scholarly journals Comparison of vascular and respiratory effects of endothelin-1 in the pig

1993 ◽  
Vol 2 (4) ◽  
pp. 287-292 ◽  
Author(s):  
M. G. Clement ◽  
M. Dimori ◽  
M. Albertini
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
High Dose ◽  
Bolus Administration ◽  
Endothelin 1 ◽  
Mean Pulmonary Arterial Pressure ◽  
Active Compliance ◽  
Pulmonary Arterial ◽  
Spontaneously Breathing ◽  
Dose Dependent

The haemodynamic and respiratory responses caused by i.v. administration of endothelin-1 (ET-1) (20–100 pmol/kg) were studied in anaesthetized spontaneously breathing pigs. Intravenous bolus administration of synthetic ET-1 (40–100 pmol/kg) caused a transient decrease followed by a long-lasting increase in mean pulmonary arterial pressure and dose dependent vasoconstriction both in the systemic and pulmonary circulations. The effect on pulmonary arterial pressure was biphasic, with an initial transient fall followed by a long-lasting dose dependent increase. A biphasic response of the systemic mean arterial pressure was demonstrated only at a high dose of ET-1 (100 pmol/kg). ET-1 administration did not significantly change breathing pattern or phasic vagal input, but caused a significant decrease in passive compliance. Passive resistances or active compliance and resistances of the respiratory system were not modified. These results suggest that in the pig ET-1 is a more potent constrictor of vascular than of bronchial smooth muscle. The vasoconstrictor activity was greater in the pulmonary than the systemic circulations.

Gestational resistance to the pulmonary vasoconstrictor effect of the TxA2 mimetic U-46619: possible mechanism

1997 ◽  
Vol 272 (6) ◽  
pp. R1734-R1739 ◽  
Author(s):  
G. Losonczy ◽  
G. Brown ◽  
I. Mucha ◽  
R. Klocke ◽  
V. Muller ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Vascular System ◽  
Late Gestation ◽  
Mechanically Ventilated ◽  
Mean Pulmonary Arterial Pressure ◽  
Vascular Sensitivity ◽  
Specific Receptors ◽  
Pulmonary Arterial ◽  
Dose Dependent

Pregnancy is associated with the reduction of vascular sensitivity to vasoconstrictor compounds. We have examined whether pregnancy in rabbits induces hyposensitivity of the pulmonary vascular system to U-46619. Anesthetized, mechanically ventilated nonpregnant (NP; n = 7) and late-pregnant (P; n = 7) rabbits were studied. The intravenous injection of 0.03, 0.1, and 0.3 microgram/kg U-46619 led to a dose-dependent elevation of mean pulmonary arterial pressure (MPAP) in NP rabbits from a baseline value of 15 +/- 1 to 22 +/- 1 mgHg. There was no significant MPAP response to intravenous administration of U-46619 in P rabbits. The pulmonary arterial pressure response of isolated, ventilated, and buffer-perfused lungs of P rabbits was also blunted (P < 0.001 vs. NP). Pulmonary arterial membrane binding of [125I]BOP, another thromboxane (Tx)A2 analog, indicated 48 +/- 16 fmol receptors/mg protein in P rabbits and 193 +/- 48 fmol receptors/mg protein in NP samples (P < 0.025). Receptor affinity [1/dissociation constant (KD)] was also lower in the tissue of P rabbits (P < 0.01 vs. NP). The urinary excretion of the stable TxA2 metabolite 11-dehydro-TxB2 was lower in P than in NP rabbits (P < 0.02), which made homologous desensitization an unlikely explanation for the changes of vascular TxA2 receptors. These results show that, in late gestation, rabbit pulmonary vascular sensitivity to U-46619 is reduced simultaneously with, and as a possible consequence of, downregulation of specific receptors.

Endothelin-1 produces pulmonary vasodilation in the intact newborn lamb

1993 ◽  
Vol 265 (4) ◽  
pp. H1318-H1325 ◽  
Author(s):  
J. Wong ◽  
P. A. Vanderford ◽  
J. R. Fineman ◽  
R. Chang ◽  
S. J. Soifer
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Newborn Lamb ◽  
Endothelin 1 ◽  
Pulmonary Vasodilator ◽  
Pulmonary Arterial ◽  
Dose Dependent Decrease ◽  
Dose Dependent

