Arnold, Nadine D.; Chang, William; Watson, Oliver; Swift, Andrew J.; Condliffe, Robin; Elliot, Charlie A.; Kiely, David G.; Suvarna, S. Kim; Gunn, Julian; Lawrie, Allan
Background— Pulmonary arterial hypertension is a devastating disease with high morbidity and mortality and limited treatment options. Recent studies have shown that pulmonary artery denervation improves pulmonary hemodynamics in an experimental model and in an early clinical trial. We aimed to evaluate the nerve distribution around the pulmonary artery, to determine the effect of radiofrequency pulmonary artery denervation on acute pulmonary hypertension induced by vasoconstriction, and to demonstrate denervation of the pulmonary artery at a histological level. Methods and Results— Histological evaluation identified a circumferential distribution of nerves around the proximal pulmonary arteries. Nerves were smaller in diameter, greater in number, and located in closer proximity to the luminal aspect of the pulmonary arterial wall beyond the pulmonary artery bifurcation. To determine the effect of pulmonary arterial denervation acute pulmonary hypertension was induced in 8 pigs by intravenous infusion of thromboxane A2 analogue. Animals were assigned to either pulmonary artery denervation, using a prototype radiofrequency catheter and generator, or a sham procedure. Pulmonary artery denervation resulted in reduced mean pulmonary artery pressure and pulmonary vascular resistance and increased cardiac output. Ablation lesions on the luminal surface of the pulmonary artery were accompanied by histological and biochemical alteration in adventitial nerves and correlated with improved hemodynamic parameters. Conclusions— Pulmonary artery denervation offers the possibility of a new treatment option for patients with pulmonary arterial hypertension. Further work is required to determine the long-term efficacy and safety. PMID:26553697
Aziz, K; Tasneem, H
Blood flow in the pulmonary artery was studied by Doppler colour flow mapping and cardiac catheterisation in 19 patients with a ductus arteriosus and different pulmonary artery pressures. In the four patients with normal pulmonary artery pressures colour Doppler flow mapping showed multicoloured wide and long systolic and diastolic jets in the pulmonary artery. In the 15 patients with raised pulmonary arterial pressure the systolic jets varied from multicoloured to red and were thinner: in patients with considerably raised pulmonary arterial pressure the jets became redder during diastole. The Doppler velocity tracings showed that in patients with normal pulmonary artery pressures the mean peak systolic velocity was higher than the mean end diastolic velocity--so that in all four the ratio of peak systolic velocity to end diastolic velocity was less than 2. The mean peak systolic velocity was much higher than the mean end diastolic velocity in 13 of the 15 patients with raised pulmonary artery pressure; this meant that the ratio of peak systolic velocity to end diastolic velocity was greater than 2 in 10 of 11 patients. The end diastolic velocity was significantly lower in those patients with raised pulmonary artery pressure than in those with normal artery pressure. There was an inverse linear correlation between the mean pulmonary artery pressure and end diastolic ductal jet velocity in 17 of the 19 patients. Colour flow mapping and this quantitative Doppler technique can detect pulmonary artery hypertension in patients with a ductus arteriosus. Images PMID:2278800
Fisher, M R; Criner, G J; Fishman, A P; Hassoun, P M; Minai, O A; Scharf, S M; Fessler, H E
In patients with emphysema being evaluated for lung volume reduction surgery, Doppler echocardiography has been used to screen for pulmonary hypertension as an indicator of increased peri-operative risk. To determine the accuracy of this test, the present authors compared the results of right heart catheterisations and Doppler echocardiograms in 163 patients participating in the cardiovascular substudy of the National Emphysema Treatment Trial. Substudy patients had both catheterisation and Doppler echocardiography performed before and after randomisation. In 74 paired catheterisations and echocardiograms carried out on 63 patients, the mean values of invasively measured pulmonary artery systolic pressures and the estimated right ventricular systolic pressures were similar. However, using the World Health Organization's definitions of pulmonary hypertension, echocardiography had a sensitivity of 60%, specificity of 74%, positive predictive value of 68% and a negative predictive value of 67% compared with the invasive measurement. Bland-Altman analysis revealed a bias of 0.37 kPa with 95% limits of agreement from -2.5-3.2 kPa. In patients with severe emphysema, echocardiographic estimates of pulmonary artery pressures correlate very weakly with right heart catheterisations, and the test characteristics (e.g. sensitivity, specificity, etc.) of echocardiographic assessments are poor.
Morais, Sandra A; Oliveira, Hugo M; de Almeida, José R; Eiras, Eduardo; Silva, Ana Catarina; Gavina, Cristina
The authors report the case of a 74-year-old man, with a history of chronic obstructive pulmonary disease (COPD), GOLD grade 3, stable for the past two decades, who was admitted to our center with severe right heart failure. The chest radiograph showed moderate heart enlargement mainly of the right atrium and pulmonary artery, similar to previous chest radiographs in the previous 20 years. The transthoracic echocardiogram showed a pulmonary artery aneurysm (PAA), dilatation of the right chambers with pulmonary artery systolic pressure of 52 mmHg, and preserved right ventricular systolic function. A thoracic computed tomography scan confirmed the presence of a giant PAA 72 mm in diameter. The patient was started on high-dose diuretics, with significant clinical improvement. After optimization of medical therapy right heart catheterization was carried out with the patient in optimal clinical condition, which revealed mild precapillary pulmonary hypertension with a mean pulmonary artery pressure of 26 mmHg. On the basis of the clinical and imaging findings a stable, giant, high-pressure, PAA was diagnosed secondary to pulmonary hypertension induced by COPD, with a 20-year follow-up without need for surgical repair, which helped in our decision to maintain medical surveillance. The recent onset of heart failure is explained by the unfavorable evolution of COPD. This case may change the attitude expressed in previous studies favoring the choice of an invasive approach to treat giant high-pressure PAAs, instead supporting the maintenance of medical treatment.
Kamimura, R; Suzuki, S; Miura, N; Miyahara, K
The lung produces many vasoactive substances originating from its vascular endothelium and plays an important part in various pathose. The present study was carried out to clarify pulmonary atherosclerosis and pulmonary arterial pressure, and to elucidate a part of the pulmonary pathosis in cholesterol-fed rabbits. Atherosclerosis was induced by feeding the animals a cholesterol-rich diet. When the rabbits were fed the cholesterol-enriched diets for 15 weeks, the grade of the atherosclerosis was severer than in 8W-feeding rabbits. The lesions of 8W-feeding rabbits were mainly composed of foam cells and fibrous components, whereas in 15W-feeding rabbits, the aggregation of foam cells beneath the endothelium of the vessel was infiltrating the media and severe stenose of the lumen was observed. In the entire pulmonary arterial system, the severe obstructive vascular lesions were localized and not diffused. The pulmonary arterial pressures of the rabbits increased slightly with time and the mean pressures were 11.3+/-0.9 (control group), 11.8+/-1.0 (8W group) and 13.7+/-1.5 mmHg (15W group) respectively. A significant difference existed in the mean pressure between the control group and 15W-feeding group, but there were no significant differences in the systolic and diastolic pressures among the three groups. In conclusion, we could induce pulmonary atherosclerosis in rabbits by feeding them a hyper-cholesterol diet but not overt pulmonary hypertension.
