Pulmonary vasodilator drugs decrease lung liquid production in fetal sheep

1995 ◽  
Vol 79 (4) ◽  
pp. 1212-1218 ◽  
Author(s):  
J. J. Cummings
Keyword(s):  
Blood Flow ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Blood Flow ◽  
Fetal Lung ◽  
Prostaglandin D2 ◽  
Fetal Sheep ◽  
Pulmonary Vasodilator ◽  
Pulmonary Arterial ◽  
Lung Liquid

To examine a potential relationship between pulmonary vasodilatation and fetal lung liquid production, I measured lung liquid production in 20 fetal sheep at 130 +/- 4 days gestation while using several agents known to increase pulmonary blood flow. Thirty-two studies were done in which left pulmonary arterial flow (Qlpa) was measured by an ultrasonic Doppler flow probe and net lung luminal liquid production (Jv) was measured by plotting the change in lung luminal liquid concentration of radiolabeled albumin, an impermeant tracer that was mixed into the lung liquid at the start of each study. Qlpa and Jv were measured during a 1- to 2-h baseline period and then during a 1- to 2-h infusion period in which the fetuses received either an intravenous infusion of acetylcholine (n = 8), prostaglandin D2 (n = 10), or the leukotriene blocker FPL-55712 (n = 7). These vasodilators work by different mechanisms, each mechanism having been implicated in the decrease in pulmonary vascular resistance seen at birth. Control (saline) infusions (n = 7) caused no change in either Qlpa or Jv over 4 h. All vasodilator agents significantly increased pulmonary blood flow and decreased Jv. Pulmonary arterial pressure did not change significantly in either the control, acetylcholine, prostaglandin, or leukotriene-blocker studies, indicating that pulmonary vascular resistance decreased. Thus agents that increase pulmonary blood flow by mechanisms that occur at birth also decrease lung liquid production in fetal lambs.

Endothelin-1 vasoactive responses in lambs with pulmonary hypertension and increased pulmonary blood flow

1995 ◽  
Vol 269 (6) ◽  
pp. H1965-H1972 ◽  
Author(s):  
J. Wong ◽  
V. M. Reddy ◽  
K. Hendricks-Munoz ◽  
J. R. Liddicoat ◽  
R. Gerrets ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Hypertension ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Blood Flow ◽  
Heart Diseases ◽  
Main Pulmonary Artery ◽  
Similar Degree ◽  
Fetal Sheep ◽  
Endothelin 1

Increased concentrations of endothelin-1 (ET-1) are found in children with congenital heart diseases that produce increased pulmonary blood flow and pulmonary hypertension, but the role of ET-1 in the pathophysiology of pulmonary hypertension is unclear. Therefore, we investigated ET-1-induced vasoactive responses and ET-1 concentrations in an animal model of pulmonary hypertension and increased pulmonary blood flow. Vascular shunts were placed between the ascending aorta and main pulmonary artery in seven late-gestation fetal sheep. Four weeks after spontaneous delivery, ET-1 increased pulmonary vascular resistance by 29.7 +/- 34.4% (P < 0.05), the ETb-receptor agonist [Ala1,3,11,15]ET-1 (4AlaET-1) had no effect, and the ETa-receptor antagonist cyclo(D-Asp-L-Pro-D-Val-L-Leu-D-Trp) (BQ-123) decreased pulmonary vascular resistance by -16.0 +/- 5.6% (P < 0.05). In contrast, in six control lambs with a similar degree of pulmonary hypertension induced by U-46619, ET-1 and 4AlaET-1 decreased pulmonary vascular resistance by 24.8 +/- 17.6, and 20.0 +/- 13.8%, respectively (P < 0.05). In addition, systemic arterial concentrations of immunoreactive ET-1 were elevated in lambs with pulmonary hypertension (29.2 +/- 9.6 vs. 15.2 +/- 10.7 pg/ml, P < 0.05). Pulmonary hypertension and increased pulmonary blood flow alters the response of ET-1 from pulmonary vasodilation to vasoconstriction. These altered responses suggest a role for ET-1 and its receptors in the pathogenesis of pulmonary hypertension secondary to increased pulmonary blood flow.

