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Biomedical subjects

M J Zinner

Publications and source records attributed to M J Zinner.

At least 109 records · Page 6Linked to original sources
PubMed1986

Substance P-induced intestinal secretion of water and electrolytes.

This study was initiated to determine if raised (carcinoid) plasma concentrations of substance P induced jejunal secretion of water and electrolytes. Five dogs had isolated and cannulated 25 cm jejunal segments perfused at 2 ml/min with a neutral, isotonic perfusate. Saline, 1.0 ml, was infused intravenously during basal and recovery periods, while substance P was administered intravenously at 75 ng/kg/min (55 pmol/kg/min) during the four 15 minute experimental periods. Infusion increased plasma SP concentrations from basal (5.8 +/- 1.3 pg/ml) to a mean plateau level of 121.2 +/- 25.2 pg/ml (mean +/- SEM). During SP infusion, intestinal secretion of water, Na+, and Cl- were documented (H2O basal +102 +/- 60 to SP -275 +/- 60; microliter/min; Na+ basal +19.8 +/- 7.2 to SP -23.2 +/- 7.5 microEq/min; Cl- basal 21.7 +/- 7.5 to SP -16.5 +/- 5.6 microEq/min). Under basal conditions, there was minimal secretion of potassium (-0.264 +/- 0.282 microEq/min); during SP infusion, K+ flux was altered to significant secretion (-1.784 +/- 0.271 microEq/min). Serum concentrations of Na and Cl were unchanged during SP infusion, but serum potassium concentrations fell from 4.64 +/- 0.12 to 3.85 +/- 0.40 mEq/l. The data demonstrate that substance P at levels noted in the carcinoid syndrome induces significant jejunal secretion of water and electrolytes in the dog.

Animals↗
PubMed1985

The influence of cholinergic and adrenergic blockade on the portal release of substance P in the cat.

The effect of efferent electrical stimulation of the divided thoracic vagus nerves on the release of substance P-like immunoreactivity (SPLI) into the portal vein was studied in anesthetized cats. Under basal conditions portal SPLI levels were fairly constant. During the first 5 min of vagal stimulation there was a significant increase of the portal plasma levels of SPLI. Since we have demonstrated that infracardiac vagal stimulation causes only minor changes in small intestinal bloodflow, a true vagal neurogenic release of SPLI seems likely. We have shown that SPLI is exclusively localized within feline gut neurons (not the enterochromaffin (EC) cells). Thus, SPLI released into the portal circulation probably represents overflow of transmitter into the circulation. Neither blockade of cholino- or adrenoceptors nor ganglionic blockade influenced the enhanced release of SPLI induced by vagal stimulation, suggesting activation of SP neurons via nonclassical receptors.

Animals↗
PubMed1985

Secretory effects of intravenous serotonin on the proximal jejunum of the awake dog.

The intestinal secretory effects of hyperserotoninemia were studied in conscious dogs with cannulated, exteriorized chronic proximal jejunal segments. A basal absorptive state for water and electrolytes was significantly changed to a secretory state for water, sodium ion, chloride ion, and potassium ion when serotonin was infused intravenously at 30 micrograms/kg per minute. This effect disappeared with the cessation of the infusion. During infusion, whole blood serotonin concentrations were similar to those in patients with the carcinoid syndrome. Diarrhea developed in all animals studied during infusion, and significant hypokalemia also occurred. These results support a primary role for serotonin in the pathogenesis of diarrhea associated with the carcinoid syndrome.

Animals↗
PubMed1985

Effect of exogenous somatostatin infusion on gastrointestinal blood flow and hormones in the conscious dog.

The purpose of this study was to investigate the effects of intravenous somatostatin infusion on gastrointestinal blood flow and hormone release in conscious dogs. Gastric, duodenal, jejunal, and pancreatic blood flows, quantitated using radioactive microspheres, were significantly decreased during somatostatin infusion (200 and 500 ng/kg min), resulting in an overall 30% reduction in summed portal blood flow. Fasting blood levels of glucose fell an average of 10 mg/dl. Immunoreactive insulin, gastrin, glucagon, and pancreatic polypeptide were all profoundly suppressed by somatostatin infusion. Our studies provide one possible explanation for somatostatin's apparent effectiveness in the control of upper gastrointestinal hemorrhage.

