Extracorporeal circulation in pregnancy: report of a case. Update and review of the literature

OBJECTIVE: To investigate the role of platelet activating factor (PAF) in the hypoxic pulmonary hypertension. MATERIAL AND METHODS: Fifteen of 30 male Wistar rats were exposed to hypoxia for 3 weeks, and another 15 rats served as controls. The pulmonary arterial pressure was examined by catheterization. The sections of rat lung were treated by the avidin-biotin-peroxidase complex method to expose the location of PAF. RESULTS: The rats developed pulmonary hypertension and right ventricular hypertrophy after hypoxic exposure. Under the light microscope, PAF is distributed on the vascular and alveolar walls of normal lung, and the content of PAF in the lung of rats with hypoxic pulmonary hypertension are remarkably higher than those of normoxic controls. CONCLUSIONS: PAF plays not only a physiological role in the rat lung, but also a pathophysiologic role in hypoxic pulmonary hypertension.     

Effects of ginkgolide B on isobaric hypoxic pulmonary hypertension in rats

We examined the effects of ginkgolide B (BN52021), a specific platelet activating factor (PAF) antagonist, on hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling. Chronic hypoxia can cause pulmonary hypertension and pulmonary vascular remodeling in rats. Treated with BN52021, the rat's pulmonary hypertension, pulmonary vascular remodeling and right ventricular hypertrophy at 3 weeks of hypoxic exposure (FiO2 = 0,10) could be reduced. The results suggest that PAF contributes to the development of chronic hypoxic pulmonary hypertension and pulmonary vascular remodeling, and PAF antagonist may be an useful agent for preventing hypoxic pulmonary hypertension.     

Long-term effects of prenatal indomethacin administration on the pulmonary circulation in rats

Mechanical properties of the adult pulmonary vasculature are affected by perinatal experience of hypoxic pulmonary hypertension. In the present study, we followed the long-term effects of perinatal pulmonary hypertension induced by means other than hypoxia in rats. Daily injections of indomethacin (1 mg.kg-1 body weight (BW)) were given to the parturient rats. Their newborn pups had significantly increased number of muscularized peripheral pulmonary vessels. Pulmonary hypertension, however, did not persist to adulthood (mean pulmonary arterial pressure (Ppa) was 17.2 +/- 1.3 torr in the experimental group and 16.4 +/- 0.8 torr in controls). Pulmonary hypertension induced in adult rats by exposure to chronic hypoxia or by acute hypoxic challenges was similar in indomethacin-treated and control rats. Normoxic perfusion pressure/flow (P/Q) plots in isolated lungs were less steep in indomethacin-treated than in control rats. Acute hypoxia increased the slope of P/Q plots in indomethacin treated rats but not in controls. The described changes in the pulmonary vasculature induced by indomethacin are similar to those found previously in adult rats born in hypoxia. We conclude that perinatal pulmonary hypertension permanently modifies the pulmonary vasculature.     

Effects of hypoxia and anisodamine on products of TXA2 and PGI2 in cultured intra-pulmonary arteriolar smooth muscle cells

The changes of contents of TXB2 and 6-Keto-PGF1a were studied in severely acute hypoxic cultured intra-pulmonary arteriolar smooth muscle cells (PASMCs) under the action of anisodamine. The results demonstrated that the contents of TXB2 and 6-Keto-PGF1a and their ratio were significantly increased in severe acute hypoxic PASMCs' medium. The content of TXB2 decreased significantly, but the content of 6-Keto-PGF1a was hardly affected by anisodamine under normoxia and hypoxia. These findings suggest that acute and severe hypoxia results in pulmonary vascular constriction through increased production of PASMCs and liberation of TXA2, or PGI2, and increased TXA2/PGI2 ratio. The latter effect of hypoxia could be prevented by anisodamine, which antagonized the effect of hypoxia induced pulmonary vasoconstriction.     

