Effect of sildenafil on the acute pulmonary vasodilator response to inhaled nitric oxide in adults with primary pulmonary hypertension

被引:111
作者
Lepore, JJ
Maroo, A
Pereira, NL
Ginns, LC
Dec, GW
Zapol, WM
Bloch, KD
Semigran, MJ
机构
[1] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Cardiol Div, Pulm & Crit Care Unit,Cardiovasc Res Ctr, Boston, MA USA
[2] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA
[3] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA
关键词
D O I
10.1016/S0002-9149(02)02586-9
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Breathing low concentrations of nitric oxide (NO) produces selective pulmonary vasodilatation and increases exercise capacity in patients with pulmonary hypertension of various etiologies,(1,2) and an acute pulmonary vasodilator response to NO inhalation has been used as a predictor of response to oral vasodilators.(3) Continuous or intermittent NO inhalation has been proposed as chronic pulmonary vasodilator therapy;(4) however, many patients with pulmonary hypertension do not have a pulmonary vasodilator response to inhaled NO, and in patients who do respond, the duration of vasodilatation after cessation of NO inhalation is brief. Inhaled NO exerts its pulmonary vasodilator effects by diffusing into pulmonary vascular smooth muscle cells and stimulating the production of cyclic guanosine 3'-5' monophosphate, a mediator of vasodilatation.(5) One approach to augment and prolong the pulmonary vasodilator effects of inhaled NO is the concomitant administration of an inhibitor of cyclic guanosine 3'-5' monophosphate metabolism. Sildenafil is a selective inhibitor of type 5 phosphodiesterase, a phosphodiesterase isoenzyme that metabolizes cyclic guanosine 3'-5' monophosphate specifically and is present in pulmonary vascular smooth muscle cells.(6) Our laboratory has recently reported that sildenafil is a selective pulmonary vasodilator in lambs with experimental pulmonary hypertension.(7) Several case reports have suggested that sildenafil has pulmonary vasodilator effects in humans,(8-10) that it can augment the pulmonary vasodilator effects of inhaled NO,(11) and that it can prevent rebound pulmonary hypertension after cessation of NO inhalation.(12,13) In this report, we describe hemodynamic effects of sildenafil administered alone and in combination with inhaled NO in a series of adult patients with primary pulmonary hypertension.
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页码:677 / +
页数:6
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