Pulmonary Arterial Blood Pressure Research Articles

COMBINED ACTION ANTIHYPERTENSIVE AGENT URAPIDIL: EFFECTIVENESS AND SAFETY IN CLINICAL PRACTICE

The paper reviews the clinical practice potential of a combined action antihypertensive medication urapidil for the treatment of patients with acute elevation of blood pressure (BP) and confirms urapidil effectiveness and good tolerability. Urapidil action mechanisms, pharmacodynamics, and pharmacokinetics are discussed, together with the results of the key clinical trials which have demonstrated antihypertensive effectiveness and safety of this agent. Additional beneficial effects of urapidil, such as reduction of the increased pulmonary artery BP and improvement of bronchial conductivity, are also described.

Percutaneous closure of a gigantic patent ductus arteriosus (PDA) with pulmonary hypertension with an atrial septal defect occluder in a 35-year-old woman

Patent ductus arteriosus (PDA) is a common form of congenital heart defects (CHD); it counts for about 5–10 % of all CHD with an incidence of one in 2,500–5,000 live births [1]. In general, volume overload of the left atrium and left ventricle caused by the shunt and pulmonary vascular disease is clear indication for closure of the defect, whereas the risk of endocarditis and aneurysm formation of the PDA is under discussion. If untreated, a large PDA will regularly lead to pulmonary hypertension, heart failure and Eisenmenger syndrome [2]. PDA was the first example of congenital heart disease to be treated by transcatheter closure, and has now become an established form of treatment for the majority of patients with very few side effects. After the initial description in 1967 by Porstmann a large variety of different devices have been described (i.e., Rashkind device, Sideris buttoned device, various PDA coils, as well as specific PDA occluder devices such as the Amplatzer PDA-occluders [3]). Nowadays, percutaneous PDA closure has proved to be safe and effective with shortand long-term results comparable to surgical closure including those cases with mild and moderate pulmonary hypertension [2]. A common problem of all commercially available devices is the inability to close PDAs larger than 14 mm diameter based on manufacturer’s recommendations. Therefore, the majority of large PDAs are often closed surgically, although there are occasional case reports of very large PDAs closed with Amplatzer VSD or ASD Occluders [4, 5]. In the following report, we describe a case of successful transcatheter closure of an extremely large PDA measuring minimal 24 mm with an off-label use of a 24 mm Occlutech Figulla Flex ASD Occluder. A 35-year-old African woman (weight 77 kg, height 167 cm, BMI 27.6) was referred to our institution with an unknown heart disease for further evaluation. Clinically, she was in apparent heart failure (New York Heart Association III), transcutaneous oxygen saturation was 96 % and auscultation revealed a pronounced second heart sound and diastolic murmur. Her exercise performance measured by a 6-min walk test was 215 m only. The ECG revealed signs of right heart pressure load, and by echocardiography the estimated right ventricle pressure was 100 mmHg. This was caused by a very large PDA. It was noteworthy that the patient was human immunodeficiency virus positive. For further hemodynamic evaluation, the patient underwent a diagnostic catheterization. The PDA had a minimal diameter of 22 mm and an ampulla of 40 mm (see Fig. 1). The systemic arterial blood pressure was 115/66 mmHg (mean 85 mmHg) and the pulmonary arterial blood pressure 107/67 mmHg (mean 85 mmHg). The calculated pulmonary vascular resistance index (PVRI) was 12.6 Wood Units and the cardiac index (CI) 5.1 l/min/m. For further testing of the pulmonary vasoreagibility, the PDA was balloon occluded with a 30-mm sizing balloon. When the balloon was stabilized in the PDA, the minimal waist measured 24 mms. Thereafter, vasoreagibility of the M. Froehle (&) N. A. Haas C. Happel K. T. Laser Department for Congenital Heart Defects, Heart and Diabetes Center, North-Rhine Westphalia, Georgstrasse 11, 32545 Bad Oeynhausen, Germany e-mail: mfroehle@hdz-nrw.de

