CRITICAL CARE
The Tipping Point
Could the complement immune system be responsible for pulmonary hypertension ?
Most patients don ’ t feel symptoms of pulmonary hypertension until it ’ s too late : Widespread , potentially irreversible changes to the entire cardiopulmonary system are already well underway . Some patients respond well to treatment . Others rapidly decline . There is no cure . With nearly $ 14 million in funding from the National Institutes of Health , an international team of researchers is investigating a potential root culprit : the destructive potential of the innate immune system .
At first glance , pulmonary hypertension looks pretty simple . It ’ s an increase in blood pressure in the lungs .
A lot of things can trigger it . Genetics , infection , drugs , tumors , metabolic dysfunction . It ’ s a complication of disease . It can occur idiopathically . It affects all ages , from newborns to the very old . It takes many forms .
But the mechanics are the same : some insult causes the pulmonary artery to constrict . The subsequent rise in pressure damages the vessels and hampers gas exchange , leading to hypoxia , which further damages the artery . Those insults trigger inflammation , and that ’ s where things seem to go awry .
Inflammation stiffens and thickens the artery , ramping up the pressure , creating an environment so hostile and diseased it warps cells ’ genetic expression at the molecular level . It doesn ’ t just affect the cardiopulmonary system . It seems to fundamentally rebuild the system . Often , the changes are irreversible ( 1 ).
Theoretically , you should be able to reverse the process , or at least stop it from progressing , by relaxing the pulmonary artery . Indeed , dozens of vasodilators have been tried , and some of them , in some situations , can slow the cycle down .
Just as often , though , they don ’ t . And when they don ’ t , there ’ s not much else .
THE VICIOUS CYCLE
In many ways , pulmonary hypertension , or PH , is still poorly understood . Still , few people in the world can claim to have done as much to understand it as pediatric critical care specialist Kurt Stenmark , MD . His work has been supported for 45 years by the longest continuously funded program project grant in the Division of Lung Diseases of the NIH . He helped found and has led the Division of Critical Care at Children ’ s Hospital Colorado since 1987 . He ’ s led the Cardiovascular Pulmonary Research Lab at the neighboring University of Colorado School of Medicine — the CVP for short — since 2005 , growing a team of more than 30 of the world ’ s foremost pulmonary hypertension researchers . He ’ s
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