As described in this month’s target of the month, pulmonary hypertension is a common consequence of cardiac disorders, pulmonary disorders (COPD), or both in combination. Unrelieved pulmonary hypertension, regardless of the underlying cause, leads to right ventricular failure. Cardiac diseases produce pulmonary hypertension via volume or pressure overload although subsequent intimal proliferation of pulmonary resistance vessels adds an obstructive element. One common cause of pulmonary hypertension is embolism.

Pulmonary embolism is the third most common cause of death in the US and has been termed the "silent killer". Autopsy results show that as many as 60% of patients that die in hospital have had a pulmonary embolism, but the diagnosis is missed in about 70% of the cases. As a result, of the 650,000 cases occurring annually, over 200,000 victims die. Acute pulmonary embolism is a dynamic process. Thrombi begin to lyse immediately after reaching the lung. Usually, lysis is complete within several weeks in the absence of preexisting cardiopulmonary disease; in some instances, even large thrombi may lyse in a few days. The physiologic alterations lessen over hours or days as pulmonary circulation improves. However, massive emboli may cause death within minutes or hours. The treatment of massive pulmonary embolism involves either surgical intervention or the use of thrombolytics followed by anti-coagulant/anti-thrombotic drugs. Roughly 0.1 to 0.5% of patients who survive acute pulmonary embolism develop chronic thromboembolic disease and without surgical intervention, survival of these patients is poor. Since only a small percentage of patients with chronic thromboembolic pulmonary hypertension are eligible for pulmonary thrombendarterectomy improved treatments of thromboembolic pulmonary hypertension are required.

In a recent study Hossein Ghofrani from Justus-Liebig-University in Germany and colleagues investigated the effects of oral sildenafil on hemodynamics and exercise capacity in 12 nonoperable chronic thromboembolic pulmonary hypertension patients. All patients were in disease progression despite sufficient long-term anticoagulation and the best supportive care and suffered from severe pulmonary hypertension. After approximately 6 months of sildenafil treatment, pulmonary hemodynamics and exercise capacity improved significantly. Therefore, oral sildenafil may offer a new option for medical treatment of this devastating disease thus expanding the market for sildenafil and offering additional indications for other PDE5 inhibitors in development.

Entry date Monday, May 19, 2003

Adapted from Ghofrani et al, Am J Respir Crit Care Med 2003 Apr 15;167(8):1139-41 - Interested in collaborating with this group? Contact LeadDiscovery or the authors direct.

Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk