The influence of post-mortem conditions on contractile and relaxant responsiveness of guinea-pig isolated tracheal smooth muscle

Abstract

Responsiveness to various contractile and relaxant agonists was assessed in tracheal preparations from guinea-pigs that had been incubated in situ at 4–37°C for 0–168h post-mortem. The potencies of histamine and acetylcholine were increased up to 168h at 4°C post-mortem and up to 24h post-mortem at 22°C. Histamine potency also increased with increasing post-mortem time at 37°C. After 48h at 22°C and 8h at 37°C, responses to all spasmogens were abolished. Increases in histamine and acetylcholine potencies were similarly observed in tracheal tissue that had been removed at death and then incubated at 4°C in oxygenated Krebs-bicarbonate solution for 0–168h. The increased potency of these drugs may be explained by epithelial damage and/or loss of an epithelium-derived inhibitory factor (EpDIF). Both basal and spasmogen-stimulated increases in intracellular phosphoinositides fell with increasing time and ambient temperature post-mortem, despite the fact that contraction in response to these agonists could still be evoked. This suggests the selective failure of this signal transduction pathway and the maintenance of responsiveness via other mechanisms. The potencies and maximum effects of relaxant agonists remained unaltered in tracheal tissue with increasing time post-mortem, suggesting little change in the function of the appropriate receptor-signal transduction processes. This study has therefore demonstrated that at 4°C, contractile and relaxant responses were preserved for up to 168h post-mortem, although the modulatory influence of the epithelium on histamine and acetylcholine responses was rapidly lost.