Circulation, Vol 80, 1207-1221, Copyright © 1989 by American Heart Association
HI Palevsky, BL Schloo, GG Pietra, KT Weber, JS Janicki, E Rubin and AP Fishman
The use of pharmacologic agents in the treatment of pulmonary hypertension
has not proved to be uniformly successful or predictable. One possible
reason for the vagaries in response is that the pulmonary vascular lesions
are not consistent. We examined the relation between the structure of the
pulmonary resistance vessels in unexplained (primary) pulmonary
hypertension and the response to pulmonary vasodilators. Our study involved
19 patients with clinically unexplained pulmonary hypertension (mean
pressure, 59 +/- 14 mm Hg). After characterizing them clinically and
performing control hemodynamic measurements, we determined the acute
effects of a series of vasodilator agents that have different mechanisms of
action. In 16 patients, lung biopsy material was related to the hemodynamic
studies; in nine patients, including six who had undergone open lung
biopsy, the hemodynamic studies were related to the pathologic changes
found at autopsy. Histologic specimens from all 19 patients were evaluated
qualitatively and sorted into three subsets of hypertensive pulmonary
arteriopathy: medial hypertrophy (with minimal intimal proliferation),
arteriopathy with plexiform lesions (associated predominantly with
concentric laminar intimal proliferation and fibrosis), and arteriopathy
with microthrombotic lesions (associated predominantly with eccentric
intimal proliferation and fibrosis). The 16 lung biopsies were also
quantitated by morphometric techniques. Using a decrease in calculated
pulmonary vascular resistance of more than 30% accompanied by a decrease in
mean pulmonary arterial pressure of at least 10% to define vasodilation,
only four patients were responders. The patients varied considerably in
their responses to different vasodilator agents. Patients with similar
clinical and hemodynamic profiles differed considerably with respect to the
nature of their pulmonary vascular obstructive lesions and their responses
to vasodilator agents. Qualitative histologic examination of lung tissue
did not provide a basis for predicting how individual patients would
respond to vasodilator agents. However, quantitative morphologic analysis
of the initial open lung biopsy specimens did prove helpful in predicting
acute responsiveness to vasodilator agents and the subsequent clinical
course of these patients with unexplained (primary) pulmonary hypertension.
An intimal area of more than 18% of the vascular cross-sectional area had
an 85% predictive value for identifying the patients who did poorly during
the first 36 months of follow-up.
ARTICLES
Primary pulmonary hypertension. Vascular structure, morphometry, and responsiveness to vasodilator agents
Department of Medicine, University of Pennsylvania, Philadelphia 19104- 4283.
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