The Management of Primary Pulmonary Hypertension

Palevsky, Harold I.; Fishman, Alfred P.

doi:10.1001/jama.1991.03460080084038

Cited by 38 publications

(14 citation statements)

References 83 publications

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“…[13][14][15][16][17][18][19][20] The acute responses to intravenous epoprostenol in this study compared with changes reported in patients with primary pulmonary hypertension are shown in Table 4. As a group, mean changes noted in both PVR and MPAP in patients with portopulmonary hypertension were slightly better than those changes seen in patients with primary pulmonary hypertension.…”

Section: Discussionmentioning

confidence: 99%

Improvement in pulmonary hemodynamics during intravenous epoprostenol (prostacyclin): A study of 15 patients with moderate to severe portopulmonary hypertension

et al. 1999

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Pulmonary hypertension associated with increased pulmonary vascular resistance (PVR) and occurring in the setting of portal hypertension is referred to as ''portopulmonary hypertension.'' Intravenous epoprostenol (prostacyclin) is a potent pulmonary and systemic vasodilator with antithrombotic properties. It can decrease PVR and pulmonary artery pressure in patients with primary (idiopathic) pulmonary hypertension. Using right-heart catheterization, we evaluated the acute pulmonary hemodynamic effects of intravenous epoprostenol in patients with moderate to severe pulmonary hypertension (mean pulmonary artery pressure [MPAP] H35 mm Hg) associated with clinical manifestations of portal hypertension. Effects of long-term infusion of epoprostenol were also evaluated. We studied 15 consecutive patients with portopulmonary hypertension; 14 underwent acute administration of epoprostenol, and no significant side effects were noted. Ten patients received continuous epoprostenol (range, 8 days-30 months). Acute changes in PVR (؊34% ؎ 18%), MPAP (؊16% ؎ 10%), and cardiac output (CO) (؉21 ؎ 18%), were statistically significant (P F .01). Long-term use of epoprostenol further lowered PVR (؊47% ؎ 12% from baseline and ؊31% ؎ 22% from the acute change; P F .05) in the 6 patients restudied by right-heart catheterization. Death occurred in 6 of 10 (60%) of those receiving long-term epoprostenol. In moderate to severe portopulmonary hypertension, intravenous epoprostenol resulted in a significant improvement (both acute and long-term) in PVR, MPAP, and CO. Potential adverse effects on portal hypertension and implications for orthotopic liver transplantation (OLT), however, require further study. (HEPATOLOGY 1999;30:641-648.)Pulmonary hypertension is defined as a mean pulmonary artery pressure (MPAP) Ͼ 25 mm Hg at rest determined by right-heart catheterization. 1 Patients with portal hypertension have multiple factors that contribute to the development of pulmonary arterial or venous hypertension. Such factors include an arterial hyperdynamic circulatory state (increased cardiac output [CO]), increased central venous volume (associated with an elevated pulmonary capillary wedge pressure [PCWP]) and pulmonary artery vasoconstriction/ obliteration (increased pulmonary vascular resistance with a normal PCWP). [2][3][4] In the setting of portal hypertension, the development of a vasoconstrictive/obliterative process affecting the pulmonary arterial bed causing increased pulmonary vascular resistance (PVR) has been described as ''portopulmonary hypertension. '' 4,5 Histopathology of the pulmonary arterial lesions associated with portal hypertension is indistinguishable from that seen in primary pulmonary hypertension.

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Section: Discussionmentioning

confidence: 99%

Improvement in pulmonary hemodynamics during intravenous epoprostenol (prostacyclin): A study of 15 patients with moderate to severe portopulmonary hypertension

et al. 1999

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“…A positive response to vasodilator therapy can be used as criteria for the potential reversibility of pulmonary hypertension. [10][11][12][13][14][15] Determination of a positive response varies among centers, but 20% to 30% decreases in PVR and mean pulmonary artery pressure are generally required. According to the data presented here, a reduction in pulmonary artery pressure into the moderately elevated range should allow OLT to be performed safely if the systemic blood pressure is not compromised by this intervention.…”

