Pharmacological properties of canine intrapulmonary blood vessels

1984 ◽  
Vol 62 (9) ◽  
pp. 1198-1202 ◽  
Author(s):  
Siow-Kee Kong ◽  
Newman L. Stephens
Keyword(s):  
Pulmonary Artery ◽  
Pulmonary Vein ◽  
Contractile Response ◽  
Pulmonary Veins ◽  
Pulmonary Arteries ◽  
Pulmonary Vasculature ◽  
Maximal Response ◽  
Response Curves ◽  
Significant Difference ◽  
Differential Responsiveness

The contractile response of ring segments of large, medium, and small pulmonary arteries and veins of the dog to histamine, norepinephrine, and serotonin have been studied. The maximum contractile response to these drugs was normalized with respect to the maximal response obtained in stimulation with 127 mM K+. The small pulmonary artery was more reactive to histamine, norepinephrine, and serotonin when compared with large and medium pulmonary arteries. The medium and large pulmonary artery showed no difference in reactivity to histamine. However, the mean effective dose (ED50) values for these agonists among the different segments of pulmonary arteries showed no significant difference. The small and medium pulmonary veins demonstrated increased reactivity to histamine, but not to norepinephrine and serotonin. The ED50 values also indicated that both small and medium veins were more sensitive to histamine when compared with the large pulmonary vein. The log concentration percent response curves for both small and medium pulmonary veins were displaced leftward (increased sensitivity) with respect to that for the large pulmonary vein. However, the reactivity and sensitivity to histamine between medium and small pulmonary veins were no different. The reactivity and sensitivity of different segments of pulmonary veins to norepinehrine and serotonin showed no significant differences among them. We conclude that histamine and other vasoactive substances, which are directly or indirectly related to mast cell degranulation, exert pharmacological effects on the pulmonary vasculature which possesses differential responsiveness at various levels of the vascular tree.

Postnatal changes in pulmonary vein responses to endothelin-1 in the normal and chronically hypoxic lung

2007 ◽  
Vol 292 (5) ◽  
pp. L1273-L1279 ◽  
Author(s):  
Margrid B. Schindler ◽  
Alison A. Hislop ◽  
Sheila G. Haworth
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Vein ◽  
Contractile Response ◽  
Pulmonary Veins ◽  
Pulmonary Arteries ◽  
Hypoxic Exposure ◽  
Fetal Life ◽  
Endothelin 1 ◽  
Age Related ◽  
Relaxant Response

The response of pulmonary arteries to endothelin-1 (ET-1) changes with age in normal pigs and is abnormal in pulmonary hypertension. The purpose of this study was to determine if the same is true of the pulmonary veins. We studied the wall structure and functional response to ET-1 in pulmonary veins from normal pigs from fetal life to adulthood and from pigs subjected to chronic hypobaric hypoxia either from birth for 3 days or from 3 to 6 days of age. In isolated normal veins, the contractile response decreased by 40% between late fetal life and 14 days of age with a concomitant twofold increase in endothelium-dependent relaxant response. The ETA antagonist BQ-123 reduced the contractile response significantly more in newborn than older animals, whereas the ET-B antagonist BQ-788 had no effect in fetal animals and maximally increased contraction at 14 days of age. Hypoxic exposure significantly increased pulmonary vein smooth muscle area and contractile response to ET-1. The relaxation response was impaired following hypoxic exposure from birth but not from 3 to 6 days of age. The ETA antagonist BQ-123 decreased contractile and increased dilator responses significantly more than in age-matched controls. Thus pulmonary veins show age-related changes similar to those seen in the pulmonary arteries with a decrease in ETA-mediated contractile and increase in ET-B-mediated relaxant response with age. Contractile response was also increased in hypoxia as in the arteries. This study suggests that pulmonary veins are involved in postnatal adaptation and the pathogenesis of pulmonary hypertension.

