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Respiratory insufficiency correlated strongly with mortality of rodents infected with West Nile virus.

Morrey JD, Siddharthan V, Wang H, Hall JO - PLoS ONE (2012)

Bottom Line: Moreover, daily subcutaneous administration of 5% dextrose in physiological saline solution did not improve survival or other disease signs.Therefore, infected hamsters did not die from starvation or dehydration.Limited vasculitis was present in the right atrium of the heart of infected hamsters, but abnormal electrocardiograms for several days leading up to mortality did not occur.

View Article: PubMed Central - PubMed

Affiliation: Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah, United States of America. john.morrey@usu.edu

ABSTRACT
West Nile virus (WNV) disease can be fatal for high-risk patients. Since WNV or its antigens have been identified in multiple anatomical locations of the central nervous system of persons or rodent models, one cannot know where to investigate the actual mechanism of mortality without careful studies in animal models. In this study, depressed respiratory functions measured by plethysmography correlated strongly with mortality. This respiratory distress, as well as reduced oxygen saturation, occurred beginning as early as 4 days before mortality. Affected medullary respiratory control cells may have contributed to the animals' respiratory insufficiency, because WNV antigen staining was present in neurons located in the ventrolateral medulla. Starvation or dehydration would be irrelevant in people, but could cause death in rodents due to lethargy or loss of appetite. Animal experiments were performed to exclude this possibility. Plasma ketones were increased in moribund infected hamsters, but late-stage starvation markers were not apparent. Moreover, daily subcutaneous administration of 5% dextrose in physiological saline solution did not improve survival or other disease signs. Therefore, infected hamsters did not die from starvation or dehydration. No cerebral edema was apparent in WNV- or sham-infected hamsters as determined by comparing wet-to-total weight ratios of brains, or by evaluating blood-brain-barrier permeability using Evans blue dye penetration into brains. Limited vasculitis was present in the right atrium of the heart of infected hamsters, but abnormal electrocardiograms for several days leading up to mortality did not occur. Since respiratory insufficiency was strongly correlated with mortality more than any other pathological parameter, it is the likely cause of death in rodents. These animal data and a poor prognosis for persons with respiratory insufficiency support the hypothesis that neurological lesions affecting respiratory function may be the primary cause of human WNV-induced death.

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Hydration supportive therapy for WNV-infected hamsters.Six days after viral challenge just before the earliest disease signs appeared and up to 14 days after viral challenge, 10 hamsters were treated s.c. with D5 dextrose solution (5% dextrose, 0.9% physiological saline); and 10 hamsters were sham-injected. The animals were monitored through day 21 for A) mortality, B) weight change, and C) disease signs such as hind limb paralysis, front leg tremors, eye lacrimation, and diarrhea. Mortality was considered a disease sign too when constructing the graph. ***P≤0.001 using log rank test.
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pone-0038672-g002: Hydration supportive therapy for WNV-infected hamsters.Six days after viral challenge just before the earliest disease signs appeared and up to 14 days after viral challenge, 10 hamsters were treated s.c. with D5 dextrose solution (5% dextrose, 0.9% physiological saline); and 10 hamsters were sham-injected. The animals were monitored through day 21 for A) mortality, B) weight change, and C) disease signs such as hind limb paralysis, front leg tremors, eye lacrimation, and diarrhea. Mortality was considered a disease sign too when constructing the graph. ***P≤0.001 using log rank test.

Mentions: Since rodents used in infectious disease models [22] typically lose considerable amounts of body weight, including those infected with WNV [23], [24], we investigated whether rodents succumb to the disease simply because of dehydration or starvation from a loss of appetite or supportive care. Six days after viral challenge just before the earliest disease signs appeared and up to 14 days after viral challenge, 10 hamsters were treated intraperitoneally (i.p.) with 10 mL/day of D5 dextrose solution (5% dextrose, 0.9% physiological saline); and 10 hamsters were sham-injected without administration of any fluid. The animals were monitored through day 21 for mortality, weight change, and disease signs such as hind limb paralysis, front limb tremors, eye lacrimation, and diarrhea. Hydration did not improve survival or disease signs, so animals were not dying from dehydration (Figure 2A and 2C).


