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  • Bouyoucef, S E, et al. (author)
  • Poster Session 2 : Monday 4 May 2015, 08
  • 2015
  • In: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
  • Journal article (peer-reviewed)
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  • Wijns, W, et al. (author)
  • Myocardial revascularization
  • 2011
  • In: REVISTA PORTUGUESA DE CARDIOLOGIA. - : Elsevier BV. - 0870-2551 .- 2174-2049. ; 30:12, s. 951-1005
  • Journal article (other academic/artistic)
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  • Ferreira, Mjv, et al. (author)
  • Poster Session 3 : Tuesday 5 May 2015, 08
  • 2015
  • In: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
  • Journal article (peer-reviewed)
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  • Anttila, V., et al. (author)
  • Direct intramyocardial injection of VEGF mRNA in patients undergoing coronary artery bypass grafting
  • 2023
  • In: Molecular Therapy. - : Elsevier BV. - 1525-0016. ; 31:3, s. 866-874
  • Journal article (peer-reviewed)abstract
    • Vascular endothelial growth factor A (VEGF-A) has therapeutic cardiovascular effects, but delivery challenges have impeded clinical development. We report the first clinical study of naked mRNA encoding VEGF-A (AZD8601) injected into the human heart. EPICCURE (ClinicalTrials.gov: NCT03370887) was a randomized, double-blind study of AZD8601 in patients with left ventricular ejection fraction (LVEF) 30%–50% who were undergoing elective coronary artery bypass surgery. Thirty epicardial injections of AZD8601 (total 3 mg) or placebo in citrate-buffered saline were targeted to ischemic but viable myocardial regions mapped using quantitative [15O]-water positron emission tomography. Seven patients received AZD8601 and four received placebo and were followed for 6 months. There were no deaths or treatment-related serious adverse events and no AZD8601-associated infections, immune reactions, or arrhythmias. Exploratory outcomes indicated potential improvement in LVEF, Kansas City Cardiomyopathy Questionnaire scores, and N-terminal pro-B-type natriuretic peptide levels, but the study is limited in size, and significant efficacy conclusions are not possible from the dataset. Naked mRNA without lipid encapsulation may provide a safe delivery platform for introducing genetic material to cardiac muscle, but further studies are needed to confirm efficacy and safety in a larger patient pool. © 2022
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  • Kalliokoski, KK, et al. (author)
  • Myocardial perfusion after marathon running
  • 2004
  • In: Scandinavian Journal of Medicine and Science in Sport. - : Wiley. - 0905-7188 .- 1600-0838. ; 14:4, s. 208-214
  • Journal article (peer-reviewed)abstract
    • We investigated the effects of acute prolonged exercise (marathon running) on cardiac function and myocardial perfusion. Cardiac dimensions and function were measured in seven endurance-trained men using echocardiography before and repeatedly after marathon (42.2 km) running (at 10 min, 150 min, and 20 h). Myocardial perfusion and perfusion resistance were measured using positron emission tomography and 15O-H2O before and 85-115 min after running. Echocardiographic indices showed only mild and clinically non-significant changes in cardiac function after running. Rate-pressure-corrected basal myocardial perfusion (0.89+/-0.13 vs. 1.20+/-0.32 mL min(-1) g(-1), P=0.04) was increased after running. Also, adenosine-stimulated perfusion tended to be higher (3.67+/-0.81 vs. 4.47+/-0.52 mL min(-1) g(-1), P=0.12) and perfusion resistance during adenosine stimulation was significantly lower after running (26+/-6 vs. 18+/-3 mmHg min g mL(-1), P=0.03). Plasma free fatty acid (FFA) concentration was significantly increased after running. These results show that marathon running does not cause marked changes in cardiac function in healthy men. Basal perfusion was increased after exercise, probably reflecting changes in fuel preferences to increased use of FFAs. Strenuous exercise also seems to enhance coronary reactivity, which could thereby serve as a protective mechanism to vascular events after exercise.