Animals↗
PubMed1985

The effects of vagal nerve stimulation on endoluminal release of serotonin and substance P into the feline small intestine.

Endoluminal release of serotonin (5-HT), substance P (SP), and motilin was quantitated after thoracic vagal nerve stimulation in the cat. In duodenum and jejunum, simultaneous release of these compounds was observed. In contrast, vagal stimulation did not augment the rate of luminal secretion of either 5-HT or SP in the distal ileum. Immunohistochemical studies demonstrated 5-HT in both enterochromaffin (EC) cells and nerves throughout the small bowel. However, we were unable to visualize any SP-containing EC cells in the cat, which suggests that the source of luminal SP in this species must be intramural nerves.

Animals↗
PubMed1985

Verapamil inhibition of the intestinal effects of substance P.

The undecapeptide substance P (SP) is contained in enterochromaffin cells and circulates in high concentrations in patients with carcinoid syndrome. We have previously reported that elevated SP levels, simulating those reported in patients with carcinoid syndrome, induce profound changes in intestinal water and electrolyte secretion, motility, and blood flow in a canine model. The purpose of this study was to attempt to block the effects of circulating carcinoid levels of SP on intestinal secretion and motility with the calcium channel blocker verapamil. In five dogs a chronic proximal jejunal Thiry-Vella loop was constructed, and after a 2-week recovery the loops were perfused with an isotonic test solution containing 14C-polyethylene glycol as a volume marker. Motor activity was measured by changes in intraluminal pressure and a motility index was calculated with computer-assisted planimetry and expressed as square millimeters per 5 minutes. After a 30-minute baseline period, SP was infused at 50 ng/kg/min for 90 minutes. SP circulating levels rose from a baseline of 6.2 +/- 1.3 pg/ml to a peak of 93.3 +/- 3.1 pg/ml during this infusion. Thirty minutes after the start of this SP infusion, a simultaneous infusion of verapamil (5.0 micrograms/kg/min) was begun at a separate site. During SP infusion there was a significant secretory response of water (-48 +/- 12 microliters/min), Na+ (-7.7 +/- 2.5 microEq/min), Cl- (-8.8 +/- 2.7 microEq/min) and K+ (-0.57 +/- 0.14 microEq/min), and hypermotility (motility index: 1479 +/- 138 mm2/5 min). When verapamil was added a reversal of secretion to net absorption was observed (water: + 116.9 +/- 15.6 microliter/min; Na+: + 13.8 +/- 2.1 microEq/min; Cl-: + 5.5 +/- 2 microEq/min; K+: + 0.38 +/- 0.9 microEq/min) (p less than 0.05). In addition, there was a reduction in motility (motility index: 853 +/- 92 mm2/5 min; p less than 0.05). These results confirm that SP has profound effects on both intestinal motility and secretion and that calcium channel blockade reduces these effects significantly.

Animals↗
PubMed1985

The pentagastrin test in the diagnosis of the carcinoid syndrome. Blockade of gastrointestinal symptoms by ketanserin.

The levels of 5-hydroxytryptamine (serotonin, 5-HT) and substance P (SP) were assayed (using high performance liquid chromatography-electron capture and radioimmunoassay methods) in the peripheral blood of 17 patients with known mid-gut carcinoids, 16 of whom had hepatic metastases. All patients had supranormal basal levels of 5-HT and SP. The clinical and hormonal changes induced by two provocation tests, intravenous pentagastrin (PG) and calcium infusion, were compared. Pentagastrin caused flushing in all the patients, induced gastrointestinal symptoms in all but one of the patients with hepatic involvement, and universally elevated circulating 5-HT levels. Pretreatment with a 5-HT2-receptor blocking agent, ketanserin, abolished the gastrointestinal effects but had virtually no influence on either 5-HT levels or flushing induced by intravenous pentagastrin. In contrast, calcium infusion induced carcinoid symptoms in only two of six patients, and this was consistently associated with stimulation of circulating serotonin levels. The authors conclude that 1) 5-HT may be responsible for the gastrointestinal symptoms in carcinoid patients, but it does not seem to play any role in flushing; 2) ketanserin may be a useful therapeutic agent in alleviating gastrointestinal symptoms in carcinoid patients; 3) differential responses to PG suggests that SP is released from a site different from that of 5-HT; 4) it is possible that SP may contribute to the mediation of flushing, but it cannot be the sole agent causing this symptom; and 5) the pentagastrin test with measurements of 5-HT levels in peripheral blood seems to be superior to calcium infusion as a provocative test in documenting the diagnosis of carcinoid disease.