Clinical manifestations of hepatopulmonary syndrome

Objective: Hepatopulmonary syndrome (HPS) occurs in one third of patients with decompensated cirrhosis and is defined by perturbed gas exchanges, arterial hypoxemia, and vasodilatation in the lungs, in the absence of primary cardiopulmonary disease. Respiratory symptoms are severe when Pa O2 levels are <60 mm Hg: centrally-induced cyanosis, dyspnea, hippocratic fingers, platypnea, and orthodeoxia. Portopulmonary hypertension (PPH) occurs in 2% of cirrhotic patients and it is suspected in hypoxemic patients presenting no pulmonary vasodilatation. It is clinically manifested by stress dyspnea, orthopnea, thoracic pain, fatigue, and dizziness. Systolic blood pressure in pulmonary artery is over 25 mm Hg and pulmonary capillary blood pressure is blocked below 15 mm Hg. Methods: A five-year (2008–2012) retrospective evaluation of pulmonary pathology occurring with hepatic cirrhosis showed 50 patients presenting dyspnea, a symptom suggesting pulmonary involvement. Echocardiography monitored the following parameters: pulmonary artery acceleration time, measured in the parsternal window; pulmonary artery systolic blood pressure was measured by means of tricuspid regurgitation method and right-atrium blood pressure was evaluated according to inferior vena cava collapse with inspiration. Results: The 50 patients in the study group presented dyspnea as a symptom suggestive of pulmonary involvement. Platypnea and orthodeoxia were present in 12% of the cases. In 88% of the cases, dyspnea did not display particular characteristics; it became stronger under stress conditions and in dorsal decubitus position, according to the pathology associated with hepatic cirrhosis. Patients’ average age was 52. There was no constant correlation between hepatic dysfunction biochemical markers and degree of dyspnea. Severe hypoxemia (SaO2 < 80%) was present in 12% of the cases. Pulmonary artery systolic blood pressure was higher in patients with portal hypertension, with measurements exceeding 35 mm Hg in 60% of the cases. Right-atrium blood pressure, evaluated according to IVC collapse with inspiration, was high (11 ± 4 mm Hg) in 62% of the cases and normal (5 mm Hg) in 36%. We considered that pulmonary hypertension associated with portal hypertension in the study group was caused by hyperdynamic status and it was not portopulmonary hypertension proper. Conclusions: Hepatopulmonary syndrome should be used among the diagnostic variants for a patient with hepatic involvement and/or portal hypertension, in whom significant hypoxemia is observed, which has no restrictive basis and is not justified by any co-occurring cardiopulmonary condition. Platypnea and orthodeoxia in a hepatic condition developing with portal hypertension increase the possibility of HPS suspicion. The only definitive and efficient treatment in hepatopulmonary syndrome is liver transplantation.

Effect of Simulated Microgravity and its Associated Mechanism on Pulmonary Circulation in Rats

ObjectiveTo study the effect of Simulated Microgravity and its Associated Mechanism on Pulmonary Circulation in Rats. MethodsRat tail-suspension model was used to simulate the physiological effects of microgravity and changes in pulmonary blood vessel morphology, pulmonary arterial and venous blood pressure, pulmonary vascular resistance, pulmonary vasomotoricity, as well as the regulation of pulmonary circulation by cytokines produced and released by the lung of rats were measured. ResultsThe walls of pulmonary blood vessels of rats were thickened, and the pulmonary artery was reconstructed with increased pulmonary vascular resistance. The pulmonary blood vessels of rats became more prone to dilation as contractions increased. Rat epithelial Adrenomedulin gene transcription and protein expression were upregulated. The level of basic fibroblast growth Factor of rat was also elevated. ConclusionFindings from the present study on rats revealed that the microgravity can affect pulmonary blood vessel structure, pulmonary arterial pressure, and pulmonary blood vessel self-regulation and cytokine production.

GW24-e0772 Clinical efficacy of Wilkins integral in patients with percutaneous balloon mitral valvuloplasty

ObjectivesTo investigate patients with mitral stenosis of the valve morphology passing through the short-term effect of balloon mitral valvuloplasty.MethodsAccording to the integral of the the wilkins ultrasound mitral valve morphology...