Wodniecki, Jan; Jacheć, Wojciech; Poloński, Lech; Tomasik, Andrzej Robert; Wojciechowska, Celina; Foremny, Ala
Primary pulmonary arterial hypertension (PPH) is a rare disease of undetermined origin and fatal prognosis. A better prognosis is associated with at least 20% reduction of either pulmonary artery pressure or pulmonary vascular resistance ("responders") in acute vasodilatory trials. Prostacycline (PGI2) or nitric oxide (NO) administration promises valuable results. NO is one of the most powerful vasodilating agents, endogenously produced by endothelial cells. It migrates from these cells to smooth muscle cells and stimulates production of cGMP, that induces smooth muscle relaxation. cGMP is hydrolyzed by 5-phopshodiesterase (PDE-5). Several papers documenting hypotensive effect in pulmonary circulation of specific PDE5 inhibitor--sildenafil (Viagra--Pfizer) have been published recently. We present a case report of a 26 year old female patient with PPH--"nonresponder" in a trial with NO--and NO responder after sildenafil administration. Initial values were: mean pulmonary artery pressure (mPAP) was 58 mmHg, pulmonary vascular resistance was 10.9 Wood's units. mPAP and PVR during NO inhalation (40 ppm) decrease from 62 to 54 mmHg and from 11.4 to 10.3 Wood's units, respectively. Measurements performed 60 minutes after 50 mg of sildenafil orally disclosed a 19% reduction of mPAP and 21% reduction of PVR. NO inhalation caused further decrease of both parameters: mPAP was decreased for additional 28% and PVR for additional 36% in comparison to initial results. Neither peripheral hypotension nor other side effects were observed. A month-long administration of sildenafil in a dose 2 x 25 mg daily reduced mPAP and PVR to values reported for the acute trial. Physical capability improved also. It was assessed as increased distance in a six-minute-walk test (280 vs. 400 m in the first week of treatment, and 330 m in a fourth week of treatment). Echocardiography showed moderate decrease of right ventricle and right atrium diameters, along with decrease of the degree of relative
Wang, Kai; Chen, Chuansi; Ma, Jianfa; Lao, Jinquan; Pang, Yusheng
The correlation between calcium-activated chloride channel (CaCC) and pulmonary arterial hypertension (PAH) induced by high pulmonary blood flow remains uncertain. In this study, we investigated the possible role and effects of CaCC in this disease. Sixty rats were randomly assigned to normal, sham, and shunt groups. Rats in the shunt group underwent abdominal aorta and inferior vena cava shunt surgery. The pulmonary artery pressure was measured by catheterization. Pathological changes, right ventricle hypertrophy index (RVHI), arterial wall area/vessel area (W/V), and arterial wall thickness/vessel external diameter (T/D) were analyzed by optical microscopy. Electrophysiological characteristics of pulmonary arterial smooth muscle cells (PASMCs) were investigated using patch clamp technology. After 11 weeks of shunting, PAH and pulmonary vascular structural remodeling (PVSR) developed, accompanied by increased pulmonary pressure and pathological interstitial pulmonary changes. Compared with normal and sham groups, pulmonary artery pressure, RVHI, W/V, and T/D of the shunt group rats increased significantly. Electrophysiological results showed primary CaCC characteristics. Compared with normal and sham groups, membrane capacitance and current density of PASMCs in the shunt group increased significantly, which were subsequently attenuated following chloride channel blocker niflumic acid (NFA) treatment. To conclude, CaCC contributed to PAH induced by high pulmonary blood flow and may represent a potential target for treatment of PAH.
Wang, Kai; Chen, Chuansi; Ma, Jianfa; Lao, Jinquan; Pang, Yusheng
The correlation between calcium-activated chloride channel (CaCC) and pulmonary arterial hypertension (PAH) induced by high pulmonary blood flow remains uncertain. In this study, we investigated the possible role and effects of CaCC in this disease. Sixty rats were randomly assigned to normal, sham, and shunt groups. Rats in the shunt group underwent abdominal aorta and inferior vena cava shunt surgery. The pulmonary artery pressure was measured by catheterization. Pathological changes, right ventricle hypertrophy index (RVHI), arterial wall area/vessel area (W/V), and arterial wall thickness/vessel external diameter (T/D) were analyzed by optical microscopy. Electrophysiological characteristics of pulmonary arterial smooth muscle cells (PASMCs) were investigated using patch clamp technology. After 11 weeks of shunting, PAH and pulmonary vascular structural remodeling (PVSR) developed, accompanied by increased pulmonary pressure and pathological interstitial pulmonary changes. Compared with normal and sham groups, pulmonary artery pressure, RVHI, W/V, and T/D of the shunt group rats increased significantly. Electrophysiological results showed primary CaCC characteristics. Compared with normal and sham groups, membrane capacitance and current density of PASMCs in the shunt group increased significantly, which were subsequently attenuated following chloride channel blocker niflumic acid (NFA) treatment. To conclude, CaCC contributed to PAH induced by high pulmonary blood flow and may represent a potential target for treatment of PAH. PMID:25755701
Pellett, A A; Johnson, R W; Morrison, G G; Champagne, M S; deBoisblanc, B P; Levitzky, M G
Using the arterial occlusion method, we compared five literature-based estimates of pulmonary capillary pressure (Ppc) with the corresponding double occlusion pressures (Pdo) in anesthetized dogs whose chests had been closed after sternotomy for instrumentation. Arterial occlusions were performed with a balloon-tipped pulmonary artery catheter that housed pressure transducers immediately proximal and distal to the balloon. Separation of the proximal and distal pressure waveforms during balloon inflation allowed us to precisely define the moment of occlusion. We fit a monoexponential curve to pressure data beginning 200 ms after the onset of occlusion and a biexponential curve to data beginning at the instant of occlusion, with data obtained over a range of vascular states (control, serotonin infusion, histamine infusion). In addition, we investigated the use of sampling of the raw data to estimate capillary pressure. Three of the five literature-based estimates of Ppc yielded values similar to Pdo. The optimal (least average difference from Pdo) interpolation/extrapolation time points of the curve fits varied, depending on the type of curve fitting and the state of the pulmonary vasculature. We also determined that a close approximation of Pdo may be derived from the raw data, as an alternative to exponential curve fitting.
Hirano, Y; Kitagawa, H; Sasaki, Y
To examine effects of thromboemboli due to dead worms on pulmonary arterial pressure (PAP), 20 to 50 dead heartworms were inserted into the pulmonary arteries of 4 heartworm uninfected dogs (uninfected group) and 11 dogs infected with heartworms (infected group). In the uninfected group, the mean PAP rose 1 week after worm insertion (10.9 to 166. mmHg), but it recovered by the 4th week. Clinical signs, hemodynamics and blood gas findings also deteriorated at the 1st week, but recovered at the 4th week. Angiographic and pathological findings indicated that blood flow recovered through the spaces between thromboemboli and vessel walls at the 4th week. The infected dogs were divided into three groups. In the infected-I group (5 dogs), the intimal lesions of the pulmonary arteries were slight, and clinical and laboratory findings showed changes similar to those of the uninfected group. In the infected-II group (4 dogs), the pulmonary arterial lesions were severe and the mean PAP was higher (25.7 mmHg) than in the uninfected group before worm insertion. An increase in PAP (34.1 mmHg) and worsening of clinical and laboratory findings were noticed till the 4th week. Thromboemboli adhered extensively to the vessel walls. Two dogs in the infected-III group died of severe dyspnea on the 9th and 10th day, and the mean PAP rose remarkably at the 1st week (from 19.4 to 28.2 mmHg). Severe pulmonary parenchymal lesions with edema or perforation were observed. From the above results, it was clarified that effects of dead worms on PAP and clinical signs depended on the severity of pulmonary arterial lesions before worm insertion.(ABSTRACT TRUNCATED AT 250 WORDS)
Armstrong, Anderson C.; Bandeira, Ângela M. P.; Correia, Luis C. L.; Melo, Humberto C. O.; Silveira, Carlos A. M.; Albuquerque, Eugênio; Moraes, Jeová C.; Silva, Antônio M. L.; Lima, João A. C.; Sobral, Dário C.
