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P Svendsen

Publications and source records attributed to P Svendsen.

At least 37 records · Page 2Linked to original sources
PubMed1997

Acid-stimulated duodenal bicarbonate secretion involves a CFTR-mediated transport pathway in mice.

BACKGROUND & AIMS: Duodenal bicarbonate secretion is an important factor in epithelial protection. The role of the cystic fibrosis transmembrane conductance regulator (CFTR) in acid-induced bicarbonate secretion is unknown. The aim of this study was to determine whether CFTR mediates acid-stimulated duodenal epithelial bicarbonate secretion. METHODS: Basal and stimulated bicarbonate secretion was examined in the cystic fibrosis murine model cftrm1UNC, which displays defective CFTR in various organs including chloride transport abnormalities in epithelia. After anesthesia, the proximal duodenum was cannulated and perfused with isotonic saline, and [HCO3-] was determined. RESULTS: Basal bicarbonate secretion was diminished in cystic fibrosis vs. normal mice, 2.8 +/- 0.7 vs. 4.7 +/- 1.7 mumol.cm-1.h-1, respectively (P < 0.001). Luminal acidification failed to elicit a bicarbonate secretory response in cystic fibrosis compared with normal littermates (peak response, 2.3 +/- 0.2 vs. 9.9 +/- 1.5 mumol.cm-1.h-1, respectively; P < 0.01). Prostaglandin E2- and vasoactive intestinal peptide-stimulated bicarbonate secretion were also significantly impaired in cystic fibrosis. Defective bicarbonate secretion in cystic fibrosis genotypes was due to decreased net fluid secretion and [HCO3-]. CONCLUSIONS: Basal and stimulated proximal duodenal bicarbonate secretion may involve a CFTR-mediated transport pathway. It is likely that CFTR, directly or indirectly, has a major functional role in mediating bicarbonate transport in the proximal duodenum.

Animals↗
PubMed1997

Hidden compartments in AVMs--a new concept.

PURPOSE: The concept of hidden compartments in cerebral arteriovenous malformations (AVMs), which is hereby launched, offers a new explanation for the neurosurgical and neuroradiological controversies concerning patients with AVMs. MATERIAL AND METHODS: Three patients who were considered completely cured of their AVMs, subsequently developed new areas of malformed vessels as revealed by later angiograms. RESULTS: These 3 cases support our hidden compartment hypothesis and are reported on here, illustrated with relevant angiograms. The clinical implications of the hidden compartment concept refer to phenomena such as AVM growth, AVM recurrence after surgical excision, irradiation or embolization as well as per- or postoperative hemorrhage and swelling. CONCLUSION: The incidence of hidden compartments in the AVM population is unknown but further studies, particularly in the realm of superselective embolization, could reveal their presence.

Adult↗
PubMed1997

Anaesthesia and basic experimental surgery of minipigs. A practical exercise.

Minipigs tolerate anaesthesia very well. The only disadvantages are the difficulties in performing venous puncture and endotracheal intubation. To overcome these the animals should be well sedated prior to induction by intravenous injection, and deeply anaesthetized prior to the introduction of the endotracheal tube. Anaesthetic regimen and several basic experimental surgical techniques will be practised.

Adjuvants, Anesthesia↗
PubMed1997

Importance of vagus nerves in duodenal acid neutralization in anesthetized pigs.

