ABSTRACT
The study investigates whether combination therapy of sildenafil with imatinib at a low dose (20 mg/kg) further ameliorates pulmonary hypertension (PH) in rats. The effects on right ventricle pressure (RVP), and right ventricle hypertrophy (RVH) were assessed in experimental monocrotaline (MCT)-induced pulmonary hypertension. Combined therapy reversed the MCT-induced increase in RVP more than each drug alone and decreased RV hypertrophy (RV/LV+ S ratio), significantly. Such additive effects toward improvement of PH may result from both pharmacodynamic and pharmacokinetic drug-drug interactions, however, further studies are required to assess its mechanistic background.
Subject(s)
Hypertension, Pulmonary/drug therapy , Imatinib Mesylate/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Sildenafil Citrate/therapeutic use , Vasodilator Agents/therapeutic use , Animals , Blood Pressure/drug effects , Heart Rate/drug effects , Hypertension, Pulmonary/chemically induced , Hypertension, Pulmonary/physiopathology , Hypertrophy, Right Ventricular/prevention & control , Male , Monocrotaline , Rats , Rats, WistarABSTRACT
Various studies have shown that physical stimuli modulate cell function and this has motivated the development of a bioreactor to engineer tissues in vitro by exposing them to mechanical loads. Here, we present a bioreactor for the physical stimulation of anterior cruciate ligament (ACL) grafts, whereby complex multi-dimensional strain can be applied to the matrices. Influences from environmental conditions to the behavior of different cells on our custom-made silk scaffold can be investigated since the design of the bioreactor allows controlling these parameters precisely. With the braided design of the presented silk scaffold we achieve maximum loads and stiffness values matching those of the human ACL. Thus, the existent degummed and wet silk scaffolds absorb maximum loads of 2030±109 N with stiffness values of 336±40 N/mm.