Development of Capabilities for Simultaneous Measurement of Pulmonary and Systemic Pressure to Support Evaluation of Pulmonary Hypertension Therapies

Pulmonary arterial hypertension (PAH) is a life threatening disease with few proven treatment options. It is important that new therapies directed at decreasing pulmonary pressure demonstrate vascular selectivity on the pulmonary bed over the systemic bed. Therefore, we establised methods to directly measure pulmonary arterial pressure (PAP) and systemic blood pressure (systemic BP) simultaneously in conscious freely moving rats using novel HD‐S21 dual pressure transmitters from DSI. Transmitters were implanted in normotensive male Sprague Dawley rats, with one catheter of transmitter placed in the pulmonary artery and the other in abdominal aorta. To create a more clinically relevant PAH model and to increase the assay window, rats were exposed to hypoxic conditions (10% O2) over two weeks which increased baseline sPAP from ~25 mmHg to ~80 mmHg, with minimal effects on systemic BP. Validation studies were performed using standard of care PAH therapies: Tadalafil and Sildenafil (PDE5 inhibitors). Both compounds had similar maximal effect on systolic PAP (sPAP) reduction (~18–22 mmHg) and modest effects on the systemic BP (10–15 mmHg) on hypoxia‐induced PAH. In conclusion, innovative capabilities to directly measure PAP and systemic BP simultaneously have been established in conscious freely moving rat, and these methods provide a powerful approach to directly compare pulmonary vs. systemic hemodynamic activities minimizing cross‐study variability with different cohort of animals and to identify PAH therapies that demonstrate pulmonary selectivity.

Intrauterine inflammation alters cardiopulmonary and cerebral haemodynamics at birth in preterm lambs

Intrauterine inflammation is associated with preterm birth and poor long-term cardiopulmonary outcomes. We aimed to determine the effect of intrauterine inflammation on the cardiopulmonary and cerebral haemodynamic transition at birth, and the response to subsequent haemodynamic challenge. Fetal instrumentation was performed at ∼112 days gestation (term is 147 days) for measurement of cardiopulmonary and cerebral haemodynamics. At 118 days, inflammation was induced by intra-amniotic administration of lipopolysaccharide (LPS; n = 7); controls (n = 5) received intra-amniotic saline. At 125 days lambs were delivered and mechanically ventilated. Arterial blood gases, pulmonary and systemic arterial blood pressures and flows were measured during the perinatal period. At 10 min a haemodynamic challenge was administered by increasing positive end-expiratory pressure. During the first 10 min after birth, LPS-exposed lambs had higher pulmonary vascular resistance and lower pulmonary blood flow and left ventricular output than controls. Carotid arterial blood flow was higher in LPS-exposed lambs than controls between 3 and 7 min after delivery, and cerebral oxygen delivery was higher at 5 min. During the haemodynamic challenge, pulmonary blood flow and left ventricular output were reduced in controls but not in LPS-exposed lambs; a transient reduction in brachiocephalic arterial pressure occurred in LPS-exposed lambs but not in controls. Intrauterine inflammation altered the cardiopulmonary and cerebral haemodynamic transition at birth and reduced the cardiopulmonary response to a haemodynamic challenge after birth. The transient reduction in brachiocephalic arterial pressure suggests intrauterine inflammation may alter cerebrovascular control following an increase in positive end-expiratory pressure.

Therapeutic effect of eNOS-transfected endothelial progenitor cells on hemodynamic pulmonary arterial hypertension

Hemodynamic pulmonary arterial hypertension (HPAH) is a common symptom in congenital heart disease (CHD) patients with a left-to-right shunt. Endothelial NO synthase (eNOS) and endothelial-like progenitor cells result in significant improvement of right ventricular systolic pressure in established pulmonary arterial hypertension (PAH) models. We hypothesized that bone marrow (BM)-derived endothelial progenitor cells (EPCs) and eNOS would prevent HPAH in a newly established rat model. The heNOS gene was cloned into a PSUCMV vector, and a high-titer adenovirus was generated. Mononuclear cells (MNCs) from rat BM were differentiated into EPCs by treatment with various cytokines, and a high purity of EPCs (>70%) was confirmed using the markers DiI ac-LDL, UEA-1, vWF and Flk-1. An ideal rat HPAH model was successfully established based on right lung lobectomy, and was confirmed by pressure measurement and histological staining. heNOS was successfully transfected into EPCs, which were then transplanted into HPAH rats. Two weeks after transplantation, the systolic pulmonary arterial blood pressure (sPAP) was significantly reduced by heNOS-EPCs treatment and by transplantation of control EPCs. The high number of muscular pulmonary arteries and the thickness of the muscular coat characteristic of HPAH rats were clearly reversed or even restored to normal levels following transplantation of EPCs, particularly eNOS-EPCs. These findings indicate a critical role of eNOS in HPAH treatment and suggest that eNOS-transfected EPCs may provide an effective strategy for HPAH treatment in CHD patients.

