The pulmonary circulation and the mechanisms which generate pulmonary hypertension are reviewed. The role of these mechanisms in the common pulmonary hypertensive states are analysed, particularly those in acute lung injury. Management options are discussed, with particular emphasis on the use of selective pulmonary vasodilators.
FoxG.A., McCormackD.G.A new look at the pulmonary circulation in acute lung injury.Thorax1992; 47: 743–747.
2.
ZapolW.M., SniderM.T.Pulmonary hypertension in severe acute respiratory failure.N Engl J Med1977; 296: 476–480.
3.
BernardG.R., ArtigasA., BrighamK.L.Report of the American-European consensus conference on ARDS: definitions, mechanisms, relevant outcomes and clinical trial coordination.Intens Care Med1994; 20: 225–232.
4.
RinaldoJ.E., RogersR.M.Adult respiratory distress syndrome. Changing concepts of lung injury and repair.N Engl J Med1982; 306: 900–909.
5.
VillarJ., SlutskyA.Is the outcome from ARDS improving?Curr Opinion Crit Care1996; 2: 79–87.
6.
FishmanA.P.Pulmonary hypertension. In: The heart:SchlantR.C., AlexanderR.W. eds, McGraw Hill, New York, 1994.
RichS., DantzkerD.R., AyresS.M.Primary pulmonary hypertension: A national prospective study.Ann Int Med1987; 107: 216–223.
16.
PalevskyH.I., SchlooB.L., PietraG.G.Primary pulmonary hypertension. Vascular structure, morphometry, and responsiveness to vasodilator agents.Circulation1989; 80: 1207–1221.
17.
PietraG.G., EdwardsW.D., KayJ.M.Histopathology of primary pulmonary hypertension: A qualitative and quantitative study of pulmonary blood vessels from 58 persons in the National Heart, Lung and Blood Institute Primary Pulmonary Hypertension Registry.Circulation1989; 80: 1198–1206.
18.
MarshallB.E., MarshallC., FraschF., HansonC.W.Role of hypoxic pulmonary vasoconstriction in pulmonary gas exchange and blood flow distribution.Intens Care Med1994; 20: 379–389.
19.
MoserK.M.Thromboembolic pulmonary hypertension. In: FishmanA.P. ed. The pulmonary circulation: Normal and abnormal; University of Pennsylvania Press, Philadelphia, PA, 1990.
HarveyR.M., FerrerM.I., RichardsD.W., CournandA.Influence of chronic pulmonary disease on the heart and circulation.Am J Med1951; 10: 719–725.
23.
EnsonY., GiuntiniC., LewisM.L.The influence of hydrogen ion concentration and hypoxia on the pulmonary circulation.J Clin Invest1964; 43: 1146–1162.
24.
AbrahamA.S., ColeR.B., GreenI.D.Factors contributing to the reversible pulmonary hypertension in patients with acute respiratory failure studied by serial observation during recovery.Circ Res1968; 23: 147–157.
25.
RinaldoJ.E.Adult respiratory distress syndrome. In: Principles of critical care:HallJ.B., SchmidtG.A., etal eds, McGraw Hill, New York, 1992.
26.
ReidL.Structural and functional reappraisal of the pulmonary arterial system. In: The scientific basis of medicine annual reviews.Athlone Press, London, 1968.
27.
FishmanA.P.Hypoxia on the pulmonary circulation—how and where it works.Circ Res1976; 38: 221–231.
28.
WarrenJ.B., MaltbyN.H., MacCormackD., BarnesP.J.Pulmonary endothelium-derived relaxing factor is impaired in hypoxia.Clin Sci1989; 77: 671–676.
29.
BrashersV.L., PeachM.J., RoseC.E.Augmentation of hypoxia-induced pulmonary vasoconstriction in the isolated rat lung by in vitro antagonists of endothelium-dependent relaxation.J Clin Invest1988; 82: 1495–1502.
MarshallB.E., HansonC.W., FraschF., MarshallC.Role of hypoxic pulmonary vasoconstriction in pulmonary gas exchange and blood flow distribution.Intens Care Med1994; 20: 379–389.