Background Schistosomiasis-associated pulmonary arterial hypertension (SPAH) is a major concern worldwide. However, the role of gender specific contributing factors in SPAH is unknown. Objective We investigated how systolic pulmonary artery pressure (SPAP) values and the presence of severe SPAP relate to gender, menopausal status, and pregnancy history in SPAH patients. Methods Seventy-nine patients diagnosed with SPAH from 2000 to 2009 were assessed and 66 were enrolled in the study. Information about age, menopausal status, pregnancy, echocardiography-derived SPAP, and invasive mean pulmonary artery pressure (mPAP) was collected from medical records. The relation between values of SPAP and mPAP and their agreement for severe disease were assessed. Regression models assessed the association of gender, menopausal status, and pregnancy history with SPAP values and the presence of severe SPAP. Results Moderate correlation and good agreement for severe disease were found between mPAP and SPAP. Mean SPAP values were similar for men and women. A trend toward higher values of SPAP was found for non-menopausal women compared to men. Higher SPAP values were found for menopausal compared to non-menopausal women; the values were non-significant after adjustment for age. Pregnancy history had no association with SPAP. Menopause and positive pregnancy had no association with severe SPAP. Conclusion In SPAH patients, neither gender, nor menopausal status, nor pregnancy history showed independent correlation with SPAP values assessed by echocardiography. PMID:23821406
Yandrapalli, Srikanth; Raza, Anoshia; Tariq, Sohaib; Aronow, Wilbert S
Heart failure (HF) is an emerging epidemic associate with significant morbidity, mortality, and health care expenditure. Although there were major advances in pharmacologic and device based therapies for the management of HF, mortality of this condition remains high. Accurate monitoring of HF patients for exacerbations is very important to reduce recurrent hospitalizations and its associated complications. With the failure of clinical signs, tele-monitoring, and laboratory bio-markers to function as early markers of HF exacerbations, more sophisticated techniques were sought to accurately predict the circulatory status in HF patients in order to execute timely pharmacological intervention to reduce frequent hospitalizations. CardioMEMSTM (St. Jude Medical, Inc., Saint Paul, Minnesota) is an implantable, wireless pulmonary arterial pressure (PAP) monitoring system which transmits the patient’s continuous PAPs to the treating health care provider in the ambulatory setting. PAP-guided medical therapy modification has been shown to significantly reduce HF-related hospitalization and overall mortality. In advanced stages of HF, wireless access to hemodynamic information correlated with earlier left ventricular assist device implantation and shorter time to heart transplantation. PMID:28163833
Soliman, D; Bolliger, D; Skarvan, K; Kaufmann, B A; Lurati Buse, G; Seeberger, M D
The clinical value of the estimation of systolic pulmonary artery pressure, based on Doppler assessment of peak tricuspid regurgitant velocity using transoesophageal echocardiography, is unclear. We studied 109 patients to evaluate the feasibility of obtaining adequate Doppler recordings, and compared Doppler estimates with values measured using a pulmonary artery catheter in a subset of 33 patients. Tricuspid regurgitation was evaluated at the mid-oesophageal level at 0-120° using Doppler echocardiography. A Doppler signal was defined as adequate if there was a ≤ 20° alignment and a full envelope. Doppler estimates of systolic pulmonary artery pressure within 10 mmHg and 15% of the value recorded with the pulmonary artery catheter were considered to be in sufficient agreement. Adequate Doppler signals were obtained in 64/109 (59%) patients before and 54/103 (52%) after surgery. Doppler estimates by transoesophageal echocardiography were within 10 mmHg and 15% of values recorded with the pulmonary artery catheter in 28/33 (75%) patients and 22/31 (55%) patients, respectively. In 7 (21%) patients, the echocardiographic Doppler measurement exceeded the measured systolic pulmonary artery pressure by more than 30%. Our study indicates that estimation of the systolic pulmonary artery pressure using transoesophageal Doppler echocardiography is not a reliable and clinically useful method in anaesthetised patients undergoing mechanical ventilation.
Tagawa, Miki; Iwai, Hidetaka; Fukatsu, Ken; Shimada, Mami; Hirabayashi, Yoshihiro
We report a case of negative-pressure pulmonary edema occurring by tracheal obstruction caused by the brachiocephalic artery. The patient had deformed thorax with cerebral palsy, which deformed thorax placing the brachiocephalic artery high over the trachea, resulting in close and tight contact between the artery and trachea. Additional deformity of the thorax associated with myotonic attacks after general anesthesia might shorten the distance between the sternal notch and the vertebral body, resulting in the tracheal obstruction by the artery.
Bridges, Elizabeth J
The integration of data from a pulmonary artery catheter when used as part of a goal-directed plan of care may benefit certain groups of critically ill patients. Integral to the successful use of the pulmonary artery catheter is to accurately obtain and interpret invasive pressure monitoring data. This article addresses commonly asked clinical questions and considerations for decision making under complex care conditions, such as obtaining hemodynamic measurements when the patient is prone or has marked respiratory pressure variations or increased intraabdominal pressure. Recommendations to optimize the invasive pressure monitoring system are presented. Finally, functional hemodynamic indices, which are more sensitive and specific indices than static indices (pulmonary artery and right artrial pressure) of the ability to respond to a fluid bolus, will be introduced.
Lorenzoni, A G; Anthony, N B; Wideman, R F
Previous hemodynamic evaluations demonstrated that pulmonary arterial pressure (PAP) is higher in broilers that are susceptible to pulmonary hypertension syndrome (PHS, ascites) than in broilers that are resistant to PHS. We compared key pulmonary hemodynamic parameters in broilers from PHS-susceptible and PHS-resistant lines (selected for 12 generations under hypobaric hypoxia) and in broilers from a relaxed (control) line. In experiment 1 the PAP was measured in male broilers in which a flow probe positioned on one pulmonary artery permitted the determination of cardiac output and pulmonary vascular resistance (PVR). The PAP and relative PVR were higher in susceptible broilers than in relaxed and resistant broilers, whereas absolute and relative cardiac output did not differ between lines. In experiment 2 male and female broilers from the 3 lines were catheterized to measure pressures in the wing vein, right atrium, right ventricle, pulmonary artery, and pulmonary veins (WP, wedge pressure). The transpulmonary pressure gradient (TPG) was calculated as (PAP-WP), with PAP quantifying precapillary pressure and WP approximating postcapillary pulmonary venous pressure. When compared with resistant and relaxed broilers, PAP values in susceptible broilers were > or =10 mmHg higher, TPG values were > or =8 mmHg higher, and WP values were < or =2 mmHg higher, regardless of sex. The combined hemodynamic criteria (elevated PAP and PVR combined with a proportionally elevated TPG) demonstrate that susceptibility to PHS can be attributed primarily to pulmonary arterial hypertension associated with increased precapillary (arteriole) resistance rather than to pulmonary venous hypertension caused by elevated postcapillary (venous and left atrial) resistance.
van Soldt, Benjamin J; Danielsen, Carl Christian; Wang, Tobias
Pythons are unique amongst snakes in having different pressures in the aortas and pulmonary arteries because of intraventricular pressure separation. In this study, we investigate whether this correlates with different blood vessel strength in the ball python Python regius. We excised segments from the left, right, and dorsal aortas, and from the two pulmonary arteries. These were subjected to tensile testing. We show that the aortic vessel wall is significantly stronger than the pulmonary artery wall in P. regius. Gross morphological characteristics (vessel wall thickness and correlated absolute amount of collagen content) are likely the most influential factors. Collagen fiber thickness and orientation are likely to have an effect, though the effect of collagen fiber type and cross-links between fibers will need further study.
