Inhibition of 20-HETE abolishes the myogenic response during NOS antagonism in the ovine fetal pulmonary circulation

2005 ◽  
Vol 289 (2) ◽  
pp. L261-L267 ◽  
Author(s):  
Thomas A. Parker ◽  
Theresa R. Grover ◽  
John P. Kinsella ◽  
John R. Falck ◽  
Steven H. Abman
Keyword(s):  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Pulmonary Circulation ◽  
Ductus Arteriosus ◽  
Combined Treatment ◽  
Specific Inhibitor ◽  
Fetal Lung ◽  
Myogenic Response ◽  
Fetal Sheep ◽  
Artery Pressure

Mechanisms that maintain high pulmonary vascular resistance (PVR) and oppose vasodilation in the fetal lung are poorly understood. In fetal lambs, increased pulmonary artery pressure evokes a potent vasoconstriction, suggesting that a myogenic response contributes to high PVR in the fetus. In adult systemic circulations, the arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) has been shown to modulate the myogenic response, but its role in the fetal lung is unknown. We hypothesized that acute increases in pulmonary artery pressure release 20-HETE, which causes vasoconstriction, or a myogenic response, in the fetal lung. To address this hypothesis, we studied the hemodynamic effects of N-methylsufonyl-12,12-dibromododec-11-enamide (DDMS), a specific inhibitor of 20-HETE production, on the pulmonary vasoconstriction caused by acute compression of the ductus arteriosus (DA) in chronically prepared fetal sheep. An inflatable vascular occluder around the DA was used to increase pulmonary artery pressure under three study conditions: control, after pretreatment with nitro-l-arginine (l-NA; to inhibit shear-stress vasodilation), and after combined treatment with both l-NA and a specific 20-HETE inhibitor, DDMS. We found that DA compression after l-NA treatment increased PVR by 44 ± 12%. Although intrapulmonary DDMS infusion did not affect basal PVR, DDMS completely abolished the vasoconstrictor response to DA compression in the presence of l-NA (44 ± 12% vs. 2 ± 4% change in PVR, l-NA vs. l-NA + DDMS, P < 0.05). We conclude that 20-HETE mediates the myogenic response in the fetal pulmonary circulation and speculate that pharmacological inhibition of 20-HETE might have a therapeutic role in neonatal conditions characterized by pulmonary hypertension.

Hemodynamic effects of endothelin-1 on ovine fetal pulmonary circulation

1991 ◽  
Vol 261 (1) ◽  
pp. R182-R187 ◽  
Author(s):  
B. A. Chatfield ◽  
I. F. McMurtry ◽  
S. L. Hall ◽  
S. H. Abman
Keyword(s):  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Pulmonary Circulation ◽  
Ductus Arteriosus ◽  
Left Lung ◽  
Hemodynamic Effects ◽  
Fetal Sheep ◽  
Flow Transducer ◽  
Artery Pressure ◽  
Endothelin 1

To determine the hemodynamic effects of endothelin-1 (ET-1) in the fetal pulmonary circulation, we studied pulmonary vascular responses to brief and prolonged intrapulmonary infusions of the peptide in nine chronically prepared late-gestation fetal sheep. Left pulmonary artery (LPA) blood flow was measured with an electromagnetic flow transducer, and a catheter placed in the LPA allowed ET-1 infusion directly into the left lung. Brief (10-min) infusions of ET-1 (12.5-100 ng/min) increased flow up to 212% of baseline without changing pulmonary artery pressure. With prolonged (120-min) infusion of ET-1 (50 ng/min), flow increased from 69 +/- 8 to 164 +/- 23 ml/min at 10 min (P less than 0.05) but then declined and was not different from baseline at 120 min. The gradient between mean pulmonary artery and aortic pressures did not change, suggesting no constriction of the ductus arteriosus. Systemic (vena caval) infusion of ET-1 (100 ng/min for 30 min) caused systemic and pulmonary hypertension, as mean pulmonary artery pressure increased from 43 +/- 1 to 51 +/- 2 mmHg (P less than 0.05) and remained elevated for 30 min after cessation of the ET-1 infusion. We conclude that intrapulmonary ET-1 is a potent fetal pulmonary vasodilator, but its dilator effect is transient during prolonged infusion. In contrast, systemic infusion causes sustained hypertension, suggesting differential effects of ET-1 on the pulmonary and systemic circulations. These findings demonstrate marked vasoactivity of ET-1 in the fetus, suggesting a potential role in the normal or abnormal transitional circulation.