Respiratory insufficiency correlated strongly with mortality of rodents infected with West Nile virus.

Morrey JD, Siddharthan V, Wang H, Hall JO - PLoS ONE (2012)

Hydration supportive therapy for WNV-infected hamsters.Six days after viral challenge just before the earliest disease signs appeared and up to 14 days after viral challenge, 10 hamsters were treated s.c. with D5 dextrose solution (5% dextrose, 0.9% physiological saline); and 10 hamsters were sham-injected. The animals were monitored through day 21 for A) mortality, B) weight change, and C) disease signs such as hind limb paralysis, front leg tremors, eye lacrimation, and diarrhea. Mortality was considered a disease sign too when constructing the graph. ***P≤0.001 using log rank test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3375279&req=5

pone-0038672-g002: Hydration supportive therapy for WNV-infected hamsters.Six days after viral challenge just before the earliest disease signs appeared and up to 14 days after viral challenge, 10 hamsters were treated s.c. with D5 dextrose solution (5% dextrose, 0.9% physiological saline); and 10 hamsters were sham-injected. The animals were monitored through day 21 for A) mortality, B) weight change, and C) disease signs such as hind limb paralysis, front leg tremors, eye lacrimation, and diarrhea. Mortality was considered a disease sign too when constructing the graph. ***P≤0.001 using log rank test.
Mentions: Since rodents used in infectious disease models [22] typically lose considerable amounts of body weight, including those infected with WNV [23], [24], we investigated whether rodents succumb to the disease simply because of dehydration or starvation from a loss of appetite or supportive care. Six days after viral challenge just before the earliest disease signs appeared and up to 14 days after viral challenge, 10 hamsters were treated intraperitoneally (i.p.) with 10 mL/day of D5 dextrose solution (5% dextrose, 0.9% physiological saline); and 10 hamsters were sham-injected without administration of any fluid. The animals were monitored through day 21 for mortality, weight change, and disease signs such as hind limb paralysis, front limb tremors, eye lacrimation, and diarrhea. Hydration did not improve survival or disease signs, so animals were not dying from dehydration (Figure 2A and 2C).

Bottom Line: Moreover, daily subcutaneous administration of 5% dextrose in physiological saline solution did not improve survival or other disease signs.Therefore, infected hamsters did not die from starvation or dehydration.Limited vasculitis was present in the right atrium of the heart of infected hamsters, but abnormal electrocardiograms for several days leading up to mortality did not occur.

View Article: PubMed Central - PubMed

Affiliation: Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, Utah, United States of America. john.morrey@usu.edu

ABSTRACT
West Nile virus (WNV) disease can be fatal for high-risk patients. Since WNV or its antigens have been identified in multiple anatomical locations of the central nervous system of persons or rodent models, one cannot know where to investigate the actual mechanism of mortality without careful studies in animal models. In this study, depressed respiratory functions measured by plethysmography correlated strongly with mortality. This respiratory distress, as well as reduced oxygen saturation, occurred beginning as early as 4 days before mortality. Affected medullary respiratory control cells may have contributed to the animals' respiratory insufficiency, because WNV antigen staining was present in neurons located in the ventrolateral medulla. Starvation or dehydration would be irrelevant in people, but could cause death in rodents due to lethargy or loss of appetite. Animal experiments were performed to exclude this possibility. Plasma ketones were increased in moribund infected hamsters, but late-stage starvation markers were not apparent. Moreover, daily subcutaneous administration of 5% dextrose in physiological saline solution did not improve survival or other disease signs. Therefore, infected hamsters did not die from starvation or dehydration. No cerebral edema was apparent in WNV- or sham-infected hamsters as determined by comparing wet-to-total weight ratios of brains, or by evaluating blood-brain-barrier permeability using Evans blue dye penetration into brains. Limited vasculitis was present in the right atrium of the heart of infected hamsters, but abnormal electrocardiograms for several days leading up to mortality did not occur. Since respiratory insufficiency was strongly correlated with mortality more than any other pathological parameter, it is the likely cause of death in rodents. These animal data and a poor prognosis for persons with respiratory insufficiency support the hypothesis that neurological lesions affecting respiratory function may be the primary cause of human WNV-induced death.

Show MeSH
Related in: MedlinePlus