Qureshi, M. Umar; Vaughan, Gareth D.A.; Sainsbury, Christopher; Johnson, Martin; Peskin, Charles S.; Olufsen, Mette S.; Hill, N.A.
A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen and coworkers (Ottesen et al., 2003; Olufsen et al., 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of ‘large’ arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the ‘smaller’ arteries and veins of radii ≥ 50µm. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment of circulatory diseases within the lung. PMID:24610385
Arian, Anahita; Moghadam, Sayyed Gholamreza Mortazavi; Kazemi, Toba; Hajihosseini, Morteza
Objective: Pulmonary hypertension is a serious complication in patients suffering from chronic obstructive pulmonary disease (COPD). The aim of this study is to investigate the effects of atorvastatin in reducing pulmonary arterial pressure in COPD patients. Methods: This double-blind, randomized trial was conducted on 42 known cases of COPD with systolic pulmonary arterial pressure of more than 25 mmHg. The patients were randomly assigned into two groups, 21 patients with atorvastatin treatment (40 mg/daily for 6 months) and 21 patients without receiving atorvastatin. All the patients participated voluntarily and provided written informed consent. The trial was registered in the Iranian Registry of Clinical Trials. Pulmonary pressure was also anticipated by Doppler echocardiography with peak pressure gradient of tricuspid regurgitation. Both groups were tested with echocardiography to measure systolic pulmonary pressure at baseline and posttreatment. Statistical analysis includes Chi-square, Student's t-test, and Wilcoxon test. P < 0.05 was considered statistically significant. Findings: The mean age was 65.8 ± 11.5 years for atorvastatin group and 63.7 ± 7.6 years for control group (P = 0.45). Baseline and posttreatment mean systolic pulmonary artery pressure (PAP) levels in the atorvastatin group were 48.9 ± 3.3 and 38.4 ± 1.9 mmHg, respectively (P = 0.007). In the control group, mean systolic PAP levels at baseline and 6 months later were 45.6 ± 3.1 and 38.9 ± 2.4 mmHg, respectively (P = 0.073). The patients treated with atorvastatin showed significant decrease in total cholesterol (P = 0.001) and low-density lipoprotein cholesterol (P = 0.008). Conclusion: A 40 mg dose of atorvastatin daily for 6 months may have beneficial effects in reducing PAP in patients with COPD. Further studies are necessary to find long-term effects of statins in COPD patients.
Soydan, Lydia C.; Kellihan, Heidi B.; Bates, Melissa L.; Stepien, Rebecca L.; Consigny, Daniel W.; Bellofiore, Alessandro; Francois, Christopher J.; Chesler, Naomi C.
Objectives To compare noninvasive estimates of pulmonary artery pressure (PAP) obtained via echocardiography (ECHO) to invasive measurements of PAP obtained during right heart catheterization (RHC) across a wide range of PAP, to examine the accuracy of estimating right atrial pressure via ECHO (RAPECHO) compared to RAP measured by catheterization (RAPRHC), and to determine if adding RAPECHO improves the accuracy of noninvasive PAP estimations. Animals Fourteen healthy female beagle dogs. Methods ECHO and RHC performed at various data collection points, both at normal PAP and increased PAP (generated by microbead embolization). Results Noninvasive estimates of PAP were moderately but significantly correlated with invasive measurements of PAP. A high degree of variance was noted for all estimations, with increased variance at higher PAP. The addition of RAPECHO improved correlation and bias in all cases. RAPRHC was significantly correlated with RAPECHO and with subjectively assessed right atrial size (RA sizesubj). Conclusions Spectral Doppler assessments of tricuspid and pulmonic regurgitation are imperfect methods for predicting PAP as measured by catheterization despite an overall moderate correlation between invasive and noninvasive values. Noninvasive measurements may be better utilized as part of a comprehensive assessment of PAP in canine patients. RAPRHC appears best estimated based on subjective assessment of RA size. Including estimated RAPECHO in estimates of PAP improves the correlation and relatedness between noninvasive and invasive measures of PAP, but notable variability in accuracy of estimations persists. PMID:25601540
Calderón-Garcidueñas, Lilian; Vincent, Renaud; Mora-Tiscareño, Antonieta; Franco-Lira, Maricela; Henríquez-Roldán, Carlos; Barragán-Mejía, Gerardo; Garrido-García, Luis; Camacho-Reyes, Laura; Valencia-Salazar, Gildardo; Paredes, Rogelio; Romero, Lina; Osnaya, Hector; Villarreal-Calderón, Rafael; Torres-Jardón, Ricardo; Hazucha, Milan J.; Reed, William
Background Controlled exposures of animals and humans to particulate matter (PM) or ozone air pollution cause an increase in plasma levels of endothelin-1, a potent vasoconstrictor that regulates pulmonary arterial pressure. Objectives The primary objective of this field study was to determine whether Mexico City children, who are chronically exposed to levels of PM and O3 that exceed the United States air quality standards, have elevated plasma endothelin-1 levels and pulmonary arterial pressures. Methods We conducted a study of 81 children, 7.9 ± 1.3 years of age, lifelong residents of either northeast (n = 19) or southwest (n = 40) Mexico City or Polotitlán (n = 22), a control city with PM and O3 levels below the U.S. air quality standards. Clinical histories, physical examinations, and complete blood counts were done. Plasma endothelin-1 concentrations were determined by immunoassay, and pulmonary arterial pressures were measured by Doppler echocardiography. Results Mexico City children had higher plasma endothelin-1 concentrations compared with controls (p < 0.001). Mean pulmonary arterial pressure was elevated in children from both northeast (p < 0.001) and southwest (p < 0.05) Mexico City compared with controls. Endothelin-1 levels in Mexico City children were positively correlated with daily outdoor hours (p = 0.012), and 7-day cumulative levels of PM air pollution < 2.5 μm in aerodynamic diameter (PM2.5) before endothelin-1 measurement (p = 0.03). Conclusions Chronic exposure of children to PM2.5 is associated with increased levels of circulating endothelin-1 and elevated mean pulmonary arterial pressure. PMID:17687455
Lam, Carolyn S. P.; Borlaug, Barry A.; Kane, Garvan C.; Enders, Felicity T.; Rodeheffer, Richard J.; Redfield, Margaret M.