scholarly journals Fasudil inhibits the myogenic response in the fetal pulmonary circulation

2008 ◽  
Vol 295 (4) ◽  
pp. H1505-H1513 ◽  
Author(s):  
Pierre Tourneux ◽  
Marc Chester ◽  
Theresa Grover ◽  
Steven H. Abman
Keyword(s):  
Blood Flow ◽  
Pulmonary Circulation ◽  
Ductus Arteriosus ◽  
Fetal Lung ◽  
Late Gestation ◽  
Time Dependent ◽  
Myogenic Response ◽  
Rock Inhibitor ◽  
Fetal Sheep ◽  
Rock Activity

In addition to high pulmonary vascular resistance (PVR) and low pulmonary blood flow, the fetal pulmonary circulation is characterized by mechanisms that oppose vasodilation. Past work suggests that high myogenic tone contributes to high PVR and may contribute to autoregulation of blood flow in the fetal lung. Rho-kinase (ROCK) can mediate the myogenic response in the adult systemic circulation, but whether high ROCK activity contributes to the myogenic response and modulates time-dependent vasodilation in the developing lung circulation are unknown. We studied the effects of fasudil, a ROCK inhibitor, on the hemodynamic response during acute compression of the ductus arteriosus (DA) in chronically prepared, late-gestation fetal sheep. Acute DA compression simultaneously induces two opposing responses: 1) blood flow-induced vasodilation through increased shear stress that is mediated by NO release and 2) stretch-induced vasoconstriction (i.e., the myogenic response). The myogenic response was assessed during acute DA compression after treatment with Nω-nitro-l-arginine, an inhibitor of nitric oxide synthase, to block flow-induced vasodilation and unmask the myogenic response. Intrapulmonary fasudil infusion (100 μg over 10 min) did not enhance flow-induced vasodilation during brief DA compression but reduced the myogenic response by 90% ( P < 0.05). During prolonged DA compression, fasudil prevented the time-dependent decline in left pulmonary artery blood flow at 2 h (183 ± 29 vs. 110 ± 11 ml/min with and without fasudil, respectively; P < 0.001). We conclude that high ROCK activity opposes pulmonary vasodilation in utero and that the myogenic response maintains high PVR in the normal fetal lung through ROCK activation.

Acute effects of partial compression of ductus arteriosus on fetal pulmonary circulation

1989 ◽  
Vol 257 (2) ◽  
pp. H626-H634 ◽  
Author(s):  
S. H. Abman ◽  
F. J. Accurso
Keyword(s):  
Blood Flow ◽  
Pulmonary Artery ◽  
Pulmonary Vascular Resistance ◽  
Pulmonary Artery Pressure ◽  
Pulmonary Circulation ◽  
Pulmonary Blood Flow ◽  
Ductus Arteriosus ◽  
Base Line ◽  
Acute Effects ◽  
Artery Pressure

To determine the acute effects of increased pulmonary artery pressure and flow on the fetal pulmonary circulation, we studied the response of pulmonary blood flow and vascular reactivity to partial compression of the ductus arteriosus in 22 chronically prepared late-gestation fetal lambs. An inflatable occluder was placed loosely around the ductus arteriosus for compression. Partial compression of the ductus rapidly increased mean pulmonary artery pressure from 45 +/- 1 to 60 +/- 1 mmHg (mean +/- SE) and left pulmonary artery blood flow from 65 +/- 6 to 151 +/- 11 ml/min at 30 min (P less than 0.001; 12 animals). Despite keeping pulmonary artery pressure constant, pulmonary blood flow steadily declined and by 2 h was not different from base-line values. Pulmonary vascular resistance initially fell during the first 30 min of partial compression but then steadily increased and remained elevated above base-line values for at least 30 min after the release of the occluder (P less than 0.001). The decline of pulmonary vascular resistance during the first 30 min of compression was blunted after treatment with the cyclooxygenase inhibitor, meclofenamate (P less than 0.001; 6 animals). Rapid incremental ductus compressions demonstrated a decrease in the slope of the pressure-flow relationship from 3.30 +/- 0.27 (control) to 1.59 +/- 0.21 ml.min-1.mmHg-1 during the postcompression period (P less than 0.001; 12 animals). The vasodilation response to small increases of fetal PO2 was markedly blunted during the postcompression period (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Prediction of Extubation Readiness Using Transthoracic Ultrasound in Preterm Infants

