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Biomedical subjects

H C McKirdy

Publications and source records attributed to H C McKirdy.

At least 19 recordsLinked to original sources
PubMed1999

Intra-luminal nicotine reduces smooth muscle tone and contractile activity in the distal large bowel.

BACKGROUND: Nicotine may be of therapeutic value in ulcerative colitis (UC), although its mechanism of action has not been established. OBJECTIVE: To examine the effect of a solution of nicotine on sustained resting pressure (tone) and contractile activity in the human colon. METHODS: Ten healthy volunteers, and seven with UC in symptomatic remission took part; all were non-smokers. All 17 subjects were given nicotine or placebo solution on two separate occasions in a randomized sequence. A water-perfused manometry catheter, with openings at 5, 10 and 15 cm from the tip, was placed by rigid sigmoidoscopy in the recto-sigmoid region. Baseline tone and activity were measured for 15 min prior to instillation of 20 ml of saline alone or with nicotine, 1.2 mg, at pH 4.5. Observations were made over the subsequent 15-20 min. RESULTS: Baseline spontaneous activity in all subjects showed both high- and low-frequency components; in three patients with UC, the low-frequency activity was of high amplitude. The nicotine reduced both tone and activity in all subjects, with reduction or abolition of the large contractions in UC. Tone in all 17 subjects was reduced significantly at 3 min after nicotine (P = 0.000015, sign test); the rate of recovery varied in individuals. Results from normals and UC did not differ significantly from each other. No significant change in tone or activity was observed with the saline solution. CONCLUSION: Intra-luminal nicotine significantly reduces both smooth muscle tone and contractile activity in the recto-sigmoid colon in both normal subjects and patients with UC.

Adult↗
PubMed1994

Inflammation impairs neurally mediated responses to electrical field stimulation in isolated strips of human gallbladder muscle.

Strips from human gallbladder removed at surgery were exposed to cholecystokinin octopeptide CCK-OP 15 nM and were subjected to electrical field stimulation (EFS) in vitro using parameters for selective stimulation of nerves (5- to 10-sec trains of 0.3-msec pulses at 10 Hz). An adjacent strip from the same specimen was processed for histological examination. These preparations were given a numerical score for inflammatory change. The strength of contraction in response to CCK-OP was inversely related to the severity of inflammation. Gallbladders with no response to EFS had a higher inflammation score (median 11, range 5-16) than those with a response (median 7, range 3-12). We conclude that inflammatory changes in human gallbladder impair responses to neural and hormonal stimulation, but we are unable to determine unequivocally in this study whether this is a result of damage to nerves or muscle cells. However, the observation that some strips were able to contract in response to CCK-OP but not to neural stimulation suggests the possibility of neural damage in gallbladder inflammation.

Cholecystitis↗
PubMed1994

Anorectal physiological testing in defecatory disorders: a prospective study.

A prospective study of anorectal physiological testing in 26 patients with obstructed defecation and 20 patients with faecal incontinence was performed. There were overlaps in individual test parameters between the two groups of patients. However, patients with severely blunted rectal sensation (maximum tolerated volume > 300 mL) and anismus were more likely to have obstructed defecation. Patients with very low anal canal pressures, a short (< 2.0 cm) anal canal, bilaterally prolonged (> 2.1 ms) pudendal nerve terminal motor latency and a grossly distorted and canal (vector symmetry index < or = to 0.75) were more likely to have faecal incontinence. Thus, patterns of anorectal physiological test results together with clinical evaluation, rather than individual test measurements, are more valuable in defining the underlying defecatory disorders and providing guidance on therapy.

Adult↗
PubMed1994

Non-adrenergic non-cholinergic inhibitory innervation shown by electrical field stimulation of isolated strips of human gall bladder muscle.

Non-adrenergic non-cholinergic (NANC) inhibitory nerves have been described in all regions of the gastrointestinal tract, but have not been shown previously in the human gall bladder. Electrical field stimulation was used in the presence of various agonists and antagonists to show NANC inhibitory innervation in strips of human gall bladder muscle. Gall bladder strips were set up isometrically in an organ bath containing oxygenated Krebs's solution. Electrical field stimulation was applied at 10 Hz, pulse width 0.3 ms and supramaximal voltage at intervals of 3 to 5 minutes. Of 60 strips that contracted in response to electrical field stimulation, 30 showed relaxation on electrical field stimulation in the presence of either carbachol (5-10 microM) or else atropine (0.5-2 microM) plus cholecystokinin octapeptide (0.01-0.1 microM) or caerulein (0.1 nM) or histamine (5-10 microM). In 22 strips this relaxation was not abolished by guanethidine (2-5 microM) showing the NANC nature of this response. The NANC relaxation was abolished by L-nitroarginine (100 microM) and this effect was partly reversible by L arginine (200 microM). All responses to electrical field stimulation were abolished by tetrodotoxin (0.2-2 microM). These results show for the first time a NANC inhibitory innervation in human gall bladder muscle. The probable neurotransmitter is nitric oxide.