36.
BoneR.C., BalkR., SlotmanG.Adult respiratory distress syndrome; sequence and importance of development of multiple organ failure.Chest1992; 101: 320–326.
37.
BrighamK.L., KarimanK., HarrisT.R., SnapperJ.R., BernardG.R., YoungS.L.Correlation of oxygenation with vascular permeability surface area, but not with lung water in humans with acute respiratory failure and pulmonary oedema.J Clin Invest1983; 72: 339–349.
38.
HarrisT.R., BernardG.R., BrighamK.L.Lung microvascular transport properties measured by multiple indicator dilution methods in patients with adult respiratory distress syndrome.Am Rev Resp Dis1990; 141: 272–280.
39.
HallJ., WoodL.D.H.Oxygen therapy in the critically ill patient. In: Principles of critical care:HallJ., SchmidtG.A., etal eds, McGraw Hill, New York, 1992.
40.
BernardG.R., ReinesH.D., HalushkaP.V.Prostacyclin and thromboxane A2 formation is increased in human sepsis syndrome.Am Rev Resp Dis1991; 144: 1095–1101.
41.
BoneR.C.The pathogenesis of sepsis.Ann Int Med1991; 115: 457–469.
42.
ChapmanM.J.Adult respiratory distress syndrome: an update.Anaes Intens Care1994; 22: 255–266.
43.
MeduriG.U., KohlerG., HeadleyS., TolleyE., StentzF., PostlethwaiteA.Inflammatory cytokines in the BAL of patients with ARDS.Chest1995; 108: 1303–1314.
44.
SibbaldW.J., DriedgerA.A., MyersM.L., ShortA.I.K., WellsG.A.Biventricular function in the adult respiratory distress syndrome.Chest1983; 84: 126–134.
45.
OliphantL.D., SibbaldW.J.Right ventricular performance in the adult respiratory distress syndrome. In: VincentJ.L., SuterP.M. eds. Update in intensive care and emergency medicine,Springer, New York, 1987.
46.
RadermacherP., SantakB., WustH.J., TarnowJ., FalkeK.J.Prostacyclin for the treatment of pulmonary hypertension in adult respiratory distress syndrome: Effects on pulmonary capillary pressure and ventilation—perfusion distributions.Anesthesiology1990; 72: 238–244.
47.
RadermacherP., SantakB.Prostacyclin and right ventricular function in patients with pulmonary hypertension associated with ARDS.Intens Care Med1990; 16: 227–232.
48.
WeisseA.B., MoschosC.B., FrankM.J., LevinsonG.E., CannillaJ.E., ReganT.J.Haemodynamic effects of staged haematocrit reduction in patients with stable cor pulmonale and severely elevated haematocrit levels.Am J Med1975; 58: 92–98.
49.
MathurP.N., PowlesP., PugsleyS.O., McEwanM.P., CampbellE.J.M.Effect of digoxin on right ventricular function in severe chronic airflow obstruction: A controlled clinical trial.Ann Int Med1981; 95: 283–288.
50.
FusterV., SteeleP.M., EdwardsW.D., GershB.J., McGoonM.D., FryeR.L.Primary pulmonary hypertension: natural history and the importance of thrombosis.Circulation1984; 70: 580–587.
51.
DantzkerD.R., BrookC.J., DehartP., LynchJ.P., WegJ.G.Ventilation-perfusion distributions in the adult respiratory distress syndrome.Am Rev Resp Dis1979; 120: 1039–1052.
52.
WoodmanseyP.A., O'TooleL., ChannerK.S., MoriceA.H.Acute pulmonary vasodilator properties of amlodipine in humans with pulmonary hypertension.Heart1996; 75: 171–173.
53.
ShoemakerW.C., AppelP.L., KramH.B., WaxmanK., LeeT.S.Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients.Chest1988; 94: 1176–1186.
54.
TuchschmidtJ., FriedJ., AstizM., RackowE.Elevation of cardiac output and oxygen delivery improves outcome in septic shock.Chest1992; 102: 206–209.
55.