Pregnancy outcome in women with pulmonary arterial hypertension: single-center experience from India

A retrospective analysis of the records of all the patients of pulmonary arterial hypertension with pregnancy at AIIMS, New Delhi, India, to study maternal and perinatal outcome and to compare outcome between severe and mild pulmonary arterial hypertension. A retrospective analysis was carried out of 30 pregnancies in women with pulmonary arterial hypertension (PAH) who delivered at ≥ 28 weeks of gestation from July 2006 through July 2012 at a tertiary care center in India. Pulmonary artery blood pressure (PABP) during the first trimester of pregnancy or before pregnancy was considered to define PABP as severe or mild, with severe cases having systolic PABP >50 mmHg on echocardiography. Out of 30 patients, 14 patients had severe PAH and 16 patients had mild PAH. Women with severe PAH had a significantly higher incidence of preterm delivery (11 vs. 3, P < 0.05), small for gestational age infants (10 vs. 2, P < 0.05) and cardiac complications (6 vs. 1, P < 0.05) compared to women with mild PAH. There was maternal mortality in a patient with Eisenmenger syndrome. In women with severe PAH and mild PAH, PABP increased in later pregnancy from 63.14 ± 7.6 to 71.57 ± 7.9 mmHg (P < 0.05) and from 40.37 ± 3.6 to 41.69 ± 4.1 mmHg (P < 0.05), respectively. Pregnancy in women with severe PAH is associated with higher maternal morbidity and adverse fetal outcome compared to pregnancy in women with mild PAH.

Distinct activity of BK channel β1-subunit in cerebral and pulmonary artery smooth muscle cells

This study was designed to test a hypothesis that the functional activity of big-conductance, Ca(2+)-activated K(+) (BK) channels is different in cerebral and pulmonary artery smooth muscle cells (CASMCs and PASMCs). Using patch-clamp recordings, we found that the activity of whole cell and single BK channels were significantly higher in CASMCs than in PASMCs. The voltage and Ca(2+) sensitivity of BK channels were greater in CASMCs than in PASMCs. Targeted gene knockout of β(1)-subunits significantly reduced BK currents in CASMCs but had no effect in PASMCs. Western blotting experiments revealed that BK channel α-subunit protein expression level was comparable in CASMCs and PASMCs; however, β(1)-subunit protein expression level was higher in CASMCs than in PASMCs. Inhibition of BK channels by the specific blocker iberiotoxin enhanced norepinephrine-induced increase in intracellular calcium concentration in CASMCs but not in PASMCs. Systemic artery blood pressure was elevated in β(1)(-/-) mice. In contrast, pulmonary artery blood pressure was normal in β(1)(-/-) mice. These findings provide the first evidence that the activity of BK channels is higher in cerebral than in PASMCs. This heterogeneity is primarily determined by the differential β(1)-subunit function and contributes to diverse cellular responses in these two distinct types of cells.

Cardiovascular and respiratory effects of incremental doses of dopamine and phenylephrine in the management of isoflurane-induced hypotension in cats with hypertrophic cardiomyopathy