Atropine↗
PubMed1993

Control of the human ileocaecal junction: an in vitro analysis of adrenergic and non-adrenergic non-cholinergic mechanisms.

Circular muscle strips from the human ileocaecal junction developed myogenic tone (sustained resting tension) in vitro and showed an obvious component of relaxation in response to electrical field stimulation. These features are considered typical of sphincteric muscle because circular muscle strips from terminal ileum 1-2 cm proximal to the junction and from the caecum or ascending colon 1-2 cm distal to the junction developed little or no tone and showed predominantly contractile responses to electrical-field stimulation. In 18 out of 29 specimens, junctional strips showed excitatory responses to adrenaline or noradrenaline. The relaxation of junctional strips was non-adrenergic non-cholinergic (NANC) in nature. Nitric oxide appears to be involved in the NANC relaxation.

Electric Stimulation↗
PubMed1992

Evidence for involvement of nitric oxide in the non-adrenergic non-cholinergic (NANC) relaxation of human lower oesophageal sphincter muscle strips.

Electrical field stimulation of circular muscle strips from human lower oesophageal sphincter reveals a predominant relaxation response. This relaxation is non-adrenergic non-cholinergic (NANC). The nitric oxide synthesis-blocking agent N omega-nitro-L-arginine (10-100 microM) reduces or abolishes this NANC relaxation, suggesting involvement of nitric oxide in the response.

Adrenergic Fibers↗
PubMed1988

Novel autonomic neurotransmitters and upper gastrointestinal function.

The evidence for, and possible roles of, inhibitory and excitatory non-adrenergic, non-cholinergic (NANC) nerves supplying smooth muscle, and the effects of putative transmitter candidates are considered for each of three main regions of the upper gastrointestinal tract: (A) the smooth muscle portion of the oesophagus and the oesophagogastric junction, (B) the stomach (fundus, body and antrum) and gastroduodenal junction and (C) the biliary tract and choledochoduodenal junction. The major points from human tissues are as follows: 1. Inhibitory (NANCI) nerves appear to be present in the muscularis externa of oesophagus, stomach and duodenum, with greater density in the circular than in the longitudinal muscle. 2. NANCI nerves are present in high density at the oesophagogastric and choledochoduodenal junctions. They may also be present at the gastroduodenal junction. The gall-bladder may have a very sparse NANCI innervation. 3. Excitatory (NANCE) nerves appear to be present throughout the upper gastrointestinal tract. 4. Many candidates need at present to be considered for the role of NANCE transmitter(s) in the human upper gastrointestinal tract but substance P still seems a likely contender for this role. 5. Fewer candidates are at present generally available for the role of NANCI transmitter(s), with VIP and ATP being leading contenders. However, in the human upper gastrointestinal tract the evidence for ATP is not good, and VIP still remains the favourite candidate except in the gall-bladder, where its role remains to be elucidated.

Animals↗
PubMed1987

Effect of drugs, hormones and electrical field stimulation on isolated muscle strips from human choledochoduodenal junction.

The behaviour of in vitro strips from the human choledochoduodenal junction would appear to be related to the anatomical location of origin of the strip. Strips from the papillary region showed low tone and obvious spontaneous rhythmic contractions (0 X 5-6/min). Strips from the region of the inferior choledochal sphincter showed, in ten out of fifteen specimens, spontaneous myogenic tone and gave a relaxation or a biphasic response (relaxation followed by contraction) to electrical field stimulation (0 X 3 ms pulses at 10 Hz for 5 s). All strips from human choledochoduodenal junction are remarkably insensitive to a variety of gastrointestinal hormones and to opioid agents.

Acetylcholine↗
PubMed1985

Effect of drugs and electrical field stimulation on circular muscle strips from human lower oesophagus.

