Effect of medroxyprogesterone on pulmonary arterial pressure, exhaled nitric oxide, ECG and arterial blood gases

BACKGROUND: Cardiopulmonary bypass can increase pulmonary vascular tone and decrease ventilation-perfusion matching by impairing the pulmonary endothelial production of nitric oxide. OBJECTIVES: We tested the hypothesis that inhalation of exogenous nitric oxide decreases the ratio of mean pulmonary arterial pressure to mean system arterial pressure and the intrapulmonary shunt fraction and increases the ratio of arterial blood oxygen tension to fraction of inspired oxygen in patients in whom the ratio of mean pulmonary arterial pressure to mean systemic arterial pressure is more than 0.50, and the ratio of arterial blood oxygen tension to fraction of inspired oxygen is less than 300 mm Hg in the first 24 hours after cardiopulmonary bypass surgery. METHODS: Only those patients who had estimates of the ratio of mean pulmonary arterial pressure to mean systemic arterial pressure and the ratio of arterial blood oxygen tension to fraction of inspired oxygen determined preoperatively were enrolled. Hemodynamic variables were recorded, and blood samples were obtained for oximetric analysis 5 minutes before and 30 minutes after inhalation of nitric oxide began. The concentration of nitric oxide inhaled was maintained at 20 parts per million. The data were analyzed by using Friedman's repeated measures analysis of variance. RESULTS: Thirteen patients were enrolled in the study. The mean preoperative ratio of mean pulmonary arterial pressure to mean systemic arterial pressure was 0.63 +/- 0.08 (standard error of the mean), and the mean preoperative ratio of arterial blood oxygen tension to fraction of inspired oxygen was 131 +/- 15 mm Hg. No differences between preoperative and postoperative values were detected. Inhalation of nitric oxide decreased the ratio of mean pulmonary arterial pressure to mean systemic arterial from 0.53 +/- 0.07 to 0.39 +/- 0.5 and increased the ratio of arterial blood oxygen tension to fraction of inspired oxygen from 167 +/- 35 mm Hg to 235 +/- 45 mm Hg. Inhalation of nitric oxide also decreased the intrapulmonary shunt fraction from 0.29 +/- 0.05 to 0.19 +/- 0.04. CONCLUSIONS: Inhalation of nitric oxide selectively decreases pulmonary vascular tone and increases ventilation-perfusion matching in patients with persistent pulmonary hypertension and hypoxemia after surgery requiring cardiopulmonary bypass. Inhalation of nitric oxide may be a valuable adjunctive therapy for these patients.

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Comparison of hormonal responses to hypotension in mature and immature fetal lambs

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1988.255.1.r67 ◽

1988 ◽

Vol 255 (1) ◽

pp. R67-R72 ◽

Cited By ~ 1

Author(s):

N. M. Rawashdeh ◽

N. D. Ray ◽

D. K. Sundberg ◽

J. C. Rose

Keyword(s):

Arterial Pressure ◽

Renin Angiotensin System ◽

Blood Gases ◽

Plasma Renin ◽

Arterial Blood Gases ◽

Hormonal Responses ◽

Angiotensin System ◽

Induced Hypotension ◽

Functional Deficit ◽

Arterial Blood

We studied norepinephrine (NE) and plasma renin activity (PRA) responses to sodium nitroprusside (NP)-induced hypotension in seven chronically catheterized fetal lambs 0.79-0.94 gestation (mature) and in seven fetuses 0.64-0.72 gestation (immature) 4 or 5 days after surgery. We infused intravenously 5% dextrose in water (DW) or NP in DW to reduce arterial pressure 30% in fetuses for 10 min. Initial infusion choice was random, and the two infusions were separated by 24-48 h. In both groups, basal NE levels were similar and doubled in response to hypotension. In mature fetuses, PRA basal levels were 6.89 +/- 1.80 ng.ml-1.h-1 and increased two- to threefold with hypotension. In immature fetuses, PRA basal levels were 2.42 +/- 0.86 ng.ml-1.h-1 and did not change with hypotension. No changes were observed with DW infusion in either group. Arterial blood gases were normal and remained unchanged. We conclude that in the lamb fetus, NE responses to hypotension are present before and are independent of the development of PRA responses and that before 0.72 gestation there is a functional deficit in the renin-angiotensin system.

