| 1. |
- Bondesson, Susanne, et al.
(författare)
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Comparison of patients undergoing enhanced external counterpulsation and spinal cord stimulation for refractory angina pectoris.
- 2008
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Ingår i: Coronary Artery Disease. - 0954-6928. ; 19:8, s. 627-634
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: As more patients survive coronary events, the prevalence of patients with refractory angina pectoris is increasing. The aim was to evaluate the effects of enhanced external counterpulsation (EECP) and spinal cord stimulation (SCS) and compare with optimal medically treated patients with refractory angina. METHODS: 153 patients with refractory angina were treated with either EECP, SCS, or were retained on their pharmacological treatment (control). Glyceryl trinitrate usage and Canadian Cardiovascular Society classification were registered at baseline, 6 and 12 months after therapy. RESULTS: Both EECP and SCS reduced the angina as compared with controls (P<0.001). Patients treated with EECP showed a more effective reduction as compared with SCS patients (P<0.05). Both treatments resulted in significantly decreased glyceryl trinitrate usage at 6 and 12 months follow-up (P<0.001). The nitrate consumed was unaltered in the controls. DISCUSSION: The results from this study show that both EECP and SCS therapy reduce angina in patients with refractory angina pectoris; the response to EECP was slightly more effective than that to SCS. Thus, EECP can be used as an alternative treatment for patients not responding to electrical stimulation. The beneficial effects in the treated groups were maintained during the 12 months follow-up period.
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| 2. |
- Bondesson, Susanne, et al.
(författare)
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Reduced peripheral vascular reactivity in refractory angina pectoris: Effect of enhanced external counterpulsation
- 2011
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Ingår i: Journal of geriatric cardiology : JGC. - 1671-5411. ; 8:4, s. 215-223
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Tidskriftsartikel (refereegranskat)abstract
- To examine if the skin microvascular bed is altered and can be modified by enhanced external counterpulsation (EECP) in patients with chronic refractory angina. Methods Twenty patients diagnosed with refractory angina were divided into EECP (n = 10) or no EECP (n = 10) groups. The data were compared to matched healthy subjects (n = 20). The cutaneous forearm microvascular blood flow was measured by Laser-Doppler flowmetry. The vascular responsiveness to iontophoretic administration of acetylcholine (ACh), sodium nitroprusside (SNP) and local skin warming were studied. Measurements of Canadian Cardiovascular Society (CCS)-class, blood pressure and plasma samples were registered. Results EECP patients showed reduced CCS-class compared to no EECP (P < 0.05). Both EECP and no EECP (P < 0.05) groups had decreased systolic blood pressure (SBP) as compared to SBP at baseline (P < 0.05). There was no difference in resting blood flow between the two refractory groups at baseline as well as after EECP and seven weeks of follow-up. Responses to heating, the responses to ACh and SNP in the cutaneous microcirculation were lower in both groups of refractory angina patients as compared to healthy subjects (P < 0.05). EECP patients corresponded positively to the treatment shown by reduced plasma level of soluble interleukin-2 receptor and CCS-class. Conclusions Refractory angina patients have reduced responsiveness in their cutaneous microcirculation to ACh, SNP and heat compared to healthy subjects. Although EECP reduced the CCS-class, this effect was not associated with improvements in responsiveness of the cutaneous microcirculation.
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| 3. |
- Andersson, Sven E, et al.
(författare)
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High NT-proBNP Is a Strong Predictor of Outcome in Elderly Heart Failure Patients.
- 2008
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Ingår i: American Journal of Geriatric Cardiology. - 1751-715X. ; 17:1, s. 13-20
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Tidskriftsartikel (refereegranskat)abstract
- All patients older than 65 years (184 men; mean age, 78+/-0.8 years/181 women; mean age, 82+/-0.6 years) seeking medical attention at the Lund University Hospital Emergency Clinic during a 2-year period who had an N-terminal prohormone brain natriuretic peptide (NT-proBNP) value >2000 pg/mL were followed up for survival. Mortality in the entire population was 21% after 3 months, 35% after 1 year, and 40% after 2 years. Multivariate analysis indicated that the NT-proBNP level and the New York Heart Association (NYHA) functional class were stronger predictors of mortality than were echocardiographic estimation of left ventricular ejection fraction or chest radiography. Patients who survived the first year were younger, had higher systolic blood pressure, had lower plasma creatinine, had lower inflammatory activity, and were treated with lower doses of furosemide. The results indicate that in this population, NT-proBNP level together with assessment of NYHA class gives the best prognostic information of 1-year mortality. (Am J Geriatr Cardiol. 2008;17:13-20).
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| 4. |
- Bondesson, Susanne, et al.
