Functional activity of bronchi from an organ donor with fatal asthma: studies on cryopreserved bronchi.
Human bronchi were taken from the lungs of a single asthmatic and 5 nonasthmatic organ donors. The tissues were slowly frozen to -70 degrees C and stored for 1-28 months in liquid nitrogen (-196 degrees C) while suspended in Krebs-Henseleit solution containing 1.8 M dimethyl sulfoxide and 0.1 M sucrose as cryoprotectants. After thawing, bronchial rings were suspended in 10 ml organ baths for isometric tension recording. Spontaneously developed tone (1.13 +/- 0.12, n = 22, vs. 0.56 +/- 0.07 g, n = 33, p < 0.001) and maximal contractile responses to histamine (1.93 +/- 0.12, n = 34, vs. 1.02 +/- 0.14 g, n = 30, p < 0.001) were significantly stronger in asthmatic than in nonasthmatic bronchi. The potency of histamine was 4 times less in asthmatic than in nonasthmatic bronchi (p < 0.001). Comparison of the maximal responses to histamine after storage at -196 degrees C for up to 28 months revealed no significant reduction of the contractile function by time of cryostorage. Salbutamol and the potassium channel opener SDZ PCO 400 were 3-4 times less potent in asthmatic than in nonasthmatic bronchi. For antagonism of histamine by ketotifen in asthmatic bronchi (pD'2 = 8.04 +/- 0.13, n = 5) 4 times higher concentrations were necessary than in nonasthmatic bronchi (pD'2 = 8.63 +/- 0.06, n = 15, p < 0.001). These data support the contention that in spite of a diminished sensitivity to histamine after fatal asthma, isolated bronchi show enhanced spontaneous and agonist-induced contractile responses whereas relaxant responses appear to be impaired.
Müller-Schweinitzer
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E
Department of Internal Medicine, University Hospital Kantonsspital, Basel, Switzerland. muellere@ubaclu.unibas.ch
Schilling
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M
Haefeli
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WE
D000328:Adult; D001249:Asthma / Q000473:pathology* / Q000503:physiopathology; D001980:Bronchi / Q000187:drug effects / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D016084:Bronchoconstriction / Q000187:drug effects; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology; D015925:Cryopreservation; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014019:Tissue Donors
D016085:Bronchoconstrictor Agents; D001993:Bronchodilator Agents