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Tissue plasminogen activator release in chronic venous hypertension due to heart failure
1University Medical Centre, Trnovo Hospital of Internal Medicine, Ljubljana, Slovenia.
Insights
Heart failure impairs blood clot breakdown, particularly in right-sided cases. This reduced fibrinolytic activity stems from poor tissue plasminogen activator release, not elevated inhibitor levels, linked to venous hypertension.
Area of Science:
- Cardiovascular Physiology
- Hemostasis and Thrombosis
- Heart Failure Pathophysiology
Background:
- Chronic venous hypertension is a known complication of heart failure.
- Fibrinolytic activity, crucial for dissolving blood clots, may be affected by heart failure.
- Previous studies suggested impaired fibrinolysis in heart failure patients.
Purpose of the Study:
- To investigate the impact of chronic venous hypertension from heart failure on blood fibrinolytic activity.
- To compare fibrinolytic markers between patients with right-sided heart failure, left-sided heart failure, and healthy controls.
- To determine the underlying mechanisms of impaired fibrinolysis in heart failure.
Main Methods:
- Measured tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) antigen and activity.
- Assessed these markers before and after 20-minute arm venous occlusion.
- Included 15 right-sided heart failure patients, 15 left-sided heart failure patients, and 30 controls.
- Monitored central venous pressure to confirm heart failure types.
Main Results:
- No significant differences in basal t-PA and PAI-1 levels were observed between groups.
- Post-occlusion, t-PA antigen increase was significantly lower in right-sided heart failure patients (28.6 ng/ml) compared to left-sided (54.5 ng/ml) and controls (45.9 ng/ml).
- PAI-1 levels and activity did not differ significantly between groups after occlusion.
Conclusions:
- The impaired increase in fibrinolytic activity in heart failure is primarily due to reduced t-PA release during venous occlusion.
- This diminished t-PA release is specific to patients with right-sided heart failure.
- Chronic systemic venous hypertension in right-sided heart failure is likely the cause of the blunted fibrinolytic response.
Abstract:
In order to study the effects of chronic venous hypertension due to heart failure on blood fibrinolytic activity, tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor 1 (PAI-1) antigen, t-PA activity and PAI activity were measured before and after venous occlusion of the arm for 20 min in 15 patients with right-sided heart failure, 15 patients with left-sided heart failure, and 30 control healthy subjects. Central venous pressure, measured by observing the jugular veins, was above 15 cm of the blood column in all patients with right-sided heart failure, and normal (below 8 cm) in all patients with left-sided heart failure and control subjects. There was no difference in the basal concentrations of t-PA (11.0, 10.2 and 10.8 ng/ml; all values medians) and PAI-1 antigens and their activities between right and left-sided heart failure and the control subjects. After the occlusion, t-PA antigen increased significantly less in right-sided heart failure (28.6 ng/ml) than in left-sided heart failure and the control subjects (54.5 and 45.9 ng/ml, respectively). It was concluded that the poor increase in fibrinolytic activity that had already been reported in patients with heart failure, was due to low t-PA release during occlusion and not to a high basal PAI level. It was limited to the patients with right-sided heart failure and was probably the consequence of chronic systemic venous hypertension.