Biomedical subjects

S Vanner

Publications and source records attributed to S Vanner.

28 records · Page 2Linked to original sources

PubMed1995

Safety profile of 5-h oral sodium phosphate regimen for colonoscopy cleansing: lack of clinically significant hypocalcemia or hypovolemia.

OBJECTIVES: Oral sodium phosphate (NaP), a colonic cleansing agent for colonoscopy that is superior to standard polyethylene glycol-based lavage solutions because of greater patient acceptance, effectiveness, and significantly less cost, causes intravascular volume depletion and hyperphosphatemia. To determine whether these changes may be near the threshold for inducing clinically serious side effects, these parameters were studied in patients receiving two doses of NaP over 5 h rather than the conventional 12-h duration. METHODS: 50 patients (27 outpatients, 23 inpatients) drank 45 ml of NaP at 1700 and 2200 h the night before colonoscopy. Patients with renal failure, active heart disease, ileus, or gross ascites were excluded. RESULTS: Serial blood tests and hemodynamic measurements demonstrated signs of intravascular volume depletion in less than 10% of outpatients but up to 40% of inpatients. None of the patients complained of postural dizziness or presyncope. All patients became hyperphosphatemic (maximum 3.72; normal < 1.30 mmol/L). Measurements of ionized calcium were significantly lower compared with baseline values (mean values 1.19 vs 1.23 mmol/L, respectively). In 44% of patients, these values were below the lower limits of normal (1.19 mmol/L) but these changes were minor (lowest value 1.07 mmol/L) and none of the patients were symptomatic. CONCLUSIONS: This study suggests that oral NaP is a safe agent in most patients for colonic cleansing, even when given using a 5-h regimen.

Blood Volume↗

PubMed1994

Corelease of neuropeptides from capsaicin-sensitive afferents dilates submucosal arterioles in guinea pig ileum.

Extrinsic sensory afferent nerves projecting to the guinea pig intestinal submucosal arterioles contain both substance P (SP) and calcitonin gene-related peptide (CGRP); selective stimulation of these nerves causes vasodilation. However, it is not known whether either or both of these neuropeptides may be responsible for this neurogenic vasodilation. To examine this question, the actions of selective SP and CGRP antagonists on vasodilations evoked by SP, CGRP, and selective stimulation of extrinsic sensory afferents with capsaicin were measured in isolated submucosal arteriolar preparations with videomicroscopy. The SP receptor antagonist CP-96,345 (200 nM) abolished the vasodilation produced by half-maximal concentration (EC50) of SP and was without effect on the vasodilation produced by EC50 concentration of CGRP. Conversely, the CGRP receptor antagonist, CGRP-(8--37) (1 microM) abolished the vasodilation to CGRP but did not alter the SP-induced vasodilation. Neither antagonist altered the muscarinic vasodilation or nerve-evoked sympathetic vasoconstriction. Maximum inhibition of the capsaicin-induced vasodilation by CP-96,345 (600 nM) was 67%, and maximum inhibition of this response by CGRP-(8--37) (2 microM) was 53%. Complete inhibition of the capsaicin-induced vasodilation occurred when both antagonists were present. It is concluded that the vasodilation in response to activation of extrinsic sensory afferents innervating submucosal arterioles is due to the corelease of SP and CGRP.

Animals↗

PubMed1993

Mucosal stimulation evokes vasodilation in submucosal arterioles by neuronal and nonneuronal mechanisms.

The effects of mechanical stimulation of intestinal mucosa on submucosal arterioles of guinea pig ileum were examined using video microscopy of in vitro preparations consisting of submucosal plexus with adjacently attached mucosa. Mucosal stimulation did not alter the diameter of relaxed vessels but dilated arterioles preconstricted with phenylephrine or the prostaglandin analogue U-46619. Tetrodotoxin (TTX) or muscarinic receptor antagonists inhibited the vasodilation evoked by mucosal stimulation in 60% of preparations examined from normal and extrinsically denervated animals. The TTX-sensitive vasodilation to mucosa stimulation was partially inhibited by the 5-hydroxytryptamine3 (5-HT3) receptor antagonist ICS 205930. The TTX-insensitive vasodilation was largely prevented when the histamine receptor antagonists cimetidine and pyrilamine and the prostaglandin synthesis inhibitor indomethacin were applied. This study has demonstrated a reflex vasodilation to mucosal stimulation in an isolated submucosal plexus preparation that involves both neuronal and nonneuronal pathways. The neuronal pathway converges on cholinergic vasodilator neurons in the submucosal ganglia. The nonneuronal pathway involves the release of 5-HT, histamine, and prostaglandins from mucosal elements; 5-HT excites cholinergic vasodilator neurons, whereas histamine and prostaglandins dilate submucosal arterioles directly.