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  • Kolh, P, et al. (author)
  • Guidelines on myocardial revascularization
  • 2010
  • In: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. - : Oxford University Press (OUP). - 1873-734X .- 1010-7940. ; 3838 Suppl, s. S1-S52
  • Journal article (peer-reviewed)
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  • Laaksonen, Marko, et al. (author)
  • Effects of exhaustive stretch-shortening cycle exercise on muscle blood flow during exercise
  • 2006
  • In: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 186:4, s. 261-270
  • Journal article (peer-reviewed)abstract
    • Abstract Aim: The influence of exhaustive stretch-shortening cycle exercise (SSC) on skeletal muscle blood flow (BF) during exercise is currently unknown. Methods: Quadriceps femoris (QF) BF was measured in eight healthy men using positron emission tomography before and 3 days after exhaustive SSC exercise. The SSC protocol consisted of maximal and submaximal drop jumps with one leg. Needle biopsies of the vastus lateralis muscles were taken immediately and 2 days after SSC for muscle endothelial nitric oxide synthase (eNOS) and interleukin-1-beta (IL-1beta) mRNA level determinations. Results: All subjects reported subjective muscle soreness after SSC (P < 0.001), which was well in line with a decrease in maximal isometric contraction force (MVC) and increase in serum creatine kinase activity (CK) (P = 0.018). After SSC muscle BF was 25% higher in entire QF (P = 0.043) and in its deep and superficial muscle regions, whereas oxygen uptake remained unchanged (P = 0.893). Muscle biopsies revealed increased IL-1beta (30 min: 152 +/- 75%, P = 0.012 and 2 days: 108 +/- 203%, P = 0.036) but decreased or unchanged eNOS (30 min; -21 +/- 57%, P = 0.050 and 2 days: +101 +/- 204%, P = 0.779) mRNA levels after SSC. Conclusion: It was concluded that fatiguing SSC exercise induces increased muscle BF during exercise, which is likely to be associated with pro-inflammatory processes in the exercised muscle.
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  • Virtanen, KA, et al. (author)
  • Differential effects of rosiglitazone and metformin on adipose tissue distribution and glucose uptake in type 2 diabetic subjects
  • 2003
  • In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 52:2, s. 283-290
  • Journal article (peer-reviewed)abstract
    • We evaluated the effects of rosiglitazone (4 mg b.i.d.) and metformin (1 g b.i.d.) monotherapy for 26 weeks on adipose tissue insulin-stimulated glucose uptake in patients (n = 41) with type 2 diabetes. Before and after the treatment, glucose uptake was measured using 2-[18F]fluoro-2-deoxyglucose and positron emission tomography and adipose tissue masses were quantified using magnetic resonance imaging. Rosiglitazone improved insulin-stimulated whole-body glucose uptake by 44% (P &lt; 0.01 vs. placebo). Mean body weight was unchanged in the rosiglitazone group, while it decreased by 2.0 kg in the metformin group (P &lt; 0.05 vs. placebo). In visceral adipose tissue, glucose uptake increased by 29% (from 17.8 ± 2.0 to 23.0 ± 2.6 μmol · kg−1 · min−1, P &lt; 0.05 vs. placebo) in the rosiglitazone group but to a lesser extent (17%) in the metformin group (from 16.2 ± 1.5 to 18.9 ± 1.7 μmol · kg−1 · min−1, P &lt; 0.05 vs. baseline). Because the visceral adipose tissue mass simultaneously decreased with both treatments (P &lt; 0.05), no change was observed in total visceral glucose uptake per depot. Rosiglitazone significantly enhanced glucose uptake in the femoral subcutaneous area, either when expressed per tissue mass (from 10.8 ± 1.2 to 17.1 ± 1.7 μmol · kg−1 · min−1, P &lt; 0.01 vs. placebo) or per whole-fat depot (P &lt; 0.05 vs. placebo). In conclusion, metformin treatment resulted in improvement of glycemic control without enhancement of peripheral insulin sensitivity. The improved insulin sensitivity of the nonabdominal subcutaneous adipose tissue during treatment with rosiglitazone partly explains the enhanced whole-body insulin sensitivity and underlies the central role of adipose tissue for action of peroxisome proliferator-activated receptor γ agonist in vivo.
