Limits...
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.

Show MeSH

Related in: MedlinePlus

Plasma ketone, creatine kinase, and blood chemistries in WNV-infected moribund hamsters.Twenty-three hamsters were injected with WNV and fifteen were injected with sham. When one WNV-injected hamster became moribund, the plasma was obtained from a corresponding non-moribund WNV-injected hamster. Numbers were unequal between the assays, because of insufficient sample volume to perform all assays. ###P≤0.001 compared to sham-infected, ***P≤0.001 compared to not-moribund infected using t-test.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3375279&req=5

pone-0038672-g003: Plasma ketone, creatine kinase, and blood chemistries in WNV-infected moribund hamsters.Twenty-three hamsters were injected with WNV and fifteen were injected with sham. When one WNV-injected hamster became moribund, the plasma was obtained from a corresponding non-moribund WNV-injected hamster. Numbers were unequal between the assays, because of insufficient sample volume to perform all assays. ###P≤0.001 compared to sham-infected, ***P≤0.001 compared to not-moribund infected using t-test.

Mentions: To determine if clinical tests could provide information as to the cause of death, such as starvation, a cohort of WNV-infected hamsters were observed for near-death condition (moribund). When one WNV-injected hamster became moribund, blood and tissues were collected from that hamster and from a corresponding not-moribund WNV-injected hamster. Sham-infected hamsters were also included. Plasma ketones, alkaline phosphatase (ALP), blood urea nitrogen (BUN), and globulin concentrations were statistically increased in moribund hamsters as compared to not-moribund or sham-infected hamsters (Figure 3). Glucose (GLU) was statistically elevated in both the moribund and not-moribund infected hamsters as compared to the sham-infected hamsters. All other chemistry panel tests were unaffected (alanine aminotransferase, albumin, creatinine, sodium, potassium, calcium, phosphorous, amylase, and total protein).


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

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

Plasma ketone, creatine kinase, and blood chemistries in WNV-infected moribund hamsters.Twenty-three hamsters were injected with WNV and fifteen were injected with sham. When one WNV-injected hamster became moribund, the plasma was obtained from a corresponding non-moribund WNV-injected hamster. Numbers were unequal between the assays, because of insufficient sample volume to perform all assays. ###P≤0.001 compared to sham-infected, ***P≤0.001 compared to not-moribund infected using t-test.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0038672-g003: Plasma ketone, creatine kinase, and blood chemistries in WNV-infected moribund hamsters.Twenty-three hamsters were injected with WNV and fifteen were injected with sham. When one WNV-injected hamster became moribund, the plasma was obtained from a corresponding non-moribund WNV-injected hamster. Numbers were unequal between the assays, because of insufficient sample volume to perform all assays. ###P≤0.001 compared to sham-infected, ***P≤0.001 compared to not-moribund infected using t-test.
Mentions: To determine if clinical tests could provide information as to the cause of death, such as starvation, a cohort of WNV-infected hamsters were observed for near-death condition (moribund). When one WNV-injected hamster became moribund, blood and tissues were collected from that hamster and from a corresponding not-moribund WNV-injected hamster. Sham-infected hamsters were also included. Plasma ketones, alkaline phosphatase (ALP), blood urea nitrogen (BUN), and globulin concentrations were statistically increased in moribund hamsters as compared to not-moribund or sham-infected hamsters (Figure 3). Glucose (GLU) was statistically elevated in both the moribund and not-moribund infected hamsters as compared to the sham-infected hamsters. All other chemistry panel tests were unaffected (alanine aminotransferase, albumin, creatinine, sodium, potassium, calcium, phosphorous, amylase, and total protein).

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