Jmh. Preuss et al., THE INFLUENCE OF POSTMORTEM CONDITIONS ON CONTRACTILE AND RELAXANT RESPONSIVENESS OF GUINEA-PIG ISOLATED TRACHEAL SMOOTH-MUSCLE, Naunyn-Schmiedeberg's archives of pharmacology, 357(4), 1998, pp. 454-465
Responsiveness to various contractile and relaxant agonists was assess
ed in tracheal preparations from guinea-pigs that had been incubated i
n situ at 4-37 degrees C for 0-168 h post-mortem The potencies of hist
amine and acetylcholine were increased up to 168 h at 4 degrees C post
-mortem and up to 24 h post-mortem at 22 degrees C. Histamine potency
also increased with increasing post-mortem time at 37 degrees C. After
48 h at 22 degrees C and 8 h at 37 degrees C, responses to all spasmo
gens were abolished. Increases in histamine and acetylcholine potencie
s were similarly observed in tracheal tissue that had been removed at
death and then incubated at 4 degrees C in oxygenated Krebs-bicarbonat
e solution for 0-168 h. The increased potency of these drugs may be ex
plained by epithelial damage and/or loss of an epithelium-derived inhi
bitory factor (EpDIF). Both basal and spasmogen-stimulated increases i
n intracellular phosphoinositides fell with increasing time and ambien
t temperature post-mortem, despite the fact that contraction in respon
se to these agonists could still be evoked. This suggests the selectiv
e failure of this signal transduction pathway and the maintenance of r
esponsiveness via other mechanisms. The potencies and maximum effects
of relaxant agonists remained unaltered in tracheal tissue with increa
sing time post-mortem, suggesting little change in the function of the
appropriate receptor-signal transduction processes. This study has th
erefore demonstrated that at 4 degrees C, contractile and relaxant res
ponses were preserved for up to 168 h post-mortem, although the modula
tory influence of the epithelium on histamine and acetylcholine respon
ses was rapidly lost.