During the cephalic phase of gastric acid secretion, vagally mediated synchronous stimulation of bicarbonate provides protection against the acid. The purpose of this study was to determine simultaneously the effect of electrical vagal stimulation (EVS) on pancreatic, hepatic, and duodenal mucosal bicarbonate secretion, thereby estimating their relative importance in vagally induced duodenal acid neutralization. Splanchnicotomy increased vagally induced pancreaticobiliary bicarbonate secretion, whereas duodenal mucosal bicarbonate secretion was unchanged. After splanchnicotomy, EVS (10 ms, 15 mA, 12 Hz) significantly increased pancreatic bicarbonate secretion (0-4.17 mmol/h), hepatic bicarbonate secretion (0.16 to 0.22 mmol/h), and duodenal mucosal bicarbonate secretion (0.17 to 0.31 mmol/h). Pancreaticobiliary bicarbonate secretion was atropine resistant, whereas vagally induced duodenal mucosal bicarbonate secretion was diminished by atropine (2.0 mg/kg). After splanchnicotomy, EVS (10 ms, 15 mA, 12 Hz) had no effect on portal plasma concentration of secretin, whereas vasoactive intestinal peptide was increased (14-29 pM). EVS at 12 Hz with varying duration (3 or 10 ms) and amplitude (3-50 mA) had no further effect on the bicarbonate secretion from the three organs. In addition, biliary [14C]mannitol clearance was shown not to be a reliable marker of canalicular bile secretion in pigs. These results suggest that in the anesthetized pig 1) vagal stimulation is only of minor importance to hepatic bicarbonate secretion; 2) vagal stimulation activates pancreatic bicarbonate secretion through both cholinergic muscarinic and noncholinergic transmission; and 3) vagal stimulation induces duodenal mucosal bicarbonate secretion mainly through cholinergic muscarinic transmission. In conclusion, these results suggest that only pancreatic and duodenal bicarbonate production play a role in vagally induced duodenal acid neutralization.

Acid-Base Equilibrium↗
PubMed1997

CFTR mediates cAMP- and Ca2+-activated duodenal epithelial HCO3- secretion.

The role of the cystic fibrosis transmembrane conductance regulator (CFTR) in duodenal alkaline secretion has not been directly examined. The aims of this series of experiments were to determine if CFTR mediates basal and stimulated duodenal epithelial HCO3- secretion. Utilizing the cystic fibrosis murine model (cftr(m1UNC)), we compared normal [CFTR(+/+)] littermates (34-46 days old) with CFTR(-/-) animals (34-39 days old). Anesthesia was induced and maintained with intraperitoneal Hypnorm-midazolam. The proximal duodenum (4-7 mm) was cannulated and perfused with 154 mM NaCl. Either forskolin (10(-6)-10(-4) M) or carbachol (10(-6)-10(-3) M) was perfused intraluminally to activate adenosine 3',5'-cyclic monophosphate (cAMP)- and Ca2+-mediated HCO3- secretion, respectively. Effluent volumes were weighed and HCO3- quantitated by back titration. Basal HCO3- secretion was diminished significantly (P < 0.01) in CFTR(-/-)vs. normal CFTR(+/+) mice (2.8 +/- 0.5 vs. 5.3 +/- 0.4 micromol x cm(-1) x h(-1)). Moreover, in CFTR(-/-) mice, both forskolin- and carbachol-stimulated peak HCO3- secretions were fourfold less compared with those in CFTR(+/+) littermates (3.7 +/- 0.2 vs. 15.6 +/- 2.1 and 4.7 +/- 0.3 vs. 14.2 +/- 2.5 micromol x cm(-1) x h(-1), respectively; P < 0.01). In conclusion, CFTR plays a significant role in mediating basal, cAMP-, and Ca2+-activated duodenal epithelial HCO3- secretion.

Animals↗
PubMed1997

Heparin-free hypothermal hemodialysis at 20 degrees C improves biocompatibility.

We investigated the effect of cooling blood to 20 degrees C on the reactions and dialysis efficiency in a model using pigs. Eighteen uremic pigs were hemodialyzed. Nine pigs were hemodialyzed cooling the blood in the dialysis filter and rewarmed using microwaves to body temperature before being returned to the pigs; no heparin was added. Nine pigs (control group) were dialyzed using heparin without blood cooling. A significant decrease in the number of leukocytes was observed after 15 min in the control group, whereas no change was observed in the hypotherm-dialyzed group. We conclude that heparin-free hemodialysis performed at 20 degrees C with microwave rewarming is possible, improving biocompatibility significantly.

Animals↗
PubMed1997

Feedback regulation of pancreatic exocrine secretion in minipigs.

