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- Rysz, S, et al.
(författare)
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COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin-aldosterone system
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 2417-
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Tidskriftsartikel (refereegranskat)abstract
- SARS-CoV-2 uses ACE2, an inhibitor of the Renin-Angiotensin-Aldosterone System (RAAS), for cellular entry. Studies indicate that RAAS imbalance worsens the prognosis in COVID-19. We present a consecutive retrospective COVID-19 cohort with findings of frequent pulmonary thromboembolism (17%), high pulmonary artery pressure (60%) and lung MRI perfusion disturbances. We demonstrate, in swine, that infusing angiotensin II or blocking ACE2 induces increased pulmonary artery pressure, reduces blood oxygenation, increases coagulation, disturbs lung perfusion, induces diffuse alveolar damage, and acute tubular necrosis compared to control animals. We further demonstrate that this imbalanced state can be ameliorated by infusion of an angiotensin receptor blocker and low-molecular-weight heparin. In this work, we show that a pathophysiological state in swine induced by RAAS imbalance shares several features with the clinical COVID-19 presentation. Therefore, we propose that severe COVID-19 could partially be driven by a RAAS imbalance.
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- Rysz, S, et al.
(författare)
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The Use of Levosimendan after Out-of-Hospital Cardiac Arrest and Its Association with Outcome-An Observational Study
- 2022
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Levosimendan improves resuscitation rates and cardiac performance in animal cardiac arrest models. The aim of this study was to describe the use of levosimendan in out-of-hospital cardiac arrest (OHCA) patients and its association with outcome. Methods: A retrospective observational study of OHCA patients admitted to six intensive care units in Stockholm, Sweden, between 2010 and 2016. Patients treated with levosimendan within 24 h from admission were compared with those not treated with levosimendan. Propensity score matching and multivariable logistic regression analysis were used to assess the association between levosimendan treatment and 30-day mortality Results: Levosimendan treatment was initiated in 94/940 (10%) patients within 24 h. The proportion of men (81%, vs. 67%, p = 0.007), initial shockable rhythm (66% vs. 37%, p < 0.001), acute myocardial infarction, AMI (47% vs. 24%, p < 0.001) and need for vasoactive support (98% vs. 61%, p < 0.001) were higher among patients treated with levosimendan. After adjustment for age, sex, bystander cardiopulmonary resuscitation, witnessed status, initial rhythm and AMI, the odds ratio (OR) for 30-day mortality in the levosimendan group compared to the no-levosimendan group was 0.94 (95% Confidence interval [CI], 0.56–1.57, p = 0.82). Similar results were seen when using a propensity score analysis comparing patients with circulatory shock. Conclusions: In this observational study of OHCA patients, levosimendan was used in a limited patient group, most often in those with initial shockable rhythms, acute myocardial infarction and with a high need for vasopressors. In this limited patient cohort, levosimendan treatment was not associated with 30-day mortality. However, a better matching of patient factors and indications for use is required to derive conclusions on associations with outcome.
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