The vascular endothelium mediates, in part, pulmonary vascular tone. Because endothelin-1 (ET-1), a paracrine hormone produced by vascular endothelial cells, has vasoactive properties, we investigated the hemodynamic effects of intrapulmonary injections of ET-1 in eight intact newborn lambs at rest and during pulmonary hypertension. At rest, ET-1 (50-1,000 ng/kg) did not change pulmonary arterial pressure. During pulmonary hypertension induced by the infusion of U46619 (a thromboxane A2 mimic), ET-1 (50-1,000 ng/kg) produced a selective dose-dependent decrease in pulmonary arterial pressure (5.8 +/- 3.9 to 32.9 +/- 6.9%; P < 0.05). Similarly, during pulmonary hypertension induced by alveolar hypoxia, ET-1 (50-500 ng/kg) produced a selective dose-dependent decrease in pulmonary arterial pressure (7.2 +/- 3.6 to 26.1 +/- 3.3%; P < 0.05). The decrease in pulmonary arterial pressure produced by ET-1 (250 ng/kg) was attenuated by N omega-nitro-L-arginine (an inhibitor of endothelium-derived nitric oxide synthesis, 23.7 +/- 3.4 vs. 12.5 +/- 4.7%; P < 0.05) and by glibenclamide (an ATP-gated potassium-channel blocker, 25.2 +/- 5.0 vs. 9.6 +/- 5.3%; P < 0.05) but not by meclofenamic acid (an inhibitor of prostaglandin synthesis). ET-1 is a pulmonary vasodilator during pulmonary hypertension in the intact newborn lamb. The vasodilating properties are mediated, in part, by release of endothelium-derived nitric oxide, and by activation of ATP-gated potassium channels.

A computed method for noninvasive MRI assessment of pulmonary arterial hypertension

2004 ◽  
Vol 96 (2) ◽  
pp. 463-468 ◽  
Author(s):  
Eric Laffon ◽  
Christophe Vallet ◽  
Virginie Bernard ◽  
Michel Montaudon ◽  
Dominique Ducassou ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Cross Sectional Area ◽  
Physical Parameters ◽  
Sectional Area ◽  
Biophysical Parameters ◽  
Cross Sectional ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Arterial ◽  
The Mean

The present method enables the noninvasive assessment of mean pulmonary arterial pressure from magnetic resonance phase mapping by computing both physical and biophysical parameters. The physical parameters include the mean blood flow velocity over the cross-sectional area of the main pulmonary artery (MPA) at the systolic peak and the maximal systolic MPA cross-sectional area value, whereas the biophysical parameters are related to each patient, such as height, weight, and heart rate. These parameters have been measured in a series of 31 patients undergoing right-side heart catheterization, and the computed mean pulmonary arterial pressure value (PpaComp) has been compared with the mean pressure value obtained from catheterization (PpaCat) in each patient. A significant correlation was found that did not differ from the identity line PpaComp = PpaCat ( r = 0.92). The mean and maximal absolute differences between PpaComp and PpaCat were 5.4 and 11.9 mmHg, respectively. The method was also applied to compute the MPA systolic and diastolic pressures in the same patient series. We conclude that this computed method, which combines physical (whoever the patient) and biophysical parameters (related to each patient), improves the accuracy of MRI to noninvasively estimate pulmonary arterial pressures.

scholarly journals Mean pulmonary arterial pressure after percutaneous mitral valvuloplasty predicts long-term adverse outcomes

2012 ◽  
Vol 31 (1) ◽  
pp. 19-25 ◽  
Author(s):  
Elisabete Jorge ◽  
Rui Baptista ◽  
Henrique Faria ◽  
João Calisto ◽  
Vítor Matos ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Adverse Outcomes ◽  
Mitral Valvuloplasty ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Arterial

Pulmonary pressor response after prostaglandin synthesis inhibition in conscious dogs

1982 ◽  
Vol 52 (3) ◽  
pp. 705-709 ◽  
Author(s):  
B. R. Walker ◽  
N. F. Voelkel ◽  
J. T. Reeves
Keyword(s):  
Cardiac Output ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Pressor Response ◽  
Conscious Dogs ◽  
Pulmonary Pressure ◽  
Time Control ◽  
Mean Pulmonary Arterial Pressure ◽  
Before And After ◽  
Pulmonary Arterial

