Functional Activity of Bronchi from an Organ Donor with Fatal Asthma: Studies on Cryopreserved Bronchi

Abstract

Human bronchi were taken from the lungs of a single asthmatic and 5 nonasthmatic organ donors. The tissues were slowly frozen to -70°C and stored for 1-28 months in liquid nitrogen (-196°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°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.

Key Words:

• Airway smooth muscle
• Fatal asthma
• Cryopreservation
• Histamine
• Ketotifen
• Beta-adrenoceptor agonists
• Potassium channel opener