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  • Anttila, V., et al. (author)
  • Synthetic mRNA Encoding VEGF-A in Patients Undergoing Coronary Artery Bypass Grafting: Design of a Phase 2a Clinical Trial
  • 2020
  • In: Molecular Therapy-Methods & Clinical Development. - : Elsevier BV. - 2329-0501. ; 18, s. 464-472
  • Journal article (peer-reviewed)abstract
    • Therapeutic angiogenesis may improve outcomes in patients with coronary artery disease undergoing surgical revascularization. Angiogenic factors may promote blood vessel growth and regenerate regions of ischemic but viable myocardium. Previous clinical trials of vascular endothelial growth factor A (VEGF-A) gene therapy with DNA or viral vectors demonstrated safety but not efficacy. AZD8601 is VEGF-A(165) mRNA formulated in biocompatible citrate-buffered saline and optimized for high-efficiency VEGF-A expression with minimal innate immune response. EPICCURE is an ongoing randomized, double-blind, placebo-controlled study of the safety of AZD8601 in patients with moderately decreased left ventricular function (ejection fraction 30% 50%) undergoing elective coronary artery bypass surgery. AZD8601 3 mg, 30 mg, or placebo is administered as 30 epicardial injections in a 10-min extension of cardioplegia. Injections are targeted to ischemic but viable myocardial regions in each patient using quantitative O-15-water positron emission tomography (PET) imaging (stress myocardial blood flow < 2.3 mL/g/min; resting myocardial blood flow > 0.6 mL/g/min). Improvement in regional and global myocardial blood flow quantified with O-15-water PET is an exploratory efficacy outcome, together with echocardiographic, clinical, functional, and biomarker measures. EPICCURE combines high-efficiency delivery with quantitative targeting and follow-up for robust assessment of the safety and exploratory efficacy of VEGF-A mRNA angiogenesis (ClinicalTrials.gov: NCT03370887).
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  • Hallsten, K, et al. (author)
  • Rosiglitazone but not metformin enhances insulin- and exercise-stimulated skeletal muscle glucose uptake in patients with newly diagnosed type 2 diabetes
  • 2002
  • In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 51:12, s. 3479-3485
  • Journal article (peer-reviewed)abstract
    • Rosiglitazone, a thiazolidinedione, enhances peripheral insulin sensitivity in patients with type 2 diabetes. Because the synergic action of insulin and exercise has been shown to be decreased in insulin resistance, the aim of this study was to compare the effects of rosiglitazone and metformin on muscle insulin responsiveness at rest and during exercise in patients with type 2 diabetes. Therefore, 45 patients with newly diagnosed or diet-treated type 2 diabetes were randomized for treatment with rosiglitazone (4 mg b.i.d.), metformin (1 g b.i.d.), or placebo in a 26-week double-blind trial. Skeletal muscle glucose uptake was measured using fluorine-18-labeled fluoro-deoxy-glucose and positron emission tomography (PET) during euglycemic-hyperinsulinemic clamp and one-legged exercise before and after the treatment period. Rosiglitazone (P &lt; 0.05) and metformin (P &lt; 0.0001) treatment lowered the mean glycosylated hemoglobin. The skeletal muscle glucose uptake was increased by 38% (P &lt; 0.01) and whole-body glucose uptake by 44% in the rosiglitazone group. Furthermore, the exercise-induced increment during insulin stimulation was enhanced by 99% (P &lt; 0.0001). No changes were observed in skeletal muscle or whole-body insulin sensitivity in the metformin group. In conclusion, rosiglitazone but not metformin 1) improves insulin responsiveness in resting skeletal muscle and 2) doubles the insulin-stimulated glucose uptake rate during physical exercise in patients with type 2 diabetes. Our results suggest that rosiglitazone improves synergic action of insulin and exercise.
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  • Hesse, B, et al. (author)
  • EANM/ESC procedural guidelines for myocardial perfusion imaging in nuclear cardiology
  • 2005
  • In: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 32:7, s. 855-897
  • Journal article (peer-reviewed)abstract
    • The European procedural guidelines for radionuclide imaging of myocardial perfusion and viability are presented in 13 sections covering patient information, radiopharmaceuticals, injected activities and dosimetry, stress tests, imaging protocols and acquisition, quality control and reconstruction methods, gated studies and attenuation-scatter compensation, data analysis, reports and image display, and positron emission tomography. If the specific recommendations given could not be based on evidence from original, scientific studies, we tried to express this state-of-art. The guidelines are designed to assist in the practice of performing, interpreting and reporting myocardial perfusion SPET. The guidelines do not discuss clinical indications, benefits or drawbacks of radionuclide myocardial imaging compared to non-nuclear techniques, nor do they cover cost benefit or cost effectiveness.