Collateral ventilation and pulmonary arterial smooth muscle in the coati

Collateral ventilation can participate in ventilation-perfusion regulation by shifting normoxic gas into hypoxic lung regions. In species lacking collateral pathways, such as cattle and swine, ventilation-perfusion balance must rely heavily on hypoxic vasoconstriction, which may explain why their muscular pulmonary arteries are much thicker than those of other animal species. The presence of these unusually muscular vessels in turn may account for the vigorous pressor response to acute hypoxia in these species. The only other species known to lack collateral ventilation is the coati. To determine whether coatis fit the pulmonary circulatory pattern of cattle and swine, we measured pulmonary arterial wall dimensions and pulmonary vascular responsiveness to acute airway hypoxia in 11 adult coatis. Hypoxia caused impressive pulmonary arterial hypertension [normoxia = 17 +/- 1 (SE) Torr, hypoxia = 40 +/- 2 Torr, cardiac output unchanged]. The medial thickness of muscular pulmonary arteries (50-300 microns) was 17.1 +/- 1.8% (SD) of external diameter, a thickness unprecedented in normotensive adult mammals. We conclude that coatis fit the pattern of other species lacking collateral ventilation, since they have thick-walled pulmonary arteries and a vigorous pressor response to hypoxia.     

The orally active nonpeptide endothelin A-receptor antagonist A-127722 prevents and reverses hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling in Sprague-Dawley rats

Exposure to hypoxia is associated with increased pulmonary artery pressure and plasma endothelin (ET-1) levels and with selective enhancement of ET-1 peptide and messenger RNA (mRNA) and endothelin-A (ET-A) receptor mRNA in rat lung. Our study tested the hypothesis that A-127722, an orally active antagonist of the ET-A receptor, can prevent hypoxia-induced pulmonary hypertension and vascular remodeling in the rat. Pretreatment with A-127722 (3, 10, and 30 mg/kg/day in drinking water for 2 days) caused dose-dependent inhibition of the pulmonary vasoconstrictor response to short-term hypoxia (10% O2, 90 min). Long-term A-127722 treatment (10 mg/kg/day in drinking water for 2 weeks) instituted 48 h before hypoxic exposure attenuated the subsequent development of pulmonary hypertension, the associated right atrial hypertrophy, and pulmonary vascular remodeling. Institution of A-127722 treatment (10 mg/kg/day in drinking water for 4 weeks) after 2 weeks of hypoxia retarded the progression of established hypoxia-induced pulmonary hypertension and right atrial hypertrophy and reversed the pulmonary vascular remodeling despite continuing hypoxic exposure. These findings support the hypothesis that endogenous ET-1 plays a major role in hypoxic pulmonary vasoconstriction/hypertension, right heart hypertrophy, and pulmonary vascular remodeling and suggest that ET-A receptor blockers may be useful in the treatment and prevention of hypoxic pulmonary hypertension in humans.     

Detection and clinical pathological significance of the expression of P21, P185, p53 proteins and mutation of ras, p53 genes in transitional cell carcinoma of the bladder

OBJECTIVE: In order to observe the effects of inhaling nitric oxide (NO) on acute lung injury (ALI). METHODS: 24 rabbits divided into 4 groups. Six rabbits injured with intravenous E. Coli endotoxin, then followed by treatment of inhaling 80 ppm NO in inspired gas. Before and after the infusion of endotoxin, the mean pulmonary arterial pressure (mPAP), mean systemic arterial pressure (mPSA) and the PaO2 were examined. The venous methemoglobin (MHb) was measured by using spectrophometer colorimitry. The extravasculur lung water was evaluated with rate of dried to wet lung weight at the end of study. RESULTS: The rabbits injured with endotoxin inhaling 80 ppm NO could rapidly reduce the mPAP, increase the PaO2 and without inducing significant change of mPSA, MHb and extravasculur lung water. CONCLUSIONS: Inhalation of 80 ppm NO can selectively cause pulmonary artery dilatation, reduce mPAP, improve pulmonary gas exchange, without producing system vasodilation and toxic effects to the rabbits.     