(författare)
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Hospital utilization and costs for spinal cord stimulation compared with enhanced external counterpulsation for refractory angina pectoris
- 2013
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Ingår i: Journal of Evaluation in Clinical Practice. - : Wiley-Blackwell Publishing Ltd. - 1356-1294 .- 1365-2753. ; 19:1, s. 139-147
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Tidskriftsartikel (refereegranskat)abstract
- Rationale, aims and objectives The aim of this study was to compare acute hospital utilization and costs for patients with refractory angina pectoris undergoing spinal cord stimulation (SCS) versus enhanced external counterpulsation (EECP). Method Seventy-three persons were included in this register study. The acute hospital utilization and costs for SCS and EECP were followed over a period from 12 months before treatment to 24 months after treatment using Patient Administrative Support in Skåne for publicly organized care. Results SCS was significantly more expensive than EECP (P < 0.001). Both SCS and EECP entailed fewer days of hospitalization for coronary artery disease in the 12-month follow-up compared with the 12 months preceding treatment. Patients treated with EECP showed an association between reduced hospital admissions and an improved Canadian Cardiovascular Society classification class compared with 1 year before treatment. A significant reduction in cost was seen in both the SCS group (P = 0.018 and P = 0.001, respectively) and the EECP group (P = 0.002 and P = 0.045, respectively) during 12 and 24 months of follow-up compared with before treatment. There were no significant differences between the groups for hospitalization days or admissions, including costs, at the different follow-ups. Conclusions Cost-effective treatment modalities such as SCS and EECP are valuable additions to medical and revascularization therapy in patients with refractory angina pectoris. Pre-existing conditions and the patient's preferences should be taken in consideration when clinicians choose between treatments for this group of patients.
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| 5. |
- Adner, Mikael, et al.
(författare)
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Contractile endothelin-B (ETB) receptors in human small bronchi
- 1996
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 9:2, s. 351-355
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Tidskriftsartikel (refereegranskat)abstract
- Endothelins (ETs) are a family of novel regulatory peptides and various lines of evidence suggest an important role for ETs in regulating pulmonary function. Two receptors for endothelin, ETA and ETB, have been found in the human lung, and according to recent studies a non-ETA receptor seems to mediate the contraction of large sized human bronchi. Several studies have emphasized the importance of small bronchi in the pathogenesis of airway disease. In the present paper, improved methodology was used which enables in vitro studies of small human bronchi down to a diameter of 0.5-1.0 mm. Using the new methodology we have tried to further characterize this receptor. Small bronchi from the distal parts of the bronchial tree were obtained from pulmonary tissue removed from 15 patients with lung cancer. They were dissected and cut into ring segments, in which isometric tension was recorded. ET-1, ET-2 and ET-3 elicited strong concentration-dependent contractions of the human small bronchus. Basically, the three peptides were equipotent with about the same maximal response. Upon reapplication, they all showed the same tachyphylaxis pattern, reaching half the initial contraction. Comparative analysis of IRL 1620, a selective ETB receptor agonist, revealed that the effect of the ETB agonist was, in all respects, similar to the responses induced by the ETs. PD 145065, a combined ETA/ETB receptor antagonist competitively inhibited the contractions induced by IRL 1620, whereas FR139317, a selective ETA receptor antagonist, was without effect. In conclusion, the present study shows that accurate measurements can be made in vitro on small human bronchi and all present data are in favour of an ETB receptor mediating endothelin-induced contraction of human bronchi smaller than 1.0 mm.
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| 6. |
- Adner, Mikael, et al.
(författare)
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Human endothelin ETA receptor antisense oligodeoxynucleotides inhibit endothelin-1 evoked vasoconstriction
- 1994
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Ingår i: European Journal of Pharmacology. - 1879-0712. ; 261:3, s. 281-284
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Tidskriftsartikel (refereegranskat)abstract
- Antisense oligodeoxynucleotides to endothelin ETA receptor mRNA were used to characterize vascular smooth muscle receptors. The concentration-response curve showed a significant attenuation of endothelin-1-induced contraction in circular segments of the human superficial temporal artery. Endothelin ETB receptor antisense or mismatch oligodeoxynucleotides showed no alteration of the endothelin-1-induced contraction. Complementary experiments with the selective endothelin ETA receptor antagonist FR139317 demonstrated a shift of the concentration-response curve to the right in a competitive manner (pA2 = 6.93). The specific method of using the receptor antisense oligodeoxynucleotides approach revealed the presence of endothelin ETA receptors mediating contraction in the human superficial temporal artery.
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| 7. |
- Adner, Mikael, et al.
