Pulmonary hemodynamic responses to brain natriuretic peptide and sildenafil in patients with pulmonary arterial hypertension.
OBJECTIVE
Brain natriuretic peptide (BNP) blunts hypoxic pulmonary hypertension in animal models, but its acute hemodynamic effects in patients with pulmonary arterial hypertension (PAH) are not known. The aim of this study was to determine if human B-type natriuretic peptide is a safe and efficacious pulmonary vasodilator in patients with PAH and if the pulmonary hemodynamic effects are potentiated by phosphodiesterase inhibition.


METHODS
Open-label study.


METHODS
Medical ICUs of three tertiary care hospitals in New England.


METHODS
Thirteen consecutive adult patients undergoing right-heart catheterization and a pulmonary vasodilator trial for the initial evaluation of PAH.


METHODS
Patients were administered inhaled nitric oxide (iNO), i.v. epoprostenol, and a 3-h infusion of BNP alone and 1 h after an oral dose of the phosphodiesterase-5 inhibitor sildenafil.


RESULTS
iNO and sildenafil alone decreased mean pulmonary artery pressure (mPAP) without a significant fall in pulmonary vascular resistance (PVR). Epoprostenol decreased both mPAP and PVR. BNP alone had no significant effect on pulmonary hemodynamics, but the combination of sildenafil plus BNP decreased mPAP and PVR for up to 6 h after stopping BNP. The decrease in mPAP with sildenafil plus BNP (+/- SE) was greater than after 1 h of sildenafil alone (44.6 +/- 3.8 to 40.6 +/- 3.9 mm Hg, p = 0.027). An acute vasodilator response, defined as a decrease in mPAP > 10 mm Hg and end mPAP < 40 mm Hg, was seen in 0 of 8 patients with iNO, 1 of 13 patients with epoprostenol, 0 of 13 patients with BNP, and 4 of 12 patients with sildenafil plus BNP. BNP decreased mean systemic arterial pressure (5.6 +/- 2.8 mm Hg) but had no effect on cardiac output or systemic vascular resistance.


CONCLUSIONS
A 3-h BNP infusion does not significantly improve pulmonary hemodynamics in most patients with PAH but is well tolerated and augments the acute pulmonary vasodilator effect of sildenafil.
Division of Pulmonary, Sleep and Critical Care Medicine, Rhode Island Hospital and Brown Medical School, Providence, RI. Electronic address: james_klinger@brown.edu.
James R
JR
Klinger
Division of Pulmonary, Sleep and Critical Care Medicine, Rhode Island Hospital and Brown Medical School, Providence, RI.
Sejal
S
Thaker
Division of Pulmonary, Sleep and Critical Care Medicine, Rhode Island Hospital and Brown Medical School, Providence, RI.
Jeanne
J
Houtchens
Division of Pulmonary and Critical Care Medicine, Tufts New England Medical Center, Tufts University School of Medicine, Boston, MA.
Ioana R
IR
Preston
Division of Pulmonary and Critical Care Medicine, Tufts New England Medical Center, Tufts University School of Medicine, Boston, MA.
Nicholas S
NS
Hill
Pulmonary Center, Boston University School of Medicine, Boston, MA.
Harrison W
HW
Farber
D000280:Administration, Inhalation; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000187:drug effects; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D011464:Epoprostenol / Q000008:administration & dosage; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000008:administration & dosage; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D010879:Piperazines / Q000008:administration & dosage*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage*
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D020097:Natriuretic Peptide, Brain; D009569:Nitric Oxide; D000068677:Sildenafil Citrate; D011464:Epoprostenol