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Systemic mapping of organ plasma extravasation at multiple stages of chronic heart failure
Oliver Kitzerow1,2, Paul Suder2, Mohanad Shukry2
1Department of Genetics Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, United States.
Insights
This study reveals that myocardial infarction (MI) causes time-dependent plasma extravasation (PEx) in multiple organs. Different organs exhibit unique PEx patterns, suggesting varied underlying mechanisms in chronic heart failure (CHF) development.
Area of Science:
- Cardiovascular Biology
- Pathophysiology
- Organ Systems Biology
Background:
- Chronic heart failure (CHF) is a prevalent condition associated with significant morbidity and mortality.
- Diffuse vasculopathy and endothelial dysfunction contribute to increased vascular permeability and plasma extravasation (PEx) in CHF.
- Previous studies have not systematically examined the time-dependent PEx in various vital organs during CHF progression.
Purpose of the Study:
- To investigate the time-dependent plasma extravasation (PEx) in multiple visceral organs following myocardial infarction (MI) in a rat model.
- To compare PEx patterns across different organs at distinct time points post-MI.
- To explore potential differences in PEx pathogenesis during the development of chronic heart failure (CHF).
Main Methods:
- Induction of chronic heart failure (CHF) in rats via myocardial infarction (MI) or sham operation.
- Quantification of plasma extravasation (PEx) using Evans Blue (EB) concentration measurements.
- Assessment of PEx at three time points: 3 days, approximately 10 weeks, and 4 months post-MI.
Main Results:
- Cardiac PEx was initially high, then moderately elevated throughout the study period.
- Lung and liver PEx were elevated early (day 3) and sustained.
- Spleen PEx increased significantly at later time points (10 weeks and 4 months), while gastrointestinal and renal PEx showed significant increases at 4 months post-MI.
Conclusions:
- Myocardial infarction (MI) induces a time-dependent plasma extravasation (PEx) response in multiple visceral organs.
- The temporal patterns of PEx vary significantly among different organs.
- These organ-specific PEx dynamics suggest distinct pathophysiological mechanisms underlying vascular dysfunction in chronic heart failure (CHF).
Abstract:
Introduction: Chronic Heart failure (CHF) is a highly prevalent disease that leads to significant morbidity and mortality. Diffuse vasculopathy is a commonmorbidity associated with CHF. Increased vascular permeability leading to plasma extravasation (PEx) occurs in surrounding tissues following endothelial dysfunction. Such micro- and macrovascular complications develop over time and lead to edema, inflammation, and multi-organ dysfunction in CHF. However, a systemic examination of PEx in vital organs among different time windows of CHF has never been performed. In the present study, we investigated time-dependent PEx in several major visceral organs including heart, lung, liver, spleen, kidney, duodenum, ileum, cecum, and pancreas between sham-operated and CHF rats induced by myocardial infarction (MI). Methods: Plasma extravasation was determined by colorimetric evaluation of Evans Blue (EB) concentrations at 3 days, ∼10 weeks and 4 months following MI. Results: Data show that cardiac PEx was initially high at day 3 post MI and then gradually decreased but remained at a moderately high level at ∼10 weeks and 4 months post MI. Lung PEx began at day 3 and remained significantly elevated at both ∼10 weeks and 4 months post MI. Spleen PExwas significantly increased at ∼10 weeks and 4 months but not on day 3 post MI. Liver PEx occurred early at day 3 and remain significantly increased at ∼10 weeks and 4 months post MI. For the gastrointestinal (GI) organs including duodenum, ileum and cecum, there was a general trend that PEx level gradually increased following MI and reached statistical significance at either 10 weeks or 4 months post MI. Similar to GI PEx, renal PEx was significantly elevated at 4 months post MI. Discussion: In summary, we found that MI generally incites a timedependent PEx of multiple visceral organs. However, the PEx time window for individual organs in response to the MI challenge was different, suggesting that different mechanisms are involved in the pathogenesis of PEx in these vital organs during the development of CHF.
