C. Hierholzer et al., Molecular and functional contractile sequelae of rat intestinal ischemia/reperfusion injury, TRANSPLANT, 68(9), 1999, pp. 1244-1254
Background. Pathophysiological states that produce intestinal ischemia/repe
rfusion injury (I/R) initiate an inflammatory cascade and cause ileus. The
aims of this study were to investigate the local cellular responses and mol
ecular mechanisms, which contribute to intestinal dysmotility after selecti
ve intestinal I/R injury,
Methods. ACI rats were subjected to 75 min SMA clamp-induced ischemia follo
wed by reperfusion and were killed at 0 min, 30 min, and 24 hr. Whole mount
s of the jejunum were used to immunohistochemically quantify alterations in
leukocytes, and circular muscle strips were used to assess organ bath musc
le function. Muscularis and mucosa extracts were isolated from the intestin
e and used for reverse transcription assisted polymerase chain reaction mRN
A measurements of granulocyte-colony stimulating factor and interleukin-6,
and for determination of nuclear factor kappa B and Stat3 activation.
Results, Intestinal I/R injury resulted in the significant recruitment of n
eutrophils and monocytes into the intestinal muscularis and a functional su
ppression in jejunal circular muscle contractions. These UR injury induced
cellular responses were preceded by the molecular activation of nuclear fac
tor kappa B, upregulation of granulocyte colony-stimulating factor and inte
rleukin-6 mRNA and phosphorylation of the downstream signaling and transcri
ption factor Stat3.
Conclusions. I/R injury evokes a molecular and cellular inflammatory respon
se within the intestinal muscularis that is associated with a subsequent de
crease in intestinal motility.