BACKGROUND: The mechanism behind the possible feedback regulation of pancreatic exocrine secretion is not well understood. METHODS: Thirteen minipigs were prepared with fistulas to the pancreatic duct and the duodenum. Peripheral venous blood was obtained for determination of secretin and cholecystokinin (CCK) levels. Four different experiments were performed: 1) diversion and reinfusion of pancreatic juice; 2) intraduodenal infusion of NaHCO3 solution, with the same volume, bicarbonate concentration, and osmolality as the collected pancreatic secretion, and reinfusion of pancreatic juice; 3) reinfusion of pancreatic secretion for 1 h before and 2 h after a meal; and 4) diversion of pancreatic secretion and intraduodenal infusion of NaHCO33 solutions before and after a meal. RESULTS: Reinfusing pancreatic juice significantly decreased pancreatic juice volume and bicarbonate output and slightly decreased the level of secretin in plasma. Alternating infusions of substitute NaHCO3 and pancreatic juice did not change pancreatic output of bicarbonate and protein, nor did it change the CCK and secretin levels in plasma. Replacing pancreatic juice with intraduodenal NaHCO3 infusions during a meal did not significantly modify the pancreatic secretion of bicarbonate and protein or the hormonal levels in blood. CONCLUSIONS: A negative feedback regulation of pancreatic exocrine secretion is present in starved minipigs. Duodenal acidity and plasma levels of secretin semm to be of importance, whereas duodenal enzyme activity and the level of CCK in plasma probably are not. A postprandial negative feedback regulation through duodenal enzymatic activity and release of CCK into blood could not be shown.

Animals↗
PubMed1997

Transarterial embolization of a direct carotid cavernous fistula with Guglielmi detachable coils.

Four patients underwent transarterial embolization of a carotid-cavernous fistula with Guglielmi detachable coils; in three cases as the initial form of treatment and in one case after treatment via transarterial balloon embolization failed. The fistulas were 2 to 3 mm in diameter on pretreatment angiograms. Complete obliteration was achieved in two patients; in the other two, minimal residual flow remained immediately after embolization but disappeared by follow-up angiography. One to four coils were used to occlude the fistulas. The internal carotid artery remained patent in all patients, and there were no complications.

Arteriovenous Fistula↗
PubMed1996

Embolization of cerebral arteriovenous malformations: Part I--Technique, morphology, and complications.

OBJECTIVE: The aim of this two-part study is to give a full account of all patients referred for embolization of arteriovenous malformations (AVMs) from 1987 to 1993. This article (Part I of II) presents the patient study, including angiographic features and their relation to the immediate outcome of embolization. METHODS: Of the 192 patients referred, 150 were subsequently treated. Most patients were referred by neurosurgeons, and 85% of the AVMs were Spetzler-Martin Grade > or = 3. We have accounted for the 42 patients who did not undergo embolization. RESULTS: Occlusion from embolization alone (total embolization) was obtained in 13% of patients. Full treatment (total embolization or embolization and then stereotactic radiation or surgery) was achieved in two-thirds of all patients (n = 100, 66%), and combined treatment with stereotactic gamma radiation was the most important part of the treatment strategy. The procedural mortality was 1.3%. The total incidence of complications after embolization was high (40%), but only 6.7% of cases were labeled severe. Of all angiographic features that were considered, large size and the presence of deep feeders were predictors of failure to achieve full treatment. Thirty-four patients with AVMs < 8 cc were included in the study. These could have been irradiated as the sole treatment. In this group of small AVMs, the results of embolization were far better than in the whole group. Fourteen of the AVMs had volumes of < 4 cc, and 10 of these (71%) were totally embolized. One patient had a hemianopsia. Among AVMs 4 to 8 cc in volume (n = 20), the total embolization rate was 15%, the full treatment rate in combination with gamma treatment was 75%, and 10% of the patients were operated on after embolization. Severe complications occurred in 15% of patients, but no complications occurred after November 1990. CONCLUSION: In a series of AVMs, most of which were regarded as unsuitable for surgical excision, two-thirds were reduced to a size suitable for gamma knife treatment or totally occluded by embolization alone. The total complication rate was high, but the combined rate of death and complications affecting lifestyle was 8.0%, equal to approximately 3.2 years of natural history.

Adolescent↗
PubMed1996

Embolization of cerebral arteriovenous malformations: Part II--Aspects of complications and late outcome.

