Perinatal pulmonary prostaglandin production

1981 ◽  
Vol 241 (5) ◽  
pp. H756-H759 ◽  
Author(s):  
C. W. Leffler ◽  
J. R. Hessler
Keyword(s):  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Electron Capture Detection ◽  
Pulmonary Resistance ◽  
Pulmonary Vasodilation ◽  
Resistance Vessels ◽  
Before And After ◽  
Fetal Lungs ◽  
Resistance Decrease

Products of reactions catalyzed by prostaglandin cyclo-oxygenase [prostaglandins (PG), thromboxanes] were analyzed by gas chromatography with electron-capture detection in the venous effluents of in situ Krebs-perfused lungs of exteriorized fetal goats and sheep before and after ventilation with air. The major products were 6-keto-PGF1 alpha and 6,15-diketo[13,14-dihydro] PGI2 without blood components. After ventilation, which decreased pulmonary vascular resistance to 63% of the before-ventilation value, lung production of 6-keto-PGF1 alpha and metabolite increased 50 and 230%, respectively. These data, in addition to earlier findings of inhibition of ventilation-induced pulmonary vasodilation by indomethacin and increased net production of PG-like material after ventilation of blood-perfused fetal lungs, support the hypothesis that ventilation of fetal lungs with air at birth increases synthesis of PGI2 by or near pulmonary resistance vessels, resulting in high local concentrations of PGI2 near its site of production. PGI2 appears to be important in the pulmonary vascular resistance decrease that is necessary for successful perinatal transition.

Low exercise pulmonary resistance is not dependent on vasodilator prostaglandins

1983 ◽  
Vol 55 (2) ◽  
pp. 558-561 ◽  
Author(s):  
J. Lindenfeld ◽  
J. T. Reeves ◽  
L. D. Horwitz
Keyword(s):  
Cardiac Output ◽  
Arterial Pressure ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Arterial Pressure ◽  
Cyclooxygenase Inhibitors ◽  
Pulmonary Resistance ◽  
Before And After ◽  
Pulmonary Arterial

In resting conscious dogs, administration of cyclooxygenase inhibitors results in modest increases in pulmonary arterial pressure and pulmonary vascular resistance, suggesting that vasodilator prostaglandins play a role in maintaining the low vascular resistance in the pulmonary bed. To assess the role of these vasodilator prostaglandins on pulmonary vascular resistance during exercise, we studied seven mongrel dogs at rest and during exercise before and after intravenous meclofenamate (5 mg/kg). Following meclofenamate, pulmonary vascular resistance rose both at rest (250 24 vs. 300 +/- 27 dyn . s . cm-5, P less than 0.01) and with exercise (190 +/- 9 vs. 210 +/- 12 dyn . s . cm-5, P less than 0.05). Systemic vascular resistance rose slightly following meclofenamate both at rest and during exercise. There were no changes in cardiac output. The effects of cyclooxygenase inhibition, although significant, were less during exercise than at rest. This suggests that the normal fall in pulmonary vascular resistance during exercise depends largely on factors other than vasodilator prostaglandins.

scholarly journals Cinaciguat, a soluble guanylate cyclase activator, causes potent and sustained pulmonary vasodilation in the ovine fetus

2009 ◽  
Vol 297 (2) ◽  
pp. L318-L325 ◽  
Author(s):  
Marc Chester ◽  
Pierre Tourneux ◽  
Greg Seedorf ◽  
Theresa R. Grover ◽  
Jason Gien ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Left Pulmonary Artery ◽  
Flow Transducer ◽  
Pulmonary Vasodilation

