Abstracts
1997 Digestive Disease Week

Differing adaptive responses of ileal and jejunal smooth muscle to denervation after small bowel transplantation.

C Shibata, BM Balsiger, WJ Anding, JA Duenes, MG Sarr. Department of Surgery, Mayo Clinic, Rochester, MN.

SBT obligates a chronic extrinsic denervation, effects of which on intestinal contractility are undefined. AIM: To determine non-immunologic effects of gut denervation on ileal and jejunal contractility 1 yr after isogeneic SBT. METHODS: Orthotopic SBT, performed in syngeneic rats, avoided immune phenomena. Full thickness muscle strips before and 1 yr after SBT were studied in tissue chambers at optimal length (L_o). We evaluated spontaneous contractile activity and responses to 1) neural blockade with tetrodotoxin (TTX), 2) establishment of non-adrenergic, non-cholinergic (NANC) state with atropine/phentolamine/propranolol, 3) cholinergic agonist bethanechol (Be), 4) adrenergic agonist norepinephrine (NE), and 5) differing frequencies (1-10 Hz) of electrical field stimulation (EFS). Contractile activity was quantitated by area under the contractile curve and dose responses (Be, NE) with ED₅₀--i.e. negative log of concentration causing a 50% effect. One year older rats served as controls. RESULTS (table): After SBT, spontaneous activity and responses to TTX and Be did not differ from controls in jejunum or ileum. Although response to NANC conditions did not vary in ileum, contractile activity decreased in jejunal controls but not jejunal SBT. Also, the ED₅₀ to NE was markedly increased (lesser concentration of NE required for 50% effect) in ileum after SBT, suggesting increased sensitivity after the sympathectomy induced by SBT. EFS induced inhibition at low (1-5 Hz) and excitation at high (10-20 Hz) frequency in all groups; inhibition at low frequency expressed as maximum % inhibition did not differ in ileum but tended to decrease after SBT in jejunum, suggesting decreased EFS-induced NANC inhibitory function. SUMMARY: One year after isogeneic SBT, ileal sensitivity to NE is markedly increased, while jejunal NANC-related inhibition (both spontaneous and EFS-induced) is decreased. CONCLUSIONS: Chronic adaptive responses to denervation of SBT differ between jejunum and ileum. Support NIH R01 DK39337 (MGS).

             Spon                          ED-50    ED-50      Max%
             Act*     TTX*    NANC*        (Be)     (NE)    inhibition
 Jejunum
  Control  3.2±0.4  3.0±0.7  2.2±0.6†      4.7±0.   5.3±0.1    215±84
  SBT      2.9±0.3  3.5±1.0  2.6±0.4       4.6±0.   4.9±0.3     87±20
 Ileum
  Control  3.2±0.5  2.8±0.5  3.4±0.6       4.9±0.   5.2±0.2     51±14
  SBT      3.8±0.3  4.1±0.5  4.0±0.4       4.8±0.   5.9±0.1‡    59±17
*g-5 min/mg tissue. †p<0.05 vs control. ‡p<0.05 vs Spon Act.