Persistent fetal pulmonary hypoperfusion after acute hypoxia

1987 ◽  
Vol 253 (4) ◽  
pp. H941-H948 ◽  
Author(s):  
S. H. Abman ◽  
F. J. Accurso ◽  
R. B. Wilkening ◽  
G. Meschia
Keyword(s):  
Blood Flow ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Blood Flow ◽  
Acute Hypoxia ◽  
Arterial Blood Flow ◽  
Adrenergic Blockade ◽  
Flow Transducer ◽  
Arterial Blood ◽  
Pulmonary Arterial

To determine the effects of duration of hypoxia on fetal pulmonary blood flow and vasoreactivity, we studied the response of the fetal pulmonary vascular bed before, during, and after prolonged (2-h) and more brief (30-min) exposures to acute hypoxia in 19 chronically instrumented unanesthetized fetal lambs. Left pulmonary arterial blood flow was measured by an electromagnetic flow transducer. Fetal PO2 was lowered by delivering 10-12% O2 to the ewe. During 2-h periods of hypoxia left pulmonary arterial blood flow decreased, and main pulmonary arterial and pulmonary vascular resistance increased. The increase in pulmonary vascular resistance was sustained throughout the 2-h period of hypoxia. After the return of the ewe to room air breathing, pulmonary vascular resistance remained elevated for at least 1 h despite the rapid correction of hypoxemia and in the absence of acidemia. In contrast, after 30 min of hypoxia, left pulmonary arterial blood flow, pulmonary arterial pressure, and pulmonary vascular resistance returned to base-line values rapidly with the termination of hypoxia. The persistent pulmonary hypoperfusion after 2 h of hypoxia was attenuated by alpha-adrenergic blockade and was characterized by a blunted vasodilatory response to increases in fetal PO2. When fetal PO2 was elevated during the posthypoxia period in the presence of alpha-blockade, pulmonary blood flow still remained unresponsive to increases in fetal PO2. We conclude that 2-h periods of acute hypoxia can decrease fetal pulmonary vasoreactivity, and we speculate that related mechanisms may contribute to the failure of the normal adaptation of the pulmonary circulation at birth.

Physical factors affecting normal and serotonin-constricted pulmonary vessels

1960 ◽  
Vol 198 (4) ◽  
pp. 864-872 ◽  
Author(s):  
Abraham M. Rudolph ◽  
Peter A. M. Auld
Keyword(s):  
Blood Flow ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Blood Flow ◽  
Venous Pressure ◽  
Physical Factors ◽  
Factors Affecting ◽  
Pulmonary Vessels ◽  
High Flows ◽  
Pulmonary Arterial

The effects of changes of pulmonary blood flow, pulmonary venous and pulmonary arterial pressure on calculated pulmonary vascular resistance were evaluated in open-chest, intact dogs, in which the pulmonary and systemic circulations were separately perfused. Similar observations were made after constricting the pulmonary vessels by continuous infusion of serotonin. An increase in pulmonary blood flow produced a decrease in pulmonary vascular resistance. At high flows, the calculated resistance in the serotonin-constricted vessels could be reduced to levels considered normal at lower flows in normal vessels. An increase of pulmonary venous pressure resulted in a decrease of calculated resistance up to pulmonary venous pressure levels of 15–20 mm Hg in ‘normal’ vessels, but in serotonin-constricted vessels, resistance continued to be decreased by increase of pulmonary venous pressure up to 25–30 mm Hg. These findings confirm that the usual formula for calculating pulmonary vascular resistance assesses only resistance to flow, but does not provide information regarding vascular tone.

A fetal-instrumented model to study age-specific responses to leukotriene D4 and prostaglandin D2 in unsedated newborn lambs

1989 ◽  
Vol 67 (6) ◽  
pp. 587-593
Author(s):  
J. Y. Coe ◽  
P. M. Olley ◽  
F. Coceani
Keyword(s):  
Blood Flow ◽  
Pulmonary Artery ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Circulation ◽  
Pulmonary Blood Flow ◽  
Main Pulmonary Artery ◽  
Right Atrial ◽  
Prostaglandin D2 ◽  
Leukotriene D4