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Contribution of peptidyl prolyl isomerase (Pin1) to development of pulmonary hypertension via pulmonary vascular endothelial cell dysfunction

European Heart Journal ◽

10.1093/ehjci/ehaa946.2233 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

S Sakai ◽

H Maruyama ◽

M Ieda

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Endothelial Cell ◽

Arterial Pressure ◽

Western Blot ◽

Caspase 3 ◽

Pulmonary Arterial Pressure ◽

Funding Source ◽

Enos Expression ◽

Pulmonary Arterial

Abstract Background Endothelial dysfunction is thought to be a major contributor to overall pathogenesis of vasculopathy seen in pulmonary hypertension (PH), which is manifested by the impaired release of nitric oxide (NO) generated through endothelial nitric oxide synthase (eNOS) in endothelial cells. Activation of human eNOS is regulated by phosphorylation at multiple sites including Thr33 and Ser114, which residues are followed by Pro. The peptidyl isomerase Pin1 specifically isomerizes the phospho-protein having Ser/Thr-Pro bond and regulates their activity. Pin1 is involved in proliferation, cell cycle, and apoptosis in cancer, by isomerizing some functional molecules such as JNK, JUN, cyclin D, BAX, etc. However, it is controversial whether direct interaction of Pin1 with eNOS and how eNOS activity is altered by Pin1, especially in PH. Purpose We aimed to clarify whether Pin1 contributes to the PH development using Pin1 knockout mice and Pin1 affects the expression of phosphorylated eNOS (p-eNOS) molecule and pulmonary arterial endothelial cell (PAEC) apoptosis. Methods and results Wild (WT) and Pin1-deficient mice (KO) were exposed to hypoxia (10% O2) or normoxia for 3 weeks to generate hypoxia-induced PH. Hypoxia-inducible factor (HIF1α) expression in lungs was significantly enhanced in WT-hypoxia (WH, n=6) and KO-hypoxia (KH, n=6), suggesting that hypoxic response was certainly occurred in these mice. Pulmonary arterial pressure did not elevate in KH compared with KO-normoxia (KN, n=6) and WT-normoxia (WN, n=6), it was significantly increased only in WH (P<0.01), indicating that KO did not develop PH by hypoxia. The gain of RV weight was parallel to the increase of pulmonary arterial pressure. Western blot showed that p-eNOS expression in lungs was significantly decreased in WH compared to WN, however, the expression was not different between KH and KN. It suggests that Pin1 plays a regulatory role in p-eNOS expression in hypoxic response. In cultured PAECs, the expression of p-eNOS and eNOS was markedly increased by siRNA-mediated Pin1 knockdown. Immunoprecipitation study showed the possibility of Pin1 binding to p-eNOS molecule. Apoptosis evaluated by caspase-3/7 activity by fluorescent assay and cleaved caspase-3 expression by Western blot was significantly increased by Pin1 overexpression in PAECs; however, it was significantly decreased by Pin1 knockdown. Moreover, the exaggeration of apoptosis induced by doxorubicin was markedly increased by Pin1 overexpression compared with control in PAECs; however, it was clearly suppressed by Pin1 knockdown. Conclusion This study suggests that endogenous Pin1 contributes to the development of PH partly via the dysfunction of PAECs, that is, by the interference with p-eNOS expression and by the increase of apoptosis inducibility to external stimuli. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): JSPS KAKENHI

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Pulmonary arterial pressure and electrocardiograms in broiler chickens infused intravenously with L-NAME, an inhibitor of nitric oxide synthase, or sodium nitroprusside (SNP), a nitric oxide donor

British Poultry Science ◽

10.1080/00071660120121544 ◽

2002 ◽

Vol 43 (2) ◽

pp. 306-312 ◽

Cited By ~ 20

Author(s):