Sphincteric muscle from human lower oesophagus may be identifiable in vitro by its ability to develop a very high level of tone (sustained resting tension). Circular muscle strips from human lower oesophagus generally behave in a similar manner to strips from the opossum oesophagus with respect to development of tone, responses to electrical field stimulation and responses to a variety of drugs. Pharmacological analysis of responses to field stimulation in strips from the region of the oesophago-gastric junction suggests that the typical biphasic response (relaxation followed by an after-contraction) is mediated by nerves which are neither adrenergic nor cholinergic. Of the substances examined only vasoactive intestinal peptide (VIP) cannot be excluded as a possible candidate for the role of inhibitory transmitter. The mechanism producing the after-contraction is not clear but it would seem unlikely that this is simply a rebound contraction. The after-contraction can be blocked independently of the relaxation by a variety of agents and is potentiated by metoclopramide.

Carbachol↗
PubMed1978

An investigation of the role of ganglia in the innervation of the rat anococcygeus muscle: an electrical and mechanical study.

1 A preparation is described which allows the rat anococcygeus muscle to be stimulated via its two extrinsic nerves. Each nerve contains both excitatory and inhibitory fibres. A ganglionated nerve plexus lies on the surface of the muscle. 2 The possibility that at least part of the excitatory pathway was interrupted as a ganglion synapse lying in one of the nodes of plexus close to the muscle was suggested by the observations that (a) the excitatory response to extrinsic nerve stimulation was reduced by the nicotinic antagonists tubocurarine (0.13 to 0.26 mM) and dihydro beta-erythroidine (0.1 to 0.14 mM). (b) Fibres from one extrinsic nerve were shown to synapse on a ganglion cell from which intracellular recordings were made while the output from this ganglion cell was traced microscopically to the muscle. 3 Intracellular recording from ganglion cells in this plexus indicated that cholinergic synaptic transmission occurred in these ganglia. Tubocurarine (0.13 mM) and hexamethonium (1.3 mM) reversibly abolished intracellularly-recorded synaptic potentials. 4 Hexamethonium (0.1 to 1 mM) initially enhanced the motor response to nerve stimulation and raised muscle tone, probably by an action involving pre- and postsynaptic sites. Subsequently, hexamethonium inhibited the response to extrinsic nerve stimulation presumably by an effect at ganglia lying along the excitatory pathway. Hexamethonium enhanced, without subsequently inhibiting, the response to exogenously added noradrenaline in both untreated and 6-hydroxydopamine-treated rats. These results suggest that the initial enhancement produced by hexamethonium involved sites at postganglionic nerve endings and on smooth muscle receptors. 5 Inhibitory responses were obtained following extrinsic nerve stimulation when the tone of the muscle was raised and the excitatory response abolished by either guanethidine (3 micron) alone or by carbachol (10 micron) followed by phentolamine (3 micron). The inhibitory response was not reduced by hexamethonium (up to 2.8 mM) tubocurarine (up to 1.3 mM) or by atropine (up to 1 micron).

Action Potentials↗
PubMed1978

Factors influencing tone in rabbit large intestine.

Pressure/volume curves obtained in the presence of papaverine have been compared with those obtained under control conditions in rabbit large intestine. Tension/length curves obtained on stimulation of the extrinsic nerve supply to the intestine have been compared with control curves. Evidence is presented for a small contribution of sustained muscular activity to the pressue/volume and tension/length curves. The effect of stretch on peak tension attained by the intestine has also been examined.

Animals↗
PubMed1977

Innervation of the rabbit rectococcygeus muscle and the functional relationship of the muscle to the terminal large intestine.

1. The rectococcygeus muscle is supplied by cholinergic motor fibres from the parasympathetic division of the autonomic nervous system. 2. The histofluorescence technique reveals a sparse adrenergic innervation. 3. When a maintained state of partial contraction is induced by carbachol, stimulation of the extrinsic sympathetic nerves produces a relaxation of the muscle which is usually followed by contraction. 4. The rectococcygeus muscle may also receive nerves which are neither adrenergic nor cholinergic. 5. Ganglion cells have been found close to and, in some preparations, within the muscle; the role of these ganglion cells is not clear. 6. It would appear that the rectococcygeus muscle and the longitudinal muscle of the rectum are not linked by a myogenic mechanism. The rectococcygeus muscle would, however, appear to be linked by nerve fibres to neighbouring structures.

Adrenergic Fibers↗