Sequential studies of the pulmonary vascular response to leukotriene D4 (LTD4) and prostaglandin D2 (PGD2) in the immediate newborn period were performed in lambs, instrumented in utero and delivered vaginally. Compounds were tested in fully conscious 1.5-day-old lambs and the study was repeated 1 week later. Bolus injections of PGD2 (0.05–2.0 μg/kg) or LTD4 (0.01–1.0 μg/kg) were made into the main pulmonary artery or aorta while pulmonary blood flow and aortic, pulmonary artery, and left and right atrial pressures were monitored continuously. PGD2 was a systemic constrictor regardless of age. In lambs 1.5 days of age, it decreased pulmonary vascular pressure and resistance by 6% (p < 0.05) and 15% (p < 0.05), respectively, while 1 week later it increased pulmonary vascular resistance by 18% (p < 0.05). In contrast, LTD4 was a pulmonary and systemic vasoconstrictor in both the early and late newborn, the threshold dose being between 0.01 and 0.05 μg/kg at either age. The decrease in pulmonary blood flow and the increase in pressure and resistance were greater in older animals. In lambs 1.5 days of age, LTD4 (1 μg/kg) increased pulmonary vascular resistance by 66.1% (p < 0.05) and 1 week later by 210% (p < 0.001). These sequential observations in the same animal indicate that unlike PGD2, LTD4 is a pulmonary vasoconstrictor regardless of age, and its effectiveness increases significantly with age. These results support previous reports that PGD2 action in the pulmonary circulation changes shortly after birth from dilation to constriction.Key words: pulmonary circulation, newborn lamb, prostaglandin D2, leukotriene D4.

Pulmonary blood flow, pressure and resistance following tetraethylammonium and aminophylline

1961 ◽  
Vol 200 (2) ◽  
pp. 287-291 ◽  
Author(s):  
M. Harasawa ◽  
S. Rodbard
Keyword(s):  
Blood Flow ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Systemic Blood Pressure ◽  
Arterial Blood Flow ◽  
Tetraethylammonium Chloride ◽  
Blood Flows ◽  
Arterial Blood ◽  
Pulmonary Arterial ◽  
Flow Pressure

The effects of tetraethylammonium chloride (TEAC) and aminophylline on the pulmonary vascular resistance were studied in thoracotomized dogs. Pulmonary arterial blood flow and pressure, and systemic blood pressure were measured simultaneously. Both drugs showed marked hypotensive effects on the systemic vessels. In every instance pulmonary arterial pressures and blood flows were reduced by TEAC given via the pulmonary artery and increased by aminophylline. However, the calculated pulmonary vascular resistance remained essentially unchanged in all experiments. These data challenge the concept that the pulmonary vessels respond to these drugs by active vasodilatation

The Eisenmenger syndrome

2011 ◽  
Keyword(s):  
Blood Flow ◽  
Natural History ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Blood Flow ◽  
Eisenmenger Syndrome ◽  
Cardiac Manifestations ◽  
High Pulmonary Vascular Resistance

Introduction 114Natural history 114Complications and extra-cardiac manifestations 114Physical signs 114Investigations 116Management 116Large communication between the systemic and pulmonary circulations at atrial, ventricular, or arterial level: → high pulmonary blood flow (L-to-R shunt);→ development of high pulmonary vascular resistance;...

Effect of high intra-alveolar O2 tensions on pulmonary circulation in perfused lungs of dogs

1965 ◽  
Vol 208 (1) ◽  
pp. 130-138 ◽  
Author(s):  
G. J. A. Cropp
Keyword(s):  
Blood Flow ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Pulmonary Circulation ◽  
Time Course ◽  
Systemic Circulation ◽  
The Body ◽  
Arterial Blood ◽  
Pulmonary Parenchyma ◽  
Pulmonary Arterial

The resistance to blood flow in the pulmonary circulation of dogs (PVR) increased when their lungs were ventilated with 95–100% oxygen and were perfused with blood that recirculated only through the pulmonary circulation; the systemic circulation was perfused independently. This increase in PVR occurred even when nerves were cut or blocked but was abolished by inhaled isopropylarterenol aerosol. Elevation of intra-alveolar Po2 without increase in pulmonary arterial blood Po2 was sufficient to increase pulmonary vascular resistance. The pulmonary venules or veins were thought to be the likely site of the constriction. These reactions were qualitatively similar to those produced by injection of serotonin or histamine into the pulmonary circulation. The time course of the response and failure to obtain it when the blood was perfused through the remainder of the body before it re-entered the pulmonary circulation are compatible with a theory that high intra-alveolar O2 tension activates a vasoconstrictor material in the pulmonary parenchyma.

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