Pulmonary Hypertension, Etiology and Pathogenesis: New Treatments and Targets

Norbert F Voelkel, Harm J Bogaard
Respiratory Drug Delivery 2010, Vol 1, pp 1-10

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Abstract:
The pulmonary circulation is one of the two blood supplies of the lung and whereas its major function as the body’s ‘oxygenator’ has been well recognized, its secondary functions: uptake and removal of circulating compounds and drugs, and synthesis and release of metabolites are often overlooked. Here we present the concept of the lung circulation and the heart as a functional interacting system and posit that a number of diseases can only be properly investigated and understood if these interactions are appreciated. It is quite likely that in many instances heart failure itself may be alleviated by successful treatment of an ailing pulmonary circulation so that the focus of locally targeted aerosol drug therapy should be extended in future to consider better ways of treating a sick lung circulation. Given that the pulmonary capillary bed constitutes the largest endothelial cell surface area of the body and that this circulation begins to fail in a wide range of diseases including those often associated with breathing impairment, it follows that endothelial cell dysfunction (ECD) of the lung will impact on downstream circulations, including the microcirculation of the heart. Most chronic and progressive lung diseases, including COPD/emphysema and congestive heart failure, which affects the venous limb of the lung circulation, involve lung vessel endothelial cells. We discuss two hypotheses, which are linked: the first hypothesis is that most chronic lung diseases also affect the heart and that congestive heart failure affects the lung circulation. The second hypothesis is that treatment of endothelial cell dysfunction of the lung capillaries may improve the prognosis in heart failure.