VPB1292 - Contribution of isoproterenol in hemostatic alterations in vivo

Background: Chronic sympathetic (over)activity is a known feature of many inflammatory diseases including sepsis and COVID-19 and is presented with high levels of circulant catecholamines that are associated with poor outcomes including thrombotic episodes derived from hemostatic alterations, multi organic failure and death.

The β-adrenergic receptor (β-AR) subtype is known for regulate cardiac function and interestingly, emerging evidence has shown that β-AR overactivity exerts deleterious effects besides of cardiac dysfunction, for instance, boosting inflammation through the enhanced expression of pro-inflammatory cytokines as TNF-α, IL-1β, IL-6 and IL-18.

Aims: Considering the known crosstalk between inflammation and coagulation/thrombosis, we aimed to explore whether β-AR stimulation promote hemostatic alterations conducing to thrombotic episodes.

Methods: Male Sprague-Dawley rats aged 8 weeks were anesthetized with isoflurane and subcutaneously injected with a single dose of the β-AR agonist, isoproterenol (ISO, 5 mg/kg of body weight) in 2 mL (4 bolus of 500 µL) or the same volume of saline (n = 3). At 3 hours blood were collected, centrifugated at 1500g for 15 minutes and plasma was undergone to hematological and coagulation analysis. Kidneys were harvested for histopathological analysis. The results are presented as ±SD. Significant differences were assessed by the t-student test (Mann-Whitney). The experimental protocols were approved by the Bioethics and Biosafety Committee of the Andrés Bello University.

Results: ISO treated rats exhibited decreased lymphocytes, red blood cells, hemoglobin and hematocrit. Conversely, granulocytes and d-dimer levels were increased in ISO rats regarding to controls. Histopathological analysis of ISO treated rats showed high vascular presence of red blood cells.

Conclusion(s): ISO stimulation promotes in vivo alterations in hemostasia that could enhance procoagulant states. Results suggest that β-AR could be considered as target to improve the treatment of patients with inflammatory diseases, to reduce hemostatic alterations and procoagulant states.