Search

Your search keyword '"Pernow, John"' showing total 813 results
Start Over Author "Pernow, John"
813 results on '"Pernow, John"'

7. Optimal timing of influenza vaccination among patients with acute myocardial infarction – Findings from the IAMI trial

Author

Akhtar, Zubair, Götberg, Matthias, Erlinge, David, Christiansen, Evald H., Oldroyd, Keith G., Motovska, Zuzana, Erglis, Andrejs, Hlinomaz, Ota, Jakobsen, Lars, Engstrøm, Thomas, Jensen, Lisette O., Fallesen, Christian O., Jensen, Svend E., Angerås, Oskar, Calais, Fredrik, Kåregren, Amra, Lauermann, Jörg, Mokhtari, Arash, Nilsson, Johan, Persson, Jonas, Islam, Abu K.M.M., Rahman, Afzalur, Malik, Fazila, Choudhury, Sohel, Collier, Timothy, Pocock, Stuart J., Pernow, John, MacIntyre, Chandini R., and Fröbert, Ole

Published
2023
Full Text
View/download PDF

8. Clinical impact of influenza vaccination after ST- and non-ST-segment elevation myocardial infarction - insights from the IAMI trial

Author

Fröbert, Ole, Götberg, Matthias, Erlinge, David, Akhtar, Zubair, Christiansen, Evald H., MacIntyre, Chandini R., Oldroyd, Keith G., Motovska, Zuzana, Erglis, Andrejs, Moer, Rasmus, Hlinomaz, Ota, Jakobsen, Lars, Engstrøm, Thomas, Jensen, Lisette O., Fallesen, Christian O., Jensen, Svend E, Angerås, Oskar, Calais, Fredrik, Kåregren, Amra, Lauermann, Jörg, Mokhtari, Arash, Nilsson, Johan, Persson, Jonas, Stalby, Per, Islam, Abu K.M.M., Rahman, Afzalur, Malik, Fazila, Choudhury, Sohel, Collier, Timothy, Pocock, Stuart J., and Pernow, John

Published
2023
Full Text
View/download PDF

9. Hypoxic erythrocytes mediate cardioprotection through activation of soluble guanylate cyclase and release of cyclic GMP

Author

Yang, Jiangning, Sundqvist, Michaela L., Zheng, Xiaowei, Jiao, Tong, Collado, Aida, Tratsiakovich, Yahor, Mahdi, Ali, Tengbom, John, Mergia, Evanthia, Catrina, Sergiu-Bogdan, Zhou, Zhichao, Carlstrom, Mattias, Akaike, Takaaki, Cortese-Krott, Miriam M., Weitzberg, Eddie, Lundberg, Jon O., and Pernow, John

Subjects
Heart diseases -- Research, Cyclic guanylic acid -- Research, Nitric oxide -- Research, Heart -- Research, Health care industry
Abstract

Red blood cells (RBCs) mediate cardioprotection via nitric oxide-like bioactivity, but the signaling and the identity of any mediator released by the RBCs remains unknown. We investigated whether RBCs exposed to hypoxia release a cardioprotective mediator and explored the nature of this mediator. Perfusion of isolated hearts subjected to ischemiareperfusion with extracellular supernatant from mouse RBCs exposed to hypoxia resulted in improved postischemic cardiac function and reduced infarct size. Hypoxia increased extracellular export of cyclic guanosine monophosphate (cGMP) from mouse RBCs, and exogenous cGMP mimicked the cardioprotection induced by the supernatant. The protection induced by hypoxic RBCs was dependent on RBC-soluble guanylate cyclase and cGMP transport and was sensitive to phosphodiesterase 5 and activated cardiomyocyte protein kinase G. Oral administration of nitrate to mice to increase nitric oxide bioactivity further enhanced the cardioprotective effect of hypoxic RBCs. In a placebo- controlled clinical trial, a clear cardioprotective, soluble guanylate cyclase-dependent effect was induced by RBCs collected from patients randomized to 5 weeks nitrate-rich diet. It is concluded that RBCs generate and export cGMP as a response to hypoxia, mediating cardioprotection via a paracrine effect. This effect can be further augmented by a simple dietary intervention, suggesting preventive and therapeutic opportunities in ischemic heart disease., Introduction There are several lines of evidence suggesting that red blood cells (RBCs), in addition to their fundamental role as transporters of oxygen, are involved in the regulation of cardiovascular [...]