Animals↗

PubMed1993

Mechanism of action of capsaicin on submucosal arterioles in the guinea pig ileum.

Vasomotor neurons in the enteric nervous system release acetylcholine to dilate submucosal arterioles, but it is not known whether sensory nerves that project to these vessels also can provide a vasodilator innervation. This possibility was examined by determining the mechanism of action of capsaicin on guinea pig ileal submucosal arterioles in vitro. Capsaicin dilated all vessels that had been preconstricted with prostaglandin F2 alpha; mean effective concentration was 11 nM, and maximal dilation occurred at 60-200 nM. The vasodilation showed marked desensitization upon repeated applications of capsaicin. Tetrodotoxin blocked the capsaicin-induced vasodilation but not the desensitization observed upon repeated application. Muscarinic receptor antagonists did not affect the actions of capsaicin. Capsaicin did not dilate arterioles whose extrinsic sensory afferent fibers had been surgically removed. Substance P and human calcitonin gene-related peptide II dilated arterioles; these dilations were not inhibited after desensitization of the capsaicin-induced vasodilation. Thus capsaicin dilates submucosal arterioles by selectively activating extrinsic afferent fibers that release vasodilator transmitter substances onto these vessels.

Animals↗

PubMed1993

Potassium currents and their modulation by muscarine and substance P in neuronal cultures from adult guinea pig celiac ganglia.

1. Intracellular microelectrode and whole-cell patch-clamp recordings were obtained from adult guinea pig celiac ganglion neurons grown in tissue culture for 7-14 days. Over 90% of neurons showed phasic-type action-potential discharge with the use of either type of recording electrode; they stained immunohistochemically for catecholamines, tyrosine hydroxylase, and neuropeptide Y. Input resistance (140 M omega) and action-potential amplitude (103 mV) were significantly greater with whole-cell than with microelectrode recordings, but other passive electrical properties were similar. 2. Five potassium currents were characterized: an apamin-sensitive after hyperpolarizing current (IAHP), an apamin and tetraethylammonium-insensitive slow IAHP, an M-like current, a transient outward IA current, and a delayed rectifier IK current. A hyperpolarization-activated cationic Ih current was also present. The first three currents were not observed with whole-cell recordings. 3. Cadmium (200 microM), cobalt (1 mM), lanthanum (30 microM), or a low calcium/high magnesium solution blocked both IAHPS and the M-like current; barium (1 mM) also blocked these currents. 4. Kinetics of the M-like current were best described by a double exponential fit to deactivating tail currents with time constants of 50 and 390 ms at -50 mV. The apamin-sensitive and slow IAHP decayed exponentially with time constants of 145 ms and 3.5 s, respectively. There was no correlation between occurrence of M-like current (95% of neurons) and slow IAHP (40% of neurons), nor any correlation between magnitude of M-like current and IAHP in those cells exhibiting both currents. 5. Muscarine and substance P (SP) caused depolarizations or inward currents (under voltage clamp) at the resting potential (-55 mV) associated with a decreased membrane conductance. The slow IAHP and the M-like current, but not the apamin-sensitive IAHP nor the IA, were blocked by muscarine and SP (IC50 3 microM and 100 nM, respectively). Muscarine and SP also decreased a "leak" potassium current. 6. We conclude that celiac neurons express two calcium-dependent IAHP currents and a calcium-dependent M-current; these are seen by fine-tipped intracellular microelectrodes but not by whole-cell patch electrodes. These currents are not required for spike frequency accommodation. Muscarine and SP reduce these currents, as well as voltage-independent leakage potassium current.

Animals↗

PubMed1991

Cholinergic and noncholinergic submucosal neurons dilate arterioles in guinea pig colon.