GattinoniL., BrazziL., PelosiP.A trial of goal-oriented haemodynamic therapy in critically ill patients.N Engl J Med1995; 333: 1025–1032.
56.
PresbergK., YanosJ., MonkR., CorbridgeT., WoodL.D.H.The role of mixed venous hypoxaemia in the pulmonary hypertension and shunt of canine low-pressure pulmonary oedema.Am Rev Resp Dis1989; 139: A416.
57.
GoldringR.M., TurinoG.M., CohenG.The catecholamines in the pulmonary arterial pressor response to hypoxia.J Clin Invest1962; 41: 1211–1220.
58.
Lupi-HerreraE., BialostozkyD., SobrinoA.The role of isoproterenol in pulmonary artery hypertension of unknown aetiology.Chest1981; 79: 292–296.
GrovesB.M., RubinL.J., FrosolonoM.F., CatoA.E., ReevesJ.T.A comparison of the acute haemodynamic effects of prostacyclin and hydralazine in primary pulmonary hypertension.Am Heart J1985; 110: 1200–1204.
61.
FullertonD.A., KirsonL.E., JonesS.D., McIntyreR.C.Adenosine is a selective pulmonary vasodilator in cardiac surgical patients.Chest1996; 109: 41–46.
62.
NiarchosA.P., WhitmanH.H., GoldsteinJ.E., LaraghJ.H.Haemodynamic effects of captopril in pulmonary hypertension of collagen vascular disease.Am Heart J1982; 104: 834–838.
63.
MalcicI., RichterD.Verapamil in primary pulmonary hypertension.Br Heart J1985; 53: 345–347.
64.
CohenM.L., KronzonI.Adverse effects of phentolamine in primary pulmonary hypertension.Ann Int Med1981; 95: 591–592.
65.
NootensM., SchraderB., KaufmannE., VestalR., LongW., RichS.Comparative acute effects of adenosine and prostacyclin in primary pulmonary hypertension.Chest1995; 107: 54–57.
66.
WeirE.K., RubinL.J., AyresS.M.The acute administration of vasodilators in primary pulmonary hypertension. Experience from the NIH registry on primary pulmonary hypertension.Am Rev Resp Dis1989; 140: 1623–1630.
67.
RichS., BrundageB.H.High-dose calcium channel blocking therapy for primary pulmonary hypertension: Evidence for long-term reduction in pulmonary arterial pressure and regression of right ventricular hypertrophy.Circulation1987; 76: 135–41.
68.
RichS., KaufmannE., LevyP.S.The effect of high doses of calcium channel blockers on survival in primary pulmonary hypertension.N Engl J Med1992; 327: 76–81.
69.
RadermacherP., HuetY., PluskwaF.Comparison of ketanserin and sodium nitroprusside in patients with severe ARDS.Anesthesiology1988; 68: 152–157.
70.
RadermacherP., SantakB., BeckerH., FalkeK.J.Prostaglandin E1 and nitroglycerin reduce pulmonary capillary pressure but worsen/ distributions in patients with ARDS. Anesthesiology1989; 70: 601–606.
71.
SibbaldW.J., DriedgerA.A., McCallumD., CunninghamD., CheungH.Nitroprusside infusion does not improve biven-tricular performance in patients with acute hypoxaemic respiratory failure.J Crit Care1986; 1: 197–203.
72.
KerinsD.M., MurrayR.Prostacyclin and Prostaglandin E1; Molecular mechanisms and therapeutic utility.Prog Hemostasis Thromb1991; 10: 307–337.
73.
HannemanL., ReinhartK., Meier-HellmannA., BredleD.L.Prostacyclin in septic shock.Chest1994; 105: 1504–1510.
74.
BurghuberO.C., SilberbauerK., HaberP., SinzingerH., ElliottM., LeithnerC.Pulmonary and anti-aggregatory effects on prosta-cyclin after inhalation and intravenous infusion.Respiration1984; 45: 450–454.
75.
DevittH.H., BurkaJ.F., JonesR., AmyR.W., KingE.G.Hemodynamic and pathologic effects of prostacyclin on oleic acid-induced pulmonary injury.Surgery1988; 103: 213–220.
76.
