| 1. |
- Bäcklin, Emelie, et al.
(författare)
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Pulmonary volumes and signs of chronic airflow limitation in quantitative computed tomography
- 2024
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Ingår i: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 44:4, s. 340-348
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundComputed tomography (CT) offers pulmonary volumetric quantification but is not commonly used in healthy individuals due to radiation concerns. Chronic airflow limitation (CAL) is one of the diagnostic criteria for chronic obstructive pulmonary disease (COPD), where early diagnosis is important. Our aim was to present reference values for chest CT volumetric and radiodensity measurements and explore their potential in detecting early signs of CAL.MethodsFrom the population-based Swedish CArdioPulmonarybioImage Study (SCAPIS), 294 participants aged 50–64, were categorized into non-CAL (n = 258) and CAL (n = 36) groups based on spirometry. From inspiratory and expiratory CT images we compared lung volumes, mean lung density (MLD), percentage of low attenuation volume (LAV%) and LAV cluster volume between groups, and against reference values from static pulmonary function test (PFT).ResultsThe CAL group exhibited larger lung volumes, higher LAV%, increased LAV cluster volume and lower MLD compared to the non-CAL group. Lung volumes significantly deviated from PFT values. Expiratory measurements yielded more reliable results for identifying CAL compared to inspiratory. Using a cut-off value of 0.6 for expiratory LAV%, we achieved sensitivity, specificity and positive/negative predictive values of 72%, 85% and 40%/96%, respectively.ConclusionWe present volumetric reference values from inspiratory and expiratory chest CT images for a middle-aged healthy cohort. These results are not directly comparable to those from PFTs. Measures of MLD and LAV can be valuable in the evaluation of suspected CAL. Further validation and refinement are necessary to demonstrate its potential as a decision support tool for early detection of COPD.
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| 2. |
- Gonon, Adrian, et al.
(författare)
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Effects of thoracic epidural analgesia on exercise-induced myocardial ischaemia in refractory angina pectoris
- 2019
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Ingår i: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 63:4, s. 515-522
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Tidskriftsartikel (refereegranskat)abstract
- Background Thoracic epidural analgesia (TEDA) was offered to patients with refractory angina pectoris. Our primary objectives were to evaluate TEDAs influence on quality of life (QoL, base for power analysis), and hypothesising that TEDA with bupivacaine during 1 month counteracts exercise-induced myocardial hypoperfusion and increase physical performance. Methods Patients with refractory angina and exercise inducible hypoperfusion, as demonstrated by myocardial perfusion imaging (MPI), were randomised to 1-month treatment with TEDA with bupivacaine (B-group, n = 9) or saline (P-group, n = 10) in a double-blind fashion. MPI and bicycle ergometry were performed before TEDA and after 1 month while subjective QoL on a visual analogue scale (VAS) reported by the patients was checked weekly. Results During this month VAS (mean [95%CI]) increased similarly in both groups (B-group from 33 [18-50] to 54 [30-78] P P amp;lt; 0.05). The B-group reduced their exertional-induced myocardial hypoperfusion (from 32% [12-52] to 21% [3-39]; n = 9; P amp;lt; 0.05), while the P-group showed no significant change (before 21% [6-35]; at 1 month 23% [6-40]; n = 10). MPI at rest did not change and no improvement in physical performance was detected in neither of the groups. Conclusions In refractory angina, TEDA with bupivacaine inhibits myocardial ischaemia in contrast to TEDA with saline. Regardless of whether bupivacaine or saline is applied intermittently every day, TEDA during 1 month improves the quality of life and reduces angina, even when physical performance remains low. A significant placebo effect has to be considered.