Recent studies have shown that vasodilator prostaglandins are continually produced by the isolated rat lung. We postulated that these vasodilators may contribute to maintenance of normal low pulmonary arterial pressure. Pulmonary pressure and cardiac output were measured in conscious dogs prior to and 30 to 60 min following administration of meclofenamate (2 mg/kg iv, followed by infusion at 2 mg . kg-1 . h-1) or the structurally dissimilar inhibitor RO–20–5720 (1 mg/kg iv, followed by infusion at 1 mg . kg-1 . h-1). The animals were also made hypoxic with inhalation of 10% O2 before and after inhibition. Time-control experiments were conducted in which only the saline vehicle was administered. Meclofenamate or RO–20–5720 caused an increase in mean pulmonary arterial pressure and total pulmonary resistance. Cardiac output and systemic pressure were unaffected. The mild hypoxic pulmonary pressor response observed was not affected by meclofenamate. Animals breathing 30% O2 to offset Denver's altitude also demonstrated increased pulmonary pressure and resistance when given meclofenamate. It is concluded that endogenous vasodilator prostaglandins may contribute to normal, low vascular tone in the pulmonary circulation.

scholarly journals Pulmonary Vasodilator Therapy in Children with Single Ventricle Physiology: Effects on Saturation and Pulmonary Arterial Pressure

2020 ◽  
Vol 41 (8) ◽  
pp. 1651-1659
Author(s):  
Ida Jeremiasen ◽  
Karin Tran-Lundmark ◽  
Nikmah Idris ◽  
Phan-Kiet Tran ◽  
Shahin Moledina
Keyword(s):  
Arterial Pressure ◽  
Single Ventricle ◽  
Pulmonary Arterial Pressure ◽  
Vasodilator Therapy ◽  
Single Ventricle Physiology ◽  
Pulmonary Vasodilators ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Vasodilator ◽  
Pulmonary Arterial ◽  
Stage 1

AbstractIn children with single ventricle physiology, increased pulmonary vascular resistance may impede surgical progression or result in failing single ventricle physiology. The use of pulmonary vasodilators has been suggested as a potential therapy. However, knowledge on indication, dosage, and effect is limited. A retrospective case notes review of all (n = 36) children with single ventricle physiology, treated with pulmonary vasodilators by the UK Pulmonary Hypertension Service for Children 2004–2017. Therapy was initiated in Stage 1 (n = 12), Glenn (n = 8), or TCPC (n = 16). Treatment indications were high mean pulmonary arterial pressure, cyanosis, reduced exercise tolerance, protein-losing enteropathy, ascites, or plastic bronchitis. Average dose of sildenafil was 2.0 mg/kg/day and bosentan was 3.3 mg/kg/day. 56% had combination therapy. Therapy was associated with a reduction of the mean pulmonary arterial pressure from 19 to 14 mmHg (n = 17, p < 0.01). Initial therapy with one or two vasodilators was associated with an increase in the mean saturation from 80 to 85%, (n = 16, p < 0.01). Adding a second vasodilator did not give significant additional effect. 5 of 12 patients progressed from Stage 1 to Glenn, Kawashima, or TCPC, and 2 of 8 from Glenn to TCPC during a mean follow-up time of 4.7 years (0–12.8). Bosentan was discontinued in 57% and sildenafil in 14% of treated patients and saturations remained stable. Pulmonary vasodilator therapy was well tolerated and associated with improvements in saturation and mean pulmonary arterial pressure in children with single ventricle physiology. It appears safe to discontinue when no clear benefit is observed.

N omega-nitro-L-arginine attenuates endothelium-dependent pulmonary vasodilation in lambs

1991 ◽  
Vol 260 (4) ◽  
pp. H1299-H1306 ◽  
Author(s):  
J. R. Fineman ◽  
M. A. Heymann ◽  
S. J. Soifer
Keyword(s):  
Arterial Pressure ◽  
Sodium Nitroprusside ◽  
Vascular Tone ◽  
Pulmonary Arterial Pressure ◽  
Competitive Inhibitor ◽  
Pulmonary Vasodilation ◽  
Pulmonary Arterial ◽  
Spontaneously Breathing ◽  
Dose Dependent Increase

To investigate the role of endothelium-derived relaxing factor (EDRF) in the regulation of resting pulmonary vascular tone and endothelium-dependent pulmonary vasodilation, we studied the hemodynamic effects of N omega-nitro-L-arginine (a new stereospecific EDRF inhibitor) in 10 spontaneously breathing lambs and then compared the hemodynamic responses to five vasodilators during pulmonary hypertension induced by the infusion of U-46619 (a thromboxane A2 mimetic) or N omega-nitro-L-arginine. N omega-nitro-L-arginine caused a significant dose-dependent increase in pulmonary arterial pressure. Pretreatment with L-arginine blocked this increase, but pretreatment with D-arginine did not, suggesting that N omega-nitro-L-arginine is a competitive inhibitor of L-arginine for EDRF production. During U-46619 infusions, acetylcholine, ATP-MgCl2, isoproterenol, sodium nitroprusside, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-bromo-cGMP) decreased pulmonary arterial pressure. During N omega-nitro-L-arginine infusions, the decrease in pulmonary arterial pressure caused by acetylcholine and ATP-MgCl2 (endothelium-dependent vasodilators) was significantly attenuated, but the decrease caused by isoproterenol, sodium nitroprusside, and 8-bromo-cGMP (endothelium-independent vasodilators) was unchanged. This study supports the hypothesis that EDRF in part mediates resting pulmonary vascular tone and endothelium-dependent pulmonary vasodilation. N omega-nitro-L-arginine is useful for studying EDRF inhibition in intact animals.

Flow through zone 1 lungs utilizes alveolar corner vessels

1991 ◽  
Vol 70 (4) ◽  
pp. 1518-1523 ◽  
Author(s):  
W. J. Lamm ◽  
K. R. Kirk ◽  
W. L. Hanson ◽  
W. W. Wagner ◽  
R. K. Albert
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Left Lung ◽  
Lateral Position ◽  
Double Lumen Endotracheal Tube ◽  
Mean Pulmonary Arterial Pressure ◽  
Flow Through ◽  
Pulmonary Arterial ◽  
Isolated Lungs

We have previously observed flows equivalent to 15% of the resting cardiac output of rabbits occurring through isolated lungs that were completely in zone 1. To distinguish between alveolar corner vessels and alveolar septal vessels as a possible zone 1 pathway, we made in vivo microscopic observations of the subpleural alveolar capillaries in five anesthetized dogs. Videomicroscopic recordings were made via a transparent thoracic window with the animal in the right lateral position. From recordings of the uppermost surface of the left lung, alveolar septal and corner vessels were classified depending on whether they were located within or between alveoli, respectively. Observations were made with various levels of positive end-expiratory pressure (PEEP) applied only to the left lung via a double-lumen endotracheal tube. Consistent with convention, flow through septal vessels stopped when PEEP was raised to the mean pulmonary arterial pressure (the zone 1-zone 2 border). However, flow through alveolar corner vessels continued until PEEP was 8-16 cmH2O greater than mean pulmonary arterial pressure (8-16 cm into zone 1). These direct observations support the idea that alveolar corner vessels rather than patent septal vessels provide the pathway for blood flow under zone 1 conditions.

The response of the pulmonary circulation to exercise during normoxia and hypoxia following pneumonectomy in the adult sheep

1989 ◽  
Vol 67 (3) ◽  
pp. 202-206 ◽  
Author(s):  
Michele Smith ◽  
Geoffrey Coates ◽  
J. Michael Kay ◽  
Hugh O'Brodovich
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Hemodynamic Response ◽  
Pulmonary Hemodynamics ◽  
Vascular Reserve ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Hemodynamic ◽  
Pulmonary Arterial ◽  
Increased Blood Flow

Pneumonectomy approximately halves the available pulmonary vascular bed. It is unknown whether the remaining lung has sufficient vascular reserve to cope with increased blood flow under stressful conditions without demonstrating abnormal pulmonary hemodynamics. To investigate this question, unanesthetized ewes with vascular catheters had hemodynamics assessed before and after a left pneumonectomy. Subsequently, on different days, the sheep were exercised on a treadmill under normoxic and hypobaric hypoxic (430 mmHg) (1 mmHg = 133.3 Pa) conditions. Pneumonectomy itself increased mean pulmonary arterial pressure by 4 mmHg. During normoxic or hypoxic exercise, the pneumonectomized sheep demonstrated a pulmonary hemodynamic response similar to normal sheep with two lungs. The pressure–flow relation for the right lung suggested the vascular reserve of the lung was not exceeded during exercise in the pneumonectomized sheep. Eighteen to 70 days after pneumonectomy there was no evidence of right ventricular hypertrophy, but there were small increases in the number of muscularized vessels less than 50 μm diameter and in the amount of muscle in normally muscularized pulmonary arteries. This study demonstrates that pneumonectomy slightly increases mean pulmonary arterial pressure. However, there is sufficient vascular reserve in the remaining lung to permit a normal hemodynamic response to exercise-induced increased blood flow even under hypoxic conditions.Key words: pulmonary hypertension, pneumonectomy, sheep.

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