GriffithT.M., EdwardsD.H., DaviesR.L., HarrisonT.J., EvansK.T.EDRF co-ordinates the behaviour of vascular resistance vessels.Nature1987; 329: 442–445.
VallanceP., CollieJ.Biology and clinical relevance of nitric oxide.Br Med J1994; 309: 453–457.
79.
KamP.C.A., GovenderG.Nitric oxide: basic science and clinical applications.Anaesthesia1994; 49: 515–521.
80.
AnggardE.Nitric oxide: mediator, murderer and medicine.Lancet1994; 343: 1199–1206.
81.
ZapolW.M., RimarS., GillisN., MarlettaM., BoskenC.H.Nitric oxide and the lung.Am J Resp Crit Care Med1994; 149: 1375–1380.
82.
FinkM.P., PayenD.The role of nitric oxide in sepsis and ARDS: synopsis of a roundtable conference held in Brussels on 18–20 March 1995.Intens Care Med1996; 22: 158–165.
StamlerJ.S.Redox signalling: nitrosylation and related target interactions of nitric oxide.Cell1994; 78: 931–936.
85.
FratacciM.D., FrostellC.G., ChenT.Y., WainJ.C., RobinsonD.R., ZapolW.M.Inhaled nitric oxide. A selective pulmonary vasodilator of heparin-protamine vasoconstriction in sheep.Anesthesiology1991; 75: 990–999.
86.
GibsonQ.H., RoughtonF.J.W.Further studies of the kinetics and equilibria of the reaction of nitric oxide with haemoproteins.Proc R Soc Lond1965; 163: 197–205.
87.
RossaintR., FalkeK., LopezF., SlamaK., PisonU.Inhaled nitric oxide for the adult respiratory distress syndrome.N Engl J Med1993; 328: 399–405.
88.
SannaA., KurtanskyA., VeriterC., StanescuD.Bronchodilator effect of inhaled nitric oxide in healthy men.Am J Resp Crit Care Med1994; 150: 1702–1704.
89.
LowensteinC.J., DinermanJ.L., SnyderS.H.Nitric oxide: A physiologic messenger.Ann Int Med1994; 120: 227–237.
90.
KubesP., SuzukiM., GraingerD.N.Nitric oxide: An endogenous modulator of leukocyte adhesion.Proc Natl Acad Sci1991; 88: 4651–4654.
91.
RobertsJ.D., RobertsC.T., JonesR.C., ZapolW.M., BlochK.D.Continuous nitric oxide inhalation reduces pulmonary arterial structural changes, right ventricular hypertrophy and growth retardation in the hypoxic newborn rat.Circ Res1995; 76: 215–222.
92.
AdatiaI., PerryS., LandzbergM., MooreP., ThompsonJ.E., WesselD.L.Inhaled nitric oxide and haemodynamic evaluation of patients with pulmonary hypertension before transplantation.J Am Coll Card1995; 25: 1656–1664.
KlemmP., ThiemermannC., WinklmaierG., MartoranaP.A., HenningR.Effects of nitric oxide synthase inhibition combined with nitric oxide inhalation in a porcine model of endotoxin shock.Br J Pharm1995; 224: 363–368.
95.
DahmP., BlomquistS., MartensonL., ThorneJ., ZoucasE.Circulatory and ventilatory effects of intermittent nitric oxide inhalation during porcine endotoxaemia.J Trauma1994; 37: 769–777.
96.
RomandJ.A., PinskyM.R., FirestoneL., ZarH.A., LancasterJ.R.Effect of inhaled nitric oxide on pulmonary haemodynamics after acute lung injury in dogs.J Appl Physiol;1994; 76: 1356–1362.
97.
PayenD., GatecelC., GuinardN.Inhalation of low dose of nitric oxide and IV L-arg in ARDS patients.Am Rev Resp Dis1993; 147: A720.
98.
PuybassetL., StewartT., RoubyJ.J.Inhaled nitric oxide reverses the increase in pulmonary vascular resistance induced by permissive hypercapnia in patients with acute respiratory distress syndrome.Anesthesiology1994; 80: 1254–1267.