scholarly journals Asymptomatic Pulmonary Vein Stenosis: Hemodynamic Adaptation and Successful Ablation

2016 ◽  
Vol 2016 ◽  
pp. 1-4
Author(s):  
John J. Lee ◽  
Denis Weinberg ◽  
Rishi Anand
Keyword(s):  
Atrial Fibrillation ◽  
Pulmonary Artery ◽  
Pulmonary Vein ◽  
Pulmonary Veins ◽  
Lung Perfusion ◽  
Atrial Fibrillation Ablation ◽  
Clinical Severity ◽  
Pulmonary Vein Stenosis ◽  
Multiple Imaging ◽  
Vein Stenosis

Pulmonary vein stenosis is a well-established possible complication following an atrial fibrillation ablation of pulmonary veins. Symptoms of pulmonary vein stenosis range from asymptomatic to severe exertional dyspnea. The number of asymptomatic patients with pulmonary vein stenosis is greater than originally estimated; moreover, only about 22% of severe pulmonary vein stenosis requires intervention. We present a patient with severe postatrial fibrillation (AF) ablation pulmonary vein (PV) stenosis, which was seen on multiple imaging modalities including cardiac computed tomography (CT) angiogram, lung perfusion scan, and pulmonary angiogram. This patient did not have any pulmonary symptoms. Hemodynamic changes within a stenosed pulmonary vein might not reflect the clinical severity of the obstruction if redistribution of pulmonary artery flow occurs. Our patient had an abnormal lung perfusion and ventilation (V/Q) scan, suggesting pulmonary artery blood flow redistribution. The patient ultimately underwent safe repeat atrial fibrillation ablation with successful elimination of arrhythmia.

Contraction to endothelin-1 in pulmonary arteries from endotoxin-treated rats is modulated by endothelium

1995 ◽  
Vol 268 (6) ◽  
pp. H2260-H2266
Author(s):  
N. P. Curzen ◽  
M. J. Griffiths ◽  
T. W. Evans
Keyword(s):  
Pulmonary Artery ◽  
Receptor Antagonist ◽  
Contractile Response ◽  
Pulmonary Arteries ◽  
The Novel ◽  
Receptor Stimulation ◽  
Thromboxane A2 Receptor ◽  
Endothelin 1 ◽  
Etb Receptor ◽  
Potent Vasoconstrictor

Sepsis is characterized by hyporesponsiveness of vascular smooth muscle to pressor agents. Levels of the potent vasoconstrictor, endothelin-1 (ET-1), are elevated in animal models of sepsis and in patients. This study assesses the contractile response of pulmonary artery from endotoxin-pretreated rats to ET-1 to determine whether this contraction is modified by the endothelium. Both intact and denuded rings from endotoxin-pretreated rats exhibited hyporesponsiveness to ET-1, but the endothelium was found to be essential for maximal ET-1-induced contraction. Upon pretreatment of vessels with the cyclooxygenase inhibitor, indomethacin (10(-5) M), the novel ETB-receptor antagonist, BQ-788 (10(-8) and 10(-6) M), and the thromboxane A2-receptor antagonist, ICI-192605 (10(-5) M), each of these agents caused a reduction in the ET-1-induced contraction of endotoxin-pretreated rat pulmonary artery only in the presence of the endothelium but had no effect in endothelium-denuded vessels or in sham-treated groups. These findings demonstrate that ET-1-induced contraction in pulmonary arteries from septic rats is partially dependent upon an endothelially derived cyclooxygenase product, the release of which appears to involve ETB-receptor stimulation.