The role of endothelial nitric oxide synthase expression in the development of pulmonary hypertension in chronically hypoxic infant swine

OBJECTIVE: Our goal was to determine the role of pulmonary endothelial nitric oxide synthase expression in the development of pulmonary hypertension in infants with congenital cyanotic heart disease. METHODS: Two groups of 4-week-old piglets were studied. In one group, the piglets were raised in an environment of 10% oxygen from 2 days of age (cyanotic, n = 6), and in the other group the piglets were raised at room air (control, n = 5). Pulmonary hemodynamics were measured in vivo for each animal, and peripheral lung biopsy specimens were obtained for Western blot analysis with the use of antiendothelial nitric oxide synthase antibody and for activity analysis with the use of the tritiated L-arginine assay. RESULTS: The piglets in the chronically hypoxic group had significant increases in mean pulmonary arterial pressure (44.0 +/- 3.8 mm Hg vs 14.8 +/- 1.2 mm Hg in controls, p = 0.0007) and pulmonary vascular resistance (7272.0 +/- 871.1 dyne x cm x sec(-5) vs 1844.5 +/- 271.2 dyne x cm x sec(-5) in controls, p = 0.002). These changes in the pulmonary hemodynamics of the hypoxic piglets were accompanied by a twofold increase in the expression of pulmonary endothelial nitric oxide synthase (p = 0.0043) but no corresponding increase in nitric oxide synthase activity. CONCLUSIONS: Raising infant piglets in an environment of 10% oxygen for 4 weeks results in significant pulmonary arterial hypertension accompanied by increased expression of nitric oxide synthase within the lung endothelium. Furthermore, the increased levels of nitric oxide synthase within the lungs of the hypoxic swine were not accompanied by a proportional increase in enzyme activity. These findings suggest that the development of pulmonary hypertension in infants with congenital cyanotic disease is not due to decreased expression of endothelial nitric oxide synthase, but instead may be related to a decreased ability of the enzyme to produce sufficient nitric oxide.     

The ETA receptor antagonist, BMS-182874, reduces acute hypoxic pulmonary hypertension in pigs in vivo

OBJECTIVE: Elevated levels of the potent vasoactive peptide endothelin (ET), have been found in pathophysiological conditions associated with pulmonary hypertension. In this study, we have investigated the effects of the ETA receptor antagonist, BMS-182874, on hypoxic pulmonary hypertension in pigs. METHODS: Pigs were subjected to acute, intermittent 15-min periods of hypoxia (FiO2 0.1). Following a first hypoxia establishing hypoxic baseline values, vehicle or BMS-182874 (10 or 30 mg/kg) was administered i.v. before a second hypoxic period. In separate groups of animals, the effects of the nitric oxide synthase inhibitor N omega-nitro-L-arginine (L-NNA) in combination with BMS-182874 (10 mg) during repeated hypoxia were investigated. The ET-1-blocking properties of BMS-182874 were studied in vivo by infusion of ET-1 during normoxia and in vitro using isolated porcine pulmonary arteries. RESULTS: The hypoxia-evoked increase in mean pulmonary artery pressure was reduced by administration of BMS-182874 (10 mg/kg i.v.; from 42 +/- 8 to 34 +/- 4 mmHg, P < 0.05 and 30 mg/kg i.v.; from 38 +/- 4 to 30 +/- 5 mmHg, P < 0.05). In addition, BMS-182874 at 30 mg/kg reduced the pulmonary vascular resistance during hypoxia (from 7.4 +/- 1.5 to 5.3 +/- 1.1 mmHg.min.l-1 P < 0.05). The hemodynamic response to repeated hypoxia was reproducible in control animals and unaffected by the cyclo-oxygenase inhibitor diclophenac (3 mg/kg). Infusion of L-NNA alone resulted in an augmented pulmonary vasoconstriction during hypoxia; pulmonary arterial pressure from 35 +/- 6 to 43 +/- 9 mmHg; P < 0.05 and vascular resistance from 7.2 +/- 1.1 to 9.9 +/- 1.8 mmHg.min.l-1; P < 0.05. L-NNA in combination with BMS-182874 (10 mg/kg) resulted in a hypoxic pulmonary vasoconstriction of similar magnitude as hypoxic baseline. In addition, BMS-182874 reduced the hemodynamic response to ET-1 in normoxic pigs and competitively antagonized the vasoconstrictor effect of ET-1 in isolated porcine pulmonary arteries. CONCLUSIONS: The non-peptide, selective ETA receptor antagonist, BMS-182874, reduces hypoxic pulmonary vasoconstriction in pigs. The reduction in pulmonary vascular response to hypoxia following BMS-182874 is at least partly independent of nitric oxide.     