To determine cardiopulmonary effects of incremental doses of dopamine and phenylephrine during isoflurane-induced hypotension in cats with hypertrophic cardiomyopathy (HCM). 6 adult cats with severe naturally occurring HCM. Each cat was anesthetized twice (once for dopamine treatment and once for phenylephrine treatment; treatment order was randomized). Hypotension was induced by increasing isoflurane concentration. Cardiopulmonary data, including measurement of plasma concentration of cardiac troponin I (cTnI), were obtained before anesthesia, 20 minutes after onset of hypotension, and 20 minutes after each incremental infusion of dopamine (2.5, 5, and 10 μg/kg/min) or phenylephrine (0.25, 0.5, and 1 μg/kg/min). Mean ± SD end-tidal isoflurane concentration for dopamine and phenylephrine was 2.44 ± 0.05% and 2.48 ± 0.04%, respectively. Cardiac index and tissue oxygen delivery were significantly increased after administration of dopamine, compared with results after administration of phenylephrine. Systemic vascular resistance index was significantly increased after administration of phenylephrine, compared with results after administration of dopamine. Oxygen consumption remained unchanged for both treatments. Systemic and pulmonary arterial blood pressures were increased after administration of both dopamine and phenylephrine. Acid-base status and blood lactate concentration did not change and were not different between treatments. The cTnI concentration increased during anesthesia and infusion of dopamine and phenylephrine but did not differ significantly between treatments. Dopamine and phenylephrine induced dose-dependent increases in systemic and pulmonary blood pressure, but only dopamine resulted in increased cardiac output. Hypotension and infusions of dopamine and phenylephrine caused significant increases in cTnI concentrations.

Validation of the isovolumetric relaxation time for the estimation of pulmonary systolic arterial blood pressure in chronic pulmonary hypertension

Transthoracic echocardiography is a useful technique for non-invasive detection of pulmonary arterial systolic pressure (PASP). Isovolumic relaxation time (IVRT) measured by Doppler tissue imaging (DTI) is a sensitive measurement of changes in pulmonary vasculature. Our aim was to validate IVRT in the echocardiographic assessment of pulmonary hypertension (PH) patients. We studied 196 PH patients (67% women, mean age 51.8 ± 16.6 years, mean PASP: 81 ± 24 mmHg) and 37 consecutive age- and sex-matched controls (58% women, mean age 44.7 ± 16.4 years, mean PASP 27.7 ± 5.5 mmHg). The estimation of PASP was derived from tricuspid regurgitation velocity according to the Bernoulli equation. The measurement of IVRT was calculated using pulsed tissue Doppler. In the PH group and in the healthy volunteers group (P < 0.0001), the average IVRT was 113.4 ± 28.5 ms [95% confidence interval (CI): 109-117] and 41 ± 12.5 ms (95% CI: 37-45), respectively. We found a strong correlation between IVRT and systolic pulmonary pressure in the PH group (r = 0.52, P < 0.0001) and a cut-off of 75 ms showed a sensitivity and specificity of 94% and 97%, respectively, for the prediction of elevated PASP. The determination of IVRT by DTI is a simple and reproducible method that correlates well with PASP. It is, therefore, a parameter to consider in the echocardiographic assessment of patients with PH, and may be particularly important when the tricuspid Doppler signal is poor.

RNAi Silencing of TNFα Attenuates Cold‐induced Pulmonary Hypertension (CIPH)

BackgroundExposure to a moderate cold temperature (5ºC) causes pulmonary hypertension. Tumor necrosis factor‐alpha (TNF‐α) was increased in lungs and pulmonary arteries of rats prior to cold‐induced elevation of pulmonary arterial blood pressure (PABP). The purpose of this study was to investigate if the upregulation of TNFα plays a role in CIPH.Methods and ResultsThree groups of male SD rats (8 rats/group) received IV delivery of adeno‐associated virus (AAV)‐carrying TNFα small hairpin RNA (TNFαshRNA), AAV‐carrying scrambled shRNA, and PBS, respectively, 3 days before exposure to a cold environment (5°C). Three additional groups with the same treatments were housed in a warm chamber (25°C) and serve as controls. Eight weeks after injection, right ventricular (RV) systolic BP (equivalent of PABP) was recorded and PA smooth muscle cells were isolated for in vitro studies. TNFαshRNA significantly decreased cold‐induced elevation of RV BP but not RV hypertrophy. TNFαshRNA prevented cold‐induced upregulation of TNFα in lungs and PAs, confirming effective silencing of TNFα. TNFα inhibition decreased cold‐induced increases in intracellular levels of O2−, calcium, and cGMP in PA SMCs. RNAi silencing of TNFα also prevented the cold‐induced increase in PCNA, a marker of cell proliferation.ConclusionsThe upregulation of TNFα may play a key role in the development of CIPH and PASMC proliferation.