Mechanical response of pulmonary artery under aerobic and hypoxic conditions

1977 ◽  
Vol 42 (3) ◽  
pp. 438-443
Author(s):  
J. F. Souhrada ◽  
D. W. Dickey
Keyword(s):  
Pulmonary Artery ◽  
Dose Response ◽  
Guinea Pigs ◽  
Main Pulmonary Artery ◽  
Maximal Response ◽  
Response Curves ◽  
Aerobic Conditions ◽  
Experimental Medium ◽  
Hypoxic Conditions ◽  
Dose Response Curves

The present study demonstrates the reactivity of isolated main pulmonary artery (MPA) from guinea pigs and rats to two vasoactive drugs, norepinephrine (NE) and histamine (H), in substrate-rich and substrate-free medium, under both aerobic (PO2 = 95 +/- 0.5 Torr) and hypoxic conditions (PO2 = 30 +/- 1 Torr). The sensitivity of MPA from guinea pigs to NE and H during aerobic conditions is not significantly affected by the absence of substrate in the experimental medium. Furthermore, it is demonstrated that in the substrate-rich experimental medium (5.5 mM glucose), the reactivity of MPA from guinea pigs to NE and H is not significantly affected by acute hypoxia as compared with the response of MPA during aerobic conditions. These experiments contrast with data obtained when substrate is absent from the experimental medium. The dose-response curves of MPA from guinea pigs to NE and H under this condition were significantly blunted during hypoxia. Following the completion of the dose-response curves during aerobic conditions, with both NE and H, spontaneous mechanical activities were seen in the guinea pig MPA. On the other hand, it was demonstrated that during aerobic and hypoxic conditions MPA's isolated from rats exhibit no physiological response to histamine even when administered in the dose required to produce the maximal response in MPA isolated from guinea pigs. The sensitivity of MPA from rats to NE during aerobic conditions is not significantly affected by the absence of substrate in the experimental medium. However, when the preparation was exposed to hypoxia, the presence of substrate failed to maintain the reactivity of MPA to norepinephrine. In addition, MPA isolated from rats demonstrated a smaller contractile response to NE than those from guinea pigs. Furthermore, no spontaneous mechanical activities were observed after norepinephrine or histamine administration. The present study, in addition to pointing out species differences, shows the important role of exogenous substrate in maintaining the reactivity of pulmonary vascular smooth muscle during hypoxia.

Disruption of cGMP production in pulmonary arteries isolated from fetal lambs with pulmonary hypertension

1995 ◽  
Vol 268 (4) ◽  
pp. H1483-H1489 ◽  
Author(s):  
R. H. Steinhorn ◽  
J. A. Russell ◽  
F. C. Morin
Keyword(s):  
Pulmonary Hypertension ◽  
Soluble Guanylate Cyclase ◽  
Ductus Arteriosus ◽  
Pulmonary Veins ◽  
Pulmonary Arteries ◽  
Fourth Generation ◽  
Response Curves ◽  
Fetal Sheep ◽  
A 23187 ◽  
Arteries And Veins

Ligation of the ductus arteriosus of the fetal sheep produces severe pulmonary hypertension at birth. Standard tissue bath techniques were used to study third- and fourth-generation pulmonary arteries and veins isolated from fetal sheep with pulmonary hypertension created by ligation of the ductus arteriosus 11–12 days before birth as well as from age-matched control sheep. Vessels pretreated with indomethacin and propranolol were submaximally preconstricted with norepinephrine before exposure to A-23187 (10(-8) to 3 x 10(-7) M), sodium nitroprusside (SNP; 10(-9) to 10(-5) M), and nitric oxide (NO) gas (1-973 ppm). Pulmonary veins in both control and ligated animals relaxed similarly and completely to A-23187, SNP, and NO. Control pulmonary arteries relaxed by 16 +/- 2% to A-23187 and relaxed completely to SNP and NO, with concentration-response curves shifted rightward of those observed in pulmonary veins. Pulmonary arteries from ligated animals did not relax at all to A-23187. SNP relaxations in ligated arteries were shifted rightward of control. Ligated arteries relaxed by only 11 +/- 5% to the highest dose of NO. However, control and ligated pulmonary arteries relaxed similarly to 8-bromoguanosine 3',5'-cyclic monophosphate (8-bromo-cGMP; 10(-5) to 10(-3) M) and atrial natriuretic peptide (10(-9) to 10(-7) M). These data are most simply explained by decreased arterial vascular smooth muscle sensitivity to NO at the level of soluble guanylate cyclase.