Aged↗
PubMed1985

The effect of somatostatin on central hemodynamics, renal blood flow, and renal function in dogs.

We investigated the effects of infusion of somatostatin (200 and 500 ng/kg/min) on central hemodynamics and renal blood flow measured with radioactive microspheres. At the lower dose infusion rate somatostatin did not alter any hemodynamic parameter, but at 500 ng/kg/min somatostatin caused minor transient bradycardia, lowered cardiac output, and increased peripheral resistance. Both infusions inhibited renal arterial flow, with decreases noted in both cortical and medullary components. The 20% fall in renal perfusion was confirmed by the hippurate clearance technique, and there was a corresponding 17% decrease in the glomerular filtration rate. In contrast, no changes were noted in urine output, urinary concentrations of sodium or potassium, or urine osmolarity. These hemodynamic and renal side effects might limit the therapeutic usefulness of somatostatin infusion.

Animals↗
PubMed1984

The effect of carcinoid levels of serotonin and substance P on hemodynamics.

Serotonin and substance P circulate in high concentrations in patients with the carcinoid syndrome. These studies were performed to evaluate the effects of intravenous infusions of serotonin and substance P to reproduce carcinoid levels of these agents on central hemodynamics, regional blood flow (using the radioactive microsphere technique), and endogenous hormone release. Serotonin did not affect mean arterial pressure but it significantly increased cardiac output, decreased systematic vascular resistance, and redistributed regional blood flow, increasing blood flow to the heart, adrenals, fundus, and antrum. Substance P significantly decreased mean arterial pressure and systemic vascular resistance, increased cardiac output, and increased blood flow to adrenal, fundus, antrum, liver, and all muscular layers of the stomach and small bowel. Neither serotonin nor substance P affected skin blood flow, nor altered circulating levels of glucose, insulin, or gastrin. Although both of these agents seem to participate in the pathogenesis of the carcinoid syndrome, our studies suggest that it is not possible to ascribe all the hemodynamic abnormalities to either.

Animals↗
PubMed1984

The effects of intravenous substance P infusion on hemodynamics and regional blood flow in conscious dogs.

substance P concentrations in plasma increase in response to a meal. The effects of intravenous substance P infusions were investigated in seven conscious dogs with doses of peptide (7 ng/kg/min) designed to reproduce the normal postprandial circulating increase in substance P. Substance P levels measured by radioimmunoassay increased 8.6 +/- 4.8 pg/ml in arterial plasma (P less than 0.05) and 3.0 +/- 1.5 pg/ml in mixed venous plasma (P less than 0.05). By use of decay equations, the calculated half-life of exogenous immunoreactive substance P was less than 30 seconds, and this corresponded to rapid abolition of the biologic effects of the peptide upon cessation of the infusion. The integration of the arterial and mixed venous concentration curves allowed calculation of the peripheral inactivation of exogenous immunoreactive substance P as 65.6%. During substance P infusion, mean arterial pressure fell 20 +/- 6 mm Hg at 5 minutes from 124 +/- 6 mm Hg (P less than 0.02). Total systemic vascular resistance was 3102 +/- 196 dynes/sec/cm5 basally, and it fell by 667 +/- 137 dynes/sec/cm5 (P less than 0.05) at 10 minutes. Plasma glucose, insulin, and cortisol concentrations did not change significantly from 83 +/- 4 mg/dl, 5.1 +/- 1.0 microU/ml, and 4.6 +/- 0.5 micrograms/dl, respectively. Radioactive 15 micron microspheres injected at times 0, 20, and 50 minutes into the infusion allowed for identification of statistically significant (P less than 0.05) increases in blood flow to the adrenal gland and the muscular layers of the fundus and the ileum. Thus the infusion of substance P to reproduce postprandial circulating levels of this peptide was followed by an orderly sequence of hemodynamic alterations in the conscious dog. Regional blood flow changes were seen in the muscular layers of the fundus and ileum, which are regions of high substance P concentration.

