title: New insights in the treatment strategy for pulmonary arterial hypertension.
abstract: BACKGROUND
  Recent advances in our understanding of the pathophysiological and molecular mechanisms involved in pulmonary arterial hypertension have led to the development of novel and rational pharmacological therapies. In addition to conventional therapy (i.e., supplemental oxygen and calcium channel blockers), prostacyclin or endothelin receptor antagonists have been recommended as a first-line therapy for pulmonary arterial hypertension. However, these treatments have potential limitations with regard to their long-term efficacy and improvement in survival. Furthermore, intravenous prostacyclin (epoprostenol) therapy, which is recommended by most experts for patients with New York Heart Association (NYHA) functional class IV, is complicated, uncomfortable for patients, and expensive because of the cumbersome administration system. Considering these circumstances, it is necessary to develop additional novel therapeutic approaches that target the various components of this multifactorial disease.
  
  
  METHODS
  In this short review, we present an overview of the current treatment options for pulmonary arterial hypertension and describe a case report with primary pulmonary hypertension. A male patient with NYHA functional class IV and showing no response to calcium channel blockers and prostacyclin exhibited significantly improved exercise tolerance and hemodynamics and long-term survival for more than 2.5 years after receiving an oral combination therapy of a phosphodiesterase type 5 inhibitor (sildenafil), phosphodiesterase type 3 inhibitor (pimobendan), and nicorandil.
  
  
  CONCLUSIONS
  We also discuss the background and plausible potential mechanisms involved in this case, as well as future perspectives in the treatment of pulmonary arterial hypertension.
authors.affiliation: Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan. saharam-tky@umin.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Sahara
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Imai
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakajima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yao
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Morita
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Hirata
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006801:Humans; D006976:Hypertension, Pulmonary / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D020108:Nicorandil / Q000627:therapeutic use; D020030:Nitric Oxide Donors / Q000627:therapeutic use; D010102:Oxygen Inhalation Therapy; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D010879:Piperazines / Q000627:therapeutic use; D011687:Purines / Q000627:therapeutic use; D011724:Pyridazines / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics; D020030:Nitric Oxide Donors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D011724:Pyridazines; D013450:Sulfones; D014665:Vasodilator Agents; D020108:Nicorandil; C041648:pimobendan; D000068677:Sildenafil Citrate