S. Weidong ◽

W. Xiaolong ◽

W. Jinyong ◽

X. Ruiping

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Arterial Pressure ◽

Sodium Nitroprusside ◽

Broiler Chickens ◽

Pulmonary Arterial Pressure ◽

Nitric Oxide Donor ◽

Pulmonary Arterial ◽

Oxide Synthase

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Thromboxane does not mediate pulmonary hypertension in phorbol ester-induced acute lung injury in dogs

Journal of Applied Physiology ◽

10.1152/jappl.1990.69.1.345 ◽

1990 ◽

Vol 69 (1) ◽

pp. 345-352 ◽

Cited By ~ 5

Author(s):

A. H. Stephenson ◽

R. S. Sprague ◽

T. E. Dahms ◽

A. J. Lonigro

Keyword(s):

Pulmonary Hypertension ◽

Acute Lung Injury ◽

Lung Injury ◽

Arterial Pressure ◽

Pulmonary Arterial Pressure ◽

Pressor Response ◽

H2 Receptor Antagonist ◽

Arterial Blood ◽

Pulmonary Arterial ◽

The Relationship

Thromboxane (Tx) has been suggested to mediate the pulmonary hypertension of phorbol myristate acetate- (PMA) induced acute lung injury. To test this hypothesis, the relationship between Tx and pulmonary arterial pressure was evaluated in a model of acute lung injury induced with PMA in pentobarbital sodium-anesthetized male mongrel dogs. Sixty minutes after administration of PMA (20 micrograms/kg iv, n = 10), TxB2 increased 10-fold from control in both systemic and pulmonary arterial blood and 8-fold in bronchoalveolar lavage (BAL) fluid. Concomitantly, pulmonary arterial pressure (Ppa) increased from 14.5 +/- 1.0 to 36.2 +/- 3.5 mmHg, and pulmonary vascular resistance (PVR) increased from 5.1 +/- 0.4 to 25.9 +/- 2.9 mmHg.l-1.min. Inhibition of Tx synthase with OKY-046 (10 mg/kg iv, n = 6) prevented the PMA-induced increase in Tx concentrations in blood and BAL fluid but did not prevent or attenuate the increase in Ppa. OKY-046 pretreatment did, however, attenuate but not prevent the increase in PVR 60 min after PMA administration. Pretreatment with the TxA2/prostaglandin H2 receptor antagonist ONO-3708 (10 micrograms.kg-1.min-1 iv, n = 7) prevented the pressor response to bolus injections of 1-10 micrograms U-46619, a Tx receptor agonist, but did not prevent or attenuate the PMA-induced increase in Ppa. ONO-3708 also attenuated but did not prevent the increase in PVR. These results suggest that Tx does not mediate the PMA-induced pulmonary hypertension but may augment the increases in PVR in this model of acute lung injury.

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Abstract 2305: Pulmonary Vascular Reactivity And Prognosis In Patients With Chronic Thromboembolic Pulmonary Hypertension

Circulation ◽

10.1161/circ.116.suppl_16.ii_503-d ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Nika Skoro-Sajer ◽

Nicklas Hack ◽

Roela Sadushi ◽

Johannes Jakowitsch ◽

Diana Bonderman ◽

...

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Arterial Pressure ◽

Vascular Reactivity ◽

Pulmonary Arterial Pressure ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Mean Pulmonary Arterial Pressure ◽

