| 1. |
- Bodelsson, Gunilla, et al.
(författare)
-
Effects of propofol on substance P-induced relaxation in isolated human omental arteries and veins
- 2000
-
Ingår i: European Journal of Anaesthesiology. - 1365-2346. ; 17:12, s. 720-728
-
Tidskriftsartikel (refereegranskat)abstract
- To elucidate if an effect of propofol on endothelium-dependent relaxation could contribute to propofol-induced vasodilation, smooth muscle relaxation of isolated human omental artery and vein segments precontracted by endothelin-1 were measured. Substance P induced a concentration-dependent relaxation (mean +/- SEM) in both artery (63 +/-8.4% of precontraction, n = 9) and vein (60+/-11%, n = 7). The relaxation was enhanced by 10(-6) M propofol (artery, 72+/-9.5%, n = 9; vein, 81+/-12%, n = 7) but not affected by 10(-7), 10(-5) and 10(-4) M propofol. In the presence of Nomega-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), 10(-6) M propofol still enhanced the substance P-induced relaxation in arteries but not veins, whereas 10(-4) M propofol inhibited the relaxation in both arteries (rightward shift of the concentration-response curve) and veins (28+/-7.5%, n = 8). In the presence of potassium chloride (to prevent hyperpolarization), the enhancement of substance P-induced relaxation by 10(-6) M propofol was abolished in both arteries and veins whereas 10(-5) and 10(-4) M propofol reduced the relaxation in arteries (38+/-13% at 10(-5) M, n = 6; 30+/-11% at 10(-4) M, n = 6) but not in veins. These results demonstrate that propofol, at lower, clinically relevant concentrations, promotes endothelium-dependent relaxation mediated via hyperpolarization in human omental arteries and via both nitric oxide and hyperpolarization in human omental veins.
|
|
| 2. |
- Karlsson, Caroline, et al.
(författare)
-
5-Hydroxytryptamine contracts human uterine artery smooth muscle predominantly via 5-HT2 receptors
- 1997
-
Ingår i: Human Reproduction. - 0268-1161. ; 12:2, s. 361-367
-
Tidskriftsartikel (refereegranskat)abstract
- Serotonergic receptors were classified in the isolated human uterine artery with intact endothelium, using agonists and antagonists for 5-hydroxytryptamine (5-HT) receptors. The efficacy for different agonists rated: alpha-methyl-5-HT (5-HT2) = 5-HT (non-selective) = 2-methyl-5-HT (5-HT3) >> sumatriptan (5-HT1), and the potency as: sumatriptan = 5-HT > 5-HT > alpha-methyl-5-HT > 2-methyl-5-HT. The contractile effects of 5-HT and alpha-methyl-5-HT were antagonized by the 5-HT2 receptor antagonist ketanserin and the non-selective antagonist methiothepin. The efficacy of sumatriptan was comparatively low. No interaction was encountered between 2-methyl-5-HT and MDL72222, suggesting an absence of 5-HT3 receptors. The results indicate that the contractile serotonergic receptor population in the human uterine artery mainly comprises 5-HT2 receptors, although a minor contribution of contractile 5-HT1 receptors cannot be excluded.
|
|
| 3. |
- Karlsson, Caroline, et al.
(författare)
-
Characterization of 5-hydroxytryptamine receptors mediating circular smooth muscle contraction in the human umbilical artery
- 1999
-
Ingår i: Gynecologic and Obstetric Investigation. - : S. Karger AG. - 1423-002X .- 0378-7346. ; 47:2, s. 102-107
-
Tidskriftsartikel (refereegranskat)abstract
- The study was performed to characterize pharmacologically the contractile 5-hydroxytryptamine (5-HT) receptors in the circular smooth muscle of the isolated human umbilical artery. Effects of agonists and antagonists for different 5-HT receptor subtypes were studied in intact endothelium vessel segments. All agonists induced concentration-dependent circular smooth muscle contractions. The potency was in declining order 5-HT > alpha-methyl-5-HT > sumatriptan >/= 2-methyl-5-HT. The effects of 5-HT and alpha-methyl-5-HT were antagonized by ketanserin, as well as methiothepin. The contractile effect of sumatriptan was antagonized by methiothepin but not by ketanserin. The 5-HT3 receptor antagonist, MDL 72222, did not affect the contraction by any of the agonists, including 2-methyl-5-HT. It is concluded that the 5-HT-induced contraction in the circular smooth muscle of the human umbilical artery seems to be mediated by a mixed population of 5-HT1-like receptors and 5-HT2 receptors.
|
|
| 4. |
- Karlsson, C, et al.