Published
2023
Full Text
View/download PDF

10. Hemoglobin β93 Cysteine Is Not Required for Export of Nitric Oxide Bioactivity From the Red Blood Cell

Author

Sun, Chiao-Wang, Yang, Jiangning, Kleschyov, Andrei L, Zhuge, Zhengbing, Carlström, Mattias, Pernow, John, Wajih, Nadeem, Isbell, T Scott, Oh, Joo-Yeun, Cabrales, Pedro, Tsai, Amy G, Townes, Tim, Kim-Shapiro, Daniel B, Patel, Rakesh P, and Lundberg, Jon O

Subjects
Clinical Research, Hematology, Cardiovascular, Blood, Alanine, Amino Acid Substitution, Animals, Biological Transport, Blood Platelets, Cysteine, Disease Models, Animal, Erythrocytes, Hemoglobins, Humans, Hypoxia, Isolated Heart Preparation, Male, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Myocardial Reperfusion Injury, Nitric Oxide, Platelet Activation, Rats, Sprague-Dawley, Skin, Vasodilation, Ventricular Function, Left, Ventricular Pressure, beta-Globins, hemoglobins, nitric oxide, nitrite, nitrosation, S-nitrosothiols, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Public Health and Health Services, Cardiovascular System & Hematology
Abstract

BACKGROUND:Nitrosation of a conserved cysteine residue at position 93 in the hemoglobin β chain (β93C) to form S-nitroso (SNO) hemoglobin (Hb) is claimed to be essential for export of nitric oxide (NO) bioactivity by the red blood cell (RBC) to mediate hypoxic vasodilation and cardioprotection. METHODS:To test this hypothesis, we used RBCs from mice in which the β93 cysteine had been replaced with alanine (β93A) in a number of ex vivo and in vivo models suitable for studying export of NO bioactivity. RESULTS:In an ex vivo model of cardiac ischemia/reperfusion injury, perfusion of a mouse heart with control RBCs (β93C) pretreated with an arginase inhibitor to facilitate export of RBC NO bioactivity improved cardiac recovery after ischemia/reperfusion injury, and the response was similar with β93A RBCs. Next, when human platelets were coincubated with RBCs and then deoxygenated in the presence of nitrite, export of NO bioactivity was detected as inhibition of ADP-induced platelet activation. This effect was the same in β93C and β93A RBCs. Moreover, vascular reactivity was tested in rodent aortas in the presence of RBCs pretreated with S-nitrosocysteine or with hemolysates or purified Hb treated with authentic NO to form nitrosyl(FeII)-Hb, the proposed precursor of SNO-Hb. SNO-RBCs or NO-treated Hb induced vasorelaxation, with no differences between β93C and β93A RBCs. Finally, hypoxic microvascular vasodilation was studied in vivo with a murine dorsal skin-fold window model. Exposure to acute systemic hypoxia caused vasodilatation, and the response was similar in β93C and β93A mice. CONCLUSIONS:RBCs clearly have the fascinating ability to export NO bioactivity, but this occurs independently of SNO formation at the β93 cysteine of Hb.

Published
2019

16. Differences in endothelial function between patients with Type 1 and Type 2 diabetes: effects of red blood cells and arginase.