OBJECTIVE: From 1987 through 1993, we performed embolizations on 150 patients with cerebral arteriovenous malformations (AVMs) at Sahlgrenska University Hospital. The patients ranged in age from 5 to 70 years (35.5 +/- 14.8 yr, mean +/- standard deviation) and were selected by neurosurgeons in Scandinavia. We analyzed the risk of complications and late outcome to have a better basis for the decision to perform embolization. METHODS: The follow-up was a personal clinical examination of all surviving patients by a neurologist. Files for all patients were also studied. RESULTS: In 34 patients, the AVMs were eliminated by embolization alone (20 patients) or by supplementary surgery (14 patients). In 66 patients, the AVMs were embolized to a size suitable for supplementary stereotactic radiation. The clinical course was stable for those 100 patients. Another group of 50 patients who had undergone embolization was only partially treated, and as a group, those patients had less favorable outcomes. The manifestations or symptoms leading to diagnosis were in concordance with other studies. Headache and epilepsy showed a positive response to treatment in patients whose AVMs had been eliminated as well as in those who received only partial treatment. A history of cerebral bleeding did not influence the prognosis of recurrent bleeding. Conversely, AVMs with feeder or nidus aneurysms were related to an increased risk of bleeding. If there was a history of bleeding in a patient with large, partially treated AVMs, the prognosis for survival was diminished. CONCLUSION: The indication for treatment increases with the occurrence of AVMs with associated aneurysms. For patients with large AVMs, a history of bleeding justifies a more aggressive approach to treatment. The reduced risk of complications during the last years of the study also increases the indication for embolization.

Adolescent↗
PubMed1996

Acid-base status and cardiovascular function in mink (Mustela vison) anaesthetized with ketamine/midazolam.

Heart rate, arterial blood pressure and blood acid-base status were determined in 18 adult female mink (mean (+/- SEM) body weight 1052 +/- 34 g) during long-term anaesthesia with either controlled ventilation (n=12) or spontaneous respiration (n=6). Surgical anaesthesia was induced by intramuscular injection of ketamine hydrochloride (Ketaminol Vet, 40.0 +/- 1.7 mg/kg) and midazolam hydrochloride (Dormicum 2.8 +/- 0.1 mg/kg) and maintained for at least 5 h by continuous intravenous infusion of this drug combination in 0.9% saline. For all animals, the mean rates of infusion of ketamine and midazolam were 48.4 +/- 1.6 and 1.61 +/- 0.12 mg/h, respectively. Following continuous infusion of the anaesthetics in isotonic saline, at a rate of 20 ml/h, a moderate 'dilution acidosis' developed, which could be corrected by replacement of part of the saline with sodium bicarbonate to a final concentration of approximately 25 mmol NaHCO3 per litre. However, when the animals were allowed to breathe spontaneously, an increase in heart rate and a combined respiratory and metabolic acidosis occurred, due to severe respiratory depression. Apart from these effects and a few cases of increased salivation, no adverse effects over time were observed on the arterial blood acid-base status and cardiovascular function of the animals during ketamine/midazolam anaesthesia. It is concluded that the procedure described for long-term anaesthesia in mink is convenient and safe for acute physiological experiments in this species, provided normal body temperature and pulmonary gas exchange is sufficiently maintained. Thus, the need for an adequately controlled artificial ventilation is strongly emphasized. Finally, a proposal for the composition of an intravenous solution, containing ketamine and midazolam hydrochloride, and sodium bicarbonate in saline, suitable for long-term anaesthesia in adult mink is presented.

Acid-Base Equilibrium↗
PubMed1996

Regional adrenal blood flow responses to adrenocorticotropic hormone after chronic embolization of the fetal placental circulation in sheep.

