Abstract
Numerous dark-brown-coloured small spots called “Wischnewski spots” are often observed in the gastric mucosa in the patients dying of hypothermia, but the molecular mechanisms through which they develop remain unclear. We hypothesised that hypothermia may activate the secretion of gastric acid and pepsin, leading to the development of the spots. To investigate this, we performed experiments using organotypic rat gastric tissue slices cultured at 37 °C (control) or 32 °C (cold). Cold loading for 6 h lowered the extracellular pH in the culture medium. The mRNA expression of gastrin, which regulates gastric acid secretion, increased after cold loading for 3 h. Cold loading increased the expression of gastric H+,K+-ATPase pump protein in the apical canalicular membrane and resulted in dynamic morphological changes in parietal cells. Cold loading resulted in an increased abundance of pepsin C protein and an elevated mRNA expression of its precursor progastricsin. Collectively, our findings clarified that cold stress induces acidification by activating gastric H+,K+-ATPase pumps and promoting pepsin C release through inducing progastricsin expression on the gastric mucosa, leading to tiny haemorrhages or erosions of the gastric mucosa that manifest as Wischnewski spots in fatal hypothermia.
Highlights
Hypothermia is defined as a decrease in the body core temperature to below 35 °C and is associated with significant morbidity and mortality[1]
The mRNA expression of histidine decarboxylase, which is the catabolic enzyme of histamine synthesis, was not changed by incubation at 32 °C (Fig. 2Bb)
We measured the abundances of gastrin and histamine in gastric slices using enzyme-linked immunosorbent assay (ELISA)
Summary
Hypothermia is defined as a decrease in the body core temperature to below 35 °C and is associated with significant morbidity and mortality[1]. Wischnewski first reported in 1895 that the presence of numerous dark-brown coloured small spots similar to gastric haemorrhages, which are termed “Wischnewski spots”, is frequently recognised in hypothermia-related death[7] (Fig. 1). Since these spots have been considered to be a classical sign of fatal hypothermia, their occurrence in fatal hypothermia has been described in the literature to vary between 40 and 100%3,8–10. We hypothesised that fatal hypothermia alone may cause an imbalance between gastric acid secretion[12] and the mucosal defence system[13] on the gastric mucosa, leading to the formation of Wischnewski spots. We found that the cold loading of rat organotypic gastric mucosa slices lowered the pH of the culture media through the activation of gastric H+,K+-ATPase pumps and increased the secretion of pepsin C through inducing the expression of PGC
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