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  • Johansson, BL, et al. (author)
  • C-peptide improves adenosine-induced myocardial vasodilation in type 1 diabetes patients
  • 2004
  • In: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 286:1, s. E14-E19
  • Journal article (peer-reviewed)abstract
    • Patients with type 1 (insulin-dependent) diabetes show reduced skeletal muscle blood flow and coronary vasodilatory function despite intensive insulin therapy and good metabolic control. Administration of proinsulin C-peptide increases skeletal muscle blood flow in these patients, but a possible influence of C-peptide on myocardial vasodilatory function in type 1 diabetes has not been investigated. Ten otherwise healthy young male type 1 diabetic patients (Hb A1c 6.6%, range 5.7-7.9%) were studied on two consecutive days during normoinsulinemia and euglycemia in a double-blind, randomized, crossover design, receiving intravenous infusion of C-peptide (5 pmol·kg-1·min-1) for 120 min on one day and saline infusion on the other day. Myocardial blood flow (MBF) was measured at rest and during adenosine administration (140 μg·kg-1·min-1) both before and during the C-peptide or saline infusions by use of positron emission tomography and [15O]H2O administration. Basal MBF was not significantly different in the patients compared with an age-matched control group, but adenosine-induced myocardial vasodilation was 30% lower ( P < 0.05) in the patients. During C-peptide administration, adenosine-stimulated MBF increased on average 35% more than during saline infusion ( P < 0.02) and reached values similar to those for the healthy controls. Moreover, as evaluated from transthoracal echocardiographic measurements, C-peptide infusion resulted in significant increases in both left ventricular ejection fraction (+5%, P < 0.05) and stroke volume (+7%, P < 0.05). It is concluded that short-term C-peptide infusion in physiological amounts increases the hyperemic MBF and left-ventricular function in type 1 diabetic patients.
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  • Kalliokoski, K.K, et al. (author)
  • Muscle fractal vascular branching pattern and microvascular perfusion heterogeneity in endurance-trained and untrained men
  • 2003
  • In: Journal of Physiology. - : Wiley. - 0022-3751 .- 1469-7793. ; 546:pt2, s. 529-35
  • Journal article (peer-reviewed)abstract
    • Less heterogeneous skeletal muscle perfusion has recently been reported in endurance-trained compared to untrained men at macrovascular level. The causes of this difference in perfusion heterogeneity are unknown as is whether the same difference is observed in microvasculature. We hypothesised that the difference could be caused by changes in muscle vascular branching pattern. Perfusion was measured in resting and exercising muscle in 14 endurance-trained and seven untrained men using [(15)O]water and positron emission tomography. Fractal dimension (D) of perfusion distribution was calculated as a measure of fractal characteristics of muscle vascular branching pattern. Perfusion heterogeneity in microvascular units (1 mm(3) samples) was estimated using the measured heterogeneity in voxels of positron emission tomography (PET) images (relative dispersion, RD = S.D./mean) and corresponding D values. D was similar between the groups (exercising muscle 1.11 +/- 0.07 and 1.14 +/- 0.06, resting muscle 1.12 +/- 0.06 and 1.14 +/- 0.03, trained and untrained, respectively). Trained men had lower perfusion (151 +/- 44 vs. 218 +/- 87 ml min(-1) kg(-1), P < 0.05) and macrovascular perfusion heterogeneity (relative dispersion 21 +/- 5 vs. 25 +/- 5 %, P < 0.05) in exercising muscle than untrained men. Furthermore, estimated perfusion heterogeneity in microvascular units in exercising muscle was also lower in trained men (33 +/- 7 vs.48 +/- 19 %, P < 0.05). These results show that fractal vascular branching pattern is similar in endurance-trained and untrained men but perfusion is less heterogeneous at both the macro- and the microvascular level in endurance-trained men. Thus, changes in fractal branching pattern do not explain the differences in perfusion heterogeneity between endurance-trained and untrained men.
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  • Kalliokoski, K K, et al. (author)
  • Perfusion distribution between and within muscles during intermittent static exercise in endurance-trained and untrained men
  • 2003
  • In: International Journal of Sports Medicine. - : Georg Thieme Verlag KG. - 0172-4622 .- 1439-3964. ; 24, s. 400-403
  • Journal article (peer-reviewed)abstract
    • We have recently shown that muscle perfusion varies between different quadriceps femoris muscles during submaximal exercise in humans. In animals, endurance training changes perfusion distribution between muscles during exercise. Whether the same is observed in humans is currently unknown. Therefore, we compared perfusion levels between different parts of the quadriceps femoris muscle group during one-legged intermittent static exercise in seven endurance-trained and seven untrained men. Muscle perfusion was measured using positron emission tomography with [ 15O]-H 2 O. In addition, relative dispersion of perfusion (standard deviation within a region/mean within a region x 100 %) within each muscle region was calculated as an index of perfusion heterogeneity within the muscles. Muscle perfusion tended to be lower in endurance-trained men (p = 0.16) and it was also different between the regions (p < 0.001). However, perfusion distributed similarly between the groups (p = 0.51). Relative dispersion of perfusion within the muscles was lower in endurance-trained men (p = 0.01) and it was also different between muscles (p < 0.001). These results suggest that endurance training does not alter perfusion distribution between muscles, but it decreases perfusion heterogeneity within the muscles.
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