Background In contrast to the wealth of data on isolated systolic hypertension involving the systemic circulation in the elderly, much less is known about age-related change in pulmonary artery systolic pressure (PASP) and its prognostic impact in the general population. We sought to define the relationship between PASP and age, evaluate which factors influence PASP and determine if PASP is independently predictive of mortality in the community. Methods and Results A random sample of Olmsted County, MN general population (N=2042) underwent echocardiography and spirometry and was followed for a median of 9 years. PASP was measured from the tricuspid regurgitation velocity. Left ventricular diastolic pressure was estimated using Doppler echocardiography (E/e' ratio) and arterial stiffening was assessed using the brachial artery pulse pressure. Among 1413 (69%) subjects with measurable PASP (63±11y; 43% male), PASP (median, 25th-75th percentile) was 26 (24-30) mmHg and increased with age (r=0.31; p<0.001). Independent predictors of PASP were age, pulse pressure and mitral E/e' (all p≤0.003). Increasing PASP was associated with higher mortality (hazard ratio 2.73 per 10 mmHg; p<0.001). In subjects without cardiopulmonary disease (any heart failure, coronary artery disease, hypertension, diabetes mellitus or chronic obstructive lung disease), the age-adjusted hazard ratio was 2.74 per 10 mmHg (p=0.016). Conclusions We provide the first population-based evidence of age-related increase in pulmonary artery pressure, its association with increasing left heart diastolic pressures and systemic vascular stiffening, as well as its negative impact on survival. Pulmonary artery pressure may serve as a novel cardiovascular risk factor and potential therapeutic target. PMID:19433755
Mejía Chew, C R; Alcolea Batres, S; Ríos Blanco, J J
Pulmonary arterial hypertension is a rare and progressive disease that mainly affects the pulmonary arterioles (precapillary), regardless of the triggering aetiology. The prevalence of pulmonary hypertension and pulmonary arterial hypertension in Spain is estimated at 19.2 and 16 cases per million inhabitants, respectively. The diagnosis of pulmonary arterial hypertension is based on haemodynamic criteria (mean pulmonary artery pressure ≥25mmHg, pulmonary capillary wedge pressure ≤15mmHg and pulmonary vascular resistance >3 Wood units) and therefore requires the implementation of right cardiac catheterisation. Sequential therapy with a single drug has been used in clinical practice. However, recent European guidelines recommend combined initial therapy in some situations. This review conducts a critical update of our knowledge of this disease according to the latest guidelines and recommendations.
Rasoulinejad, Mehrnaz; Moradmand Badie, Sina; Salehi, Mohammad Reza; Seyed Alinaghi, Seyed Ahmad; Dehghan Manshadi, Seyed Ali; Zakerzadeh, Nahid; Foroughi, Maryam; Jahanjo Amin Abad, Fatemeh; Moradmand Badie, Banafsheh
Pulmonary hypertension is rare but is one of the complications that occur due to HIV infection. Symptoms of HIV-associated pulmonary arterial hypertension are often non-specific but the main symptom of the disease is dyspnea. In this cross-sectional study, we measured systolic pulmonary arterial pressure (SPAP) by echocardiographic methods among HIV-positive patients who received ART. This research is a descriptive, cross-sectional study of 170 HIV-positive patients that was conducted in Imam-Khomeini hospital, Tehran, Iran during 2011-2013. All patients regularly received antiretroviral therapy at least for recent 2 years. There were not any cardiopulmonary symptoms (cough, dyspnea, exertional fatigue and chest discomfort) in these patients. All participants underwent echocardiography to estimate SPAP. The participants comprised 108 males (63.5%) and 62 females (46.5%). The mean age of patients was 41 years old, and the mean duration of HIV infection was 5.5 years. The mean CD4 cell count was 401 cell/µl. The principal regimen of antiretroviral therapy included two nucleoside reverse transcriptase inhibitor (NRTI) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) in the hospital. The mean of systolic pulmonary arterial pressure was 25 mmHg in the participants; 156 (93.4%) of them had SPAP ≤ 30 mmHg (normal), six (3.6%) had SPAP: 31-35 mmHg (borderline) and five (3%) had SPAP > 35 mmHg (pulmonary hypertension). Our results indicated a significant increase of pulmonary hypertension in asymptomatic HIV-positive patients that had no association with any other risk factor. Also, antiretroviral therapy was not a risk factor for pulmonary hypertension in this study.
Das, Mrinalendu; Mahindrakar, Pallavi; Das, Debasis; Behera, Sukanta Kumar; Chowdhury, Saibal Roy; Bandyopadhyay, Biswajit
The usual presentation of anomalous left coronary artery from pulmonary artery is severe left-sided heart failure and mitral valve insufficiency presenting during the first months of life. The manifestations of left heart failure may be masked if pulmonary artery pressure remains high. We believe this is a rarest of rare case of anomalous left coronary artery from pulmonary artery with severe mitral stenosis and pulmonary hypertension in which pulmonary hypertension, along with good collateral circulation helped to preserve left ventricular function.
Naeije, R; Huez, S; Lamotte, M; Retailleau, K; Neupane, S; Abramowicz, D; Faoro, V
Altitude exposure is associated with decreased exercise capacity and increased pulmonary vascular resistance (PVR). Echocardiographic measurements of pulmonary haemodynamics and a cardiopulmonary exercise test were performed in 13 healthy subjects at sea level, in normoxia and during acute hypoxic breathing (1 h, 12% oxygen in nitrogen), and in 22 healthy subjects after acclimatisation to an altitude of 5,050 m. The measurements were obtained after randomisation, double-blinded to the intake of placebo or the endothelin A receptor blocker sitaxsentan (100 mg·day(-1) for 7 days). Blood and urine were sampled for renal function measurements. Normobaric as well as hypobaric hypoxia increased PVR and decreased maximum workload and oxygen uptake (V'(O(2),max)). Sitaxsentan decreased PVR in acute and chronic hypoxia (both p<0.001), and partly restored V'(O(2),max), by 30 % in acute hypoxia (p<0.001) and 10% in chronic hypoxia (p<0.05). Sitaxsentan-induced changes in PVR and V'(O(2),max) were correlated (p = 0.01). Hypoxia decreased glomerular filtration rate and free water clearance, and increased fractional sodium excretion. These indices of renal function were unaffected by sitaxsentan intake. Selective endothelin A receptor blockade with sitaxsentan improves mild pulmonary hypertension and restores exercise capacity without adverse effects on renal function in hypoxic normal subjects.
Marabotti, Claudio; Scalzini, Alessandro; Chiesa, Ferruccio
The presence of circulating gas bubbles has been repeatedly reported after uncomplicated SCUBA dives. The clinical and pathophysiological relevance of this phenomenon is still under debate but some experimental data suggest that silent bubbles may have a damaging potential on pulmonary endothelial cells. The aim of the present study was to evaluate the possible hemodynamic effect on pulmonary circulation of post-dive circulating gas bubbles. To this aim, 16 experienced divers were studied by Doppler-echocardiography in basal conditions and 2.0 ± 0.15 h after an uncomplicated, unrestricted recreational SCUBA dive. At the post-dive examination, circulating bubbles were present in 10/16 subjects (62.5%). Divers with circulating bubbles showed a significant post-dive increase of pulmonary systolic arterial pressure (evaluated by the maximal velocity of the physiological tricuspid regurgitation; P < 0.01)) and right ventricular internal dimension (P < 0.05). Divers without circulating bubbles showed no significant change in cardiac anatomy and pulmonary arterial pressure. Both groups showed a significant post-dive decrease of transmitral E/A ratio (index of left ventricular diastolic function: subjects with bubbles P < 0.01; subjects without bubbles P < 0.05). These results seem to indicate that circulating gas bubbles may lead to a hemodynamically relevant increase of pulmonary arterial pressure, able to induce an acute right ventricular dilation. Post-dive diastolic function changes, observed in both groups, may be explained by a preload reduction due to immersion natriuresis. The results of the present study add some evidence that post-dive circulating bubbles, although symptomless, have an easily detectable pathogenetic potential, inducing unfavorable hemodynamic changes in the lesser circulation.