Attenuation of the Extract from Moringa Oleifera on Monocrotaline-Induced Pulmonary Hypertension in Rats

The purpose of this study was to determine the effects of an extract from Moringa oleifera (MO) on the development of monocrotaline (MCT)-induced pulmonary hypertension (PH) in Wistar rats. An ethanol extraction was performed on dried MO leaves, and HPLC analysis identified niaziridin and niazirin in the extract. PH was induced with a single subcutaneous injection of MCT (60 mg/kg) which resulted in increases in pulmonary arterial blood pressure (Ppa) and in thickening of the pulmonary arterial medial layer in the rats. Three weeks after induction, acute administration of the MO extract to the rats decreased Ppa in a dose-dependent manner that reached statistical significance at a dose of 4.5 mg of freeze-dried extract per kg body weight. The reduction in Ppa suggested that the extract directly relaxed the pulmonary arteries. To assay the effects of chronic administration of the MO extract on PH, control, MCT and MCT+MO groups were designated. Rats in the control group received a saline injection; the MCT and MCT+MO groups received MCT to induce PH. During the third week after MCT treatment, the MCT+MO group received daily i.p. injections of the MO extract (4.5 mg of freeze-dried extract/kg of body weight). Compared to the control group, the MCT group had higher Ppa and thicker medial layers in the pulmonary arteries. Chronic treatments with the MO extract reversed the MCT-induced changes. Additionally, the MCT group had a significant elevation in superoxide dismutase activity when normalized by the MO extract treatments. In conclusion, the MO extract successfully attenuated the development of PH via direct vasodilatation and a potential increase in antioxidant activity.

Pulmonary arterial distensibility - 2D phase contrast vs 2D bSSFP

Summary Main pulmonary artery distensibility is a strong predictor of mortality in patients with pulmonary arterial hypertension. This study shows that either 2D PC or 2D bSSFP can be used to reliably non-invasively assess it by measuring MPA relative area change. Background The pulmonary circulation is a highly compliant system that generates little resistance to blood flow. However, in the presence of pulmonary arterial hypertension (PAH), blood pressure and vascular resistance in the pulmonary circulation are elevated. This leads to distension and stiffening of the main pulmonary artery (MPA) and vessel wall remodeling, which in itself may influence stiffness [1]. Proximal arterial distensibility is a parameter that depends mainly on the anatomy (geometry) of the vessel and can be estimated noninvasively with cross-sectional imaging techniques. In particular, the relative area change (RAC) of the MPA, which is inversely proportional to arterial stiffness, is a strong predictor of mortality in patients with PAH [2]. The purpose of this study was to compare two non-invasive magnetic resonance imaging (MRI) methods for quantification of MPA distensibility using an acute PAH dog model. Methods Six adult female beagles were anesthetized with isoflurane. MRI was performed prior to and following injection of micro-beads into the right atrium and ventricle to induce PAH, resulting 12 comparison studies. The presence of PAH was confirmed by right heart catheterization (RHC). All MR images were acquired on a 3T scanner (MR750, GE Healthcare, Waukesha, WI). Double-oblique images perpendicular to the direction of the flow in the MPA were obtained using ECG-triggered 2D CINE balanced steady-state free precession (bSSFP) and through-plane velocity-encoded 2D phase contrast (PC) at the same level [3]. PC and bSSFP images were segmented using dedicated cardiovascular analysis software (CV-Flow and and MASS-Analysis, respectively, Medis, Leiden, NL). Maximum and minimum MPA areas (Amax and Amin, respectively) were used to calculate RAC = (Amax-Amin)/Amax. Bland-Altman analysis was used to study the differences between PC and bSSFP to calculate Amax ,A min, and RAC. Student t-test was used to evaluate statistical significance of the differences between techniques in all three paramenters. Results The mean values for RAC, Amax and Amin were 36.38 ±7.86%, 241.98±71.62cm 2 , and 157.06±58.51cm 2 for PC, respectively and 31.14±6.95%, 220.88±62.76cm 2 ,a nd 155.34±58.38cm 2 for bSSFP, respectively (p=0.10, 0.45, and 0.94, respectively). The mean differences for RAC, Amax and Amin were -5.23±8.44%, -21.10±40.67cm 2 , -1.72±40.89cm 2 , respectively. Conclusions No statistically significant difference is present between PC and bSSFP for measuring RAC, Amax or Amin .T he differences between the two methods for measuring these parameters are small suggesting that either technique (PC or bSSFP) can be used to reliably non-invasively measure MPA distensibility. A benefit of using PC for measuring RAC is that it can also be used to quantify blood flow. Funding