Thromboembolic Pulmonary Hypertension ◽

Pulmonary Arterial ◽

Relative Change

Hemodynamic responder status defined as an acute decrease of mean pulmonary arterial pressure (mPAP)>10mmHg and below 40mmHg is associated with improved outcome in patients (pts) with pulmonary arterial hypertension (PAH). Pulmonary vascular reactivity to nitric oxide (NO) is controversial in chronic thromboembolic pulmonary hypertension (CTEPH). We speculated that the magnitude of the acute decrease in mean pulmonary artery pressure (mPAP) after exposure to NO might reflect the degree of small vessel disease in CTEPH and thus, affect long-term outcome. Methods: Right heart catheterization was performed in 62 (55 Â ± 15 years, 32 female) pts with major-vessel CTEPH, at baseline and during inhalation of 40ppm NO. Within 25Â±15 days patients underwent pulmonary endarterectomy (PEA). Pts were followed for 11.3Â±26 months. Predictors of survival were analyzed by Cox regression analysis, and survival was described by Kaplan-Meier curves. Results: Significant reductions in mean pulmonary arterial pressure (mPAP; p<0.001), pulmonary vascular resistance (PVR; p<0.001) and an increase in mixed venous oxygen saturation following NO inhalation were demonstrated (p<0.001) by a paired t-test. Stepwise multivariate analysis revealed the relative change of PVR after NO inhalation as a predictor of survival. Patients whose PVR during NO inhalation declined below 789.8 dynes.s.cm-5 had significantly better outcome than patients with above median PVR. There was a strong negative correlation between the relative change of PVR under NO and recurrent pulmonary hypertension after PEA (p=0.02). Conclusions: Patients with operable CTEPH demonstrated acute pulmonary vascular reactivity, mostly not corresponding to a complete responder status, but accounting for a wide range of decreases of mPAP [change of mPAP (%) (−10.9Â±14)] and PVR [change of PVR (%) (−17 Â±15)]. Reduction of PVR under 800 dynes.s.cm-5 after inhalation of NO was associated with better outcome. Responsiveness to inhaled nitric oxide is a predictor for mid-term survival in adult patients with CTEPH undergoing PEA.

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Effects of lung inflation on pulmonary arterial blood volume in intact dogs

Journal of Applied Physiology ◽

10.1152/jappl.1975.38.4.675 ◽

1975 ◽

Vol 38 (4) ◽

pp. 675-680 ◽

Cited By ~ 3

Author(s):

A. Wanner ◽

S. Zarzecki ◽

M. A. Sackner

Keyword(s):

Arterial Pressure ◽

Blood Volume ◽

Lung Volume ◽

Pulmonary Arterial Pressure ◽

Valsalva Maneuver ◽

Lung Inflation ◽

Arterial Blood ◽

Mueller Maneuver ◽

Pulmonary Arterial ◽

Arterial Blood Volume

The isolated effects of alterations of lung inflation and transmural pulmonary arterial pressure (pressure difference between intravascular and pleural pressure) on pulmonary arterial blood volume (Vpa) were investigated in anesthetized intact dogs. Using transvenous phrenic nerve stimulation, changes in transmural pulmonary arterial pressure (Ptm) at a fixed transpulmonary pressure (Ptp) were produced by the Mueller maneuver, and increases in Ptp at relatively constant Ptm by a quasi-Valsalva maneuver. Also, both Ptm and Ptp were allowed to change during open airway lung inflation. Vpa was determined during these three maneuvers by multiplying pulmonary blood flow by pulmonary arterial mean transit time obtained by an ether plethysmographic method. During open airway lung inflation, mean (plus or minus SD) Ptp increased by 7.2 (plus or minus 3.7) cmH2O and Ptm by 4.3 (plus or minus 3.4) cmH2O for a mean increase in Vpa by 26.2 (plus or minus 10.7) ml. A pulmonary arterial compliance term (Delta Vpa/Delta Ptm) calculated from the Mueller maneuver was 3.9 ml/cmH2O and an interdependence term (Delta Vpa/Delta Ptp) calculated from the quasi-Valsalva maneuver was 2.5 ml/cmH2O for a 19% increase in lung volume, and 1.2 ml/cmH2O for an increase in lung volume from 19% to 35%. These findings indicate that in normal anesthetized dogs near FRC for a given change in Ptp and Ptm the latter results in a greater increase of Vpa.

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Fetal pulmonary vasodilation after exogenous platelet-activating factor

Journal of Applied Physiology ◽

10.1152/jappl.1991.70.2.778 ◽

1991 ◽

Vol 70 (2) ◽

pp. 778-787 ◽

Cited By ~ 7

Author(s):

F. J. Accurso ◽

S. H. Abman ◽

R. B. Wilkening ◽

G. S. Worthen ◽

P. Henson

Keyword(s):