Author

Tengbom, John, Kontidou, Eftychia, Collado, Aida, Jiangning Yang, Alvarsson, Michael, Brinck, Jonas, Rössner, Sophia, Zhichao Zhou, Pernow, John, and Mahdi, Ali

Subjects
TYPE 2 diabetes, TYPE 1 diabetes, ERYTHROCYTES, ARGINASE, ENDOTHELIUM diseases
Abstract

The mechanisms underlying endothelial dysfunction in Type 1 and Type 2 diabetes (T1DM and T2DM) are unresolved. The red blood cells (RBCs) with increased arginase activity induce endothelial dysfunction in T2DM, but the implications of RBCs and the role of arginase inhibition in T1DM are unexplored. We aimed to investigate the differences in endothelial function in patients with T1DM and T2DM, with focus on RBCs and arginase. Thirteen patients with T1DM and twenty-six patients with T2DM, matched for HbA1c and sex were included. In vivo endothelium-dependent and -independent vasodilation (EDV and EIDV) were assessed by venous occlusion plethysmography before and after administration of an arginase inhibitor. RBCs were co-incubated with rat aortic segments for 18h followed by evaluation of endothelium-dependent (EDR) and -independent relaxation (EIDR) in isolated organ chambers. In vivo EDV, but not EIDV, was significantly impaired in patients with T2DM compared with patients with T1DM. Arginase inhibition resulted in improved EDV only in T2DM. RBCs from patients with T2DM induced impaired EDR but not EIDR in isolated aortic segments, whereas RBCs from patients with T1DM did not affect EDR nor EIDR. The present study demonstrates markedly impaired EDV in patients with T2DM in comparison with T1DM. In addition, it highlights the divergent roles of RBCs and arginase in mediating endothelial dysfunction in T1DM and T2DM. While endothelial dysfunction is mediated via RBCs and arginase in T2DM, these phenomena are not prominent in T1DM thereby indicating distinct differences in underlying mechanisms. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

23. High-Dose Simvastatin Exhibits Enhanced Lipid-Lowering Effects Relative to Simvastatin/Ezetimibe Combination Therapy

Author

Snowden, Stuart G, Grapov, Dmitry, Settergren, Magnus, D'Alexandri, Fabio Luiz, Haeggström, Jesper Z, Fiehn, Oliver, Hyötyläinen, Tuulia, Pedersen, Theresa L, Newman, John W, Orešič, Matej, Pernow, John, and Wheelock, Craig E

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Heart Disease, Cardiovascular, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Aged, Analysis of Variance, Anticholesteremic Agents, Azetidines, Ceramides, Cholesterol, Cholesterol, LDL, Discriminant Analysis, Double-Blind Method, Drug Administration Schedule, Drug Combinations, Ezetimibe, Simvastatin Drug Combination, Female, Humans, Hypercholesterolemia, Male, Middle Aged, Phosphatidylcholines, Simvastatin, Sphingomyelins, Treatment Outcome, Triglycerides, eicosanoids, ezetimibe, hydroxymethylglutaryl-CoA reductase inhibitors, lipids, mass spectrometry, simvastatin, Genetics, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

Statins are the frontline in cholesterol reduction therapies; however, their use in combination with agents that possess complimentary mechanisms of action may achieve further reductions in low-density lipoprotein cholesterol. Thirty-nine patients were treated with either 80 mg simvastatin (n=20) or 10 mg simvastatin plus 10 mg ezetimibe (n=19) for 6 weeks. Dosing was designed to produce comparable low-density lipoprotein cholesterol reductions, while enabling assessment of potential simvastatin-associated pleiotropic effects. Baseline and post-treatment plasma were analyzed for lipid mediators (eg, eicosanoids and endocannabinoids) and structural lipids by liquid chromatography tandem mass spectrometry. After statistical analysis and orthogonal projections to latent structures multivariate modeling, no changes were observed in lipid mediator levels, whereas global structural lipids were reduced in response to both monotherapy (R(2)Y=0.74; Q(2)=0.66; cross-validated ANOVA P=7.0×10(-8)) and combination therapy (R(2)Y=0.67; Q(2)=0.54; cross-validated ANOVA P=2.6×10(-5)). Orthogonal projections to latent structures modeling identified a subset of 12 lipids that classified the 2 treatment groups after 6 weeks (R(2)Y=0.65; Q(2)=0.61; cross-validated ANOVA P=5.4×10(-8)). Decreases in the lipid species phosphatidylcholine (15:0/18:2) and hexosyl-ceramide (d18:1/24:0) were the strongest discriminators of low-density lipoprotein cholesterol reductions for both treatment groups (q