Maternal Outcome in Pregnancy Complicated With Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH), including Eisenmenger syndrome, has a risk of mortality in pregnancy of 10-40%. The aim of this study was to investigate whether pulmonary artery blood pressure (PABP) is a prognostic factor for pregnancy outcome in patients with PAH. The subjects were 42 patients with PAH during pregnancy. Severe and mild cases were defined by PABP before and during the first 14 weeks of pregnancy, with severe cases having mean PABP >40 mmHg by catheterization or systolic PABP >50 mmHg on echocardiography. Eighteen women chose termination of pregnancy before 14 weeks, leaving 24 women (10 mild, 14 severe) for analysis. The women with severe PAH delivered earlier (35.4 vs. 31.5 weeks, P<0.05) and had higher rates of small-for-gestational-age infants (0/10 vs. 7/14, P<0.01). Among the women with severe PAH, the New York Heart Association class dropped by 1 in 9 cases, by 2 in 3 cases, and remained the same in 2 cases as pregnancy progressed, whereas among the women with mild PAH, the class dropped by 1 in 1 case and 9 women remained in the same class. Among the severe cases, 1 woman died and there was 1 fetal death; PABP markedly increased in later pregnancy from 54 to 74 mmHg (catheter measurement) and from 78 to 93 mmHg (echocardiography) (P<0.05). The level of PABP before or in the early stage of pregnancy is an important predictor of pregnancy outcome.

Oxygen Radicals and Substance P in Perinatal Hypoxia-Exaggerated, Monocrotaline-Induced Pulmonary Hypertension

Perinatal hypoxia has been observed to cause more aggressive pulmonary hypertension in human. Several mediators such as reactive oxygen species (ROS) and substance P are believed to be crucial in the mechanism of inducing pulmonary hypertension. This study was designed to test whether substance P and ROS play a role in perinatal hypoxia-exaggerated, monocrotaline (MCT)-induced pulmonary hypertension. Normoxic Wistar rats (weighing 258 ± 9 g, n = 31) were divided into two groups: control (n = 16) and MCT (n = 15). Perinatal hypoxia Wistar rats (weighing 260 ± 19 g, n = 49) were divided into six groups: Hypoxia (n = 8), Hypoxia+MCT (n = 8), Hypoxia+capsaicin (CP)+MCT (n = 7), Hypoxia+MCT+1,3-dimethyl-2-thiourea (DMTU)E (n = 10), Hypoxia+MCT+DMTUL (n = 9), and Hypoxia+MCT+ hexa(sulfobutyl) fullerenes (HSF) (n = 7). Rats in the control group received saline injections. MCT (60 mg/kg, s.c.) was given three weeks prior to the functional examination. Chronic capsaicin pretreatment was performed to deplete substance P. Hydroxyl radical scavenger DMTU (500 mg/kg) was intraperitoneally (i.p.) injected early (DMTUE ) or late (DMTUL ) after MCT. Antioxidant HSF (10 mg/kg, i.p.) was given once daily for three weeks following MCT. MCT treatment caused significant increases in pulmonary arterial pressure (Ppa) and substance P level in lung tissue in normoxic rats. The MCT-induced increase in pulmonary arterial blood pressure was exaggerated by perinatal hypoxia, but this exaggeration was attenuated by either capsaicin pretreatment or antioxidant administrations. These results suggest that both ROS and substance P are involved in perinatal hypoxia-augmented, MCT-induced pulmonary hypertension.