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| 3. |
- Gonon, Adrian T
(författare)
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The role of endothelin during myocardial ischaemia and reperfusion : pathophysiological mechanisms and interactions with nitric oxide
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Acute myocardial infarction followed by reperfusion results in accelerated necrosis of irreversibly injured myocytes as well as induction of lethal injury to reversibly injured cells. Polymorphonuclear leukocytes (PMNs) are major participants in the reperfusion-initiated inflammation. Myocardial ischaemia and reperfusion are associated with changes in synthesis, release and vascular actions of endothelial factors. The production of the endothelium-derived relaxing factor nitric oxide (NO) is impaired, and the production/release of the vasoconstrictor endothelin-1 (ET-1) is enhanced. The aim of the studies was to investigate the pathophysiological mechanisms of ET-1 and its interactions with NO during ischaemia and reperfusion. 1. Administration of the selective ETA receptor antagonist LU 135252 to anaesthetized pigs limited the extent of myocardial necrosis by 50% and the increase in myocardial tissue levels of ET-like immunoreactivity (ET-LI) following 45 min of ischaemia and 4 h of reperfusion. The degree of cardioprotection achieved by systemic i.v. administration prior to ischaemia was the same as that obtained by local i.c. infusion into the area at risk during the last min of ischaemia and early reperfusion. 2. LU 135252 protected the isolated rat heart from contractile dysfunction following ischaemia and reperfusion in the presence, but not in absence of PMNs. The outflow of PMNs in the coronary effluent was 4 times higher in the group given LU 135252 than in the vehicle group. Administration of ET-1 together with PMNs resulted in complete loss of contractile function and no outflow of PMNs. The recovery of the outflow of PMNs in the coronary effluent correlated significantly with the recovery of myocardial function. 3. Myeloperoxidase (MPO) activity in the ischaemic/reperfused myocardium as an index of PMN accumulation in the pig was significantly lower following i.c. administration of LU 135252 in comparison to vehicle. There was a significant correlation between the infarct size and MPO activity. 4. Perfusion with the NO synthase inhibitor L-NNA reduced coronary flow in the isolated rat heart. Pre-treatment with the mixed ETA/ETB bosentan and the selective ETA receptor antagonist BQ-123, but not the selective ETB receptor antagonist BQ-788 attenuated the coronary vasoconstrictor response induced by NOS inhibition. Bosentan increased ET-LI in the coronary effluent two-fold, whereas L-NNA did not affect the release of ET-LI. 5. Cardioprotection by the selective ETA receptor antagonist LU 135252 was not affected by co-administration of L-arginine in the pig in vivo. Inhibition of NO synthase reversed the cardioprotective effect of LU 135252 as well as the attenuation of ET-LI levels in ischaemic/reperfused myocardium induced by the ETA receptor antagonist. In conclusion, ET-1 contributes to myocardial ischaemia and reperfusion injury by activation of the ETA receptor. Selective blockade of the ETA receptor protects the heart from ischaemia and reperfusion injury. The cardioprotective effect seems to be related to inhibition of PMN-induced myocardial injury and preserved production of NO.
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| 4. |
- Grishenkov, Dmitry, 1983-, et al.
(författare)
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In search of the optimal ultrasound heart perfusion imaging platform
- 2015
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Ingår i: Journal of ultrasound in medicine. - : Wiley. - 0278-4297 .- 1550-9613. ; 34:9, s. 1599-1605
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveQuantification of the myocardial perfusion by contrast echocardiography (CEC) remains a challenge. Existing imaging phantoms used to evaluate the performance of ultrasound scanners do not comply with perfusion basics in the myocardium, where perfusion and motion are inherently coupled.MethodsTo contribute towards an improvement, we developed a CEC perfusion imaging platform based on isolated rat heart coupled to the ultrasound scanner. Perfusion was assessed using three different types of contrast agent: dextran-based Promiten®, phospholipid-shelled SonoVue®, and polymer-shelled MB-pH5-RT. The myocardial video-intensity was monitored over time from contrast administration to peak and two characteristic constants were calculated using exponential fit (A representing capillary volume and b representing inflow velocity).ResultsAcquired experimental evidence demonstrates that the application of all three types of contrast agent allow ultrasonic estimation of myocardial perfusion in the isolated rat heart. Video-intensity maps show that an increase in contrast concentration increases the late plateau values, A, mimicking increased capillary volume. Estimated values of the flow, proportional to Axb, increase when the pressure of the perfusate column increases from 80 to 110 cm of water. This finding is in agreement with the true values of the coronary flow increase measured by the flowmeter attached to the aortic cannula.ConclusionsThe described CEC perfusion imaging platform holds promise for standardized evaluation and optimization of ultrasound contrast perfusion imaging where real time inflow curves at low acoustic power semi-quantitatively reflect coronary flow.
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| 5. |
- Grishenkov, Dmitry, 1983-, et al.