2020 ◽  
Author(s):  
Reem M. Soliman ◽  
Yasser Elsayed ◽  
Reem N. Said ◽  
Abdulaziz M. Abdulbaqi ◽  
Rania H. Hashem ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Preterm Infants ◽  
Pulmonary Artery Pressure ◽  
Neonatal Intensive Care ◽  
Ductus Arteriosus ◽  
Interventricular Septum ◽  
Area Under The Curve ◽  
Left Ventricular ◽  
Predictive Values ◽  
Artery Pressure

ABSTRACTObjectiveTo test the hypothesis that a lung ultrasound severity score (LUSsc) and assessment of left ventricular eccentricity index of the interventricular septum (LVEI) by focused heart ultrasound can predict extubation success in mechanically ventilated preterm infants with respiratory distress syndrome (RDS).DesignProspective observational study of premature infants <34 weeks’ of gestation age supported with mechanical ventilation due to RDS. LUSsc and LVEI were performed on postnatal days 3 and 7 by an investigator who was masked to infants’ ventilator parameters and clinical conditions. RDS was classified based on LUSsc into mild (score 0–9) and moderate-severe (score 10–18). A receiver operator curve was constructed to assess the ability to predict extubation success. Pearson’s correlation was performed between LVEI and pulmonary artery pressure (PAP).SettingLevel III neonatal intensive care unit, Cairo, Egypt.ResultsA total of 104 studies were performed to 66 infants; of them 39 had mild RDS (LUSsc 0–9) and 65 had moderate-severe RDS (score ≥10). LUSsc predicted extubation success with a sensitivity and a specificity of 91% and 69%; the positive and negative predictive values were 61% and 94%, respectively. Area under the curve (AUC) was 0.83 (CI: 0.75-0.91). LVEI did not differ between infants that succeeded and failed extubation. However, it correlated with pulmonary artery pressure during both systole (r=0.62) and diastole (r=0.53) and with hemodynamically significant patent ductus arteriosus (r=0.27 and r=0.46, respectively).ConclusionLUSsc predicts extubation success in preterm infants with RDS whereas LVEI correlates with high PAP.

Effect of oxygen upon pulmonary circulation in acclimatized man at high altitude

1965 ◽  
Vol 20 (2) ◽  
pp. 239-243 ◽  
Author(s):  
H. N. Hultgren ◽  
J. Kelly ◽  
H. Miller
Keyword(s):  
Pulmonary Artery ◽  
High Altitude ◽  
Sea Level ◽  
Pulmonary Artery Pressure ◽  
Pulmonary Circulation ◽  
Arterial Oxygen ◽  
Artery Pressure ◽  
Oxygen Breathing ◽  
Hypoxic Vasoconstriction ◽  
Arteriolar Resistance

The response to breathing 100% oxygen was studied in 26 acclimatized residents of the Peruvian Andes at altitudes of 12,300 and 14,200 ft. Arterial oxygen saturation increased from 86% to 96%. Mean pulmonary artery pressure decreased by 5 mm Hg and cardiac output did not change. Calculated pulmonary arteriolar resistance was lowered. Pulmonary artery pressure during oxygen breathing was not decreased to normal values observed at sea level. The data suggest the presence of two factors responsible for the increase in pulmonary arteriolar resistance at high altitude: 1) hypoxic vasoconstriction which is reversed by oxygen breathing and 2) anatomic alterations which are not affected by oxygen breathing. Oxygen breathing at high altitude also produced a slowing of the heart rate and increased the relative height of the secondary or tidal wave of the brachial arterial pressure pulse. pulmonary arteriolar resistance and 100% oxygen; arterial pulse contour–effect of 100% oxygen at high altitude; pulmonary arteriolar resistance–nature of in high altitude; hypoxic vasoconstriction at high altitude–reversal by 100% oxygen breathing; oxygen breathing–comparison of effect on pulmonary circulation at high altitude and sea level Submitted on May 8, 1964

scholarly journals Targeted blocking of gene expression for CGRP receptors elevates pulmonary artery pressure in hypoxic rats