99.
YoungJ.D., BramptonW.J., KnightonJ.D., FinferS.R.Inhaled nitric oxide in acute respiratory failure in adults.Br J Anaesth1994; 73: 499–502.
100.
PuybassetL., RoubyJ.J., MourgeonE.Inhaled nitric oxide in acute respiratory failure; dose-response curves.Intens Care Med1994; 20: 319–327.
101.
SitbonO., BrenotF., DenjeanA.Inhaled nitric oxide as a screening vasodilator agent in primary pulmonary hypertension. A dose-response study and comparison with prostacyclin.Am J Resp Crit Care Med1995; 151: 384–389.
102.
SemigranM.J., CockrillB.A., KacmarekR.Haemo-dynamic effects of inhaled nitric oxide in heart failure.J Am Coll Card1994; 24: 982–988.
103.
RichG.F., LowsonS.M., JohnsR.A., DaughertyM.O., UnclesD.R.Inhaled nitric oxide selectively decreases pulmonary vascular resistance without impairing oxygenation during one-lung ventilation in patients undergoing cardiac surgery.Anes-thesiology1994; 80: 57–62.
104.
AbmanS.H., GriebelJ.L., ParkerD.K., SchmidtJ.M., SwantonD., KinsellaJ.P.Acute effects of inhaled nitric oxide in children with severe hypoxaemic respiratory failure.J Pediatr1994; 124: 881–888.
105.
KaramanoukianH.L., GlickP.L., ZayekM.Inhaled nitric oxide in congenital hypoplasia of the lungs due to diaphragmatic hernia or oligohydramnios.Pediatrics1994; 94: 715–718.
106.
RozeJ.C., StormeL., ZupanV., MorvilleP., Dinh-XuanA.T., MercierJ.C.Echocardiographic investigation of inhaled nitric oxide in newborn babies with severe hypoxaemia.Lancet1994; 344: 303–304.
107.
GerlachH., RossaintR., PappertD., FalkeK.J.Time-course and dose-response of nitric oxide inhalation for systemic oxygenation and pulmonary hypertension in patients with adult respiratory distress syndrome.Eur J Clin Invest1993; 23: 499–502.
108.
LowsonS.M., RichG.F., McArdleP.A., JaidevJ., MorrisG.N.The response to varying concentrations of inhaled nitric oxide in patients with acute respiratory distress syndrome.Anesth Analg1996; 82: 574–581.
109.
SamamaC.M., DiabyM., FellahiJ.L.Inhibition of platelet aggregation by inhaled nitric oxide in patients with ARDS.Anesthesiology1995; 83: 56–65.
110.
GerlachH., PappertD., LewandowskiK., RossaintR., FalkeK.J.Long-term inhalation with evaluated low doses of nitric oxide for selective improvement of oxygenation in patients with adult respiratory distress syndrome.Intens Care Med1993; 19: 443–449.
111.
ZapolW.M.Minidose inhaled nitric oxide: less is better.Intens Care Med1993; 19: 433–434.
112.
BigatelloL.M., HurfordW.E., KacmarekR.M., RobertsJ.D., ZapolW.M.Prolonged inhalation of nitric oxide in patients with severe adult respiratory distress syndrome.Anes-thesiology1994; 80: 761–770.
113.
WysockiM., DelclauxC., RoupieE.Additive effect on gas exchange of inhaled nitric oxide and intravenous almitrine bismesylate in the adult respiratory distress syndrome.Intens Care Med1994; 20: 254–259.
114.
MillerO.I., TangS.F., KeechA., CelermajerJ.S.Rebound pulmonary hypertension on withdrawal from inhaled nitric oxide.Lancet1995; 346: 51–52.
115.
NishimuraM., HessD., KacmrekR.M., RitzR., HurfordW.E.Nitrogen dioxide production during mechanical ventilation with nitric oxide in adults.Anesthesiology1995; 82: 1246–1254.
116.
Clutton-BrockJ.Two cases of poisoning by contamination of nitrous oxide with the higher oxides of nitrogen during anaesthesia.Br J Anaesth1967; 39: 388–392.
117.
