| 1. |
- Ericsson, Peter, et al.
(författare)
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Gastrin release: Antrum microdialysis reveals a complex neural control.
- 2010
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 161, s. 22-32
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Tidskriftsartikel (refereegranskat)abstract
- We used microdialysis to monitor local gastrin release in response to food, acid blockade and acute vagal excitation. For the first time, gastrin release has been monitored continuously in intact conscious rats in a physiologically relevant experimental setting in a fashion that minimizes confounding systemic effects. Microdialysis probes were placed in the submucosa on either side of the antrum, 3days before the experiments. The concentration of gastrin in the antral submucosal compartment was 5-10 times higher than in serum regardless of the prandial state. The rats were conscious during microdialysis except when subjected to electrical vagal stimulation. Acid blockade (omeprazole treatment of freely fed rats for 4days), or bilateral sectioning of the abdominal vagal trunks (fasted rats), raised the gastrin concentration in blood as well as microdialysate. The high gastrin concentration following omeprazole treatment was not affected by vagotomy. Vagal excitation stimulated the G cells: electrical vagal stimulation and pylorus ligation (fasted rats) raised the gastrin concentration transiently in both serum and microdialysate. Food intake induced a 2- to 3-fold increase in serum gastrin, while gastrin in antral microdialysate increased 10- to 15-fold. In unilaterally vagotomized rats, food evoked a prompt peak gastrin release followed by a gradual decline on the intact side. On the vagotomized side of the antrum, the peak response seemed to be reduced while the microdialysate gastrin concentration remained elevated. Thus, unilateral vagotomy surprisingly raised the integrated gastrin response to food on the denervated side compared to the intact side, indicating that vagotomy suppresses an inhibitory as well as a stimulating effect on the G cells. While local infusion of atropine was without effect, infusion of the neuronal blocker tetrodotoxin (TTX) (which had no effect on basal gastrin) virtually abolished the food-evoked gastrin response and lowered the high microdialysate gastrin concentration in omeprazole-treated rats by 65%. We conclude that activated gastrin release, unlike basal gastrin release, is highly dependent on a neural input: 1) Vagal excitation has a transient stimulating effect on the G cells. The transient nature of the response suggests that the vagus has not only a prompt stimulatory but also a slow inhibitory effect on gastrin release. 2) Although vagal denervation did not affect the gastrin response to anacidity, the TTX experiments revealed that both food-evoked and anacidity-evoked gastrin release depends on neural input.
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| 2. |
- Ericsson, Peter, et al.
(författare)
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Gastrin response to candidate messengers in intact conscious rats monitored by antrum microdialysis.
- 2010
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 163, s. 24-30
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Tidskriftsartikel (refereegranskat)abstract
- We monitored gastrin release in response to locally applied candidate messengers in intact conscious rats. Earlier studies have been performed on anaesthetized animals, isolated pieces of antrum, or purified preparations of gastrin cells. In this study we created an experimental situation to resemble physiological conditions, using reverse microdialysis to administer regulatory peptides and amines that might affect gastrin secretion. Microdialysis probes were implanted in the submucosa of the antrum of the rat stomach. Three days later, putative messenger compounds were administered via the probe. Their effects on basal (24h fast) and omeprazole-stimulated (400mumol/kg/day, 4days peroral administration) gastrin release were monitored by continuous measurement (3h) of gastrin in the perfusate (radioimmunoassay). Fasted rats (low microdialysate gastrin, 2.1+/-0.1pmoll(-1)) were used to study stimulation of gastrin release. Omeprazole-treated rats (high microdialysate gastrin, 95.8+/-6.7pmoll(-1)) were used to study suppression of gastrin release. The following agents raised the concentration of microdialysate gastrin (peak response): gastrin-releasing peptide (GRP) (11-fold increase at a near-maximal dose), carbachol (5-fold increase), serotonin (2-fold increase) and isoprenaline (20-fold increase). Adrenaline and noradrenaline induced transient but powerful elevation (40- and 20-fold increase). Somatostatin, galanin and bradykinin (at near-maximal doses) suppressed omeprazole-stimulated gastrin release (50% decrease). Calcitonin gene-related peptide, ghrelin, gastric inhibitory peptide, motilin, neurotensin, neuromedin U-25, peptide YY and vasoactive intestinal peptide were without effect on gastrin release, as were aspartate, gamma-aminobutyric acid, glutamate, glycine, dopamine and histamine. The results support the view that G cells operate under neurocrine/paracrine control. They were stimulated by agents present in enteric neurons (GRP, galanin, choline ester and catechol amines) and in gastric endocrine cells (serotonin). They were inhibited by somatostatin (D cell peptide), galanin (neuropeptide) and by the inflammatory agent bradykinin.