Thapsigargin stimulates increased NO activity in hypoxic hypertensive rat lungs and pulmonary arteries

1996 ◽  
Vol 80 (4) ◽  
pp. 1336-1344 ◽  
Author(s):  
M. Muramatsu ◽  
R. C. Tyler ◽  
D. M. Rodman ◽  
I. F. McMurtry
Keyword(s):  
Pulmonary Artery ◽  
Chronic Hypoxia ◽  
Pulmonary Arteries ◽  
Male Rats ◽  
Pulmonary Vasculature ◽  
No Production ◽  
Low Concentrations ◽  
Pulmonary Vascular Endothelium ◽  
Increased Sensitivity ◽  
Stimulation Of

This study addressed the controversy of whether endothelium-derived nitric oxide (NO) activity is increased or decreased in the hypertensive pulmonary vasculature of chronically hypoxic rats. Thapsigargin, a receptor-independent Ca2+ agonist and stimulator of endothelial NO production, was used to compare NO-mediated vasodilation in perfused lungs and conduit pulmonary artery rings isolated from adult male rats either kept at Denver's altitude of 5,280 ft (control pulmonary normotensive rats) or exposed for 4-5 wk to the simulated altitude of 17,000 ft (chronically hypoxic pulmonary hypertensive rats). Under baseline conditions, thapsigargin (10(-9)-10(-7) M) caused vasodilation in hypertensive lungs and vasoconstriction in normotensive lungs. Whereas the sustained vasodilation in hypertensive lungs was reversed to vasoconstriction by the inhibitor of NO synthase N(omega)-nitro-L-arginine (L-NNA; 10(-4) M), a transient vasodilation to thapsigargin in acutely vasoconstricted normotensive lungs was potentiated. As measured by a chemiluminescence assay, the recirculated perfusate of hypertensive lungs accumulated considerably higher levels of NO-containing compounds that did normotensive lungs, and thapsigargin-induced stimulation of NO-containing compounds accumulation was greater in hypertensive than in normotensive lungs. Similarly, low concentrations of thapsigargin (10(-10)-10(-9) M) caused greater endothelium-dependent L-NNA-reversible relaxation of hypertensive than of normotensive pulmonary artery rings. The increased sensitivity of hypertensive arteries to thapsigargin-induced relaxation was eliminated in nominally Ca(2+)-free medium and was not mimicked by ryanodine, a releaser of intracellular Ca2+. These results with thapsigargin, which acts on endothelial cells to stimulate Ca2+ influx and a sustained rise in intracellular Ca2+ concentration, support the idea that pulmonary vascular endothelium-derived NO activity is increased rather than decreased in chronic hypoxia-induced pulmonary hypertension in rats.

Embryonic and Early Fetal Development of Human Lung Vasculature and Its Functional Implications

2000 ◽  
Vol 3 (5) ◽  
pp. 439-449 ◽  
Author(s):  
Daphne E. deMello ◽  
Lynne M. Reid
Keyword(s):  
Pulmonary Artery ◽  
Human Lung ◽  
Pulmonary Veins ◽  
Pulmonary Vasculature ◽  
Human Embryos ◽  
Vascular Structure ◽  
Serial Sections ◽  
Peripheral Airways ◽  
Functional Implications ◽  
Airway Branching

