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Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with a poor prognosis and limited treatment options. Many compounds have shown efficacy in preclinical models of this condition, but only pirfenidone and nintedanib have been approved for clinical use. It is widely accepted that the current animal models of IPF need to be improved and in this review we have critically evaluated the current state of play of preclinical models of IPF and discuss the challenges facing this field. The popular model of a single intratracheal (I.T.) administration of bleomycin could be adapted to provide a more progressive fibrosis as is thought to occur in humans. Furthermore, currently the majority of new drugs are investigated in preclinical models of IPF are dosed using a prophylactic dosing regimen, whereas patients are almost always treated after the fibrosis is well established. Using a therapeutic dosing regimen in preclinical models would be a better way to establish potential efficacy of new drugs. The most popular endpoints examined in pre-clinical models of IPF are histological scoring and lung collagen content. However in IPF patients imaging and lung function tests are more commonly used as end points. We propose that examining more clinically relevant endpoints in pre-clinical models could also provide give a better indication of a compound's potential efficacy on endpoints measured in patients.

Objective-To investigate the efficacy and safety of transcatheter radiofrequency-assisted valve dilatation for infants with pulmonary valve atresia and intact ventricular septum as an alternative to the use of laser heated wires.Design-Prospective clinical study. Setting-Three paediatric cardiology centres.Patients-Four children (aged 5-101 days, weight 2'8-4-3 kg) with pulmonary valve atresia and intact ventricular septum underwent percutaneous radiofrequency-assisted valve dilatation. Methods-After delineating the atretic valve by angiography, 0-020 inch or 0-018 inch radiofrequency wires were used to perforate the atretic valve. The valve was then dilated with conventional balloon dilatation catheters up to the valve annulus diameter.Results-In all four cases the radiofrequency wire perforated the atretic pulmonary valve and balloon dilatation was successful. In one patient the radiofrequency wire also passed through the anterior wall of the pulmonary artery causing tamponade which required surgical repair shortly afterwards. This patient died from sepsis six days later. One patient died three weeks after the procedure from septicaemia and a paradoxical coronary embolus. Two patients were discharged after 4 and 14 days respectively.Conclusions-Radiofrequency-assisted valve dilatation is a promising alternative to the recently developed laser wire technique. The major advantages are a reduction in cost and improved safety for the staff performing the procedure. (Br HeartJ_ 1993;69:347-351) Patients with pulmonary valve atresia and intact ventricular septum present a formidable therapeutic challenge to both surgeons and cardiologists. Despite the recent improved outlook for patients with many congenital heart defects this defect continues to be associated with a high mortality. Currently the most common surgical approach to neonates and infants consists of creating a systemic to pulmonary artery shunt together with an open pulmonary valvotomy either at the same or at a later procedure. The final corrective operation entails closure of the atrial septal defect and the systemic to pulmonary shunt but can only be performed if the right ventricle develops sufficiently.Alternatively further palliative shunting procedures or a Fontan repair are required if the right ventricle remains hypoplastic. We, and others, have recently shown the feasibility of percutaneous transcatheter "hot tip" laserassisted balloon dilatation.' 2 In some patients this approach can replace some or all of the conventional operative stages. To overcome some disadvantages associated with the use of lasers, we have investigated the use of transcatheter radiofrequency-assisted balloon dilatation of the pulmonary valve as an alternative and report our initial experience. Patients and methods PATIENTSPatient 1-A full term male infant with a birth weight of 2-8 kg became cyanosed and hypotensive a few hours after birth. After emergency resuscitation he was ventilated and prostaglandin and dobutamine infusions were started. Echocardiograph...