(författare)
-
Endothelium-derived prostanoids reduce 5-hydroxytryptamine-induced contraction in the human uterine artery
- 1998
-
Ingår i: Human Reproduction. - 0268-1161. ; 13:7, s. 1947-1951
-
Tidskriftsartikel (refereegranskat)abstract
- The contribution of endothelium-linked mechanisms to the contraction induced by 5-hydroxytryptamine (5-HT) was investigated in the isolated human uterine artery. 5-HT contracted the uterine artery concentration-dependently. Removal of the endothelium or treatment with the cyclooxygenase inhibitor indomethacin potentiated the contractile response to 5-HT. The nitric oxide synthase inhibitor L-N(G)-monomethyl-arginine (L-NMMA) did not influence the contraction induced by 5-HT. Indomethacin did not affect the response to 5-HT in endothelium-denuded vessels. The 5-HT1 receptor agonist 5-carboxyamidotryptamine (5-CT) did not relax precontracted arteries. Removal of the endothelium did not change the response to 5-HT in the presence of the 5-HT(1B/D) receptor antagonist GR127935 and the 5-HT1A and 5-HT1B receptor antagonist -pindolol. The 5-HT1B receptor antagonist SB224289 did not affect the contraction induced by 5-HT. The results indicate that the 5-HT-induced contraction in the human uterine artery is accompanied by the release of an endothelium-derived relaxing factor (EDRF). This EDRF seems to be a prostanoid, probably prostacyclin (PGI2). The endothelium-linked mechanism seems to be mediated via a 5-HT1 receptor, but it is not possible to further classify the receptor subtype by the information obtained in this study.
|
|
| 5. |
- Berkestedt, Ingrid, et al.
(författare)
-
Early depletion of contact system in patients with sepsis : a prospective matched control observational study
- 2018
-
Ingår i: APMIS. - : Wiley. - 0903-4641 .- 1600-0463. ; , s. 892-898
-
Tidskriftsartikel (refereegranskat)abstract
- Activation of the contact system generates bradykinin from high-molecular-weight kininogen and has been suggested to participate in the pathophysiology of sepsis. To test this, we prospectively measured bradykinin and high-molecular-weight kininogen levels in a cohort of sepsis patients requiring intensive care. From 29 patients meeting criteria for sepsis or septic shock according to Sepsis-3, blood was sampled within 24 h and on the fourth day following admittance to intensive care. Patients planned for neurosurgery served as matched controls. Sequential organ failure assessment score and 90-day mortality was registered. Bradykinin levels (median [interquartile range]) were lower in sepsis patients (79 [62–172] pg/ml) compared to controls (130 [86–255] pg/ml, p < 0.025) and did not correlate with mortality or severity of circulatory derangement. High-molecular-weight kininogen levels were lower in sepsis patients (1.6 [0.8–4.8] densitometry units) compared to controls (4.4 [2.9–7.7] densitometry units, p < 0.001), suggesting previous contact system activation. High-molecular-weight kininogen levels were lower in non-survivors than survivors (p = 0.003) and negatively correlated to severity of circulatory derangement. We conclude that a role for bradykinin in later stages of severe sepsis must be challenged. Low high-molecular-weight kininogen concentrations suggest that the decrease in bradykinin is due to substrate depletion.
|
|
| 6. |
- Berkestedt, Ingrid, et al.
(författare)
-
Elevated Plasma Levels of Antimicrobial Polypeptides in Patients with Severe Sepsis.
