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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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Telemetric 2-lead electrocardiograms from WNV-infected hamsters taken over the course of disease.Example of normal ECG from a hamster (#229) at day 0 where the erroneous signal was identified by a drop in the signal strength. Example of abnormal ECGs of two infected hamsters at time of death (#74) and within 6 hr of death (#239).
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pone-0038672-g004: Telemetric 2-lead electrocardiograms from WNV-infected hamsters taken over the course of disease.Example of normal ECG from a hamster (#229) at day 0 where the erroneous signal was identified by a drop in the signal strength. Example of abnormal ECGs of two infected hamsters at time of death (#74) and within 6 hr of death (#239).

Mentions: To investigate heart disease as a possible cause of death, ECGs from resting hamsters were monitored by telemetry over the course of disease (Figure 4). To eliminate erroneous ECG tracings using the computer software, poor tracings were identified and eliminated when the signal strength was low. For example, hamster #229 had normal ECG where the erroneous signals were identified by a drop in signal strength. Within the limits of a 2-lead telemetry, ECG functions of the computer program allowed us to determine that there were no consistent pathological patterns (ST elevation, ectopic P waves, arrhythmia, tachycardia or bradycardia, and fibrillation) to account for heart disease as the cause of death. We did observe varied abnormal ECGs occurring within hours of the death (Figure 4) that were consistent with the death process, but we did not interpret these pathological events as the cause of mortality developing from the WNND over the course of days. Moreover, the ECG abnormalities just before mortality varied between animals.


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

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

Telemetric 2-lead electrocardiograms from WNV-infected hamsters taken over the course of disease.Example of normal ECG from a hamster (#229) at day 0 where the erroneous signal was identified by a drop in the signal strength. Example of abnormal ECGs of two infected hamsters at time of death (#74) and within 6 hr of death (#239).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0038672-g004: Telemetric 2-lead electrocardiograms from WNV-infected hamsters taken over the course of disease.Example of normal ECG from a hamster (#229) at day 0 where the erroneous signal was identified by a drop in the signal strength. Example of abnormal ECGs of two infected hamsters at time of death (#74) and within 6 hr of death (#239).
Mentions: To investigate heart disease as a possible cause of death, ECGs from resting hamsters were monitored by telemetry over the course of disease (Figure 4). To eliminate erroneous ECG tracings using the computer software, poor tracings were identified and eliminated when the signal strength was low. For example, hamster #229 had normal ECG where the erroneous signals were identified by a drop in signal strength. Within the limits of a 2-lead telemetry, ECG functions of the computer program allowed us to determine that there were no consistent pathological patterns (ST elevation, ectopic P waves, arrhythmia, tachycardia or bradycardia, and fibrillation) to account for heart disease as the cause of death. We did observe varied abnormal ECGs occurring within hours of the death (Figure 4) that were consistent with the death process, but we did not interpret these pathological events as the cause of mortality developing from the WNND over the course of days. Moreover, the ECG abnormalities just before mortality varied between animals.

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