Recently, we have identified in the mouse three processes involved in the early development of pulmonary vasculature: angiogenesis for branching of central vessels, vasculogenesis (lakes in the mesenchyme) for peripheral vessels, and a lytic process to establish luminal connection between the two. We have established that these three processes also operate in the human by studying serial sections of human embryos and early fetuses. Vascular lakes of hematopoietic cells appear at stage 13, i.e., 4+ weeks gestational age (GA), the first intrapulmonary vascular structure to appear. At stage 20 (50.5 days GA), a venous network with luminal connections to central pulmonary veins (PV) is present. Airways have not yet reached these regions of lung.At its first intrapulmonary appearance, the pulmonary artery (PA) is small and thick walled: it runs with the airway but its branching is slower, so many peripheral airways are not accompanied by a PA branch. By contrast, the PV has a peripheral patent network well before the PA.In the pseudoglandular phase, airway branching continues, and the PA catches up so that small PA branches are found with all airways. Later in this phase small nonmuscular vessels lie in the mesenchyme close to airway epithelium.By the early canalicular phase and the age of viability, continuity between pulmonary artery and the peripheral capillary network must be established. In a 10-week fetus several structures suggesting a breakthrough site were seen. Air-blood barrier structure is first seen at 19 weeks. Thus in the lung, the PA and PV are dissociated in their timing and pattern of branching. Early veins are present diffusely through the mesenchyme and establish central luminal connection to the main pulmonary vein before airway or artery are present at this level.

In vivo treatment with endotoxin induces nitric oxide synthase in rat main pulmonary artery

1995 ◽  
Vol 268 (3) ◽  
pp. L509-L518 ◽  
Author(s):  
M. J. Griffiths ◽  
S. Liu ◽  
N. P. Curzen ◽  
M. Messent ◽  
T. W. Evans
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Contractile Response ◽  
Main Pulmonary Artery ◽  
Pulmonary Arteries ◽  
No Synthase ◽  
Oxide Synthase ◽  
Lps Treatment

Our aim was to demonstrate increased NO activity from inducible NO synthase (iNOS) in pulmonary arteries (PA) from rats treated with endotoxin [lipopolysaccharide (LPS), 20 mg/kg ip]. LPS treatment diminished the contractile response of PA to potassium chloride (KCl) and phenylephrine (PE) and increased levels of guanosine 3',5'-cyclic monophosphate (cGMP) in endothelium-denuded vessels. Both the NO synthase (NOS) antagonists NG-monomethyl-L-arginine (L-NMMA; nonselective) and aminoguanidine (selective for iNOS) enhanced PE-induced contraction in endothelium-denuded vessels from LPS-treated rats. Furthermore, L-NMMA-induced contraction of endothelium-denuded vessels from LPS-treated rats was stereospecifically antagonized by L-arginine and associated with decreased cGMP levels. These data suggest that NO is produced in increased amounts from PA smooth muscle after LPS treatment. LPS treatment caused increased expression of mRNA for iNOS in PA. This effect of LPS was attenuated by pretreatment with dexamethasone, suggesting that induction of NOS in PA smooth muscle underlies the increased NO activity associated with LPS administration.

P984Residual gaps in the ablation line and requirement for carina ablation during contact force-guided radiofrequency pulmonary vein isolation: determinants and prognostic implications

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M J Mulder ◽  
M J B Kemme ◽  
M J W Gotte ◽  
H A Hauer ◽  
G J M Tahapary ◽  
...  
Keyword(s):  
Pulmonary Vein ◽  
Pulmonary Vein Isolation ◽  
Contact Force ◽  
Pulmonary Veins ◽  
Survival Analyses ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Prognostic Implications ◽  
Ablation Line ◽  
Af Recurrence