Section: Discussionmentioning

confidence: 99%

Severe pulmonary hypertension in liver transplant candidates

Ramsay¹

1997

Liver Transplantation

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Advanced liver disease with portal hypertension may be associated with pulmonary hypertension. A review of 1,205 consecutive liver transplant patients was made to assess the incidence and severity of pulmonary hypertension in patients with end-stage liver disease. Postoperative data were reviewed to determine if outcome was influenced and, in patients with severe pulmonary hypertension, whether pulmonary hypertension was reversed after transplantation. The hemodynamic data of 5 patients who were found to have severe pulmonary hypertension before transplantation and did not receive transplants were also reviewed. The incidence of pulmonary hypertension in the patients who received transplants was 8.5% (n ‫؍‬ 102; mean pulmonary artery pressure, G25 mmHg). The incidence of mild pulmonary hypertension was 6.72% (n ‫؍‬ 81; systolic pulmonary artery pressure, 30 to 44 mmHg); that of moderate pulmonary hypertension was 1.16% (n ‫؍‬ 14; systolic pulmonary artery pressure, 45 to 59 mmHg); and that of severe pulmonary hypertension was 0.58% (n ‫؍‬ 7; systolic pulmonary artery pressure, G60 mmHg). Mild and moderate pulmonary hypertension did not influence the outcome of the procedure. Severe pulmonary hypertension was associated with mortality rates of 42% at 9 months posttransplantation and 71% at 36 months posttransplantation. Only 2 of 7 patients with severe pulmonary hypertension have survived liver transplantation with a good quality of life. The remaining 5 patients continued to deteriorate with progressive right heart failure with no evidence of amelioration of the pulmonary hypertension. This experience supports the view that in most patients who have severe pulmonary hypertension associated with advanced liver disease, it is caused by fixed pathological changes in the pulmonary vasculature, is not reversible with liver transplantation, and is associated with a very high perioperative mortality rate. Copyright 1997 by the American Association for the Study of Liver DiseasesA review of perioperative data was undertaken to establish the incidence of pulmonary hypertension in the first 1,205 consecutive orthotopic liver transplant (OLT) patients at Baylor University Medical Center (BUMC) and to elucidate whether the presence of pulmonary hypertension influenced the clinical outcome. Mild to moderate pulmonary hypertension has not been reported to contribute to mortality after transplant or to influence the clinical outcome. 1-3 On the other hand, severe primary pulmonary hypertension carries a significant perioperative risk and in many cases limits the quality of postoperative survival. 4 All records of OLT patients with severe pulmonary hypertension were studied in detail in an attempt to establish criteria for likely success of OLT in these patients. Patients and MethodsWe have defined pulmonary hypertension as a mean pulmonary artery pressure of 25 mmHg or greater and a pulmonary vascular resistance (PVR) of greater than 120 dyne · s Ϫ1 · cm Ϫ5 . 3 Pulmonary hypertension was then arbitrarily divided into three gro...

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“…failure syndrome, and pulmonary hypertension (1)(2)(3)(4)(5)(6). However, prolonged exposure to increased concentrations of oxygen induces diffuse pulmonary injuries, excessive inflammation, and lung fibrosis.…”

mentioning

confidence: 99%

eNOS-β-Actin Interaction Contributes to Increased Peroxynitrite Formation during Hyperoxia in Pulmonary Artery Endothelial Cells and Mouse Lungs

Kondrikov

Elms

Fulton

et al. 2010

Journal of Biological Chemistry

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Oxygen toxicity is the most severe side effect of oxygen therapy in neonates and adults. Pulmonary damage of oxygen toxicity is related to the overproduction of reactive oxygen species (ROS). In the present study, we investigated the effect of hyperoxia on the production of peroxynitrite in pulmonary artery endothelial cells (PAEC) and mouse lungs. Incubation of PAEC under hyperoxia (95% O 2 ) for 24 h resulted in an increase in peroxynitrite formation. Uric acid, a peroxynitrite scavenger, prevented hyperoxia-induced increase in peroxynitrite. The increase in peroxynitrite formation is accompanied by increases in nitric oxide (NO) release and endothelial NO synthase (eNOS) activity. We have previously reported that association of eNOS with ␤-actin increases eNOS activity and NO production in lung endothelial cells. To study whether eNOS-␤-actin association contributes to increased peroxynitrite production, eNOS-␤-actin interaction were inhibited by reducing ␤-actin availability or by using a synthetic peptide (P326TAT) containing a sequence corresponding to the actin binding site on eNOS. We found that disruption of eNOS-␤-actin interaction prevented hyperoxia-induced increases in eNOS-␤-actin association, eNOS activity, NO and peroxynitrite production, and protein tyrosine nitration. Hyperoxia failed to induce the increases in eNOS activity, NO and peroxynitrite formation in COS-7 cells transfected with plasmids containing eNOS mutant cDNA in which amino acids leucine and tryptophan were replaced with alanine in the actin binding site on eNOS. Exposure of mice to hyperoxia resulted in significant increases in eNOS-␤-actin association, eNOS activity, and protein tyrosine nitration in the lungs. Our data indicate that increased association of eNOS with ␤-actin in PAEC contributes to hyperoxia-induced increase in the production of peroxynitrite which may cause nitrosative stress in pulmonary vasculature.Oxygen therapy is an important element of the management of various conditions such as adult or neonatal respiratory distress syndrome, circulatory shock, infection, multiple-organ failure syndrome, and pulmonary hypertension (1-6). However, prolonged exposure to increased concentrations of oxygen induces diffuse pulmonary injuries, excessive inflammation, and lung fibrosis. The hyperoxia-induced damages to lung cells have been attributed to the generation of reactive oxygen species (ROS) 2 and subsequent formation of more potent oxidants such as peroxynitrite (ONOO Ϫ ) (7,8). Several studies have suggested that endothelial nitric-oxide synthase (eNOS) plays an important role in the pathogenesis of oxygen toxicity (8, 9). It has been reported that hyperoxia increases eNOS activity and nitric oxide (NO) release from endothelial cells (9, 10). Inhibition of eNOS using L-NAME or knock-out of eNOS reduces peroxynitrite-mediated cytotoxicity in hyperoxic cellular damage in retina (9, 11). However, the mechanism for hyperoxia-induced increases in eNOS activity and NO release has not been clarified. In the present study,...

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The Management of Primary Pulmonary Hypertension

Cited by 38 publications

References 83 publications

Improvement in pulmonary hemodynamics during intravenous epoprostenol (prostacyclin): A study of 15 patients with moderate to severe portopulmonary hypertension

Improvement in pulmonary hemodynamics during intravenous epoprostenol (prostacyclin): A study of 15 patients with moderate to severe portopulmonary hypertension

Severe pulmonary hypertension in liver transplant candidates

eNOS-β-Actin Interaction Contributes to Increased Peroxynitrite Formation during Hyperoxia in Pulmonary Artery Endothelial Cells and Mouse Lungs

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