Efficiency of targeted delivery of streptokinase based on fibrin-specific liposomes in the in vivo experiment.

Acute thrombosis has a narrow therapeutic window and remains the leading cause of morbidity and mortality, while thrombolytic therapy has limited efficacy and risk of side effects. We have developed and investigated new fibrin-specific systems for local drug delivery to increase efficiency while minimizing the side effects of streptokinase. The experiment was carried out on dogs with 2-h thrombi in the femoral artery received intravenous injections of streptokinase, liposome-bound and free streptokinase at 40/60% ratio, and immunoliposomes.

Quantitative and qualitative analysis of pulmonary arterial hypertension fibrosis using wide-field second harmonic generation microscopy.

We demonstrated that wide-field second harmonic generation (SHG) microscopy of lung tissue in combination with quantitative analysis of SHG images is a powerful tool for fast and label-free visualization of the fibrosis pathogenesis in pulmonary arterial hypertension (PAH). Statistical analysis of the SHG images revealed changes of the collagen content and morphology in the lung tissue during the monocrotaline-induced PAH progression in rats. First order statistics disclosed the dependence of the collagen overproduction on time, the second order statistics indicated tightening of collagen fiber network around blood vessels and their spreading into the alveolar region.

Dependence of the Rate and Completeness of Fibrin Clot Destruction on the Acoustic Dose and Ultrasound Intensity.

The kinetics of fibrin clot destruction under catheter-delivered 32- to 45-kHz ultrasound (US) has been studied at 36°C-38°C in isotonic saline solution. A pseudo-first-order rate constant increased linearly from 0.06/min to 0.

Selexipag for the Treatment of Pulmonary Arterial Hypertension.

Background: In a phase 2 trial, selexipag, an oral selective IP prostacyclin-receptor agonist, was shown to be beneficial in the treatment of pulmonary arterial hypertension.

Methods: In this event-driven, phase 3, randomized, double-blind, placebo-controlled trial, we randomly assigned 1156 patients with pulmonary arterial hypertension to receive placebo or selexipag in individualized doses (maximum dose, 1600 μg twice daily). Patients were eligible for enrollment if they were not receiving treatment for pulmonary arterial hypertension or if they were receiving a stable dose of an endothelin-receptor antagonist, a phosphodiesterase type 5 inhibitor, or both.

Macitentan and morbidity and mortality in pulmonary arterial hypertension.

Background: Current therapies for pulmonary arterial hypertension have been adopted on the basis of short-term trials with exercise capacity as the primary end point. We assessed the efficacy of macitentan, a new dual endothelin-receptor antagonist, using a primary end point of morbidity and mortality in a long-term trial.

Methods: We randomly assigned patients with symptomatic pulmonary arterial hypertension to receive placebo once daily, macitentan at a once-daily dose of 3 mg, or macitentan at a once-daily dose of 10 mg.

Ultrasound-assisted thrombolysis with streptokinase improves thrombus resolution with minimal distal embolisation.

Catheter-directed ultrasound (US) has a synergistic effect on thrombus with streptokinase (SK). We aimed to assess whether a new method of arterial thrombolysis based on a combination of short-term US and intravenous SK administration can improve efficacy and minimize distal embolisation as compared to these two interventions applied separately. Experiments have been done on 23 mongrel dogs with ligature-induced femoral thrombosis divided into groups treated with (i) enzymatic thrombolysis (intravenous SK, n = 6), (ii) 36 kHz US-assisted thrombolysis (n = 6), (iii) US+SK applied together (n = 6), and (iv) control group with no treatment (n = 5).

Effects of low frequency ultrasound on some properties of fibrinogen and its plasminolysis.

Background: Pharmacological thrombolysis with streptokinase, urokinase or tissue activator of plasminogen (t-PA), and mechanical interventions are frequently used in the treatment of both arterial and venous thrombotic diseases. It has been previously reported that application of ultrasound as an adjunct to thrombolytic therapy offers unique potential to improve effectiveness. However, little is known about effects of the ultrasound on proteins of blood coagulation and fibrinolysis.

Combined low-frequency ultrasound and streptokinase intravascular destruction of arterial thrombi in vivo.

To prevent a distal embolization in the course of ultrasound (US) angioplasty, we combined US thrombus disruption in peripheral artery in vivo with simultaneous administration of streptokinase (SK). Acute thrombosis was induced in the femoral arteries of 23 dogs. Two hours after thrombus formation, thrombus destruction was performed using US (36 kHz) and by a combined US+SK (75,000 U/kg) administration.