1. Using isolated pulmonary resistance vessels from mature fetal lamb and chronically instrumented lambs (8-17 days old), we have examined whether hypoxic pulmonary vasoconstriction is sustained by activation of a constrictor mechanism or suppression of a dilator mechanism. 2. Hypoxia contracted both arteries and veins in vitro, and the contraction was greater with the former. After removing the endothelium, arteries responded faster to hypoxia, but the magnitude of the response remained unchanged. 3. Hypoxic arteries, unlike normally oxygenated arteries, did not contract with either indomethacin (2-8 uM) or NT-nitro-L-arginine methyl ester (L-NAME, 100 UM). The same vessels relaxed with sodium nitroprusside (SNP, 0.001-10 /1M) but not with bradykinin (0-1-100 nM).4. Endothelin-1 (ET-1, 0-01-10 nM) contracted isolated arteries and veins under normoxic and hypoxic conditions. In both vessels, the contraction was fast in onset and subsidence, and was inhibited by the ETA receptor antagonist BQ123 (1 /SM). The ET-1 precursor, big ET-1 (100 nM), also contracted arteries and veins, but compared with ET-1 its action was slower in development. Big ET-1 contraction, unlike ET-1 contraction, was curtailed by the inhibitor of the ET-1 -converting enzyme, phosphoramidon (50 ,UM). 5. ET-1 (01-10 nM) had no effect on isolated arteries precontracted with a thromboxane A2 (TXA2) analogue (ONO-11113) and treated with BQ123 (10 ,UM). Under the same conditions, ET-1 relaxed the veins. Accordingly, in the absence of BQ123 treatment, the selective ETB receptor agonist IRL-1620 (0-1-100 nM) relaxed the contracted veins but not the arteries.6. BQ123 (10/M) inhibited the constriction of isolated arteries and veins to hypoxia.Likewise, in the conscious lamb a bolus of BQ123 (0 4 mg kg-', injected into the pulmonary artery) curtailed the rise in pulmonary vascular resistance (Rpa) brought about by alveolar hypoxia without changing significantly systemic vascular resistance (Ra0). Under normoxia, Rpa was insignificantly affected by BQ123.7. The results indicate that pulmonary resistance arteries are more susceptible to hypoxia than the veins, and that hypoxic vasoconstriction does not require an intact endothelium to occur. Hypoxic tone is ascribed primarily to intramural generation of ET-1, while removal of the tonic action of a relaxant may only have an accessory role in the response.It is well known that the pulmonary vasculature constricts optimal matching of blood flow to alveolar hypoxia when ambient oxygen tension falls below the normal range (Fishman, 1990). In its extreme manifestation, hypoxic (reviewed by Fishman, 1990). This response is evident in vasoconstriction may lead to pulmonary hypertension

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We hypothesized that vibrations created by the pulmonary circulation would create sound like the vocal cords during speech and that subjects with pulmonary artery hypertension (PAH) might have a unique sound signature. We recorded heart sounds at the cardiac apex and the second left intercostal space (2LICS), using a digital stethoscope, from 27 subjects (12 males) with a median age of 7 years (range: 3 months-19 years) undergoing simultaneous cardiac catheterization. Thirteen subjects had mean pulmonary artery pressure (mPAp) < 25 mmHg (range: 8-24 mmHg). Fourteen subjects had mPAp ≥ 25 mmHg (range: 25-97 mmHg). We extracted the relative power of the frequency band, the entropy, and the energy of the sinusoid formants from the heart sounds. We applied linear discriminant analysis with leave-one-out cross validation to differentiate children with and without PAH. The significance of the results was determined with a t test and a rank-sum test. The entropy of the first sinusoid formant contained within an optimized window length of 2 seconds of the heart sounds recorded at the 2LICS was significantly lower in subjects with mPAp ≥ 25 mmHg relative to subjects with mPAp < 25 mmHg, with a sensitivity of 93% and specificity of 92%. The reduced entropy of the first sinusoid formant of the heart sounds in children with PAH suggests the existence of an organized pattern. The analysis of this pattern revealed a unique sound signature, which could be applied to a noninvasive method to diagnose PAH.Keywords: pulmonary hypertension, congenital heart disease, auscultation, machine learning, language recognition. Untreated pulmonary artery hypertension (PAH) is a progressive, fatal disease. 1 It complicates many conditions and may affect up to 100 million people worldwide. 2,3 PAH is difficult to diagnose because symptoms appear late in the disease course and the findings on clinical examination are missed easily.The finding on auscultation of a loud pulmonary component of the second heart sound (S2) in PAH has led to the exploration of phonocardiographic associations between S2 and pulmonary artery pressure (PAp) in the time domain. 4-10 However, precise demarcation, timing, and segmentation of the components of S2 remain challenging. [7][8][9][11][12][13] We have explored instead quantitative information in the frequency domain of heart sounds that distinguish between subjects with and without PAH. 14 The relative power of the frequencies between 21 and 22 Hz of the heart sounds recorded at the second left intercostal space (2LICS) was significantly reduced in subjects with PAH. 14 However, there was a 22% error in detecting PAH. Therefore, by investigating further the recordings in these same subjects, we sought to explore other features of the heart sounds in this specific frequency domain that might contain a unique feature that would identify subjects with PAH.Normal speech patterns have a unique signature related to vocal cord vibration, which can be used, for example, to recognize a speaker as male or female...