To ascertain whether repeated hypoxic stress would alter the response of the adrenal cortex to adrenocorticotropic hormone (ACTH), by premature activation of the hypothalamic-pituitary-adrenal axis, we studied fetal sheep subjected to daily reduction of arterial oxygen content by embolization of the fetal placental circulation with 15 microns microspheres for 8 days from about day 124 of gestation (term approximately 147 days) and sham-embolized controls. Starting before the final embolization (or sham-embolization) on day 8, and continuing for 24 h, the fetus was given an intravenous infusion of ACTH1-24 (0.5 microgram/h) or vehicle. Fetal and maternal blood samples were taken for determination of immunoreactive cortisol, and regional adrenal and fetal placental blood flows were measured by the microsphere technique at three time points: 1 h before infusion, 3 h after the start of the infusion (1 h after embolization), and after 24 h of infusion. Prior to infusion of ACTH or vehicle, fetal placental blood flow was lower in microsphere-embolized fetuses than in sham-embolized controls (199 +/ 15 vs 292 +/- 25 ml/min per 100 g tissue; mean +/- S.E.; P<0.01). However, plasma cortisol and adrenal cortical blood flow did not differ between embolized fetuses and controls. Adrenal vascular responses to the 24-h infusion of ACTH were similar in embolized and sham-embolized fetuses. Adrenal cortical blood flow increased 3-fold (P<0.05) due to decreased vascular resistance (P<0.01), with no change in adrenal medullary blood flow. Thus, while daily embolization of the fetal placental circulation caused a sustained decrease in cotyledonary blood flow, no evidence of altered responsiveness of the adrenal cortex to ACTH was found in these experiments.

Adrenal Glands↗
PubMed1996

Importance of gastrin-releasing peptide on acid-induced secretin release and pancreaticobiliary and duodenal bicarbonate secretion.

BACKGROUND: Exogenous gastrin-releasing peptide (GRP) stimulates the release of secretin from the small intestine and pancreaticobiliary bicarbonate secretion in pigs. As acid is the principal stimulant of secretin release, the purpose of this study was to examine the importance of GRP in acid-induced secretin release and to determine whether GRP contributes to the regulatory function of acid-induced pancreaticobiliary bicarbonate secretion in anaesthetized pigs. METHODS AND RESULTS: Intravenous infusion of GRP (500 pmol/kg.h) increased significantly portal vein plasma concentrations of secretin from 1.3 to 5.4 pmol/l and GRP from 0.5 to 340 pmol/l, pancreatic bicarbonate secretion from 0.01 to 5.9 mmol/h, and hepatic bicarbonate secretion from 0.3 to 3.3 mmol/h, whereas duodenal mucosal bicarbonate secretion remained unchanged. Intravenous infusion of the GRP antagonist BIM-26226 completely abolished the GRP-induced secretin release and pancreatic and hepatic bicarbonate secretion. Furthermore, repeated infusions of GRP did not cause desensitization, and BIM-26226 therefore proved to be an effective GRP antagonist. Duodenal perfusion with acid (pH 1.5, 3.8 mmol/h) significantly increased portal vein plasma concentrations of secretin from 0.4 to 2.8 pmol/l, pancreatic bicarbonate secretion from 0.005 mmol/h to 0.19 mmol/h, hepatic bicarbonate secretion from 0.63 to 2.17 mmol/h, and duodenal mucosal bicarbonate secretion from 0.1 to 1.20 mmol/h. Of importance, infusion of BIM-26226 did not significantly alter the effect of intraduodenal acidification on plasma secretin release and pancreaticobiliary and duodenal bicarbonate secretion. CONCLUSIONS: Thus, we conclude that GRP likely plays an insignificant role in a possible peptidergic regulation of acid-induced intestinal secretin release and that GRP has no regulatory function in acid-induced pancreaticobiliary bicarbonate secretion. Furthermore, GRP has no effect on duodenal bicarbonate secretion.

Animals↗
PubMed1995

Shear stress in cerebral arteries supplying arteriovenous malformations.