Giant Dilatation of the Right Coronary Aortic Bulb with Compression of the Right Ventricular Outflow Tract Mimicking a Ventricular Septal Defect: Diagnostic workup Using Echocardiography, Heart Catheterization, and Cardiac Computed Tomography

Annuloaortic ectasia is a relatively rare diagnosis. Herein, we report an unusual case of an annuloaortic ectasia with asymmetric dilatation of the right coronary bulb mimicking a membranous ventricular septal defect (VSD) with Eisenmenger reaction by transthoracic echocardiography. Aortic angiography showed a dilated aortic root and moderate aortic regurgitation. Right cardiac catheterization, on the other hand, exhibited normal pulmonary artery blood pressure and normal pulmonary resistance, whereas normal venous gas values were measured throughout the caval vein and the right atrium, excluding relevant left-right shunting. Further diagnostic workup by cardiac computed tomography angiography (CCTA) unambiguously illustrated the asymmetric geometry of the ectatic aortic cusp and root causing compression of the right heart and of the right ventricular (RV) outflow tract. After review of echocardiographic acquisitions, the blood flow detected between the left and right ventricles (mimicking VSD) was interpreted as turbulent inflow from the left ventricle into the ectatic right coronary cusp. Furthermore, elevated pulmonary artery blood pressure measured by echocardiography was attributed to “functional pulmonary stenosis” due to compression of the RV outflow tract by the aorta, as demonstrated by CCTA.

Activation of the Peroxisome Proliferator-Activated Receptor Preventing the Monocrotaline-Induced Pulmonary Hypertension

The purpose of this study was to investigate the role of peroxisome proliferator-activated receptor gamma (PPARγ) in the development of the monocrotaline (MCT)- induced pulmonary hypertension. Rosiglitazone (TZD) was used to activate the PPARγin this study. Sixty-four Wistar rats (BW = 114.1 ±1.2 g) were divided into five groups: control, MCT, MCT+vehicle (VEH, 15% alcohol), MCT+TZD, and TZD. Rats in the control group received injection of 0.5 ml saline intraperitoneally. Pulmonary hypertension was induced by one bolus injection of MCT (60 mg/kg, sc). Two weeks after MCT treatment, rats were daily treated with either 0.5 ml of 15% alcohol in the MCT+VEH group or TZD (10 mg/kg, ip) in the MCT+TZD group. In the TZD group, the same doses of TZD were given in the saline-treated rats on the corresponding days of the MCT+TZD group. Pulmonary arterial blood pressures were measured on the 22nd day post MCT. Comparing to the control group, the MCT administration caused significant increases in the pulmonary arterial pressure as well as the weight ratio of right ventricle (RV) to the sum of left ventricle and septum (LV+S), and the thickness of the vessel walls, indicating the development of pulmonary hypertension. The TZD treatment significantly attenuated the severity of pulmonary hypertension. However, the endogenous antioxidant enzymes in lung tissues, including superoxide dismutase, glutathione and catalase, were in similar levels among all groups. Therefore, the PPARγattenuated pulmonary hypertension may not be related to the antioxidant pathway.

Risk Factors for Persistent Pulmonary Hypertension of the Newborn

In utero, pulmonary blood flow is closely circumscribed and oxygenation and ventilation occur via the placental circulation. Within the first few breaths of air-breathing life, the perinatal pulmonary circulation undergoes a dramatic transition as pulmonary blood flow increases 10-fold and the pulmonary arterial blood pressure decreases by 50% within 24 hours of birth. With the loss of the placental circulation, the increase in pulmonary flow enables oxygen to enter the bloodstream. The physiologic mechanisms that account for the remarkable transition of the pulmonary circulation include establishment of an air-liquid interface, rhythmic distention of the lung, an increase in shear stress and elaboration of nitric oxide from the pulmonary endothelium. If the perinatal pulmonary circulation does not dilate, blood is shunted away from the lungs at the level of the patent foramen ovale and the ductus arteriosus leading to the profound and unremitting hypoxemia that characterizes persistent pulmonary hypertension of the newborn (PPHN), a syndrome without either optimally effective preventative or treatment strategies. Despite significant advances in treatment, PPHN remains a major cause of morbidity and mortality in neonatal centers across the globe. While there is information surrounding factors that might increase the risk of PPHN, knowledge remains incomplete. Cesarean section delivery, high maternal body mass index, maternal use of aspirin, nonsteroidal anti-inflammatory agents and maternal diabetes mellitus are among the factors associated with an increased risk for PPHN. Recent data suggest that maternal use of serotonin reuptake inhibitors might represent another important risk factor for PPHN.