(författare)
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Ultrasound contrast agent loaded with nitric oxide as a theranostic microdevice : Theranostic contrast agent loaded with nitric oxide
- 2015
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Ingår i: Drug Design, Development and Therapy. - 1177-8881. ; 9, s. 2409-2419
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Tidskriftsartikel (refereegranskat)abstract
- The current study describes novel multifunctional polymer-shelled microbubbles (MBs) loaded with nitric oxide (NO) for integrated therapeutic and diagnostic applications, i.e. theranostics, of myocardial ischemia. We used gas filled MBs with an average diameter of 4 µm stabilized by a biocompatible shell of poly(vinyl)alcohol. In vitro acoustic tests showed a sufficient enhancement of the backscattered power (20 dB) acquired from the MBs suspension. The values of attenuation coefficient (0.8 dB/cm MHz) and phase velocities (1517 m/s) were comparable to those reported for the soft tissue. Moreover, polymer MBs demonstrate increased stability compared to clinically approved contrast agents with fracture threshold of about 900 kPa. In vitro chemiluminescence measurements demonstrated that dry powder of NO-loaded MBs releases its gas content in about 2 hours following an exponential decay profile with an exponential time constant equal 36 min. The application of high power ultrasound pulse (MI=1.2) on the MBs resuspended in saline decreases the exponential time constant from 55 to 4 min in air saturated solution and from 17 to 10 min in degased solution. Thus, ultrasound-triggered release of NO is achieved. Cytotoxicity tests indicate that phagocytosis of the MBs by macrophages starts within 6 to 8 hours. This is suitable time for initial diagnostics, treatment and monitoring of the therapeutic effect using single injection of the proposed multifunctional MBs.
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| 6. |
- Grishenkov, Dmitry, 1983-, et al.
(författare)
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Ultrasound contrast agent loaded with nitric oxide as a theranostic microdevise for myocardial ischemia
- 2013
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Ingår i: European Heart Journal Cardiovascular Imaging.
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Konferensbidrag (refereegranskat)abstract
- Cardiovascular disease (CVD) accounts for 1/3 of total global deaths worldwide. The most widespread CVD is ischemic heart disease. It is the leading cause of death in both genders, equally diagnosed in developed and developing countries with mortality exponentially increasing with age. Efforts of healthcare system should be primary focused on prevention, timely detection, efficient differentiation and instant treatment of the disease.
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| 7. |
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| 8. |
- Karlsson, Lars O, 1975, et al.
(författare)
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Opioid receptor agonist Eribis peptide 94 reduces infarct size in different porcine models for myocardial ischaemia and reperfusion
- 2011
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999 .- 1879-0712. ; 651:1-3, s. 146-151
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Tidskriftsartikel (refereegranskat)abstract
- Eribis peptide 94 (EP 94) is a novel enkephalin analog, thought to interact with the and delta-opioid receptors. The purpose of the present study was to examine the cardioprotective potential of EP 94 in two clinically relevant porcine models of myocardial ischaemia and reperfusion, and to investigate if such an effect is associated with an increased expression of endothelial nitric oxide synthase (eNOS). Forty-one anesthetized pigs underwent 40 min of coronary occlusion followed by 4 h of reperfusion. In Protocol I, balloon occlusion of the left anterior descending artery was performed with concurrent intravenous administration of (A) vehicle (n = 7), (B) EP 94 (1 ug/kg) after 5, 12, 19 and 26 min of ischaemia (n = 4) or (C) EP 94 (1 ug/kg) after 26, 33, 40 min of ischaemia (n = 6). In Protocol II, open-chest pigs were administered (D) vehicle (n = 6) or (E) 0.2 ug/kg/min of EP 94 (n = 6) through an intracoronary infusion into the jeopardized myocardium, started after 30 min of ischaemia and maintained for 15 min. The hearts were stained and the protein content of eNOS measured. EP 94 reduces infarct size when administered both early and late during ischaemia compared with vehicle (infarct size group A 61.6 +/- 2%, group B 50.2 +/- 3% and group C 49.2 +/- 2%, respectively, P < 0.05), as well as when infused intracoronary (infarct size group D 82.2 +/- 3.9% and group E 61.2 +/- 2.5% respectively, P < 0.01). Phosphorylated eNOS Ser(I177) in relation to total eNOS was significantly increased in the group administered EP 94. indicating activation of nitric oxide production.
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