Wright, Stephen P.; Granton, John T.; Esfandiari, Sam; Goodman, Jack M.
Key points A consistent inverse hyperbolic relationship has been observed between pulmonary vascular resistance and compliance, although changes in pulmonary artery wedge pressure (PAWP) may modify this relationship.This relationship predicts that pulmonary artery systolic, diastolic and mean pressure maintain a consistent relationship relative to the PAWP.We show that, in healthy exercising human adults, both pulmonary vascular resistance and compliance decrease in relation to exercise‐associated increases in PAWP.Pulmonary artery systolic, diastolic and mean pressures maintain a consistent relationship with one another, increasing linearly with increasing PAWP.Increases in PAWP in the setting of exercise are directly related to a decrease in pulmonary vascular compliance, despite small decreases in pulmonary vascular resistance, thereby increasing the pulsatile afterload to the right ventricle. Abstract The resistive and pulsatile components of right ventricular afterload (pulmonary vascular resistance, Rp; compliance, Cp) are related by an inverse hyperbolic function, expressed as their product known as RpCp‐time. The RpCp‐time exhibits a narrow range, although it may be altered by the pulmonary artery wedge pressure (PAWP). Identifying the determinants of RpCp‐time should improve our understanding of the physiological behaviour of pulmonary arterial systolic (PASP), diastolic (PADP) and mean (mPAP) pressures in response to perturbations. We examined the effect of exercise in 28 healthy non‐athletic adults (55 ± 6 years) who underwent right heart catheterization to assess haemodynamics and calculate Rp and Cp. Measurements were made at rest and during two consecutive 8–10 min stages of cycle ergometry, at targeted heart‐rates of 100 beats min–1 (Light) and 120 beats min–1 (Moderate). Cardiac output increased progressively during exercise. PASP, PADP, mPAP and PAWP increased for Light exercise, without any further rise for Moderate
Fatemian, Marzieh; Herigstad, Mari; Croft, Quentin P P; Formenti, Federico; Cardenas, Rosa; Wheeler, Carly; Smith, Thomas G; Friedmannova, Maria; Dorrington, Keith L; Robbins, Peter A
Pulmonary ventilation and pulmonary arterial pressure both rise progressively during the first few hours of human acclimatization to hypoxia. These responses are highly variable between individuals, but the origin of this variability is unknown. Here, we sought to determine whether the variabilities between different measures of response to sustained hypoxia were related, which would suggest a common source of variability. Eighty volunteers individually underwent an 8-h isocapnic exposure to hypoxia (end-tidal P(O2)=55 Torr) in a purpose-built chamber. Measurements of ventilation and pulmonary artery systolic pressure (PASP) assessed by Doppler echocardiography were made during the exposure. Before and after the exposure, measurements were made of the ventilatory sensitivities to acute isocapnic hypoxia (G(pO2)) and hyperoxic hypercapnia, the latter divided into peripheral (G(pCO2)) and central (G(cCO2)) components. Substantial acclimatization was observed in both ventilation and PASP, the latter being 40% greater in women than men. No correlation was found between the magnitudes of pulmonary ventilatory and pulmonary vascular responses. For G(pO2), G(pCO2) and G(cC O2), but not the sensitivity of PASP to acute hypoxia, the magnitude of the increase during acclimatization was proportional to the pre-acclimatization value. Additionally, the change in G(pO2) during acclimatization to hypoxia correlated well with most other measures of ventilatory acclimatization. Of the initial measurements prior to sustained hypoxia, only G(pCO2) predicted the subsequent rise in ventilation and change in G(pO2) during acclimatization. We conclude that the magnitudes of the ventilatory and pulmonary vascular responses to sustained hypoxia are predominantly determined by different factors and that the initial G(pCO2) is a modest predictor of ventilatory acclimatization.
Carratu, Pierluigi; Scoditti, Cristina; Maniscalco, Mauro; Seccia, Teresa Maria; Di Gioia, Giuseppe; Gadaleta, Felice; Cardone, Rosa Angela; Dragonieri, Silvano; Pierucci, Paola; Spanevello, Antonio; Resta, Onofrio
Background Endothelin-1 (ET-1) and Nitric Oxide (NO) are crucial mediators for establishing pulmonary artery hypertension (PAH). We tested the hypothesis that their imbalance might also occur in COPD patients with PAH. Methods The aims of the study were to measure exhaled breath condensate (EBC) and circulating levels of ET-1, as well as exhaled NO (FENO) levels by, respectively, a specific enzyme immunoassay kit, and by chemiluminescence analysis in 3 groups of subjects: COPD with PAH (12), COPD only (36), and healthy individuals (15). In order to evaluate pulmonary-artery systolic pressure (PaPs), all COPD patients underwent Echo-Doppler assessment. Results Significantly increased exhaled and circulating levels of ET-1 were found in COPD with PAH compared to both COPD (p < 0.0001) only, and healthy controls (p < 0.0001). In COPD with PAH, linear regression analysis showed good correlation between ET-1 in EBC and PaPs (r = 0.621; p = 0.031), and between arterial levels of ET-1 and PaPs (r = 0.648; p = 0.022), while arterial levels of ET-1 inversely correlated with FEV1%, (r = -0.59, p = 0.043), and PaPs negatively correlated to PaO2 (r = -0.618; p = 0.032). Significantly reduced levels of FENO were found in COPD associated with PAH, compared to COPD only (22.92 ± 11.38 vs.35.07 ± 17.53 ppb; p = 0.03). Thus, we observed an imbalanced output in the breath between ET-1 and NO, as expression of pulmonary endothelium and epithelium impairment, in COPD with PAH compared to COPD only. Whether this imbalance is an early cause or result of PAH due to COPD is still unknown and deserves further investigations. PMID:18822124
Bourry, N; Chabrot, P; Jeannin, G; Filaire, M; Charpy, C; Bay, J O; Kemeny, J L; Caillaud, D; Escande, G; Boyer, L
Pulmonary artery sarcoma is a rare tumor. We present a case of intimal sarcoma arising from right pulmonary artery and left lower pulmonary vein observed in a 44-year-old man with a non-productive cough. Computed tomographic scans and magnetic resonance imaging showing filling defect enhancement contributed early, suggesting the diagnosis of primary vascular tumor, hypothesis confirmed by pathologist findings.