Published
2014

24. Influenza Vaccination After Myocardial Infarction: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial

Author

Fröbert, Ole, Götberg, Matthias, Erlinge, David, Akhtar, Zubair, Christiansen, Evald H., MacIntyre, Chandini R., Oldroyd, Keith G., Motovska, Zuzana, Erglis, Andrejs, Moer, Rasmus, Hlinomaz, Ota, Jakobsen, Lars, Engstrøm, Thomas, Jensen, Lisette O., Fallesen, Christian O., Jensen, Svend E, Angerås, Oskar, Calais, Fredrik, Kåregren, Amra, Lauermann, Jörg, Mokhtari, Arash, Nilsson, Johan, Persson, Jonas, Stalby, Per, Islam, Abu K.M.M., Rahman, Afzalur, Malik, Fazila, Choudhury, Sohel, Collier, Timothy, Pocock, Stuart J., and Pernow, John

Published
2021
Full Text
View/download PDF

30. Extracellular vesicles and their non‐coding RNA cargos: Emerging players in cardiovascular disease.

Author

Collado, Aida, Gan, Lu, Tengbom, John, Kontidou, Eftychia, Pernow, John, and Zhou, Zhichao

Abstract

Extracellular vesicles (EVs), including exosomes, microvesicles and apoptotic bodies, have recently received attention as essential mechanisms for cell‐to‐cell communication in cardiovascular disease. EVs can be released from different types of cells, including endothelial cells, smooth muscle cells, cardiac cells, fibroblasts, platelets, adipocytes, immune cells and stem cells. Non‐coding (nc)RNAs as EV cargos have recently been investigated in the cardiovascular system. Up‐ or downregulated ncRNAs in EVs have been shown to play a crucial role in various cardiovascular diseases. Communication via EV‐derived ncRNAs can occur between cells of the same type and between different types of cells involved in the pathophysiology of cardiovascular disease. In the present review, we highlight the important aspects of diverse cell‐derived EVs and their ncRNA cargos as disease mediators and potential therapeutic targets in atherosclerosis, coronary artery disease, ischaemic heart disease and cardiac fibrosis. In addition, we summarize the potential of EV‐derived ncRNAs in the treatment of cardiovascular disease. Finally, we discuss the different methods for EV isolation and characterization. A better understanding of the specific role of EVs and their ncRNA cargos in the regulation of cardiovascular (dys)function will be of importance for the development of diagnostic and therapeutic tools for cardiovascular disease. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

32. Clinical impact of influenza vaccination after ST- and non-ST-segment elevation myocardial infarction - from the IAMI trial

Author

Froebert, Ole, Goetberg, Matthias, Erlinge, David, Akhtar, Zubair, Christiansen, Evald H., MacIntyre, Chandini R., Oldroyd, Keith G., Motovska, Zuzana, Erglis, Andrejs, Moer, Rasmus, Hlinomaz, Ota, Jakobsen, Lars, Engstrom, Thomas, Jensen, Lisette O., Fallesen, Christian O., Jensen, Svend E., Angeras, Oskar, Calais, Fredrik, Karegren, Amra, Lauermann, Jörg, Mokhtari, Arash, Nilsson, Johan, Persson, Jonas, Stalby, Per, Islam, Abu K. M. M., Rahman, Afzalur, Malik, Fazila, Choudhury, Sohel, Collier, Timothy, Pocock, Stuart J., Pernow, John, Froebert, Ole, Goetberg, Matthias, Erlinge, David, Akhtar, Zubair, Christiansen, Evald H., MacIntyre, Chandini R., Oldroyd, Keith G., Motovska, Zuzana, Erglis, Andrejs, Moer, Rasmus, Hlinomaz, Ota, Jakobsen, Lars, Engstrom, Thomas, Jensen, Lisette O., Fallesen, Christian O., Jensen, Svend E., Angeras, Oskar, Calais, Fredrik, Karegren, Amra, Lauermann, Jörg, Mokhtari, Arash, Nilsson, Johan, Persson, Jonas, Stalby, Per, Islam, Abu K. M. M., Rahman, Afzalur, Malik, Fazila, Choudhury, Sohel, Collier, Timothy, Pocock, Stuart J., and Pernow, John

