tetano
Editor, Senior Moderator
Antiviral Res. 2011 Aug 17. [Epub ahead of print]
Use of plethysmography in assessing the efficacy of antivirals in a mouse model of pandemic influenza A virus.
Julander JG, Hagloch J, Latimer S, Motter N, Dagley A, Barnard DL, Smee DF, Morrey JD.
Source
Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Sciences, Utah State University, 4700 Old Main Hill, Logan, UT 84322-5600, United States.
Abstract
The recently emerged swine-origin H1N1 influenza A virus (IAV) caused a pandemic outbreak in 2009 with higher risk of severe disease among children and pregnant women in their third trimester (Van Kerkhove et al., 2011), and is continuing to be important seasonal IAV strain. Mice are commonly used in antiviral studies as models of influenza disease, which utilize morbidity and mortality to assess the efficacy of a test compound. Here, we investigated the utility of unrestrained plethysomography to quantify the lung function of IAV-infected BALB/c mice. Administration of a lethal dose (∼30X LD(50)) of pandemic H1N1 IAV resulted in a rapid decline in breath volume, as determined by a significant (P<0.001) decrease in the pressure associated with inspiration and expiration detected as early as 2days after virus challenge. Severe disease was also accompanied by a significant (P<0.05) increase in breath time on 8dpi. Plethysmography parameters correlated with weight loss and other parameters of disease such as gross pathology and the weight of the lung. Breath time was reduced in surviving mice challenged with a sublethal dose of virus as compared with normal controls, and is a predictive indicator of outcome in these mice. In antiviral studies, the use of plethysmography resulted in the detection of a clear and rapid treatment response, which was similar to other non-invasive parameters, such as weight change. Oseltamivir and ribavirin significantly (P<0.001) improved parameters of lung function, particularly mean breath volume, as early as 2dpi and in a dose-dependent manner. Moreover, a combination of these two drugs further improved these parameters. Plethysmography provides a sensitive evaluation of lung function in IAV-infected mice in response to antiviral therapy.
Copyright ? 2011. Published by Elsevier B.V.
PMID:
21867731
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21867731
Use of plethysmography in assessing the efficacy of antivirals in a mouse model of pandemic influenza A virus.
Julander JG, Hagloch J, Latimer S, Motter N, Dagley A, Barnard DL, Smee DF, Morrey JD.
Source
Institute for Antiviral Research, Department of Animal, Dairy and Veterinary Sciences, Utah State University, 4700 Old Main Hill, Logan, UT 84322-5600, United States.
Abstract
The recently emerged swine-origin H1N1 influenza A virus (IAV) caused a pandemic outbreak in 2009 with higher risk of severe disease among children and pregnant women in their third trimester (Van Kerkhove et al., 2011), and is continuing to be important seasonal IAV strain. Mice are commonly used in antiviral studies as models of influenza disease, which utilize morbidity and mortality to assess the efficacy of a test compound. Here, we investigated the utility of unrestrained plethysomography to quantify the lung function of IAV-infected BALB/c mice. Administration of a lethal dose (∼30X LD(50)) of pandemic H1N1 IAV resulted in a rapid decline in breath volume, as determined by a significant (P<0.001) decrease in the pressure associated with inspiration and expiration detected as early as 2days after virus challenge. Severe disease was also accompanied by a significant (P<0.05) increase in breath time on 8dpi. Plethysmography parameters correlated with weight loss and other parameters of disease such as gross pathology and the weight of the lung. Breath time was reduced in surviving mice challenged with a sublethal dose of virus as compared with normal controls, and is a predictive indicator of outcome in these mice. In antiviral studies, the use of plethysmography resulted in the detection of a clear and rapid treatment response, which was similar to other non-invasive parameters, such as weight change. Oseltamivir and ribavirin significantly (P<0.001) improved parameters of lung function, particularly mean breath volume, as early as 2dpi and in a dose-dependent manner. Moreover, a combination of these two drugs further improved these parameters. Plethysmography provides a sensitive evaluation of lung function in IAV-infected mice in response to antiviral therapy.
Copyright ? 2011. Published by Elsevier B.V.
PMID:
21867731
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21867731