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Cardiovascular collapse and vascular permeability changes in an ovine model of methicillin-resistant Staphylococcus
Collette C Jonkam1, Matthias Lange, Daniel L Traber
1Department of Anesthesiology, The University of Texas Medical Branch and Shriners Hospital for Children, Galveston, Texas, USA. ccjonkam@utmb.edu
Abstract:
Methicillin-resistant Staphylococcus aureus (MRSA) infections with severe outcomes such as sepsis and septic shock are progressively increasing in both the community and in hospital settings. We hypothesized that overexpression of reactive nitrogen and oxygen species and vascular endothelial growth factor (VEGF) play a pivotal role in cardiovascular collapse associated with vascular hyperpermeability in MRSA sepsis. Twelve sheep were surgically prepared and randomized into a control (noninjured; n = 6) and a sepsis (injured; n = 6) group. Animals in the sepsis group were subjected to cotton smoke inhalation and instillation of 2.5 x 10(11) colony-forming units of live MRSA into both lungs. Cardiovascular variables in the control group remained stable, whereas the MRSA sepsis group developed a hypotensive and hyperdynamic circulatory shock state beginning at 6 h associated with significantly increased vascular permeability evidenced by increased prefemoral lymph flow starting at 12 h and permeability index from 12 to 18 h, higher fluid accumulation from 12 to 24 h, and significantly decreased plasma protein concentration and oncotic pressure beginning at 6 h compared with control animals. Myocardial 3-nitrotyrosine (3-NT) protein, poly (adenosine diphosphate-ribose), and VEGF mRNA expressions measured after the 24-h experiment were significantly increased in the injured animals as well. These results evidence that excessive production of reactive radicals and VEGF may play a major role in cardiovascular collapse and vascular hyperpermeability in MRSA sepsis.
Insights
Severe Methicillin-resistant Staphylococcus aureus (MRSA) sepsis causes cardiovascular collapse. Excessive reactive radicals and vascular endothelial growth factor (VEGF) contribute to this shock and vascular hyperpermeability.
Area of Science:
- Cardiovascular Physiology
- Infectious Diseases
- Pathophysiology
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) infections are increasing, leading to severe outcomes like sepsis and septic shock.
- Cardiovascular collapse and vascular hyperpermeability are critical complications of MRSA sepsis.
Purpose of the Study:
- To investigate the role of reactive nitrogen and oxygen species and vascular endothelial growth factor (VEGF) in MRSA sepsis-induced cardiovascular collapse.
- To examine the impact of MRSA sepsis on vascular permeability and myocardial markers.
Main Methods:
- A sheep model was used, with animals subjected to cotton smoke inhalation and MRSA instillation.
- Cardiovascular variables, vascular permeability, fluid accumulation, plasma protein concentration, and myocardial expressions of 3-nitrotyrosine (3-NT) and VEGF were measured.
Main Results:
- MRSA sepsis induced a hypotensive and hyperdynamic circulatory shock state.
- Increased vascular permeability, fluid accumulation, and decreased plasma protein/oncotic pressure were observed in septic animals.
- Myocardial 3-NT protein, poly (ADP-ribose), and VEGF mRNA expressions were significantly elevated in the MRSA sepsis group.
Conclusions:
- Excessive production of reactive radicals and VEGF plays a significant role in cardiovascular collapse during MRSA sepsis.
- These factors contribute to the development of vascular hyperpermeability in MRSA sepsis.
- Understanding these mechanisms is crucial for managing severe MRSA infections.
