Related Experiment Videos
Long-term Urokinase Therapy and Isovolemic Hemodilution: A Clinical and Hemodynamic Comparison in Patients with
1Medizinische Klinik und Poliklinik B, Klinik für Kardiologie, Pneumologie und Angiologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany
Insights
Long-term urokinase therapy significantly reduced angina symptoms and improved hemodynamics in patients with severe coronary artery disease. Isovolemic hemodilution showed no significant benefit, suggesting urokinase is a more effective anti-ischemic treatment.
Area of Science:
- Cardiology
- Hematology
Background:
- Symptomatic coronary artery disease (CAD) often presents refractory angina.
- Long-term urokinase therapy and isovolemic hemodilution (IVH) have shown anti-ischemic effects.
- A direct comparison between urokinase therapy and IVH in CAD patients is lacking.
Purpose of the Study:
- To compare the anti-ischemic effectiveness of long-term urokinase therapy versus isovolemic hemodilution in patients with refractory angina pectoris and end-stage CAD.
- To assess the impact of these therapies on clinical symptoms, rheologic parameters, and invasive hemodynamic measurements.
Main Methods:
- A 12-week study comparing urokinase therapy (n=11) with isovolemic hemodilution (n=9) in patients with clinical functional class III CAD.
- Both interventions were administered in addition to maximal conventional treatment.
- Clinical symptoms, rheologic parameters (fibrinogen, plasma viscosity, hematocrit, whole blood viscosity), and hemodynamic parameters (at rest and during exercise) were assessed before and after treatment.
Main Results:
- Urokinase therapy significantly reduced anginal events, fibrinogen levels, and plasma viscosity.
- Isovolemic hemodilution significantly decreased hematocrit and whole blood viscosity but did not improve clinical symptoms or other rheologic parameters.
- Urokinase therapy improved resting hemodynamic parameters, notably reducing pulmonary capillary wedge pressure, while IVH showed no significant hemodynamic changes.
Conclusions:
- Long-term intermittent urokinase therapy effectively reduces clinical symptoms and improves resting pulmonary capillary wedge pressure in patients with severe CAD.
- The observed hemodynamic improvements with urokinase may be attributed to enhanced myocardial perfusion via rheological effects on the coronary microcirculation.
- Isovolemic hemodilution appears to offer no significant benefit in this patient population.
Abstract:
Antiischemic effectiveness of long-term urokinase therapy and isovolemic hemodilution therapy has been reported in patients with symptomatic coronary artery disease, but both interventions have never been compared. In patients with refractory angina pectoris and end-stage coronary artery disease (clinical functional class III), isovolemic hemodilution (n = 9) (hydroxyethyl starch solution 6%, 1-2 times/week), and urokinase therapy (n = 11) (500,000 U urokinase per i.v. injection, 3 times a week) were performed over a period of 12 weeks, each additionally to maximal conventional treatment. Apart from the assessment of clinical symptoms and rheologic parameters, invasive hemodynamic measurements were carried out at rest and during exercise testing before and after treatment. After treatment with urokinase, patients showed a significant reduction of clinical symptoms (from 19.8 +/- 6.5 to 5.0 +/- 4.3 anginal events/week, p < 0.001), fibrinogen (from 410 +/- 88 to 238 +/- 40 mg/dl, p < 0.001), plasma viscosity (from 1.45 +/- 0.10 to 1.33 +/- 0.03 mPa x s-1, p < 0.01), and no changes of hematocrit (from 0.45 +/- 0.02 to 0.45 +/- 0.02) and whole blood viscosity (from 4.7 +/- 0.5 to 4.4 +/- 0.7 mPa x s-1); however, hemodilution resulted in a decrease of hematocrit (from 0.46 +/- 0.01 to 0.39 +/- 0.01, p < 0.001) and whole blood viscosity (from 4.7 +/- 0.5 to 4.0 +/- 0.3 mPa x s-1, p < 0.001) and no changes of initially comparable levels of clinical symptoms, fibrinogen, and plasma viscosity. Hemodynamic parameters at rest improved after urokinase therapy with a reduction of pulmonary capillary wedge pressure (from 9.1 +/- 5.1 to 5.5 +/- 2.8 mmHg, p < 0.05) at comparable levels of systemic vascular resistance (from 1510 +/- 340 to 1420 +/- 510 dyn x s x cm-5). Hemodilution did not result in any significant hemodynamic changes. Apart from clinical symptoms, long-term intermittent urokinase therapy reduces pulmonary capillary wedge pressure at rest. This may reflect an improved diastolic function due to a rheological enhancement of myocardial perfusion at the level of the coronary microcirculation. Isovolemic hemodilution seems to be of no benefit.