Pharmacological and histopathological aspects of 1-methyl-4-phenyl-4-hydroxy-piperidine (MPIP)

The inhibitory effects of Radix Astragali (RA) on hypoxic structural remodeling of intra-acinar pulmonary arteries (IAPA) and pulmonary hypertension (PHT) were studied in rats, which were fed in hypoxic environment under normal atmospheric pressure (10% O2 10 hours/day). 60 rats were divided into 3 groups; hypoxia group, hypoxia+RA group and control group. On the 15th and 30th day of hypoxia, right ventricular systolic pressure (RVSP) and right ventricle hypertrophy index (RVHI) were measured and pulmonary vessel changes were studies under light and electronic microscopes and morphometric analysis. Compared with the hypoxia+RA group, RA could prevent IAPA wall cell damage and dilate the constricted IPIA induced by hypoxia. RA could also inhibit hypertrophic changes in the tunica media and proliferation of adventitial cells of the IAPA and muscularization of non-muscular arteries. Therefore, preserving the IAPA wall cells and dilating IAPA by RA may play an important role in inhibiting structural remodeling of IAPA and pulmonary hypertension.     

Potentiation of sufentanil by clonidine in PCEA with or without basal infusion

The purpose of the present study was to observe whether inflammatory mediators, such as: Prostaglandin E2 (PGE2), Bradykinin (BK), Histamine (HIS), Platelet active factor (PAF) and 5-hydroxytryptamine (5-HT), directly triggered the release of CGRP from perivascular nerves in isolated rat mesenteric arterial bed. The results showed that PGE2 (1-100 mumol/L) and BK (5-10 mumol/L) caused time- and concentration-dependent CGRP release, but HIS, PAF and 5-HT did not show significant effects. Our data indicate that PGE2 and BK are the major inflammatory mediators in triggering the release of CGRP from the perivascular CGRP-containing nerve.     

Awareness and attitudes concerning BRCA gene testing

We studied the changes in pulmonary hemodynamics induced by arm-stretching exercise in 12 patients with chronic pulmonary emphysema (CPE) and 9 control subjects (Controls). Both patients and control subjects underwent right heart catheterization with inspired gas analysis at rest and during exercise for the 6 minute-exercise test. Mean pulmonary arterial pressure (mPAP) in patients with CPE significantly increased from 18.5 +/- 3.9 mmHg at rest to 25.7 +/- 5.1 mmHg during exercise without decreased oxygen tension of the arterial blood. Both mPAP and total pulmonary resistance increased in proportion to the increases in cardiac output. Mixed venous plasma atrial natriuretic peptide (ANP) was significantly evaluated during exercise in patients with CPE, but did not in Controls. There were a significantly positive relationships between ANP and mPAP, and a significantly negative relationships between ANP and PvO2 during exercise. These results suggest that pulmonary hypertension during light exercise in cases of CPE may be caused by deterioration of the pulmonary capillary bed, and that ANP may be a useful indicator for evaluating pulmonary hypertension in patients with CPE.     