Impaired nitric oxide-cGMP signaling contributes to severe pulmonary hypertension after birth, which may in part be due to decreased soluble guanylate cyclase (sGC) activity. Cinaciguat (BAY 58-2667) is a novel sGC activator that causes vasodilation, even in the presence of oxidized heme or heme-free sGC, but its hemodynamic effects have not been studied in the perinatal lung. We performed surgery on eight fetal (126 ± 2 days gestation) lambs (full term = 147 days) and placed catheters in the main pulmonary artery, aorta, and left atrium to measure pressures. An ultrasonic flow transducer was placed on the left pulmonary artery to measure blood flow, and a catheter was placed in the left pulmonary artery for drug infusion. Cinaciguat (0.1–100 μg over 10 min) caused dose-related increases in pulmonary blood flow greater than fourfold above baseline and reduced pulmonary vascular resistance by 80%. Treatment with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an sGC-oxidizing inhibitor, enhanced cinaciguat-induced pulmonary vasodilation by >120%. The pulmonary vasodilator effect of cinaciguat was prolonged, decreasing pulmonary vascular resistance for >1.5 h after brief infusion. In vitro stimulation of ovine fetal pulmonary artery smooth muscle cells with cinaciguat after ODQ treatment resulted in a 14-fold increase in cGMP compared with non-ODQ-treated cells. We conclude that cinaciguat causes potent and sustained fetal pulmonary vasodilation that is augmented in the presence of oxidized sGC and speculate that cinaciguat may have therapeutic potential for severe neonatal pulmonary hypertension.

Effect of indomethacin on pulmonary vascular response to ventilation of fetal goats

1978 ◽  
Vol 234 (4) ◽  
pp. H346-H351 ◽  
Author(s):  
C. W. Leffler ◽  
T. L. Tyler ◽  
S. Cassin
Keyword(s):  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Fetal Lung ◽  
Rapid Decrease ◽  
Vascular Response ◽  
Pulmonary Vasodilation ◽  
Prostaglandin Synthase ◽  
Perfused Lung ◽  
Lung Preparation ◽  
Indomethacin Treatment

The effect of indomethacin treatment of the pulmonary vasodilation caused by ventilation of the fetal lung with air was evaluated in anesthetized, exteriorized, fetal goats by means of an open-chest, pump-perfused lung preparation. The decrease in pulmonary vascular resistance that occurs when the fetal lung is ventilated with air consists of two components: 1) a rapid decrease in pulmonary vascular resistance during the first 30 s of ventilation; 2) a slower decline, which continues through the first 10-20 min or more of ventilation. Indomethacin has no effect on the first component. The second component is absent following indomethacin pretreatment. The effect of indomethacin treatment is more pronounced in immature fetuses (less than 90% gestation) than in mature fetuses. Prostaglandin synthase activity appears to be important in the pulmonary vasodilation caused by ventilation of the fetal lungs with air.

Selective Pulmonary Vasodilation by Intravenous Infusion of an Ultrashort Half-life Nucleophile/Nitric Oxide Adduct 

1998 ◽  
Vol 88 (1) ◽  
pp. 190-195 ◽  
Author(s):  
Christophe Adrie ◽  
Mona W. Hirani ◽  
Alexandra Holzmann ◽  
Larry Keefer ◽  
Warren M. Zapol ◽  
...  
Keyword(s):  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Circulation ◽  
Half Life ◽  
Pulmonary Vasculature ◽  
Prostaglandin F2alpha ◽  
Pulmonary Vasodilation ◽  
Pulmonary Vasodilator ◽  
Healthy Sheep ◽  
Inhaled No