Abstract

Background Influenza vaccination early after myocardial infarction (MI) improves prognosis but vaccine effectiveness may differ dependent on type of MI. Methods A total of 2,571 participants were prospectively enrolled in the Influenza vaccination after myocardial infarction (IAMI) trial and randomly assigned to receive in-hospital inactivated influenza vaccine or saline placebo. The trial was conducted at 30 centers in eight countries from October 1, 2016 to March 1, 2020. Here we report vaccine effective-ness in the 2,467 participants with ST-segment elevation MI (STEMI, n = 1,348) or non-ST-segment elevation MI (NSTEMI, n = 1,119). The primary endpoint was the composite of all-cause death, MI, or stent thrombosis at 12 months. Cumulative incidence of the primary and key secondary endpoints by randomized treatment and NSTEMI/STEMI was estimated using the Kaplan-Meier method. Treatment effects were evaluated with formal interaction testing to assess for effect modification. Results Baseline risk was higher in participants with NSTEMI. In the NSTEMI group the primary endpoint occurred in 6.5% of participants assigned to influenza vaccine and 10.5% assigned to placebo (hazard ratio [HR], 0.60; 95% CI, 0.39-0.91), compared to 4.1% assigned to influenza vaccine and 4.5% assigned to placebo in the STEMI group (HR, 0.90; 95% CI, 0.54-1.50, P = .237 for interaction). Similar findings were seen for the key secondary endpoints of all-cause death and cardiovascular death. The Kaplan-Meier risk difference in all-cause death at one year was more pronounced in participants with NSTEMI (NSTEMI: HR, 0.47; 95% CI 0.28-0.80, STEMI: HR, 0.86; 95% CI, 0.43-1.70, interaction P = .028). Conclusions The beneficial effect of influenza vaccination on adverse cardiovascular events may be enhanced in patients with NSTEMI compared to those with STEMI., Funding Agencies|Swedish Heart-Lung Foundation [20150284]; Danish Heart Foundation [16-R107-A6596-22958]; ALF Grants; Nyckelfonden; Region Orebro, Sweden; SanofiPasteurr, Lyon, France

Published
2023
Full Text
View/download PDF

33. Long-Term Effects of Oxygen Therapy on Death or Hospitalization for Heart Failure in Patients With Suspected Acute Myocardial Infarction

Author

Jernberg, Tomas, Lindahl, Bertil, Alfredsson, Joakim, Berglund, Ellinor, Bergström, Olle, Engström, Anders, Erlinge, David, Herlitz, Johan, Jumatate, Raluca, Kellerth, Thomas, Lauermann, Jörg, Lindmark, Krister, Lingman, Markus, Ljung, Lina, Nilsson, Carina, Omerovic, Elmir, Pernow, John, Ravn-Fischer, Annica, Sparv, David, Yndigegn, Troels, Östlund, Ollie, James, Stefan K., and Hofmann, Robin

Published
2018
Full Text
View/download PDF

34. The red blood cell as a mediator of endothelial dysfunction in patients with familial hypercholesterolemia and dyslipidemia

Author

Mahdi, Ali, primary, Wodaje, Tigist, additional, Kövamees, Oskar, additional, Tengbom, John, additional, Zhao, Allan, additional, Jiao, Tong, additional, Henricsson, Marcus, additional, Yang, Jiangning, additional, Zhou, Zhichao, additional, Nieminen, Anni I., additional, Levin, Malin, additional, Collado, Aida, additional, Brinck, Jonas, additional, and Pernow, John, additional