Outside diameter of isolated submucosal arterioles in guinea pig colon were monitored to examine vasodilator innervation to these gastrointestinal microvessels. Electrical stimulation of intrinsic submucosal ganglia dilated submucosal arterioles that had been preconstricted with vasopressin or norepinephrine. In approximately 50% of arterioles examined, the muscarinic receptor antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, 10 nM) abolished nerve-evoked vasodilations; 4-DAMP (500 nM) only partially inhibited the response in the other 50%. No significant differences in the nerve-evoked vasodilations were observed after extrinsic denervation of sympathetic and sensory fibers and removal of myenteric neurons by surgical myectomy. Immunohistochemistry demonstrated both substance P (SP) and vasoactive intestinal polypeptide (VIP) fiber projections to arterioles after sensory denervation and myectomy. Superfusion with muscarine and SP, but not with VIP or calcitonin gene-related peptide (CGRP), also dilated the arterioles; concentrations of muscarine and SP producing half-maximal responses were 35 and 6 nM, respectively. However, local pressure ejection of both CGRP and VIP dilated the arterioles. The SP receptor antagonist [D-Arg1,D-Phe5,D-Trp7,9,Leu11]SP reduced vasodilations in response to ganglionic stimulation as well as to pressure ejection of both SP and VIP. This study demonstrates that submucosal arterioles in the guinea pig distal colon receive a cholinergic as well as a noncholinergic vasodilator input from neurons in the submucosal plexus. SP and VIP are both likely candidates as the noncholinergic vasodilator transmitter to colonic gastrointestinal microvessels.

Animals↗

PubMed1990

Effects of 5-HT3 receptor antagonists on 5-HT and nicotinic depolarizations in guinea-pig submucosal neurones.

1. Intracellular recordings were made from neurones of the guinea-pig submucosal plexus. The effects of several 5-hydroxytryptamine3 (5-HT3) receptor antagonists on depolarizations produced by ionophoretic application of 5-HT and acetylcholine, as well as on fast excitatory postsynaptic potentials (fast e.p.s.ps) produced by nerve stimulation were examined. 2. ICS 205-930, GR 38032F, MDL 72222, cocaine and curare all inhibited the fast e.p.s.p. as well as the depolarizations in response to 5-HT and acetylcholine (ACh) ionophoresis in a dose-dependent fashion. 3. IC50 values for ICS 205-930, GR 38032F, MDL 72222, cocaine and curare in inhibiting the 5-HT mediated depolarizations were 12 nM, 100 nM, 3 microM, 3 microM and 20 microM, respectively. 4. IC50 values for ICS 205-930, GR 38032F, MDL 72222, cocaine and curare in inhibiting the nicotinic depolarizations were 4 microM, 12 microM, 11 microM, 6 microM and 17 microM, respectively. Similar IC50 values were obtained for inhibition of the fast e.p.s.ps by these antagonists. 5. The nicotinic receptor blocker, hexamethonium, inhibited the nicotinic depolarization and the fast e.p.s.p. with IC50 values of 10 microM. Hexamethonium (10 microM-5 mM) did not alter the depolarization induced by 5-HT. 6. These results demonstrate that the pharmacological profile of 5-HT3 receptors present on submucosal neurones is identical to that of 5-HT3 receptors on myenteric neurones and, thus, provide evidence that the enteric neuronal 5-HT3 receptor forms a receptor subtype distinct from that characterized in other parts of the autonomic nervous system.

Acetylcholine↗

PubMed1990

Characterization of vasopressin actions in isolated submucosal arterioles of the intestinal microcirculation.