Background PROLI/NO (C5H7N3O4Na2 x CH3OH) is an ultrashort-acting nucleophile/NO adduct that generates NO (half-life 2 s at 37 degrees C and pH 7.4). Because of its short half-life, the authors hypothesized that intravenous administration of this compound would selectively dilate the pulmonary vasculature but cause little or no systemic hypotension. Methods In eight awake healthy sheep with pulmonary hypertension induced by 9,11-dideoxy-9alpha,11alpha-methanoepoxy prostaglandin F2alpha, the authors compared PROLI/NO with two reference drugs-inhaled NO, a well-studied selective pulmonary vasodilator, and intravenous sodium nitroprusside (SNP), a nonselective vasodilator. Sheep inhaled 10, 20, 40, and 80 parts per million NO or received intravenous infusions of 0.25, 0.5, 1, 2, and 4 microg x kg-1 x min-1 of SNP or 0.75, 1.5, 3, 6, and 12 microg x kg-1 x min-1 of PROLI/NO. The order of administration of the vasoactive drugs (NO, SNP, PROLI/NO) and their doses were randomized. Results Inhaled NO selectively dilated the pulmonary vasculature. Intravenous SNP induced nonselective vasodilation of the systemic and pulmonary circulation. Intravenous PROLI/NO selectively vasodilated the pulmonary circulation at doses up to 6 microg x kg-1 x min-1, which decreased pulmonary vascular resistance by 63% (P < 0.01) from pulmonary hypertensive baseline values without changing systemic vascular resistance. At 12 microg x kg-1 x min-1, PROLI/NO decreased systemic and pulmonary vascular resistance and pressure. Exhaled NO concentrations were higher during PROLI/NO infusion than during SNP infusion (P < 0.01 with all data pooled). Conclusions The results suggest that PROLI/NO could be a useful intravenous drug to vasodilate the pulmonary circulation selectively.

Endothelin blockade augments pulmonary vasodilation in the ovine fetus

1996 ◽  
Vol 81 (6) ◽  
pp. 2481-2487 ◽  
Author(s):  
D. Dunbar Ivy ◽  
John P. Kinsella ◽  
Steven H. Abman
Keyword(s):  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Vascular Tone ◽  
Ductus Arteriosus ◽  
Left Lung ◽  
Late Gestation ◽  
Converting Enzyme ◽  
Pulmonary Vasodilation ◽  
Vasodilator Response ◽  
Ovine Fetus

Ivy, D. Dunbar, John P. Kinsella, and Steven H. Abman.Endothelin blockade augments pulmonary vasodilation in the ovine fetus. J. Appl. Physiol. 81(6): 2481–2487, 1996.—The physiological role of endothelin-1 (ET-1) in regulation of vascular tone in the perinatal lung is controversial. Recent studies suggest that ET-1 contributes to high basal pulmonary vascular resistance in the normal fetus, but its role in the modulation of pulmonary vascular tone remains uncertain. We hypothesized that high ET-1 activity opposes the vasodilator response to some physiological stimuli such as increased pressure. To test the hypothesis that ET-1 modulates fetal pulmonary vascular responses to acute and prolonged physiological stimuli, we performed a series of experiments in the late-gestation ovine fetus. We studied the hemodynamic effects of two ET-1 antagonists, BQ-123 (a selective ETA-receptor antagonist) and phosphoramidon (a nonselective ET-1-converting enzyme inhibitor) during mechanical increases in pressure due to partial ductus arteriosus compression in chronically prepared late-gestation fetal lambs. In control studies, partial ductus arteriosus compression decreased the ratio of pulmonary arterial pressure to pulmonary artery flow in the left lung 34 ± 6% from baseline. Intrapulmonary infusions of BQ-123 (0.5 μg/min for 10 min; 0.025 μg/min for 2 h) or phosphoramidon (1.0 mg/min for 10 min) augmented the peak vasodilator response during ductus arteriosus compression (52 ± 3 and 49 ± 6% from baseline, respectively, P < 0.05 vs. control). In addition, unlike the transient vasodilator response to ductus arteriosus compression in control studies, ET-1 blockade with BQ-123 or phosphoramidon prolonged the increase in flow caused by ductus arteriosus compression. In summary, ETA-receptor blockade and ET-1-converting enzyme inhibition augment and prolong fetal pulmonary vasodilation during partial compression of the ductus arteriosus. We conclude that ET-1 activity modulates acute and prolonged responses of the fetal pulmonary circulation to changes in vascular pressure. We speculate that ET-1 contributes to regulation and maintenance of high pulmonary vascular resistance in the normal ovine fetal lung.