Published
2022
Full Text
View/download PDF

35. Hyperbaric oxygen for treatment of long COVID-19 syndrome (HOT-LoCO): protocol for a randomised, placebo-controlled, double-blind, phase II clinical trial

Author

Kjellberg, Anders, primary, Abdel-Halim, Lina, additional, Hassler, Adrian, additional, El Gharbi, Sara, additional, Al-Ezerjawi, Sarah, additional, Boström, Emil, additional, Sundberg, Carl Johan, additional, Pernow, John, additional, Medson, Koshiar, additional, Kowalski, Jan H, additional, Rodriguez-Wallberg, Kenny A, additional, Zheng, Xiaowei, additional, Catrina, Sergiu, additional, Runold, Michael, additional, Ståhlberg, Marcus, additional, Bruchfeld, Judith, additional, Nygren-Bonnier, Malin, additional, and Lindholm, Peter, additional

Published
2022
Full Text
View/download PDF

39. Red blood cell eNOS is cardioprotective in acute myocardial infarction

Author

Cortese-Krott, Miriam M., primary, Suvorava, Tatsiana, additional, Leo, Francesca, additional, Heuser, Sophia K., additional, LoBue, Anthea, additional, Li, Junjie, additional, Becher, Stefanie, additional, Schneckmann, Rebekka, additional, Srivrastava, Tanu, additional, Erkens, Ralf, additional, Wolff, Georg, additional, Schmitt, Joachim P., additional, Grandoch, Maria, additional, Lundberg, Jon O., additional, Pernow, John, additional, Isakson, Brant E., additional, Weitzberg, Eddie, additional, and Kelm, Malte, additional

Published
2022
Full Text
View/download PDF

40. Downregulation of eNOS and preserved endothelial function in endothelial-specific arginase 1-deficient mice

Author

Heuser, Sophia K., primary, LoBue, Anthea, additional, Li, Junjie, additional, Zhuge, Zhengbing, additional, Leo, Francesca, additional, Suvorava, Tatsiana, additional, Olsson, Annika, additional, Schneckmann, Rebekka, additional, Guimaraes Braga, Drielle D., additional, Srivrastava, Tanu, additional, Montero, Lidia, additional, Schmitz, Oliver J., additional, Schmitt, Joachim P., additional, Grandoch, Maria, additional, Weitzberg, Eddie, additional, Lundberg, Jon O., additional, Pernow, John, additional, Kelm, Malte, additional, Carlström, Mattias, additional, and Cortese-Krott, Miriam M., additional

Published
2022
Full Text
View/download PDF

42. The size of myocardial infarction and peri-infarction edema are not major determinants of diastolic impairment after acute myocardial infarction

Author

Sundqvist, Martin G, primary, Verouhis, Dinos, additional, Sörensson, Peder, additional, Henareh, Loghman, additional, Persson, Jonas, additional, Saleh, Nawzad, additional, Settergren, Magnus, additional, Witt, Nils, additional, Böhm, Felix, additional, Pernow, John, additional, Tornvall, Per, additional, and Ugander, Martin, additional

Published
2022
Full Text
View/download PDF

43. Hyperbaric Oxygen for Treatment of Long COVID Syndrome (HOT-LoCO); Protocol for a Randomised, Placebo-Controlled, Double-Blind, Phase II Clinical Trial

Author

Kjellberg, Anders, primary, Abdel-Halim, Lina, additional, Hassler, Adrian, additional, Gharbi, Sara El, additional, Al-Ezerjawi, Sarah, additional, Boström, Emil, additional, Sundberg, Carl Johan, additional, Pernow, John, additional, Medson, Koshiar, additional, Kowalski, Jan, additional, Rodriguez-Wallberg, Kenny A, additional, Zheng, Xiaowei, additional, Catrina, Sergiu-Bogdan, additional, Runold, Michael, additional, Ståhlberg, Marcus, additional, Bruchfeld, Judith, additional, Nygren-Bonnier, Malin, additional, and Lindholm, Peter, additional