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| 3. |
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| 4. |
- Holm, Jonas, et al.
(författare)
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EuroSCORE II and N-terminal pro-B-type natriuretic peptide for risk evaluation : an observational longitudinal study in patients undergoing coronary artery bypass graft surgery
- 2014
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Ingår i: British Journal of Anaesthesia. - : Oxford University Press. - 0007-0912 .- 1471-6771. ; 113:1, s. 75-82
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Tidskriftsartikel (refereegranskat)abstract
- Background: Postoperative heart failure remains the major cause of death after cardiac surgery. As N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a predictor for postoperative heart failure, the aim was to evaluate if preoperative NT-proBNP could provide additional prognostic information to the recently launched EuroSCORE II.Methods: A total of 365 patients with acute coronary syndrome (ACS) undergoing isolated coronary artery bypass graft (CABG) surgery were studied prospectively. Preoperative NT-proBNP and EuroSCORE II were evaluated with regard to severe circulatory failure after operation according to prespecified criteria. To assess what clinical outcomes are indicated by NT-proBNP levels in different risk categories, the patients were stratified according to EuroSCORE II. Based on receiver operating characteristics analysis, these cohorts were assessed with regard to preoperative NT-proBNP below or above 1028 ng litre(-1). The follow-up time averaged 4.4 (0.7) yr.Results: Preoperative NT-proBNP >= 1028 ng litre(-1) [odds ratio (OR) 9.9,95% confidence interval (CI) 1.01-98.9; P=0.049] and EuroSCORE II (OR 1.24, 95% CI 1.06-1.46; P=0.008) independently predicted severe circulatory failure after operation. In intermediate-risk patients (EuroSCORE II 2.0-10.0), NT-proBNP >= 1028 ng litre(-1) was associated with a higher incidence of severe circulatory failure (6.6% vs 0%; P=0.007), renal failure (14.8% vs 5.4%; P=0.03), stroke (6.6% vs 0.7%; P=0.03), longer intensive care unit stay [37 (35) vs 27 (38) h; P=0.002], and worse long-term survival.Conclusions: Combining EuroSCORE II and preoperative NT-proBNP appears to improve risk prediction with regard to severe circulatory failure after isolated CABG for ACS. NT-proBNP may be particularly useful in patients at intermediate risk according to EuroSCORE II.
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| 5. |
- Holm, Jonas, 1971-
(författare)
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Markers of hemodynamic state and heart failure as predictors for outcome in cardiac surgery : with special reference to mixed venous oxygen saturation and natriuretic peptides
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Postoperative heart failure or low cardiac output syndrome is the major cause for morbidity and mortality in cardiac surgery. Unfortunately commonly used methods to assess hemodynamic state and heart failure are not well documented with regard to outcome. The aim for this dissertation was to study the predictive values of postoperative Mixed Venous Oxygen saturation (SvO2) and preoperative NT-proBNP for outcomes related to postoperative heart failure.SvO2 was studied retrospectively in two cohorts of patients, one cohort operated with isolated Aortic Valve Replacement (AVR) for aortic stenosis, (n=396) and one operated with isolated Coronary Artery Bypass Grafting (CABG), (n=2755). SvO2 measured early after surgery, on admission to the intensive care unit (ICU), predicted postoperative morbidity and mortality. Our results suggest that, on admission to ICU SvO2 < 55 - 60% after AVR and SvO2 < 60% after CABG merits increased attention.Preoperative NT-proBNP was studied in a cohort of patients with acute coronary syndrome (ACS) undergoing CABG with or without concomitant procedure. These patients (n=383) were included prospectively and evaluated with regard to mortality and severe circulatory failure postoperatively by an end-points committee blinded to NT-proBNP results. Preoperative NT-proBNP ≥ 1028 ng/L independently predicted increased risk for severe circulatory failure postoperatively in patients with ACS undergoing isolated CABG. Preoperative NT-proBNP provided additional prognostic information to EuroSCORE II in this cohort, particularly in patients at intermediate risk. Preoperative NT-proBNP appears to be markedly higher in patients having CABG with concomitant procedures than in patients undergoing isolated CABG. Further studies are warranted to identify preoperative NTproBNP risk thresholds for different heart conditions and surgery-specific cohorts.In conclusion this dissertation shows that:Postoperative SvO2 on admission to ICU is a prognostic marker for morbidity and mortality after AVR and CABG.Preoperative NT-proBNP ≥ 1028 ng/L independently predicts severe circulatory failure postoperatively in patients undergoing isolated CABG and provides additional prognostic information to EuroSCORE II.The high negative predictive value of the identified cutoff levels for preoperative NTproBNP and postoperative SvO2 could be useful for pre and postoperative decisionmaking.
