Endothelium-dependent pulmonary artery responses in chronic heart failure: influence of pulmonary hypertension.
OBJECTIVE
The purpose of this study was to determine whether pulmonary artery responses to acetylcholine are abnormal in patients with chronic heart failure.


BACKGROUND
Defective pulmonary artery endothelium-dependent responses have been observed in chronic heart failure models in animals. However, pulmonary artery endothelial responses in humans with chronic heart failure are unknown.


METHODS
Twenty-two patients with chronic treated heart failure (12 with secondary pulmonary hypertension, Group I; 10 with normal pulmonary artery pressure, Group II) and 8 control patients constituted the study groups. Intravascular ultrasound measurements of pulmonary artery area just beyond the tip of an 8F infusion sheath were obtained in response to acetylcholine (10(-6), 10(-5) and 10(-4) mol/liter). The 10(-6) mol/liter infusion was repeated after methylene blue infusion. Indomethacin (5 micrograms/ml) was sequentially added to this combination in 17 patients.


RESULTS
There were no significant differences among the three groups in vascular area responses to the lowest concentration (10(-6) and 10(-5) mol/liter) of acetylcholine, but the 10(-4) mol/liter infusion resulted in significant constriction in Group II patients (p < 0.05, analysis of variance [ANOVA]). Pretreatment with methylene blue in Group II also resulted in significant pulmonary artery vasoconstriction to even the 10(-6) mol/liter acetylcholine infusion (10.4 +/- 7.8% in Group II vs. 1.7 +/- 3.9% in the control group and 0.1 +/- 4.3% in Group I, p < 0.05, ANOVA). The addition of indomethacin resulted in reversal of the constriction in Group II patients.


CONCLUSIONS
These responses indicate that the pulmonary artery endothelium may play a significant role in inhibiting vasoconstriction in patients with chronic heart failure who maintain normal pulmonary artery pressure.
Porter
T R
TR
McGuire Veterans Affairs Medical Center, Medical College of Virginia, Richmond.
Taylor
D O
DO
Cycan
A
A
Fields
J
J
Bagley
C W
CW
Pandian
N G
NG
Mohanty
P K
PK
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology*; D000368:Aged; D000704:Analysis of Variance; D016022:Case-Control Studies; D002407:Catheterization, Swan-Ganz; D002908:Chronic Disease; D003251:Constriction, Pathologic / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D006333:Heart Failure / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D016555:Matched-Pair Analysis; D008751:Methylene Blue / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D011669:Pulmonary Wedge Pressure; D012720:Severity of Illness Index; D014463:Ultrasonography
D009569:Nitric Oxide; D000109:Acetylcholine; D008751:Methylene Blue; D007213:Indomethacin