Arteries supplying cerebral arteriovenous malformations (AVMs) are known to dilate with time. These changes are reversible, and the feeders have been shown to slowly decrease in calibre after removal of the AMV. There is evidence that arteries alter their internal diameters in response to sustained changes of blood flow so that shear stress is kept constant. This implies that blood flow-induced shear stress might be the driving force for remodelling of the cerebral vascular network in the presence of an AVM, and for reversion of these changes after radical operation. The objective of this study is to examine the hypothesis that the shear stress in cerebral arteries supplying AMVs is of the same magnitude as in arteries supplying normal brain tissue in spite of larger blood flow rate. Fifteen patients with supratentorial cerebral AVMs admitted for endovascular treatment were examined with transcranial Doppler ultrasound in the distal Willisian vessels. Vessel calibres were measured in angiograms with magnification correction. Shear stress was estimated assuming a constant value for blood viscosity. Corresponding arteries in the cerebral hemisphere with AVM and in the contralateral one were compared in pairs. Thirty-four pairs of homonymous arteries were studied. The arteries on the AVM side presented larger calibres, higher axial blood flow velocities, lower pulsatility index and larger blood flow rates than the contralateral side. There was a clear positive correlation between blood flow velocities and vessel calibres. The estimates of shear stress did not differ significantly in corresponding arteries of both hemispheres (p = 0.18). The results indicate a precise adjustment of cerebral arterial calibre and blood flow-induced shear stress that presumably induces the progressive dilation of AVM feeders, and the slow regression of the vessel calibres to average dimensions after removal of the lesion. Each vessel seems to remodel itself in response to long-term changes in blood flow rate so that the vessel calibre is reshaped to maintain a constant level of wall shear stress.

Adolescent↗
PubMed1995

Effect of arginine vasopressin on regional adrenal blood flow and plasma cortisol concentration in fetal sheep.

OBJECTIVE: To determine whether arginine vasopressin (AVP) at plasma concentrations measured during moderate hypoxemia affects adrenal blood flow. STUDY DESIGN: Regional blood flows were measured in 5 unanesthetized normoxemic fetuses (124-128 days' gestation) during a 24-h intravenous infusion of AVP in isotonic saline solution. Another 5 fetuses received an infusion of vehicle. Blood flows were determined before the infusion and at 2 h and 24 h from its onset using radionuclide-labeled microspheres. RESULTS: At 2 h and 24 h of AVP infusion, fetal plasma concentrations of IR-AVP had risen from 4.7 +/- 0.9 pg/ml to 9.8 +/- 1.1 pg/l and 9.4 +/- 0.7 pg/ml, respectively. Thus we achieved plasma concentrations of IR-AVP comparable to those previously reported during moderate hypoxemia. There was no significant effect of treatment on fetal plasma concentrations of immunoreactive adrenocorticotropic hormone (ACTH) or cortisol. AVP infusion significantly decreased fetal heart rate and raised cotyledonary blood flow from 198 +/- 18 ml/min per 100 g to 235 +/- 17 ml/min and 218 +/- 10 ml/min per 100 g at 2 h and 24 h, respectively, from the start of the AVP infusion. Basal values for adrenal medullary and cortical blood flows were similar in the AVP and saline groups, and did not change significantly during the infusions. CONCLUSION: These findings suggest that the rise in adrenal blood flow seen after hypoxemia is not due to a direct action of systemic AVP, but is attributable to other influences, likely including changes in circulating ACTH.

Adrenal Glands↗
PubMed1995

Transarterial embolization of cerebral arteriovenous malformations: improvement of results with experience.

PURPOSE: To present the treatment outcome after embolization of arteriovenous malformations. METHODS: All patients with cerebral arteriovenous malformations treated in 1987 and 1988 (27 patients, group I) and in 1992 and 1993 (35 patients, group II) were compared regarding treatment results and clinical outcome. RESULTS: Complications of the treatment occurred in 52% of group I and 22% of group II patients. Severe complications occurred in 11 % and 0%, respectively. There were no treatment deaths. Thirty percent of the arteriovenous malformations in the first group were totally occluded or made accessible for gamma knife treatment, compared with 69% of the arteriovenous malformations in the second group. The clinical outcome improved from 56% with an excellent or good outcome in group I, to 89% in group II. The follow-up time is much shorter in group II, 1.5 versus 5.5 years in group I. CONCLUSION: A definite improvement in treatment outcome has been achieved. The clinical outcome seems to have improved as well, although the shorter follow-up time makes this conclusion less certain.

Adolescent↗