Lee, Youngjae; Choi, Wooshin; Lee, Donghoon; Chang, Jinhwa; Kang, Ji-Houn; Choi, Jihye
Caudal pulmonary artery diameter (CPAD) to body surface area (BSA) ratios were measured in ventrodorsal thoracic radiographs to assess the correlation between CPAD to BSA ratios and systolic pulmonary arterial pressure (PAP) in dogs. Thoracic radiographs of 44 dogs with systolic pulmonary arterial hypertension (PAH) and 55 normal dogs were evaluated. Systolic PAP was estimated by Doppler echocardiography. CPADs were measured at their largest point at the level of tracheal bifurcation on ventrodorsal radiographs. Both right and left CPAD to BSA ratios were significantly higher in the PAH group than in the normal group (p < 0.0001). Linear regression analysis showed positive associations between PAP and right and left CPAD to BSA ratio (right, p = 0.0230; left, p = 0.0012). The receiver operating characteristic curve analysis revealed that the CPAD to BSA ratio had moderate diagnostic accuracy for detecting PAH. The operating point, sensitivity, specificity, and area under the curve were 28.35, 81.40%, 81.82%, and 0.870; respectively, for the right side and 26.92, 80.00%, 66.67%, and 0.822, respectively, for the left. The significant correlation of CPAD to BSA ratio with echocardiography-estimated systolic PAP supports its use in identifying PAH on survey thoracic radiographs in dogs. PMID:26645336
Kandhi, Sharath; Qin, Jun; Froogh, Ghezal; Jiang, Houli; Luo, Meng; Wolin, Michael S.; Huang, An
We tested the hypothesis that suppression of epoxyeicosatrienoic acid (EET) metabolism via genetic knockout of the gene for soluble epoxide hydrolase (sEH-KO), or female-specific downregulation of sEH expression, plays a role in the potentiation of pulmonary hypertension. We used male (M) and female (F) wild-type (WT) and sEH-KO mice; the latter have high pulmonary EETs. Right ventricular systolic pressure (RVSP) and mean arterial blood pressure (MABP) in control and in response to in vivo administration of U46619 (thromboxane analog), 14,15-EET, and 14,15-EEZE [14,15-epoxyeicosa-5(z)-enoic acid; antagonist of EETs] were recorded. Basal RVSP was comparable among all groups of mice, whereas MABP was significantly lower in F-WT than M-WT mice and further reduced predominantly in F-KO compared with M-KO mice. U46619 dose dependently increased RVSP and MABP in all groups of mice. The increase in RVSP was significantly greater and coincided with smaller increases in MABP in M-KO and F-WT mice compared with M-WT mice. In F-KO mice, the elevation of RVSP by U46619 was even higher than in M-KO and F-WT mice, associated with the least increase in MABP. 14,15-EEZE prevented the augmentation of U46619-induced elevation of RVSP in sEH-KO mice, whereas 14,15-EET-induced pulmonary vasoconstriction was comparable in all groups of mice. sEH expression in the lungs was reduced, paralleled with higher levels of EETs in F-WT compared with M-WT mice. In summary, EETs initiate pulmonary vasoconstriction but act as vasodilators systemically. High pulmonary EETs, as a function of downregulation or deletion of sEH, potentiate U46619-induced increases in RVSP in a female-susceptible manner. PMID:26498250
Gupta, Rajinder K.; Himashree, G.; Singh, Krishan; Soree, Poonam; Desiraju, Koundinya; Agrawal, Anurag; Ghosh, Dishari; Dass, Deepak; Reddy, Prassana K.; Panjwani, Usha; Singh, Shashi Bala
Exaggerated pulmonary pressor response to hypoxia is a pathgonomic feature observed in high altitude pulmonary edema (HAPE) susceptible mountaineers. It was investigated whether measurement of basal pulmonary artery pressure (Ppa) and brain natriuretic peptide (BNP) could improve identification of HAPE susceptible subjects in a non-mountaineer population. We studied BNP levels, baseline hemodynamics and the response to hypoxia (FIo2 = 0.12 for 30 min duration at sea level) in 11 HAPE resistant (no past history of HAPE, Control) and 11 HAPE susceptible (past history of HAPE, HAPE-S) subjects. Baseline Ppa (19.31 ± 3.63 vs 15.68 ± 2.79 mm Hg, p < 0.05) and plasma BNP levels (52.39 ± 32.9 vs 15.05 ± 9.6 pg/ml, p < 0.05) were high and stroke volume was less (p < 0.05) in HAPE-S subjects compared to control. Acute hypoxia produced an exaggerated increase in heart rate (p < 0.05), mean arterial pressure (p < 0.05) and Ppa (28.2 ± 5.8 vs 19.33 ± 3.74 mm Hg, p < 0.05) and fall in peripheral oxygen saturation (p < 0.05) in HAPE-S compared to control. Receiver operating characteristic (ROC) curves showed that Ppa response to acute hypoxia was the best variable to identify HAPE susceptibility (AUC 0.92) but BNP levels provided comparable information (AUC 0.85). BNP levels are easy to determine and may represent an important marker for the determination of HAPE susceptibility. PMID:26892302
Jin, Tao; Zhang, Chong; Feng, Zhiying; Ni, Yiming
Primary pulmonary artery sarcoma is an uncommon tumor. We report a case of a 73-year-old male patient with a two-week history of palpitations and shortness of breath, aggravated for two days and was believed to be pulmonary hypertension. Emergency heart ultrasound after admission presented a massive pulmonary embolism in the pulmonary artery. The patient's condition was successfully managed with urgent pulmonary artery embolectomy. The patient demonstrated improvement in hemodynamics after the operation. Histologic and immunohistochemical assays were performed and a diagnosis was made as primary pulmonary artery sarcoma arising from the left pulmonary artery. Resection of the tumor is recommended for the treatment of this rare malignant tumor. The corresponding chemotherapy, follow-up and prognosis are described as well in this case report.
Fatemian, Marzieh; Herigstad, Mari; Croft, Quentin P. P.; Formenti, Federico; Cardenas, Rosa; Wheeler, Carly; Smith, Thomas G.; Friedmannova, Maria; Dorrington, Keith L.
Key points Lung ventilation and pulmonary artery pressure rise progressively in response to 8 h of hypoxia, changes described as ‘acclimatization to hypoxia’. Acclimatization responses differ markedly between humans for unknown reasons.We explored whether the magnitudes of the ventilatory and vascular responses were related, and whether the degree of acclimatization could be predicted by acute measurements of ventilatory and vascular sensitivities.In 80 healthy human volunteers measurements of acclimatization were made before, during, and after a sustained exposure to 8 h of isocapnic hypoxia.No correlation was found between measures of ventilatory and pulmonary vascular acclimatization.The ventilatory chemoreflex sensitivities to acute hypoxia and hypercapnia all increased in proportion to their pre‐acclimatization values following 8 h of hypoxia. The peripheral (rapid) chemoreflex sensitivity to CO2, measured before sustained hypoxia against a background of hyperoxia, was a modest predictor of ventilatory acclimatization to hypoxia. This finding has relevance to predicting human acclimatization to the hypoxia of altitude. Abstract Pulmonary ventilation and pulmonary arterial pressure both rise progressively during the first few hours of human acclimatization to hypoxia. These responses are highly variable between individuals, but the origin of this variability is unknown. Here, we sought to determine whether the variabilities between different measures of response to sustained hypoxia were related, which would suggest a common source of variability. Eighty volunteers individually underwent an 8‐h isocapnic exposure to hypoxia (end‐tidal P O2=55 Torr) in a purpose‐built chamber. Measurements of ventilation and pulmonary artery systolic pressure (PASP) assessed by Doppler echocardiography were made during the exposure. Before and after the exposure, measurements were made of the ventilatory sensitivities to acute isocapnic hypoxia (GpO2) and
... What Is Pulmonary Hypertension? To understand pulmonary hypertension (PH) it helps to understand how blood ows throughout ... is too high, it is called pulmonary hypertension (PH). How the pressure in the right side of ...