YoungJ.D., DyarO.J.Delivery and monitoring of inhaled nitric oxide.Intens Care Med1996; 22: 77–86.
118.
YoungJ.D., DyarO., XiongL., HowellS.Methaemoglobin production in normal adults inhaling low concentrations of nitric oxide.Intens Care Med1994; 20: 581–584.
119.
WesselD.L., AdatiaI., ThompsonJ.E., HickeyP.R.Delivery and monitoring of inhaled nitric oxide in patients with pulmonary hypertension.Crit Care Med1994; 22: 930–938.
120.
ChannickR.N., NewhartJ.W., JohnsonF.Pulsed delivery of inhaled nitric oxide in patients with primary pulmonary hypertension.Chest1996; 109: 1545–1549.
121.
HogmanM., FrostellC.Bleeding time prolongation and NO inhalation.Lancet1993; 341: 1664–1665.
122.
ShielF.O.M.Morbid anatomical changes in the lungs of dogs after inhalation of higher oxides of nitrogen during anaesthesia.Br J Anaesth1967; 39: 413–424.
123.
GreenbaumR., BayJ., HargreavesM.D.Effects of higher oxides of nitrogen on the anaesthetised dog.Br J Anaesth1967; 39: 393–403.
124.
GastonB., DrazenJ.M., LoscalzoJ., StamlerJ.S.The biology of nitrogen oxides in the airway.Am J Resp Crit Care Med1994; 149: 538–551.
125.
PickettJ.A., MoorsA.H., LatimerR.D., MahmoodN., GhoshS., OduroA.The role of soda lime during administration of inhaled nitric oxide.Br J Anaesth1994; 72: 683–685.
126.
Centers for disease control.Recommendations for occupational safety and health standards.MMWR1988; 37(Suppl): 21.
127.
TibballsJ., HochmannM., CarterB., OsborneA.An appraisal of techniques for administration of gaseous nitric oxide.Anaesth Intens Care1993; 21: 844–847.
WatkinsD.N., JenkinsI.R., RankinJ.M., ClarkeG.M.Inhaled NO in severe acute respiratory failure—its use in intensive care and description of a delivery system.Anaesth Intens Care1993; 21: 861–875.
130.
MoutafisM., HatahetZ., CastelainM.H., RenaudinM.H., MonnotA., FischlerM.Validation of a simple method assessing nitric oxide and nitrogen dioxide concentrations.Intens Care Med1995; 21: 537–541.
131.
VaneJ.R., BottingR.M.Pharmacodynamic profile of prosta-cyclin.Am J Cardiol1995; 75: 3A–10A.
132.
VaneJ.R., AnggardE.E., BottingR.M.Regulatory functions of the vascular endothelium.N Engl J Med1990; 323: 27–36.
133.
SzczeklikA., GryglewskiR.J., NizankowskaE., NizankowskiR., MusialJ.Pulmonary and anti-platelet effects of intravenous and inhaled prostacyclin in man.Prostaglandins1978; 16: 651–660.
134.
SzczeklikA., GryglewskiR.J., NizankowskiR., MusialJ., PielanR., MrukJ.Circulatory and anti-platelet effects of intravenous prostacyclin in healthy men.Pharm Res Comm1978; 10: 545–556.
135.
TremoliE., ColliS., PaolettiR.Mode of action of PGI2 and its stable derivative iloprost on platelets and leukocytes.Thrombosis Research1990; Suppl XI: 33–42.
136.
LongW.A., RubinL.J.Prostacyclin and PGE1: Treatment of pulmonary hypertension.Am Rev Resp Dis1987; 136: 773–776.
137.
BihariD.J., TinkerJ.The therapeutic value of vasodilator prostaglandins in multiple organ failure associated with sepsis.Intens Care Med1988; 15: 2–7.
HymanA.L., SpannhakeE.W., KadowitzP.J.Prostaglandins and the lung.Am Rev Resp Dis1978; 117: 111–136.
140.
BenumofJ.L.Respiratory physiology and function during anaesthesia. In: Anaesthesia:Miller, ed, Churchill Livingstone, New York1994.
141.
