ABSTRACT
BACKGROUND: A balanced endogenous level of bioavailable nitric oxide (NO) plays a key role in maintaining cardiovascular homeostasis. The bioactive NO level in the cardiomyocytes was much reduced during sepsis. However, it is clinically challenging for the NO gas therapy due to the lack of spatial and temporal release system with precise control. The purpose of this study is to design a NO-releasing biomaterial with heart-targeted capability responsive to the infectious microenvironment, thus ameliorating lipopolysaccharide (LPS)-induced cardiac dysfunction. RESULTS: The heart-targeted NO delivery and in situ releasing system, PCM-MSN@LA, was synthesized using hollow mesoporous silica nanoparticles (MSN) as the carrier, and L-arginine (LA) as the NO donor. The myocardial delivery was successfully directed to heart by specific peptide (PCM) combined with low-intensity focused ultrasound (LIFU) guidance. The myocardial system synthesized NO from the LA released from PCM-MSN@LA in the presence of increased endogenous nitric oxide synthase (NOS) activity induced by LPS. This targeted NO release in situ achieved extraordinary protective effects against LPS-challenged myocardial injury by reducing the recruitment of inflammatory cells, inhibiting oxidative stress and maintaining the mitochondria integrity. In particular, this protection was not compromised by simultaneous circulation collapse as an adverse event in the context. CONCLUSIONS: PCM-MSN@LA + LIFU exhibited extraordinary cardioprotective effects against severe sepsis in the hearts of LPS-treated animals without the side effect of NO diffusion. This technology has great potential to be served as a novel therapeutic strategy for sepsis-induced myocardial injury.
Subject(s)
Nitric Oxide , Sepsis , Animals , Lipopolysaccharides , Myocardium , Myocytes, Cardiac , Sepsis/drug therapyABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused a worldwide pandemic and poses a serious public health risk. It has been proven that lung ultrasound can be extremely valuable in the diagnosis and treatment of the disease, which could also minimize the number of exposed healthcare workers and equipment. Because healthcare workers in ultrasound departments are in close contact with patients who might be infected or virus carriers, it is extremely important that they be provided sufficient protection. Extremely aggressive protection should be avoided because it might lead to a lack of protection equipment for the hospital. Guidance on proper protection management should be provided in detail, for example, how to choose personal protective equipment, how to disinfect the environment. To address these problems, on behalf of the Chinese Ultrasound Doctors Association, Chinese PLA Professional Committee of Ultrasound in Medicine, Beijing Institute of Ultrasound in Medicine and Chinese Research Hospital Association Ultrasound Professional Committee, the authors have summarized the recommendations for effective protection according to existing hygienic standards, their experience and available literature. After the recommendations were completed, two online conferences were held on January 31, 2020 and February 7, 2020, at which the recommendations were discussed in detail. A modified version of the work was circulated and finally approved by all authors, and is the present Chinese Expert Consensus on Protection for Ultrasound Healthcare Workers against COVID-19.