- 2010
-
Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 2:5, s. 478-482
-
Tidskriftsartikel (refereegranskat)abstract
- We wanted to investigate if plasma levels of antimicrobial polypeptides (AMPs) are increased in severe sepsis and if they correlate with severity and mortality. Samples were collected from 31 sepsis patients at the intensive care unit. The Sequential Organ Failure Assessment (SOFA) score and 90-day mortality were registered, and inflammatory markers and AMP levels were measured by ELISA. A median SOFA score (13) and cardiovascular SOFA score (3) indicated multiorgan failure with severe circulatory derangement, and elevated cytokine levels indicated inflammatory activation. Levels of bactericidal/permeability-increasing protein, heparin-binding protein, alpha-defensins and lactoferrin but not LL-37 were elevated in sepsis patients compared with controls. Bactericidal/permeability-increasing protein levels correlated with mortality, with lower levels in survivors. Levels of all AMPs, except LL-37, positively correlated with the cardiovascular SOFA score. In conclusion, levels of several AMPs are increased in sepsis and correlate with circulatory derangement. This probably reflects neutrophil activation as part of an innate immune response.
|
|
| 7. |
- Berkestedt, Ingrid, et al.
(författare)
-
Endogenous antimicrobial peptide LL-37 induces human vasodilatation.
- 2008
-
Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 1471-6771 .- 0007-0912. ; 100, s. 803-809
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: /st> Septic shock includes blood vessel dilatation and activation of innate immunity, which in turn causes release of antimicrobial peptides such as LL-37. It has been shown that LL-37 can attract leucocytes via the lipoxin A(4) receptor (ALX, FPRL1). ALX is also present in vascular endothelial cells. To explore possible ways of pharmacological intervention in septic shock, we investigated if LL-37 can affect vascular tone. METHODS: /st> Human omental arteries and veins were obtained during abdominal surgery, and circular smooth muscle activity was studied in organ baths. Gene expression was studied using reverse transcriptase-polymerase chain reaction. RESULTS: /st> LL-37, at micromolar concentrations, induced a concentration- and endothelium-dependent relaxation in vein but not in artery segments precontracted by endothelin-1. The relaxation was profoundly reduced by potassium chloride (30 mM) to inhibit endothelium-derived hyperpolarizing factor (EDHF), whereas it was less affected by the NOS inhibitor, l-N(G)-nitroarginine methyl ester, and not at all by indomethacin. The ALX agonist, WKYMVm, also induced a relaxation and both the relaxations induced by LL-37 and WKYMVm were inhibited by the ALX antagonist, WRWWWW. ALX was expressed in the vein endothelium. CONCLUSIONS: /st> We demonstrate, for the first time, that the human antimicrobial peptide, LL-37, induces endothelium-dependent relaxation in human omental veins mediated via an effect on endothelial ALX. The relaxation involves the release of nitric oxide and EDHF but not prostanoids. LL-37 released from white blood cells could contribute to blood vessel dilatation during sepsis and treatment with ALX antagonists might be successful.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Bjurstrom, M. F., et al.
(författare)
-
Acute reduction of cerebrospinal fluid volume prior to spinal anesthesia : implications for sensory block extent
- 2020
-
Ingår i: Minerva Anestesiol. - 1827-1596. ; 86:6, s. 636-644
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Multiple patient and clinical characteristics contribute to the variable outcome of spinal anesthesia (SPA). Acute reduction of cerebrospinal fluid (CSF) volume may alter the effect of SPA. The objective of the present study was to test if aspiration of 10 mL CSF immediately prior to SPA is associated with higher extent of sensory block. METHODS: Interventional cohort study. One hundred and two patients undergoing total hip arthroplasty (THA) were included. Fifty-one patients underwent sampling of 10 mL CSF prior to SPA (CSF aspiration group); 51 consecutive patients were used as controls. The primary outcome was the extent of sensory block to cold stimulus 20 minutes after injection of hyperbaric bupivacaine. Secondary outcome measures included duration of motor block and incidence of failed SPA. RESULTS: Acute reduction of CSF volume by 10 mL increased the extent of sensory anesthesia (mean thoracic level [T] 4.3+/-2.4 vs. 7.1+/-2.6, P<0.001). There were no significant between-group differences regarding motor block duration (P>/=0.30) or failed SPA (three of 51 [CSF aspiration group] vs. one of 51 [control group], P=0.31). In a retrospective data analysis, 10 of 13 patients in the CSF aspiration group who had previously received SPA had a higher sensory block after 10 mL CSF aspiration compared to the previous SPA (T4.1 [range, 0-11] vs. T8.2 [4-10], P<0.01). CONCLUSIONS: Acute reduction of CSF volume by 10 mL prior to SPA leads to a higher thoracic level of sensory block.
|
|