HyslopS., de NucciG.The mechanisms and significance of the coupled release of endothelium-derived relaxing factor (EDRF) and prostacyclin (PGI2) from endothelial cells.Wien Klin Wochenschr1991; 103: 422–434.
142.
GryglewskiR.J.Interactions between nitric oxide and prosta-cyclin.Sem Thrombosis Hemostasis1993; 19: 158–166.
143.
HermillerJ.B., BambachD., ThompsonJ.M.Vasodilators and prostaglandin inhibitors in primary pulmonary hypertension.Ann Int Med1982; 97: 480–489.
144.
MeyrickB., NiedermeyerM.E.Pulmonary hypertension and increased vasoreactivity caused by repeated indomethacin treatment in sheep.J Appl Physiol1985; 59: 443–452.
145.
CampbellW.B., HalushkaP.V.Lipid-derived autacoids. In: The pharmacological basis of therapeutics; HardmanJ.G., LimbirdL.E. eds, McGraw Hill, New York, 1996.
146.
HablerO., KleenM., ZwisslerB.Inhalation of prosta-cyclin (PGI2) for 8 hours does not produce signs of acute pulmonary toxicity in healthy lambs.Intens Care Med1996; 22: 426–433.
147.
WelteM., ZwisslerB., HabazettlH., MessmerK.PGI2 aerosol versus nitric oxide for selective pulmonary vasodilation in hypoxic pulmonary vasoconstriction.Eur Surg Res1993; 25: 329–339.
148.
ZobelG., DacarD., RodlS., FriehsI.Inhaled nitric oxide versus inhaled prostacyclin and intravenous versus inhaled prosta-cyclin in acute respiratory failure with pulmonary hypertension in piglets.Pediatric Research1995; 38: 198–204.
149.
McKayC.R., BrundageB.H., PortsT.A., ParmleyW.W., ChatterjeeK.Long-term clinical results after vasodilator evaluation in patients with primary and secondary pulmonary hypertension: acute haemodynamic comparisons and long-term survival.Int J Card1989; 22: 311–319.
150.
RubinL.J., MendozaJ., HoodM.Treatment of primary pulmonary hypertension with continuous intravenous prosta-cyclin.Ann Int Med1990; 112: 485–491.
151.
LongW., RubinL.J.Randomized trial of conventional therapy alone vs conventional therapy and continuous infusions of prostacyclin in primary pulmonary hypertension.Am Rev Resp Dis1993; 147: A538.
152.
VirgoliniI., FitschaP., LinetO.I., O'GradyJ., SinzingerH.A double-blind, placebo-controlled trial of intravenous prosta-cyclin in 108 patients with ischaemic peripheral vascular disease.Prostaglandins1990; 39: 657–664.
153.
HaywoodG.A., AdamsK.F., GheorghiadeM., McKennaW.J.Is there a role for epoprostenol in the management of heart failure?Am J Cardiol1995; 75: 44A–50A.
154.
BihariD., SmithiesM., GimsonA., TinkerJ.The effects of vasodilation with prostacyclin on oxygen delivery and uptake in critically ill patients.N Engl J Med1987; 317: 397–403.
155.
PascualJ.M., FiorelliA.I., BellottiG.M., StolfN.A., JaleneA.D.Prostacyclin in the management of pulmonary hypertension after heart transplant.J Heart Transplant1990; 9: 644–651.
156.
GoldmanA.P., DeliusR.E., DeanfieldJ.E., MacraeD.J.Nitric oxide is superior to prostacyclin for pulmonary hypertension after cardiac operations.Ann Thor Surg1995; 60: 300–306.
ZwisslerB., WelteM., MessmerK.Effects of inhaled prosta-cyclin as compared with inhaled nitric oxide on right ventricular performance in hypoxic pulmonary vasoconstriction.J Cardiothorac Vasc Anaes1995; 9: 283–289.
159.
PappertD., BuschT., GerlachH., LewandowskiK., Rader-macherP., RossaintR.Aerosolized prostacyclin versus inhaled nitric oxide in children with severe acute respiratory distress syndrome.Anesthesiology1995; 82: 1507–1511.