2003 ◽  
Vol 285 (1) ◽  
pp. L86-L96 ◽  
Author(s):  
Xin Qing ◽  
Ingegerd M. Keith
Keyword(s):  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Pulmonary Circulation ◽  
Protective Role ◽  
Cgrp Receptor ◽  
Sprague Dawley ◽  
Artery Pressure ◽  
Receptor Component ◽  
Technical Control

We previously described the protection by calcitonin gene-related peptide (CGRP) against hypoxic pulmonary hypertension. Here, we examine the roles of its putative receptor RDC-1 and receptor activity-modifying protein (RAMP) 1 in mediating this protection by selectively inhibiting their synthesis. RAMP1 is an accessory protein for another putative CGRP receptor, calcitonin receptor-like receptor. Antisense oligodeoxyribonucleotides (ASODNs, 5 mg·kg-1·day-1 or 5 and 10 mg·kg-1·day-1 for RDC-1) targeting RAMP1 and RDC-1 mRNAs were chronically infused to the pulmonary circulation of male Sprague-Dawley rats during 7 days of normoxia or hypobaric hypoxia (380 mmHg), and α-CGRP ASODN was used as a technical control. CGRP, RAMP1, and RDC-1 ASODNs significantly elevated pulmonary artery pressure (PPA) in chronic hypoxic rats compared with hypoxic mismatched ASODN (MMODN) and saline vehicle controls. CGRP and RAMP1 ASODNs raised PPA in normoxic rats briefly exposed to 10% O2 above MMODN and saline controls. Moreover, normoxic rats treated with CGRP ASODN had higher basal pulmonary vascular tone compared with controls. These data confirm the protective role of CGRP in the pulmonary circulation and suggest that endogenous RAMP1 and RDC-1 are essential in regulation of PPA in hypoxia. This is the first in vivo evidence supporting RDC-1 and RAMP1 as functional CGRP receptor and receptor component.

scholarly journals Validity of Estimation of Pulmonary artery Pressure Using Continuous wave Doppler Echocardiography in Patient with Patent Ductus Arteriosus (PDA)

2012 ◽  
Vol 7 (1) ◽  
pp. 10-12 ◽  
Author(s):  
Chaudhury Meshkat Ahmed ◽  
Sohel Mahmud Arafat ◽  
Muhammad Khaled Hasan ◽  
Abed Hussain Khan ◽  
Lima Asrin Sayami ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Patent Ductus Arteriosus ◽  
Pulmonary Artery Pressure ◽  
Doppler Echocardiography ◽  
Continuous Wave ◽  
Heart Diseases ◽  
Ductus Arteriosus ◽  
Artery Pressure ◽  
Bedside Test ◽  
Patent Ductus

Pulmonary artery pressure is one of the most important parameter for evaluating the status of pulmonary vascular bed for patients of PDA, which helps in formulating treatment strategy. This study was carried out in National Institute of Cardiovascular Diseases and Hospital (NICVD) and National Centre for Control of Rheumatic Fever and Heart Diseases, Dhaka, Bangladesh. Pulmonary artery pressure was recorded noninvasively using Doppler echocardiography and the it was correlated with those obtained from haemodynamic studies done at cardiac catheterization. Estimation of pulmonary artery pressure using Doppler derived measurement of pressure gradient across patent ductus arteriosus correlated well with that of simultaneous catheterization measured values. Doppler echocardiography is a cheap, simple, noninvasive bedside test for measuring pulmonary artery systolic and diastolic pressure in patient with PDA. DOI: http://dx.doi.org/10.3329/uhj.v7i1.10202 UHJ 2011; 7(1): 10-12

scholarly journals HEMODYNAMIC VALIDATION OF DOPPLER DERIVED PULMONARY ARTERY PRESSURE IN PATENT DUCTUS ARTERIOSUS

1987 ◽  
Vol 21 (4) ◽  
pp. 192A-192A
Author(s):  
Norman N Musewe ◽  
Jeffrey F Smallhorn ◽  
Lee N Benson ◽  
Patricia M Burrows ◽  
Robert M Freedom ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Patent Ductus Arteriosus ◽  
Pulmonary Artery Pressure ◽  
Ductus Arteriosus ◽  
Artery Pressure ◽  
Patent Ductus
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