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

Epithelial damage greatly increases the flux of a low molecular weight tracer 99mtechnetium-diethylenetriamine penta-acetic acid (99mTc-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 99mTc-DTPA flux. The cervical trachea was filled with Krebs-Henseleit solution containing 99mTc-DTPA. Tracheal arterial flow was measured and tracheal venous blood collected. The lumen was exposed to 100 microM 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 99mTc-DTPA permeability coefficient from -5.3 x 10(-7) to -400 +/- 130 x 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 Q1a = +6.4 +/- 0.8%, Q1v = +6.2 +/- 6.2%; Hist 2 Q1a = +36.7 +/- 12.2%, Q1v = +35.4 +/- 8.8%). Similar changes did not occur in the controls. Venous 99mTc-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 99mTc-DTPA concentration.