Assessment of Autonomic and Non-Autonomic Components of Resting Hindlimb Vascular Resistance and Reactivity to Pressor Substances in Renal Hypertensive Rabbits

1976 ◽  
Vol 51 (s3) ◽  
pp. 57s-59s
Author(s):  
J. A. Angus ◽  
M. J. West ◽  
P. I. Korner
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Vascular Resistance ◽  
Structural Changes ◽  
Resistance Vessels ◽  
Structural Differences ◽  
Before And After ◽  
Autonomic Blockade ◽  
Autonomic Component

1. Hindlimb vascular resistance (HVR) was measured before and after pharmacological autonomic blockade in unanaesthetized renal cellophan-wrap hypertensive or normotensive rabbits with previously implanted Doppler ultrasonic flowmeters. 2. When the blood pressure was restored to resting values after autonomic block, the elevated resting HVR in the hypertensive rabbits was entirely accounted for by an increased non-autonomic component (i.e. HVR after block). If the pressure was not restored after block the autonomic component (i.e. resting HVR minus non-autonomic HVR) was overestimated and the non-autonomic component was underestimated. 3. During maximum vasodilatation the minimum HVR was significantly higher in the hypertensive rabbits than in the normotensive group, probably due to structural differences of resistance vessels. 4. Reactivity of the hindlimb bed to noradrenaline, angiotensin II and vasopressin injections was approximately twice as great in the hypertensive rabbits as in the sham-operated group, probably as a consequence of the structural changes.

scholarly journals Increased Red Blood Cell Stiffness Increases Pulmonary Vascular Resistance and Pulmonary Arterial Pressure

2016 ◽  
Vol 138 (2) ◽  
Author(s):  
David A. Schreier ◽  
Omid Forouzan ◽  
Timothy A. Hacker ◽  
John Sheehan ◽  
Naomi Chesler
Keyword(s):  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Arterial Compliance ◽  
Cell Stiffness ◽  
The Third ◽  
Vascular Impedance ◽  
Increased Risk ◽  
Before And After ◽  
Pulmonary Arterial ◽  
The Impact

Patients with sickle cell anemia (SCD) and pulmonary hypertension (PH) have a significantly increased risk of sudden death compared to patients with SCD alone. Sickled red blood cells (RBCs) are stiffer, more dense, more frequently undergo hemolysis, and have a sixfold shorter lifespan compared to normal RBCs. Here, we sought to investigate the impact of increased RBC stiffness, independent of other SCD-related biological and mechanical RBC abnormalities, on the hemodynamic changes that ultimately cause PH and increase mortality in SCD. To do so, pulmonary vascular impedance (PVZ) measures were recorded in control C57BL6 mice before and after ∼50 μl of blood (Hct = 45%) was extracted and replaced with an equal volume of blood containing either untreated RBCs or RBCs chemically stiffened with glutaraldehyde (Hct = 45%). Chemically stiffened RBCs increased mean pulmonary artery pressure (mPAP) (13.5 ± 0.6 mmHg at baseline to 23.2 ± 0.7 mmHg after the third injection), pulmonary vascular resistance (PVR) (1.23 ± 0.11 mmHg*min/ml at baseline to 2.24 ± 0.14 mmHg*min/ml after the third injection), and wave reflections (0.31 ± 0.02 at baseline to 0.43 ± 0.03 after the third injection). Chemically stiffened RBCs also decreased cardiac output, but did not change hematocrit, blood viscosity, pulmonary arterial compliance, or heart rate. The main finding of this study is that increased RBC stiffness alone affects pulmonary pulsatile hemodynamics, which suggests that RBC stiffness plays an important role in the development of PH in patients with SCD.