Pyridoxalated hemoglobin polyoxyethylene conjugate does not restore hypoxic pulmonary vasoconstriction in ovine sepsis

OBJECTIVES: Hypoxic pulmonary vasoconstriction, a protective mechanism, minimizes perfusion of underventilated lung areas to reduce ventilation-perfusion mismatching. We studied the effects of sepsis on hypoxic pulmonary vasoconstriction and attempted to determine whether hypoxic pulmonary vasoconstriction is influenced by pyridoxalated hemoglobin polyoxyethylene conjugate, a nitric oxide scavenger. DESIGN: Prospective, randomized, controlled experimental study with repeated measures. SETTING: Investigational intensive care unit at a university medical center. SUBJECTS: Nineteen female merino sheep, divided into three groups: group 1, controls (n = 5); group 2, sheep with sepsis (n = 6); and group 3, septic sheep treated with pyridoxalated hemoglobin polyoxyethylene conjugate (n = 8). INTERVENTIONS: All sheep were instrumented for chronic study. An ultrasonic flow probe was placed around the left pulmonary artery. After a 5-day recovery, a tracheostomy was performed and a double-lumen endotracheal tube was placed. Animals in groups 2 and 3 received a 48-hr infusion of live Pseudomonas aeruginosa (6 x 10(4) colony-forming units/kg/hr). After 24 hrs, sheep in group 3 received pyridoxalated hemoglobin polyoxyethylene conjugate (20 mg/kg/hr) for 16 hrs; sheep in groups 1 and 2 received only the vehicle. Hypoxic pulmonary vasoconstriction was repeatedly tested by unilateral hypoxia of the left lung with 100% nitrogen. Hypoxic pulmonary vasoconstriction was assessed as the change in left pulmonary blood flow. MEASUREMENTS AND MAIN RESULTS: In the animals in group 1, left pulmonary blood flow decreased by 62 +/- 8 (SEM)% during left lung hypoxia and remained stable during repeated hypoxic challenges throughout the study period. After 24 hrs of sepsis, left pulmonary blood flow decreased from 56 +/- 10% to 26 +/- 2% (group 2) and from 50 +/- 8% to 23 +/- 6% (group 3). In the sheep in group 2, there was no adaptation over time. Pulmonary shunt fraction increased. Pyridoxalated hemoglobin polyoxyethylene conjugate had no effect on hypoxic pulmonary vasoconstriction or pulmonary shunt. The animals receiving the bacterial infusion developed a hyperdynamic circulatory state with hypotension, decreased systemic vascular resistance, and increased cardiac output. Pyridoxalated hemoglobin polyoxyethylene conjugate increased mean arterial pressure and systemic vascular resistance but did not influence cardiac index. Pulmonary arterial pressure was increased during sepsis and increased even further after pyridoxalated hemoglobin polyoxyethylene conjugate administration. Oxygenation and oxygen delivery and uptake were not affected by pyridoxalated hemoglobin polyoxyethylene conjugate. CONCLUSIONS: Hypoxic pulmonary vasoconstriction is blunted during sepsis and there is no adaptation over time. It is not influenced by pyridoxalated hemoglobin polyoxyethylene conjugate. Pyridoxalated hemoglobin polyoxyethylene conjugate reversed hypotension and, with the exception of an increase in pulmonary arterial pressure, had no adverse effects on hemodynamics or oxygenation.     