Animals↗
PubMed1983

The hemodynamic effects of intravenous infusions of serotonin in conscious dogs.

The effects of exogenously infused serotonin on central and regional hemodynamics were investigated in 14 dogs. Using intravenous doses that mimic postprandial levels of serotonin, we were able to demonstrate no changes in cardiac output or mean arterial pressure. However, there were region-specific changes in blood flow. Blood flow to the fundus, antrum, brain, heart, and skeletal muscle were increased by both the low-dose (4 micrograms/kg-min) and the high-dose (10 micrograms/kg-min) infusions. In contrast, blood flow to the kidney, spleen, and liver decreased. Whole blood 5-HT levels were measured in mixed venous blood and systemic arterial blood. Based on the differences between serotonin levels in these two circulations, pulmonary inactivation of exogenously infused serotonin was calculated to be 44%. The half-life of exogenous serotonin was measured at 1.2 min. The data thus suggest that at doses which mimic those released from the intestinal enterochromaffin cells, serotonin may play a role in mediating postprandial hemodynamic responses.

Animals↗
PubMed1983

Endoluminal substance P as a cause of mucosal hyperemia in the feline gut by a nonneural mechanism.

Exogenous substance P (SP) was perfused into the lumen of the proximal jejunum in 16 fasted cats at a rate of 6.04 +/- 1.96 ng/min. Regional blood flow was measured by radioactive microspheres after successive 15-minute perfusions with saline (basal), neural blockers, SP, and saline. Endoluminal SP caused mucosal hyperemia in the perfused jejunal segment that was not blocked by preperfusion of the segment with lidocaine (2% or 4%) or tetrodotoxin (3 X 10(-7) M). In addition, there was no increase in blood flow to any other organ tested, gastrointestinal or systemic. Local luminal SP levels rose but there was no significant rise in portal SP levels, indicating that the peptide was not absorbed. The data suggest that SP acts locally by a nonneural mechanism to influence local gastrointestinal blood flow.

Animals↗
PubMed1982

Effect of xenopsin on blood flow, hormone release, and acid secretion.

We investigated the effects of the neurotensin analogue xenopsin on regional blood flow, central hemodynamics, and stimulated acid secretion in awake conscious dogs. Organ blood flow, estimated using the radioactive microsphere technique, was significantly increased during the xenopsin infusion to the adrenals, pancreas, and ileum. There was no change in mean arterial pressure or cardiac output (measured by thermodilution). Along with changes in blood flow, there was a significant increase in the hormone output from the pancreas. These included rises in plasma pancreatic polypeptide, insulin, and glucagon. There also was a rise in plasma cortisol levels during the infusion. Substance P levels rose slowly but significantly during the xenospin infusion. There was no change in plasma gastrin levels. Xenopsin produced a significant inhibition of tetragastrin-stimulated gastric acid output. Thus, xenopsin appears to have region-specific influence on blood flow that correlates with region-specific hormonal secretion. In addition, xenopsin, like its mammalian analogue neurotensin, is an inhibitor of stimulated gastric acid secretion. A mammalian xenopsinlike peptide may well be involved in the modulation of gastrointestinal function.

Adrenal Glands↗
PubMed1982

Local regulation of blood flow in the feline jejunum. A possible role for endoluminally released substance P.

