ABSTRACT
There is evidence that vasoactive intestinal polypeptide (VIP) participates in inhibitory neuromuscular transmission (NMT) in the internal anal sphincter (IAS). However, specific details concerning VIP-ergic NMT are limited, largely because of difficulties in selectively blocking other inhibitory neural pathways. The present study used the selective P2Y1 receptor antagonist MRS2500 (1 µm) and the nitric oxide synthase inhibitor N(G)-nitro-l-arginine (l-NNA; 100 µm) to block purinergic and nitrergic NMT to characterize non-purinergic, non-nitrergic (NNNP) inhibitory NMT and the role of VIP in this response. Nerves were stimulated with electrical field stimulation (0.1-20 Hz, 4-60 s) and the associated changes in contractile and electrical activity measured in non-adrenergic, non-cholinergic conditions in the IAS of wild-type and VIP(-/-) mice. Electrical field stimulation gave rise to frequency-dependent relaxation and hyperpolarization that was blocked by tetrodotoxin. Responses during brief trains of stimuli (4 s) were mediated by purinergic and nitrergic NMT. During longer stimulus trains, an NNNP relaxation and hyperpolarization developed slowly and persisted for several minutes beyond the end of the stimulus train. The NNNP NMT was abolished by VIP6-28 (30 µm), absent in the VIP(-/-) mouse and mimicked by exogenous VIP (1-100 nm). Immunoreactivity for VIP was co-localized with neuronal nitric oxide synthase in varicose intramuscular fibres but was not detected in the VIP(-/-) mouse IAS. In conclusion, this study identified an ultraslow component of inhibitory NMT in the IAS mediated by VIP. In vivo, this pathway may be activated with larger rectal distensions, leading to a more prolonged period of anal relaxation.
Subject(s)
Anal Canal/innervation , Muscle Relaxation/drug effects , Neural Inhibition/drug effects , Vasoactive Intestinal Peptide/metabolism , Animals , Deoxyadenine Nucleotides/pharmacology , Electric Stimulation , Enzyme Inhibitors/pharmacology , Gene Expression , In Vitro Techniques , Membrane Potentials/drug effects , Membrane Potentials/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , Muscle Relaxation/genetics , Myocytes, Smooth Muscle/physiology , Nerve Fibers/physiology , Neural Inhibition/genetics , Neuromuscular Junction/drug effects , Nitroarginine/pharmacology , Purinergic P2Y Receptor Antagonists/pharmacology , Tetrodotoxin/pharmacology , Vasoactive Intestinal Peptide/geneticsABSTRACT
A method for the quick preparation of refractory venous ulcer beds for autografting is described. Irrespective of their clinical or bacteriological state, ulcer granulations and other products of frustrated healing are shaved in layers down to an even and surgically clean base using an ordinary skin grafting knife. Our experience with 32 consecutive patients (58 ulcers) is reported. The mean duration of hospital stay, the patient being completely healed on discharge, was 18.3 days. This represents a decrease of more than 3 weeks when compared to a previously used standard method. No investigation into the question of recurrence was carried out as available evidence, which is critically reviewed, indicates no significant relation between the method of grafting and the incidence of recurrence.