EDRF inhibition attenuates the increase in pulmonary blood flow due to oxygen ventilation in fetal lambs

1992 ◽  
Vol 73 (5) ◽  
pp. 2151-2157 ◽  
Author(s):  
P. Moore ◽  
H. Velvis ◽  
J. R. Fineman ◽  
S. J. Soifer ◽  
M. A. Heymann
Keyword(s):  
Blood Flow ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Blood Flow ◽  
Vascular Tone ◽  
Competitive Inhibitor ◽  
In Utero ◽  
Prostaglandin Synthesis ◽  
Arginine Infusion ◽  
Pulmonary Vasodilation

At birth, pulmonary vasodilation occurs during rhythmic distension of the lungs and oxygenation. Inhibition of prostaglandin synthesis prevents pulmonary vasodilation during rhythmic distension of the lungs but not during oxygenation. Because endothelium-derived relaxing factor (EDRF) modulates pulmonary vascular tone at birth, at rest, and during hypoxia in older animals, we hypothesized that EDRF may modulate pulmonary vascular tone during oxygenation in fetal lambs. We studied the responses to N omega-nitro-L-arginine, a competitive inhibitor of EDRF synthesis, in nine near-term fetal lambs and to drug vehicle in six of these lambs and the subsequent responses to in utero ventilation with 95% O2 in these fetal lambs. In all fetal lambs, prostaglandin synthesis was prevented by meclofenamate. N omega-nitro-L-arginine increased pulmonary and systemic arterial pressures by 28% (P < 0.05) and 31% (P < 0.05), respectively, and decreased pulmonary blood flow by 83% (P < 0.05). In the controls, ventilation with 95% O2 increased pulmonary blood flow by 1,050% (P = 0.05) without changing pressures, thereby decreasing pulmonary vascular resistance by 88% (P = 0.05). During N omega-nitro-L-arginine infusion, ventilation with 95% O2 increased pulmonary blood flow by 162% (P = 0.05) and decreased pulmonary vascular resistance by 74% (P = 0.05). This suggests that EDRF may play an important role in modulating resting pulmonary vascular tone in fetal lambs and in the vasodilatory response to ventilation with O2 in utero.

Comparison of the effect of inhaled anaesthetic with intravenous anaesthetic on pulmonary vascular resistance measurement during cardiac catheterisation

2014 ◽  
Vol 25 (2) ◽  
pp. 368-372 ◽  
Author(s):  
Leonie A. Giesen ◽  
Michelle White ◽  
Robert M.R. Tulloh
Keyword(s):  
Pulmonary Hypertension ◽  
Pilot Study ◽  
Pulmonary Vascular Resistance ◽  
Systemic Vascular Resistance ◽  
Vascular Resistance ◽  
Anaesthetic Agent ◽  
Preliminary Evidence ◽  
Systemic Resistance ◽  
Pulmonary Resistance ◽  
Intravenous Anaesthetic

AbstractBackground: Children with pulmonary hypertension routinely undergo pulmonary vascular resistance studies to assess the disease severity and vasodilator responsiveness. It is vital that results are accurate and reliable and are not influenced by the choice of anaesthetic agent. However, there are anecdotal data to suggest that propofol and inhalational agents have different effects on pulmonary vascular resistance. Methods: A total of 10 children with pulmonary hypertension were selected sequentially to be included in the study. To avoid confounding because of baseline anatomic or demographic details, a crossover protocol was implemented, using propofol or isoflurane, with time for washout in between each agent and blinding of the interventionalist. Results: Pulmonary and systemic vascular resistance were not significantly different when using propofol or isoflurane. However, the calculated resistance fraction – ratio of pulmonary resistance to systemic resistance – was significantly lower when using propofol than when using isoflurane. Conclusions: Although no difference in pulmonary vascular resistance was demonstrated, this pilot study suggests that the choice of anaesthetic agent may affect the calculation of relative pulmonary and systemic vascular resistance, and provides some preliminary evidence to favour propofol over isoflurane. These findings require replication in a larger study, and thus they should be considered in future calculations to make informed decisions about the management of children with pulmonary hypertension.

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