Serotonin and substance P of gastrointestinal origin have been measured by radioimmunoassay in the bowel lumen under basal and stimulated conditions. To investigate the possibility that local blood flow may be influenced by these endoluminal hormones, 26 cats were studied with exogenous serotonin and substance P infused endoluminally into isolated proximal jejunal segments in vivo. Regional blood flow was measured by using the radioactive microsphere technique before, during, and after the endoluminal instillation of two doses of substance P (3.9 and 30 ng/min) or serotonin (0.9 and 21 micrograms/min). Neither dose of substance P changed systemic blood pressure. Substance P at the low dose caused an increase in blood flow to the experimental jejunal mucosa (from 53 +/- 10 ml/min per 100 g to 102 +/- 20 ml/min per 100 g, P less than 0.01). The higher dose of endoluminal substance P similarly increased blood flow to the experimental jejunal mucosal fraction, and also increased blood flow to the experimental jejunal muscularis fraction (from 17 +/- 3 ml/min per 100 g to 23 +/- 3 ml/min per 100 g, P less than 0.02). Serotonin increased blood flow to the experimental jejunal muscularis only at the high dose (17 +/- 4 ml/min per 100 g to 25 +/- 4 ml/min per 100 g tissue, P less than 0.01). These results provide evidence for a dose-related local effect of endoluminal substance P on gastrointestinal blood flow.

Animals↗
PubMed1982

A clinical trial of cimetidine in acute pancreatitis.

A prospective randomized clinical trial was carried out to evaluate the efficacy of cimetidine in the treatment of acute pancreatitis. One hundred and sixteen patients with a clinical diagnosis of acute pancreatitis and an elevated serum amylase level were included in the study. All patients were treated with fluids, given intravenously, analgesia and nasogastric tube suction, if required. In addition, on a random basis, 52 received cimetidine given intravenously and 64 did not. There were no significant differences in the clinical courses of the two groups.

Acute Disease↗
PubMed1982

Effect of cervical and thoracic vagal stimulation on luminal serotonin release and regional blood flow in cats.

In acute experiments on 14 cats, the transected vagus nerves were stimulated at two levels (10 V, 5 ms, 10 Hz, 10 mA, 15 min). Fifteen-centimeter proximal jejunal segments were perfused with saline (1.0 ml/min). Basal luminal immunoreactive serotonin secretion averaged 206 +/- 67 ng/5 min. After stimulation of the vagus nerves, there was an immediate two- to threefold increase in the rate of secretion of immunoreactive serotonin into the lumen. There were no significant differences in the stimulated secretory rates that resulted from stimulation at the cervical or thoracic levels. Shortly after cessation of vagal stimulation, immunoreactive serotonin secretory rates returned to basal. Vagal nerve stimulation did not result in any change in peripheral or portal venous blood concentrations of serotonin. In 12 additional cats, the effects of stimulation of the vagus nerves at the cervical and thoracic levels on regional blood flow, as determined using the microsphere technique, were compared. Cervical vagal stimulation resulted in hypotension, bradycardia, decreased perfusion of the heart, kidney, and small and large bowels, but preservation of the perfusion of the fundus and antrum. In contrast, stimulation of the transected nerves in the chest stimulated gastric blood flow but did not alter either flow to other viscera or central hemodynamics.

Animals↗
PubMed1979

Effect of altered intestinal water transport on rabbit ileal blood flow.

A method is described for measuring ileal blood flow in the anesthetized (pentobarbital sodium) rabbit by the intraventricular injection of microspheres (15 micrometer) labeled with cerium-141 or chromium-51; with this method the amount of labeled microspheres lodging in the tissue is proportional to the blood flow. Blood flow to the ileal mucosa plus submucosa could be separated from flow to the ileal muscularis propria plus serosa by this technique. Simultaneous and sequential injections of radiolabeled microspheres gave similar measurements of ileal blood flow and did not affect ileal water absorption. Increasing ileal water absorption by treatment with the glucocorticoid methylprednisolone (3 mg/100 g per day for 3 days) increased blood flow to both compartments of the ileum and also to the colon, liver, and kidneys; methylprednisolone treatment did not alter blood flow when studies were performed before the methylprednisolone-induced increase in ileal water absorption had occurred. In contrast, intestinal secretagogues that induced both active ileal secretion (purified cholera toxin and serotonin) and passive ileal secretion (hypertonic mannitol) did not affect ileal blood flow. These studies indicate that increased ileal water absorption is associated with increased ileal blood flow, whereas intestinal secretion is not necessarily associated with an alteration in ileal blood flow.

Animals↗