160.
BindlL., FahnenstichH., PeukertU.Aerosolised prostacyclin for pulmonary hypertension in neonates.Arch Dis Childhood1994; 71: F214–16.
161.
ZwisslerB., RankN., JaenickeU.Selective pulmonary vasodilation by inhaled prostacyclin in a newborn with congenital heart disease and cardiopulmonary bypass.Anes-thesiology1995; 82: 1512–1516.
162.
HaasN.A., Schulze-NeickI., LangeP.E.Intratracheal prosta-cyclin for resuscitation in primary pulmonary hypertension.Lancet1995; 346: 643.
163.
WalmrathD., SchneiderT., PilchJ., SchermulyR., GrimmingerF., SeegerW.Effects of aerosolized prostacyclin in severe pneumonia.Am J Resp Crit Care Med1995; 151: 724–731.
164.
BeinT., KeylC., PfeieferM., MetzC.Administration of aerosolized prostacyclin in patients with severe respiratory failure and pulmonary hypertension.Chest1995; 108: 119S.
165.
WebbS.A.R., StottS., van HeerdenPV.The use of inhaled aerosolized prostacyclin (IAP) in the treatment of pulmonary hypertension secondary to pulmonary embolism.Intens Care Med1996; 22: 353–355.
166.
van HeerdenP.V., WebbS.A.R., HeeG., CorkeronM., ThompsonW.R.Inhaled aerosolized prostacyclin as a selective pulmonary vasodilator for the treatment of severe hypoxaemia.Anaesth Intens Care1996; 24: 87–90.
167.
van HeerdenP.V., BlytheD., WebbS.A.R.Inhaled aerosolized prostacyclin and nitric oxide as selective pulmonary vasodilators in ARDS—a pilot study.Anaesth Intens Care1996; 24: 564–568.
168.
WalmrathD., SchneiderT., SchermulyR., OlschewskiH., GrimmingerF., SeegerW.Direct comparison of inhaled nitric oxide and aerosolized prostacyclin in ARDS.Am J Resp Crit Care Med1996; 153: 991–996.
169.
ColemanD.M., KellyH.W., McWilliamsB.C.Determinants of aerosolized albuterol delivery to mechanically ventilated infants.Chest1996; 109: 1607–1613.
170.
FullerH.D., DolovichM.B., PosmituckG., PackW.W., NewhouseM.T.Pressurised aerosol versus jet aerosol delivery to mechanically ventilated patients—comparison of doses to the lungs.Am Rev Resp Dis1990; 141: 440–444.
171.
WatterbergK.L., ClarkA.R., KellyH.W., MurphyS.Delivery of aerosolized medication to intubated babies.Ped Pulmonol1991; 10: 136–141.
172.
BahkleY.S., FerreiraS.H.Lung metabolism of eicosanoids. In: FishmanA.P., FisherA.B., eds: Handbook of physiology, section 3, Am Phys Soc, Bethesda, 1985.
GardinerP.J., CopasJ.L., ElliottR.D., CollierH.O.J.Tracheo-bronchial irritancy of inhaled prostaglandins in the conscious cat.Prostaglandins1978; 15: 303–315.
175.
OlschewskiH., WalmrathD., SchermulyR., GhofraniA., GrimmingerF., SeegerW.Aerosolized prostacyclin and iloprost in severe pulmonary hypertension.Ann Int Med1996; 124: 820–824.
176.
HildebrandM., NieuweboerB., SchuttA.Development and validation of a sensitive and specific radioimmunoassay for the determination of cicaprost in biological samples.J Immunoassay1994; 15: 171–190.
177.
DrewsG., SpiegelH.U., HermsdorfT., DettmerD., RichterV., HaussJ.Cytoprotective effects of a stable prostacyclin analog and a calcium channel blocker: A study on isolated rat hepatocytes.Transplantation Proceedings1995; 27: 2799.
178.
SajiT., OzawaY., NakayamaT.Short and long-term effects of the new oral prostacyclin analogue, beraprost sodium, in patients with severe pulmonary hypertension.J Cardiol1996; 27: 197–205.