Arterial Pressure ◽

Pulmonary Arterial Pressure ◽

Ductus Arteriosus ◽

Platelet Activating Factor ◽

Vena Cava ◽

Arterial Blood Flow ◽

High Dose ◽

Pulmonary Vasodilation ◽

Arterial Blood ◽

Pulmonary Arterial

To determine the fetal pulmonary vascular response to platelet-activating factor (PAF), we studied the hemodynamic effects of the infusion of PAF directly into the left pulmonary artery in 21 chronically catheterized fetal lambs. Left pulmonary arterial blood flow (Q) was measured with electromagnetic flow transducers. Ten-minute infusions of low-dose PAF (10-100 ng/min) produced increases in Q from a baseline of 71 +/- 5 to 207 +/- 20 ml/min (P less than 0.001) without changes in pulmonary arterial pressure. Pulmonary vasodilation with PAF was further confirmed through increases in Q with brief (15-s) infusions and increases in the slope of the pressure-flow relationship as assessed by rapid incremental compressions of the ductus arteriosus during PAF infusion. Infusion of Lyso-PAF had no effect on Q or pulmonary arterial pressure. Treatment with CV-3988, a selective PAF receptor antagonist, but not with meclofenamate, atropine, or diphenhydramine and cimetidine blocked the response to PAF infusion and did not affect baseline tone. Systemic infusion of high-dose PAF (300 ng/min) through the fetal inferior vena cava increased pulmonary arterial pressure (46.5 +/- 1.0 to 54.8 +/- 1.9 mmHg, P less than 0.01) and aorta pressure (44.3 +/- 1.0 to 52.7 +/- 2.2 mmHg, P less than 0.01) while also increasing Q. Neither PAF nor CV-3988 changed the gradient between pulmonary arterial and aorta pressures, suggesting that PAF does not affect ductal tone. We conclude that PAF is a potent fetal pulmonary vasodilator and that the effects are not mediated through cyclooxygenase products or by cholinergic or histaminergic effects.

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Effect of tonsillectomy and/or adenoidectomy on pulmonary arterial pressure in adults

Open Medicine ◽

10.2478/s11536-008-0074-2 ◽

2008 ◽

Vol 3 (4) ◽

pp. 482-486

Author(s):

Saeed Abdelwhab ◽

Khaled. Dessoukey ◽

Gamal Lotfy ◽

Ashraf Alsaeed ◽

Hesham Anwar

Keyword(s):

Pulmonary Artery ◽

Arterial Pressure ◽

Pulmonary Artery Pressure ◽

Pulmonary Arterial Pressure ◽

Arterial Oxygen ◽

Artery Pressure ◽

Mean Pulmonary Arterial Pressure ◽

Arterial Blood ◽

Pulmonary Arterial ◽

Group 1

AbstractThe aim of the study was to determine the mean pulmonary pressure in adult with hypertrophic tonsils and adenoids and to clarify whether tonsillectomy and adenoidectomy has any effect on mean pulmonary arterial pressure of these adult. The study was carried out on 50 patients with diagnosis of upper airway obstruction resulting from hypertrophied tonsils and adenoids (group1). 25 adults were assigned as control with similar age and sex distribution (group2). For study subjects Routine general Examinations, BMI, ECG, Chest X ray, Arterial blood gases and Echocardiography were done. Mean pulmonary arterial pressure was measured by using Doppler Echocardiography preoperatively and mean 3–4 months postoperatively in all subjects. Elevated PAP (pulmonary artery pressure) was found in 15 patients (30%) in group 1 preoperatively. Mean PAP was 28.34 ±5.11 mmHg preoperative in group 1 and 19.84 ± 5.0 mmHg in group 2 (p <0.001). PAP decrease to 22.38 ±4.28 mmHg postoperatively in group 1 (p <0.001). Arterial oxygen saturation (spo2%) increase from 93.5 ± 1.9% preoperatively to 95.3 ± 1.3% post operatively (p < 0.001). percent reduction of PAP postoperatively correlates to age (t=−2.3, p= 0.02), preoperative PAP (p =0.01) but no correlation was found with BMI. In conclusions, this Study showed that obstructed adenoid and hypertrophy of tonsils causes higher mean pulmonary artery pressure in adult & revealed that tonsil& adenoid is effective therapeutic measure in such patients. With early intervention is necessary to avoid progressive cardiopulmonary disease.

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