Effect of 764-3 and ligustrazine on collagen content of extrapulmonary arteries during chronic hypoxia

OBJECTIVE: Effect of two antifibrotic Chinese drugs, 764-3 and ligustrazine, on collagen content in chronic hypoxic pulmonary hypertensive extrapulmonary arterial wall were examined. METHODS: Since collagen contains more than 10% hydroxyproline by weight and in other proteins there are almost no hydroxyproline, collagen content was expressed as micrograms of hydroxyproline. Hydroxyproline was determined by calorimetric method after oxidized by chloramine T. RESULTS: Both 764-3 and ligustrazine significantly inhibited the increase of pulmonary arterial pressure and elevation of hydroxyproline content in extrapulmonary arterial wall during chronic hypoxia. CONCLUSIONS: 764-3 and ligustrazine may be two hopeful therapeutic drugs for chronic hypoxic pulmonary hypertension.     

Effects of hypoxia on the hemodynamic actions of prostaglandin E1

The effect of prostaglandin E1 (PGE1) on central and peripheral hemodynamics was studied in seven conscious dogs under conditions of normoxia and hypobaric hypoxia to ascertain if hypoxia attenuated the cardiovascular actions of PGE1. Silastic catheters were chronically implanted in the pulmonary artery, left atrium, and aorta. Acute hypoxia was produced in a hypobaric chamber maintained at 446 mmHg pressure (14,000 feet). PGE1 at sea level (normoxia) resulted in significant increases in heart rate, cardiac output, left ventricular stroke work and pulmonary blood volume as well as significant decreases in aortic, pulmonary arterial, and left atrial pressures. During hypobaric hypoxia, PGE1 produced essentially identical effects on all hemodynamic parameters except pulmonary blood volume and pulmonary arterial pressure where marked attenuation of PGE1 action occurred.     

Increased prevalence of hypertension and long-term arsenic exposure

A possible role of endothelin (ET)-1 in mediating hypoxic pulmonary vasoconstriction (HPV) was examined by comparing haemodynamic differences between ET-1-induced vasoconstriction and HPV in isolated perfused rat lungs. An ETA receptor antagonist (BQ123) was also employed to assess the effects of ET-1. The pulmonary arterial pressure (Ppa) was significantly increased by alveolar hypoxia (3% O2) and by ET-1 (5 nM). The pulmonary microvascular pressure was not changed by hypoxia, but increased more than two-fold by ET-1 (P < 0.01). Hypoxia significantly increased pulmonary arterial resistance (P < 0.01) while ET-1 significantly increased pulmonary venous resistance (P < 0.01), and slightly increased arterial resistance. Lung weight was increased by ET-1 and decreased by hypoxia, accompanied by similar Ppa responses in both cases. BQ123 (10(-6) M and 10(-5) M) did not influence the changes in Ppa and lung weight induced by hypoxia or angiotensin II (0.3 micrograms). BQ123 did, however, suppress (P < 0.05) the increase in Ppa and lung weight induced by 5 nM ET-1. Thus, it appears unlikely that ET-1 is involved in changes in pulmonary vascular tone during acute HPV.     

Synergistic effect of type II phospholipase A2 and platelet-activating factor on Mac-1 surface expression and exocytosis of gelatinase granules in human neutrophils: evidence for the 5-lipoxygenase-dependent mechanism

Stimulation of human neutrophils with inflammatory mediators such as TNF-alpha or platelet-activating factor (PAF) induces translocation of adhesion molecule Mac-1 (CD11b/CD18) from secretory vesicles to the plasma membrane. Type II phospholipase A2 (PLA2-II) also induces translocation of Mac-1 from secretory vesicles. However, there are more Mac-1 molecules in gelatinase granules and specific granules than in secretory vesicles. Therefore, different combinations of PLA2-II and other mediators were examined for their ability to induce gelatinase granules and specific granules to induce Mac-1 surface expression. The combination of PLA2-II and PAF synergistically increased Mac-1 surface expression, and the effect was greater than the combinations of PLA2-II with TNF-alpha, IL-8, or FMLP. Additionally, the combination of PLA2-II and PAF induced exocytosis of both secretory vesicles and gelatinase granules, which did not occur with either PLA2-II alone or PAF alone. The induction was accompanied by marked production of leukotriene B4. AA861, an inhibitor of 5-lipoxygenase, did not inhibit exocytosis of secretory vesicles but did inhibit exocytosis of gelatinase granules and decrease Mac-1 surface expression. It was also found that Ca2+ influx is essential for 5-lipoxygenase activation, because Ni2+, which blocks the influx of extracellular Ca2+, inhibited the production of leukotriene B4. These results suggest that stimulation by the combination of PLA2-II and PAF, unlike stimulation by each mediator alone, causes exocytosis of gelatinase granules via the 5-lipoxygenase pathway, resulting in a synergistic increase in neutrophil Mac-1 surface expression during inflammatory processes.     

