asthmatics [1]. On inhalation it causes bronchoconstriction in man -asthmatics, atopics [2], and normals [3] -and also in animals [4,5].The mechanism of MBS-induced bronchoconstriction is still uncertain. In solution it forms the bisulphite ion and SO 2 [6]. Some [7], but not all [4,8], studies in man have shown that the bronchoconstriction is blocked by muscarinic antagonists. Its effect is also inhibited by drugs that inhibit sensory nerves, e.g. nedocromil sodium [9,10] and cromoglycate [9], and in the guinea-pig its action is reduced by capsaicin pretreatment [4] and inhibited by neurokinin 1 and 2 (NK 1 and NK 2 ) receptor antagonists [11], suggesting the involvement of tachykinins released from sensory nerve endings.MBS-induced bronchoconstriction is also blocked by frusemide [12,13]. Frusemide is effective against a variety of other indirectly acting bronchoconstrictor stimuli, including distilled water aerosols [14], exercise [15] and allergen [16]. The mechanism appears to be unrelated to its diuretic action. The airway effects could be due to the release of the bronchodilator prostaglandin E 2 (PGE 2 ) [17]. However, more recent evidence has shown that flurbiprofen, a cyclo-oxygenase inhibitor, partly blocks the effects of MBS on bronchoconstriction and also enhances the effect of frusemide [18]. This implies that MBS may cause the release of bronchoconstrictor prosta...

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“…Matsui et al make the intriguing suggestion that cell shrinkage could play a sensory role in signaling hypertonicity of the ASL to the microvasculature below (6). Indeed, it was shown years ago that blood flow to the airway submucosa is stimulated by breathing dry air (16) and by hypertonic luminal fluid (17,18). Moreover, several studies (19,20) have shown that airway epithelia can release smooth muscle-relaxing factors such as nitric oxide (21), and perhaps other vasoactive agents when their luminal surfaces are exposed to hypertonic solution (Figure 1).…”

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confidence: 99%

Airway plumbing

Hanrahan¹

2000

J. Clin. Invest.

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Osmolality alters tracheal blood flow and tracer uptake in anesthetized sheep

Cited by 18 publications

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Tracheal epithelial damage alters the effects of luminal histamine on blood flow and tracer flux in anaesthetized sheep

Tracheal epithelial damage alters the effects of luminal histamine on blood flow and tracer flux in anaesthetized sheep

Sodium metabisulphite causes epithelial damage and increases sheep tracheal blood flow and permeability

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