Developing therapeutic methods for the prevention of progressive pulmonary arterial remodelling and treatment of right ventricular heart failure

Abstract

A significant proportion of patients with congenital heart disease, in particular those with increased pulmonary blood flow, will develop pulmonary arterial hypertension (PAH). Research underway by a team at the Tokushima University's Department of Paediatrics aims to investigate and eventually implement innovative methods to diagnose and treat patient suffering from this condition. The team is led by Professor Yasunobu Hayabuchi, a paediatric cardiologist who has published more than 100 articles in cardiology and cardiovascular pathophysiology and is primarily involved in treating infants and children suffering from congenital heart diseases, who is working closely with his colleague Dr Yukako Homma. "PAH is a chronic refractory disease with the clinical conditions of persistently elevated pulmonary arterial pressure and pulmonary vascular resistance from various causes, and a poor prognosis with progressive exacerbation of right heart failure and respiratory failure," explains Hayabuchi. What makes this disease very difficult to diagnose in the first place, but even in cases where the disease has significantly progressed, is that hypertension in the pulmonary artery manifests with no apparent reason. Despite the fact that the respective symptoms of this disease are evident, such as shortness of breath, especially during walking or exercise, chest pain and fainting episodes, it is often hard to identify PAH because these symptoms may be confused with other diseases that cause hypoxia in blood and promote hypertension. Nevertheless, say Hayabuchi, the major pathological finding that characterises PAH is the narrowing of the pulmonary arterial lumen that can come as a result of three distinct factors. "These include abnormal constriction of peripheral small pulmonary arteries to less than 500m in diameter, vascular remodelling from the over-proliferation of vascular endothelial, smooth muscle, and other cells and resistance to apoptosis, and the formation of thrombus in the respective affected sites." However, and owing to the fact that pulmonary arteries carry blood from the right side of the heart to the lungs, PAH leads to right heart failure and ultimately death if left untreated. This is exactly why Hayabuchi and his team have dedicated their research on investigating the pathophysiology of this disease in order to implement innovative approaches that can improve the diagnosis and the treatment of this disease. "We study the pathophysiological condition of pulmonary arterial hypertension and therapeutic methods from the viewpoint of the prevention of progressive pulmonary arterial remodelling and treatment of right ventricular heart failure," outlines Hayabuchi.