Published
2022
Full Text
View/download PDF

47. Safety and efficacy of the 5-lipoxygenase-activating protein inhibitor AZD5718 in patients with recent myocardial infarction:The phase 2a FLAVOUR study

Author

Prescott, Eva, Angerås, Oskar, Erlinge, David, Grove, Erik L., Hedman, Marja, Jensen, Lisette O., Pernow, John, Saraste, Antti, Åkerblom, Axel, Svedlund, Sara, Rudvik, Anna, Knöchel, Jane, Lindstedt, Eva Lotte, Garkaviy, Pavlo, Gan, Li Ming, Gabrielsen, Anders, Prescott, Eva, Angerås, Oskar, Erlinge, David, Grove, Erik L., Hedman, Marja, Jensen, Lisette O., Pernow, John, Saraste, Antti, Åkerblom, Axel, Svedlund, Sara, Rudvik, Anna, Knöchel, Jane, Lindstedt, Eva Lotte, Garkaviy, Pavlo, Gan, Li Ming, and Gabrielsen, Anders

Abstract

Background: Leukotrienes are pro-inflammatory vasoactive lipid mediators implicated in the pathophysiology of atherosclerotic cardiovascular disease. We studied the effect of the 5-lipoxygenase-activating protein inhibitor AZD5718 on leukotriene biosynthesis and coronary microvascular function in a single-blind, phase 2a study. Methods: Patients 7–28 days after myocardial infarction (±ST elevation), with <50% left anterior descending coronary artery stenosis and Thrombolysis in Myocardial Infarction flow grade ≥ 2 after percutaneous coronary intervention, were randomized 2:1:2 to once-daily AZD5718 200 mg or 50 mg, or placebo, in 4- and 12-week cohorts. Change in urine leukotriene E4 (uLTE4) was the primary endpoint, and coronary flow velocity reserve (CFVR; via echocardiography) was the key secondary endpoint. Results: Of 129 randomized patients, 128 received treatment (200 mg, n = 52; 50 mg, n = 25; placebo, n = 51). Statistically significant reductions in uLTE4 levels of >80% were observed in both AZD5718 groups versus the placebo group at 4 and 12 weeks. No significant changes in CFVR were observed for AZD5718 versus placebo. Adverse events (AEs) occurred in 12/18, 3/6 and 6/13 patients receiving 200 mg, 50 mg and placebo, respectively, in the 4-week cohort, and in 27/34, 14/19 and 24/38 patients, respectively, in the 12-week cohort. Serious AEs in seven patients receiving AZD5718 and four receiving placebo were not treatment-related, and there were no deaths. Conclusions: In patients with recent myocardial infarction, AZD5718 was well tolerated, and leukotriene biosynthesis was dose-dependently inhibited. No significant changes in CFVR were detected. ClinicalTrials.gov identifier: NCT03317002.

Published
2022

48. Oxygen Therapy in Suspected Acute Myocardial Infarction

Author

Hofmann, Robin, James, Stefan K., Jernberg, Tomas, Lindahl, Bertil, Erlinge, David, Witt, Nils, Arefalk, Gabriel, Frick, Mats, Alfredsson, Joakim, Nilsson, Lennart, Ravn-Fischer, Annica, Omerovic, Elmir, Kellerth, Thomas, Sparv, David, Ekelund, Ulf, Linder, Rickard, Ekström, Mattias, Lauermann, Jörg, Haaga, Urban, Pernow, John, Östlund, Ollie, Herlitz, Johan, and Svensson, Leif

Published
2017
Full Text
View/download PDF

50. Reply to letter to the editor by Lou et al

Author

Verouhis, Dinos, Sörensson, Peder, Gourine, Andrey, Henareh, Loghman, Persson, Jonas, Saleh, Nawzad, Settergren, Magnus, Sundqvist, Martin, Tornvall, Per, Witt, Nils, Böhm, Felix, and Pernow, John

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results