Abstract Background Pulmonary vein isolation (PVI) is not always achieved after initial encircling of the pulmonary veins (PVs). Additional touch-up lesions are frequently required to close residual gaps, which may occur both in the initial ablation line and on the intervenous carina. Purpose We aimed to identify determinants and prognostic implications of residual gaps during index radiofrequency PVI. Methods Two hundred fourteen AF (atrial fibrillation) patients (57% paroxysmal, 61% male, mean age 62±9 years) undergoing contact force-guided PVI were studied. Residual gaps after initial encircling of the PVs were targeted for additional ablation and were classified as either gap ablation in the initial WACA (wide-area circumferential ablation) circle or carina ablation, depending on the site of earliest activation. After a waiting period of at least 30 minutes, persistence of PVI was tested through administration of 9–18 mg intravenous adenosine. Pre-procedural cardiac computed tomography imaging was used to assess left atrial and PV anatomy. Carina width was defined as the distance between ipsilateral superior and inferior PV ostia. Ablation procedures were analyzed to define the perimeter of the WACA circle. Results One hundred thirty-three patients (62%) required additional ablation lesions beyond the initial WACA circles to achieve complete PVI. Gap ablation was required in the left WACA circle in 34 patients (16%) and in the right WACA circle in 49 patients (23%). Left and right carina ablation were required in 50 (23%) and 83 (39%) patients, respectively. Multivariate analyses identified carina width and perimeter of the WACA circle as independent predictors of requirement for ipsilateral carina ablation, whereas paroxysmal AF and the perimeter of the WACA circle were associated with requirement of gap ablation in the initial WACA circle. Recurrence of atrial tachyarrhythmias was documented in 73 patients (34%) at 12 months follow-up. Kaplan–Meier survival analyses demonstrated a significantly higher rate of recurrence in patients with one or more residual gaps in the ablation line (43% vs. 30%, p=0.019, figure A), whereas no significant difference between patients with and without requirement of carina ablation was found (38% and 29%, respectively; p=0.111, figure B). Kaplan-Meier survival analyses Conclusion Residual gaps in the initial WACA circle were associated with increased AF recurrence rate after PVI, whereas residual gaps on the intervenous carina had no statistically significant impact on AF recurrence. Consequently, gaps occurring in the ablation line and gaps on the intervenous carina may represent different mechanisms and may have different prognostic implications.

Pulmonary Vasculopathy in Idiopathic Spontaneous Pneumothorax in Young Subjects

2000 ◽  
Vol 124 (5) ◽  
pp. 717-720 ◽  
Author(s):  
Pamela V. Cyr ◽  
Lydia Vincic ◽  
J. Michael Kay
Keyword(s):  
Pulmonary Artery ◽  
Chronic Inflammation ◽  
Spontaneous Pneumothorax ◽  
Lung Resection ◽  
Pulmonary Veins ◽  
Pulmonary Arteries ◽  
Vascular Lesions ◽  
Pulmonary Vascular Disease ◽  
Young Subjects ◽  
Medial Hypertrophy

Abstract Background.—We have encountered instances where young subjects with idiopathic spontaneous pneumothorax have been needlessly referred for investigation of pulmonary hypertension because surgical pathologists have misinterpreted the significance of medial hypertrophy and intimal fibrosis of muscular pulmonary arteries in lung resection specimens. Methods.—We reviewed 20 cases of idiopathic spontaneous pneumothorax and determined the prevalence and severity of medial and intimal lesions in the pulmonary arteries and pulmonary veins. We correlated the vascular changes with inflammation and fibrosis in the lung. Results.—Pulmonary artery medial hypertrophy was seen in 15% of cases, pulmonary artery intimal fibrosis in 90% of cases, and pulmonary vein intimal fibrosis in 80% of cases. In 95% of cases, the lung showed some fibrosis and chronic inflammation. There was a significant positive correlation between pulmonary artery medial thickness and lung fibrosis and inflammation scores. Conclusions.—Pulmonary artery medial hypertrophy and intimal fibrosis of pulmonary arteries and pulmonary veins are commonly seen in resected lung tissue from patients with idiopathic spontaneous pneumothorax. The vascular lesions are probably secondary to chronic inflammation and fibrosis in the adjacent lung. They are not clinically significant and do not represent hypertensive pulmonary vascular disease.

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