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| 6. |
- Holm, Jonas, et al.
(författare)
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Mixed venous oxygen saturation is a prognostic marker after surgery for aortic stenosis
- 2010
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Ingår i: ACTA ANAESTHESIOLOGICA SCANDINAVICA. - : Blackwell Publishing Ltd. - 0001-5172 .- 1399-6576. ; 54:5, s. 589-595
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Tidskriftsartikel (refereegranskat)abstract
- Background Adequate monitoring of the hemodynamic state is essential after cardiac surgery and is vital for medical decision making, particularly concerning hemodynamic management. Unfortunately, commonly used methods to assess the hemodynamic state are not well documented with regard to outcome. Mixed venous oxygen saturation (SvO(2)) was therefore investigated after cardiac surgery. Methods Detailed data regarding mortality were available on all patients undergoing aortic valve replacement for isolated aortic stenosis during a 5-year period in the southeast region of Sweden (n=396). SvO(2) was routinely measured on admission to the intensive care unit (ICU) and registered in a database. A receiver operating characteristics (ROC) analysis of SvO(2) in relation to post-operative mortality related to cardiac failure and all-cause mortality within 30 days was performed. Results The area under the curve (AUC) was 0.97 (95% CI 0.96-1.00) for mortality related to cardiac failure (P=0.001) and 0.76 (95% CI 0.53-0.99) for all-cause mortality (P=0.011). The best cutoff for mortality related to cardiac failure was SvO(2) 53.7%, with a sensitivity of 1.00 and a specificity of 0.94. The negative predictive value was 100%. The best cutoff for all-cause mortality was SvO(2) 58.1%, with a sensitivity of 0.75 and a specificity of 0.84. The negative predictive value was 99.4%. Post-operative morbidity was also markedly increased in patients with a low SvO(2). Conclusion SvO(2), on admission to the ICU after surgery for aortic stenosis, demonstrated excellent sensitivity and specificity for post-operative mortality related to cardiac failure and a fairly good AUC for all-cause mortality, with an excellent negative predictive value.
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| 7. |
- Holm, Jonas, et al.
(författare)
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Mixed venous oxygen saturation predicts short- and long-term outcome after coronary artery bypass grafting surgery: a retrospective cohort analysis
- 2011
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Ingår i: British Journal of Anaesthesia. - : Oxford University Press (OUP). - 0007-0912 .- 1471-6771. ; 107:3, s. 344-350
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Tidskriftsartikel (refereegranskat)abstract
- Background. Complications of an inadequate haemodynamic state are a leading cause of morbidity and mortality after cardiac surgery. Unfortunately, commonly used methods to assess haemodynamic status are not well documented with respect to outcome. The aim of this study was to investigate SV(O2) as a prognostic marker for short-and long-term outcome in a large unselected coronary artery bypass grafting (CABG) cohort and in subgroups with or without treatment for intraoperative heart failure. less thanbrgreater than less thanbrgreater thanMethods. Two thousand seven hundred and fifty-five consecutive CABG patients and subgroups comprising 344 patients with and 2411 patients without intraoperative heart failure, respectively, were investigated. SV(O2) was routinely measured on admission to the intensive care unit (ICU). The mean (SD) follow-up was 10.2 (1.5) yr. less thanbrgreater than less thanbrgreater thanResults. The best cut-off for 30 day mortality related to heart failure based on receiver-operating characteristic analysis was SV(O2) 60.1%. Patients with SV(O2) andlt;60% had higher 30 day mortality (5.4% vs 1.0%; P andlt; 0.0001) and lower 5 yr survival (81.4% vs 90.5%; P andlt; 0.0001). The incidences of perioperative myocardial infarction, renal failure, and stroke were also significantly higher, leading to a longer ICU stay. Similar prognostic information was obtained in the subgroups that were admitted to ICU with or without treatment for intraoperative heart failure. In patients admitted to ICU without treatment for intraoperative heart failure and SV(O2) andgt;= 60%, 30 day mortality was 0.5% and 5 yr survival 92.1%. less thanbrgreater than less thanbrgreater thanConclusions. SV(O2) andlt;60% on admission to ICU was related to worse short- and long-term outcome after CABG, regardless of whether the patients were admitted to ICU with or without treatment for intraoperative heart failure.