(författare)
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Regional variation in appearance of vascular contractile endothelin-B receptors following organ culture
- 1998
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Ingår i: Cardiovascular Research. - 1755-3245. ; 37:1, s. 254-262
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to investigate the appearance of contractile endothelin (ET)-B receptors following organ culture in different vascular regions. METHOD: The contractile responses of vascular smooth muscle induced by ET-1 and the selective ETB receptor agonist sarafotoxin 6c (S6c) were investigated in circular segments representing eight vascular regions in the rat (aorta, femoral artery, mesenteric artery, branch of the mesenteric artery, proximal and distal parts of the caudal artery, femoral and mesenteric veins). To allow the ETB receptor to be expressed, the segments were placed in organ culture for 1 to 5 days. Pharmacological characterisation of the ET receptors was performed in mesenteric arterial segments. All contractile responses were measured in percentage of K(+)-induced contraction. RESULTS: ET-1 induced strong concentration-dependent contractions of all fresh (not cultured) segments. S6c had negligible effects on all fresh vessels with the exception of the mesenteric vein, where a small contraction was seen. After 1 day of organ culture all tested segments, with the exception of aorta and the proximal part of the caudal artery, showed concentration-dependent contractile responses to S6c which were further augmented after 5 days of culture. The ET-1-induced responses were only slightly affected by organ culture. Contractions induced by S6c were more enhanced in small arteries and veins than in larger arteries. Furthermore, the S6c-induced response was more pronounced in the mesenteric region as compared to the hindlimb. In fresh mesenteric arterial segments FR139317 (ETA receptor antagonist) and bosentan (ETA/ETB receptor antagonist) but not IRL 2500 (ETB receptor antagonist) shifted the ET-1-induced concentration-response curve in parallel to the right. In contrast, after organ culture the S6c-induced concentration-response curves were shifted parallel to the right in the following potency order: IRL 2500 > bosentan > FR139317. CONCLUSION: During normal conditions, the ETA receptor is the dominating mediator of endothelin-induced contraction in eight different vascular regions. Furthermore, this study indicates that most of the vessels have the ability to develop contractile ETB receptors and that this plasticity differs in vascular regions.
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| 8. |
- Ahnstedt, Hilda, et al.
(författare)
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Cytokines and growth factors modify the upregulation of contractile endothelin ET(A) and ET(B) receptors in rat cerebral arteries after organ culture.
- 2012
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708. ; 205:2, s. 266-278
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Experimental cerebral ischemia and organ culture of cerebral arteries induce an increased endothelin ET(B) receptor-mediated contraction. The aim of the present study was to examine if cytokines and growth factors, known to be activated in ischemia, can influence the expression and function of endothelin receptors after organ culture. Methods: Rat middle cerebral arteries were cultured for 24 h at 37°C in humidified 5% CO(2) and air in culture medium alone, or with tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), platelet-derived growth factor (PDGF), epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF). Concentration-response curves were obtained for sarafotoxin 6c (ET(B) receptor agonist) and endothelin-1 (here ET(A) receptor agonist, because of ET(B) receptor desensitization). The receptor mRNA expression was examined by real-time PCR and the protein expression by immunohistochemistry and Western blot. Results: TNF-α (100 ng/ml) and EGF (20 ng/ml) potentiated the ET(B) receptor-mediated contraction (increase in pEC(50) without change in E(max) ). bFGF (10 ng/ml) and IL-1β (10 ng/ml) induced an enhanced ET(A) receptor-mediated contraction. bFGF (10 ng/ml) significantly increased the ET(B) mRNA level, and EGF (20 ng/ml) increased the ET(A) receptor protein. Increased ET(B) receptor mRNA and protein level also were observed after treatment with IL-1β (10 ng/ml). Conclusion: The present study show that TNF-α, IL-1β, EGF and bFGF can modify the expression and function of endothelin receptors during organ culture. Since there is similar receptor upregulation in experimental stroke, the effect of cytokines and growth factors on endothelin receptor upregulation is an interesting aspect to study in vivo.
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| 9. |
- Ahnstedt, Hilda, et al.
(författare)
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Human cerebrovascular contractile receptors are upregulated via a B-Raf/MEK/ERK-sensitive signaling pathway.
- 2011
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Ingår i: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Cerebral ischemia results in a rapid increase in contractile cerebrovascular receptors, such as the 5-hydroxytryptamine type 1B (5-HT1B), angiotensin II type 1 (AT1), and endothelin type B (ETB) receptors, in the vessel walls within the ischemic region, which further impairs local blood flow and aggravates tissue damage. This receptor upregulation occurs via activation of the mitogen-activated protein kinase pathway. We therefore hypothesized an important role for B-Raf, the first signaling molecule in the pathway. To test our hypothesis, human cerebral arteries were incubated at 37°C for 48 h in the absence or presence of a B-Raf inhibitor: SB-386023 or SB-590885. Contractile properties were evaluated in a myograph and protein expression of the individual receptors and activated phosphorylated B-Raf (p-B-Raf) was evaluated immunohistochemically. RESULTS: 5-HT1B, AT1, and ETB receptor-mediated contractions were significantly reduced by application of SB-590885, and to a smaller extent by SB-386023. A marked reduction in AT1 receptor immunoreactivity was observed after treatment with SB-590885. Treatment with SB-590885 and SB-386023 diminished the culture-induced increase of p-B-Raf immunoreactivity. CONCLUSIONS: B-Raf signaling has a key function in the altered expression of vascular contractile receptors observed after organ culture. Therefore, specific targeting of B-Raf might be a novel approach to reduce tissue damage after cerebral ischemia by preventing the previously observed upregulation of contractile receptors in smooth muscle cells.
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