The effect of the ETA receptor antagonist (CI-1020) in rats with established hypoxic pulmonary hypertension

ETA receptor antagonists have previously been shown to prevent the development of pulmonary hypertension induced by chronic hypoxia in the rat. Clinically, however, patients present with already established pulmonary hypertension. We have investigated the effects of the ETA receptor antagonist CI-1020 in rats previously adapted to chronic hypoxia. Two protocols were followed. Rats (n=32) were divided into two batches of four groups: normoxic controls in air for 10 days (NC10), chronic hypoxic controls in hypoxia for 10 days (CHC10), chronic hypoxic vehicle treated in hypoxia for 20 days (CHV20) and chronic hypoxic drug treated in hypoxia for 20 days (CHT20). Ten days after the onset of hypoxia, oral treatment with drug (40 mg/kg per day) or vehicle was started. Animal weight, ratio of right ventricular weight to left ventricular weight including septum (RV/LV+S) and percentage of double elastic lamina (DEL) were determined. In the second study, 12 rats were divided into three groups; normoxic controls in air for 20 days (NC20), (CHV20) and (CHT20). After 10 days hypoxia, oral treatment with drug (40 mg/kg per day) or vehicle was started. Isolated perfused lung preparations were then used to determine pulmonary artery pressure and pulmonary vascular resistance. Treatment with CI-1020 reduced the increase in RV/LV+S and the percentage DEL induced by chronic hypoxia and significantly lowered the increase in pulmonary resistance in isolated perfused lungs from chronically hypoxic animals. These results suggest that CI-1020 could have an important role in the treatment and reversal of established pulmonary vascular remodelling.     

Effect of aerosol heparin on the development of hypoxic pulmonary hypertension in the guinea pig

Chronic hypoxia produces pulmonary artery hypertension through vasoconstriction and structural remodeling of the pulmonary vascular bed. The present study was designed to test the effect of heparin administered via aerosol on the development of hypoxic pulmonary hypertension. Anesthetized, intubated, and mechanically ventilated guinea pigs received an aerosol of either 2 ml normal saline (hypoxic control, HC) or 4,500 units of heparin diluted in 2 ml normal saline via an ultrasonic nebulizer (hypoxic heparin, HH). After 24 h of recovery, the animals were placed in a hypoxic chamber (10% O2) for 10 days. Animals kept in room air served as normoxic controls (NC). Hypoxia increased mean pulmonary artery pressure from 11 +/- 1 (SEM) mm Hg in NC to 24 +/- 1 mm Hg in HC (p < 0.05). Pulmonary artery pressure was significantly lower in HH-treated animals (20 +/- 1 mm Hg, p < 0.05 versus HC) as was the total pulmonary vascular resistance (0.15 +/- 0.01 in HH versus 0.20 +/- 0.01 mm Hg/ml/min in HC, p < 0.05). There was no difference in cardiac output (146 +/- 12 in HH versus 126 +/- 7 ml/min in HC), hematocrit (57 +/- 2 in HH versus 56 +/- 2% in HC), partial thromboplastin time (30 +/- 2 in HH versus 32 +/- 3 s in HC), prothrombin time (46 +/- 1 in HH versus 48 +/- 4 s in HC) or room air arterial blood gas values after 10 days of hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)