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| 8. |
- Kumar, Rajesh, et al.
(författare)
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Proghrelin peptides: Desacyl ghrelin is a powerful inhibitor of acylated ghrelin, likely to impair physiological effects of acyl ghrelin but not of obestatin A study of pancreatic polypeptide secretion from mouse islets.
- 2010
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 164, s. 65-70
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Proghrelin, produced by the ghrelin (A-like) cells of the gastric mucosa, gives rise to cleavage products, including desacyl ghrelin, acyl ghrelin and obestatin. The products are thought to be secreted concomitantly. In an earlier study we found acyl ghrelin and obestatin, but not desacyl ghrelin, to suppress the release of hormones from isolated islets of mouse and rat pancreas. RESULTS: Using isolated mouse pancreatic islets to study the suppression of the spontaneous secretion of pancreatic polypeptide (PP) by acyl ghrelin and obestatin, we determined the EC(50) values for the two peptides. For acyl ghrelin it was 2x10(-13)M (ranging from 1.7 to 2.8x10(-13)M), for obestatin it was 10(-13)M (ranging from 0.3 to 1.1x10(-13)M). The Hill coefficient (i.e. the midpoint slope) for the acyl ghrelin dose-response curve was 0.30 (ranging from 0.21 to 0.35); the corresponding value for obestatin was 0.35 (ranging from 0.21 to 0.35). The PP-releasing effect of acyl ghrelin, but not that of obestatin, was counteracted by desacyl ghrelin. The acyl ghrelin dose-response curve was shifted to the right in a parallel manner by increasing concentrations of desacyl ghrelin. A Schild plot was constructed with a slope of 0.78, giving an apparent pA(2) value of 14. CONCLUSIONS: The results favour the view that acyl ghrelin and obestatin suppress spontaneous PP secretion at physiologically relevant concentrations and that they act on separate receptors. However, we conclude also that desacyl ghrelin acts as a competitive, surmountable (and quite potent) inhibitor of acyl ghrelin. In view of the allegedly high circulating concentrations of desacyl ghrelin it is to be expected that the effect of acyl ghrelin - but not that of obestatin - will be impaired, in fact probably severely blunted by desacyl ghrelin, thereby compromising the functional significance of circulating acyl ghrelin. In addition, we suggest that isolated pancreatic islets are well suited for studies of receptors to acyl ghrelin and obestatin, and that suppression of PP secretion represents a convenient way to measure the effect of both these peptides.
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| 9. |
- Svedjeholm, Rolf, et al.
(författare)
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A metabolic protective strategy could improve long-term survival in patients with LV-dysfunction undergoing CABG
- 2010
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Ingår i: Scandinavian Cardiovascular Journal. - Oslo, Norway : Taylor & Francis. - 1401-7431 .- 1651-2006. ; 44:1, s. 45-58
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Adverse outcome after CABG is closely related to postoperative heart failure precipitated by ischemia and myocardial infarction. Restrictive use of inotropes is therefore desirable. Patients with preoperative left ventricular dysfunction are a high-risk group in this respect. To reduce myocardial oxygen expenditure we evolved a metabolic strategy for perioperative care.Design: Observational study on 104 consecutive patients with severe left ventricular dysfunction undergoing CABG. The metabolic strategy implied physiological measures to minimize myocardial oxygen expenditure including restrictive use of inotropes and specific measures such as extended CPB and metabolic support to facilitate myocardial recovery. Hemodynamic state was primarily assessed by mixed venous oxygen saturation (SvO(2)). Follow-up averaged 9.7 +/- 1.4 years. Results: LVEF was 0.30 +/- 0.05 (range 0.20-0.37) and 3.5 +/- 1.3 vessels were bypassed. Inotropes were used in 6.7% for weaning from CPB. Increase of s-creatinine by >= 50% compared to preoperative values was observed in 2.9%. Logistic EuroSCORE was 8.3% whereas observed 30-day mortality was 1.0%. Crude 5-year survival was 89.4%.Conclusions: The metabolic strategy allowed restrictive use of inotropes and was associated with encouraging long-term survival. Renal function was well preserved suggesting that SvO(2) served as an adequate marker of circulation. Randomized trials with metabolic support are warranted.
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| 10. |
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