Submucosal arterioles are the final resistance vessels of the mesenteric circulation; they supply intestinal mucosa and smooth muscle and contribute significantly to total mesenteric resistance. Characterization of receptors present on submucosal arterioles has not been carried out, because these vessels have not been accessible to study by previous methods. We have used a novel optical method for on-line tracking of outside diameter from in vitro preparations of submucosal arterioles in the ileum and colon of guinea pigs, rabbits, and humans to characterize the vasoconstrictor responses to vasopressin as well as other vasopressor agents along the gastrointestinal tract. All ileal submucosal arterioles showed smoothly graded constrictor responses, whereas colonic arterioles from each species exhibited rhythmic vasoconstrictions. Vasopressin constricted guinea pig and human submucosal arterioles (EC50, 1 nM) by activating classical V1 receptors; dissociation equilibrium constants (Kd) for the V1 antagonist d(CH2)5 Tyr (Me) arginine vasopressin were 1-3 nM. This antagonist was 10-50-fold more potent in inhibiting vasopressin constrictions in rabbit submucosal arterioles (Kd = 0.05-0.1 nM). No evidence for the presence of V2 receptors was obtained in any arteriole, and no significant differences in the alpha 1-adrenoceptor-mediated constrictions were observed in these vessels. Results from this study suggest the presence of heterogeneity of V1 receptors in submucosal arterioles; these differences appear to be species dependent. Our results also suggest that intrinsic vasoconstrictor properties of submucosal arterioles differ along the length of the gastrointestinal tract; these differences appear to be species independent.

Animals↗

PubMed1988

Compartmentalization of motor units in the cat neck muscle, biventer cervicis.

1. The neck muscle biventer cervicis is supplied by five separate nerve bundles that originate from segments C2-C5 and enter the muscle at different rostrocaudal levels. We have used the glycogen-depletion method to investigate the distribution of muscle fibers supplied by each nerve bundle and also the extent of motor-unit territories supplied by single motoneurons in the C3 segment. 2. Prolonged intermittent stimulation of each nerve bundle produced glycogen depletion in a compartment of muscle fibers that ran only a fraction of the whole-muscle length. The depleted compartment was separated by tendinous inscriptions from adjacent, serially arranged compartments that were supplied by different nerve bundles. Thus the muscle was divided into five in-series compartments, arranged in the same rostrocaudal sequence as the nerves by which they were supplied. 3. Six fast, glycolytic (FG) and five fast, oxidative-glycolytic (FOG) motor units were depleted by repetitive intracellular stimulation of their antidromically identified motoneurons in the C3 segment. The fibers of each motor unit were confined to a striplike subvolume whose cross-sectional area was only 20-40% of that for the whole compartment in which it was located. Single motor units contained an average of 408 extrafusal fibers (range: 262-582 fibers), and these were distributed with an average density of 20 fibers/mm2 in cross sections through their motor domains. No significant differences were found between the numbers or densities of fibers in FG and FOG motor units. 4. The specialized in-series organization of compartments has functional implications because the forces generated by one compartment of motor units must be transmitted through other in-series compartments of muscle fibers rather than directly onto skeletal attachments. The confined distribution of muscle fibers belonging to a single motor unit suggests that an additional level of organization may exist within individual compartments. The implications of these features for the physiological behavior and neural control of biventer cervicis are discussed.

Animals↗

PubMedDate not supplied

Use of oral sodium phosphate colonic lavage solution by Canadian colonoscopists: pitfalls and complications.

Oral sodium phosphate (NaP) has become an attractive alternative to polyethylene glycol (PEG) for colonic cleansing before colonoscopy, but it potentially has greater complications. This study surveyed members of the Canadian Association of Gastroenterology (CAG) to determine how these colonic lavage agents are used and what complications have been encountered. The Dillman survey technique produced responses from 67% of the 400 members who perform colonoscopy. For the larger out-patient group, respondents used NaP more frequently than PEG (46% versus 35%, respectively, P < 0.015). Respondents used NaP and PEG with similar frequencies for the in-patient group (44% versus 43%). Of respondents using NaP, 45% reported excluding its use in patients with renal failure, 30% with heart disease, 13% with incomplete bowel obstruction and 9% with extreme age. Symptoms suggestive of hypovolemia were reported in 9% of those using NaP compared with 3% using PEG (P < 0.02). Three patients receiving NaP developed acute renal failure. A greater proportion of those using NaP had small unexplained aphthous ulcers (16%) and excessive luminal bubbling (24%) compared with PEG users (3%, P < 0.00001 and 14%, P < 0.03, respectively). These data demonstrate that members of CAG use NaP more frequently than PEG as the colonic lavage solution before colonoscopy. A greater number reported complications with NaP versus PEG, and a significant proportion of the respondents appeared to be unaware of the potential for these complications in specific clinical circumstances.

Canada↗