Effect of extrinsic denervation in a canine model of jejunoileal autotransplantation on mechanical and electrical activity of jejunal circular smooth muscle

Abstract

Little is known about the acute and chronic effects of the intestinal transplantation on smooth muscle contractile physiology. Our aim was to determine the effects of the denervation necessitated by jejunoileal autotransplantation on membrane potential and contractile activity. Six dogs underwent a model of jejunoileal autotransplantation that specifically avoids ischemia/reperfusion injury (by maintaining blood flow to the gut during the "transplantation" procedure). Strips of jejunal circular muscle were studied sequentially before and 2 and 8 weeks after denervation by recording mechanical and intracellular electrical activities in vitro. The amplitude of spontaneous contractions (X +/- SD) was increased (P < 0.05) at 2 compared to 0 weeks (126 +/- 19 vs 77 +/- 32 g/g; P < 0.05) but markedly decreased at 8 weeks (7 +/- 2 g/g). Contraction frequency, resting membrane potential, and amplitude of slow waves were unchanged across these time points. Bethanechol (10(-7)-10(-4) M) and substance P (10(-8)-10(-6) M) dose-dependently increased contractile activity at all time points, but the absolute change in amplitude was decreased at 8 weeks. The amplitude of inhibitory junction potentials (IJPs) and duration of inhibition of contractile activity in the presence of cholinergic and adrenergic blockade increased at 2 and 8 weeks; off-contraction amplitude was decreased at 8 weeks (P < 0.05). These effects may occur via changes in neurotransmitter release, changes in regulation of membrane receptors, or alteration of characteristics of the membrane threshold potential.