Neary, Joseph M.; Lund, Gretchen K.; Holt, Timothy N.; Garry, Franklyn B.; Mohun, Timothy J.; Breckenridge, Ross A.
Abstract Bovine pulmonary hypertension, brisket disease, causes significant morbidity and mortality at elevations above 2,000 m. Mean pulmonary arterial pressure (mPAP) is moderately heritable, with inheritance estimated to lie within a few major genes. Invasive mPAP measurement is currently the only tool available to identify cattle at risk of hypoxia-induced pulmonary hypertension. A genetic test could allow selection of cattle suitable for high altitude without the need for invasive testing. In this study we evaluated three candidate genes (myosin heavy chain 15 [MYH15], NADH dehydrogenase flavoprotein 2, and FK binding protein 1A) for association with mPAP in 166 yearling Angus bulls grazing at 2,182 m. The T allele (rs29016420) of MYH15 was linked to lower mPAP in a dominant manner (CC 47.2 ± 1.6 mmHg [mean ± standard error of the mean]; CT/TT 42.8 ± 0.7 mmHg; P = 0.02). The proportions of cattle with MYH15 CC, CT, and TT genotypes were 55%, 41%, and 4%, respectively. Given the high frequency of the deleterious allele, it is likely that the relative contribution of MYH15 polymorphisms to pulmonary hypertension is small, supporting previous predictions that the disease is polygenic. We evaluated allelic frequency of MYH15 in the Himalayan yak (Bos grunniens), a closely related species adapted to high altitude, and found 100% prevalence of T allele homozygosity. In summary, we identified a polymorphism in MYH15 significantly associated with mPAP. This finding may aid selection of cattle suitable for high altitude and contribute to understanding human hypoxia-induced pulmonary hypertension. PMID:25621163
Swärd, Karl; Sadegh, Mardjaneh K; Mori, Michiko; Erjefält, Jonas S; Rippe, Catarina
Caveolae are invaginations in the plasma membrane that depend on caveolins and cavins for maturation. Here, we investigated the pulmonary phenotype in mice lacking cavin-1. Bright field and electron-microscopy showed that the cavin-1-deficient mice lacked caveolae in the lung, had an increased lung tissue density, and exhibited hypertrophic remodeling of pulmonary arteries. The right ventricle of the heart moreover had an increased mass and the right ventricular pressure was elevated. A microarray analysis revealed upregulation of Arg1 and downregulation of Ddah1, molecules whose altered expression has previously been associated with pulmonary arterial hypertension. Taken together, this work demonstrates vascular remodeling and increased pulmonary blood pressure in cavin-1 deficient mice and associates this phenotype with altered expression of Arg1 and Ddah1. PMID:24303100
Mooney, Deirdre M.; Fung, Erik; Doshi, Rahul N.; Shavelle, David M.
Heart failure (HF) is a costly, challenging and highly prevalent medical condition. Hospitalization for acute decompensation is associated with high morbidity and mortality. Despite application of evidence-based medical therapies and technologies, HF remains a formidable challenge for virtually all healthcare systems. Repeat hospitalizations for acute decompensated HF (ADHF) can have major financial impact on institutions and resources. Early and accurate identification of impending ADHF is of paramount importance yet there is limited high quality evidence or infrastructure to guide management in the outpatient setting. Historically, ADHF was identified by physical exam findings or invasive hemodynamic monitoring during a hospital admission; however, advances in medical microelectronics and the advent of device-based diagnostics have enabled long-term ambulatory monitoring of HF patients in the outpatient setting. These monitors have evolved from piggybacking on cardiac implantable electrophysiologic devices to standalone implantable hemodynamic monitors that transduce left atrial or pulmonary artery pressures as surrogate measures of left ventricular filling pressure. As technology evolves, devices will likely continue to miniaturize while their capabilities grow. An important, persistent challenge that remains is developing systems to translate the large volumes of real-time data, particularly data trends, into actionable information that leads to appropriate, safe and timely interventions without overwhelming outpatient cardiology and general medical practices. Future directions for implantable hemodynamic monitors beyond their utility in heart failure may include management of other major chronic diseases such as pulmonary hypertension, end stage renal disease and portal hypertension. PMID:26500556
Shomaf, Maha; Obeidat, Nathir; Najjar, Saleh
Pulmonary artery sarcomas (PAS) are extremely rare sarcomas of uncertain histogenesis that often mimic pulmonary thromboemboli. This is a report of a 60-year-old female patient who presented with recurrent chest pain and cough. The patient was first diagnosed with pulmonary embolism but she did not improve on anticoagulant therapy. Follow-up imaging studies revealed a mass in the left hilar region extending into the pulmonary trunk and branches of the left pulmonary artery. The tru-cut biopsy revealed an undifferentiated sarcoma. The patient died 10 months after her initial presentation. PMID:26425600
Records from yearling Angus (n = 10,647) cattle from elevation 2,340 m were used in genetic analysis of pulmonary arterial pressure (PAP). Bulls were developed within a grain-supplemented performance test, whereas heifers and steers were grazed. The BovineSNP50 Beadchip was used to genotype a subset...
Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role
Montani, David; Günther, Sven; Dorfmüller, Peter; Perros, Frédéric; Girerd, Barbara; Garcia, Gilles; Jaïs, Xavier; Savale, Laurent; Artaud-Macari, Elise; Price, Laura C; Humbert, Marc; Simonneau, Gérald; Sitbon, Olivier
Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role
Kotwica, Tomasz; Szumarska, Joanna; Staniszewska-Marszalek, Edyta; Mazurek, Walentyna; Kosmala, Wojciech
Pulmonary artery aneurysm (PAA) is an uncommon lesion, which may be associated with different etiologies including congenital cardiovascular diseases, systemic vasculitis, connective tissue diseases, infections, and trauma. Idiopathic PAA is sporadically diagnosed by exclusion of concomitant major pathology. We report a case of a 56-year-old female with an idiopathic pulmonary artery dilatation identified fortuitously by echocardiography and confirmed by contrast-enhanced computed tomography. Neither significant pulmonary valve dysfunction nor pulmonary hypertension and other cardiac abnormalities which might contribute to the PAA development were found. Here, we describe echocardiographic and computed tomography findings and review the literature on PAA management.
D'Enfert, J; Mathieu-Daudé, J C; Grolleau, D; Saussine, M; Allien, M; Chaptal, P A; du Cailar, J
Variations in oncotic pressure-pulmonary artery diastolic pressure gradient and in intrapulmonary shunt were studied in two groups of patients undergoing surgery with extracorporeal circulation for aortocoronary bypass of excision of an aneurysm. The two groups, differed only in terms of the E.C.C. bath (Group A: Ringer Lactate; Group B: DDextran 60,000). The effects of E.C.C. on these parameters were as follows: - decrease in both groups in the gradient (OP-PAP) (respectively P < 0.001 and P < 0.01) but with a more marked decrease in group A than in group B (P < 0.05) with non-negativisation of the gradient in that group; - non-significant variations in Qs/Qt in both groups without any correlation with gradient (OP-PAP). The onset of pulmonary oedema associated with a decrease in gradient (OP-PAP) leads to the suggestion of the use of Dextrans in pathological situations where OP is low or PAP high and all the more so when both of these factors are present.
Kalogeropoulos, Andreas P.; Siwamogsatham, Sarawut; Hayek, Salim; Li, Song; Deka, Anjan; Marti, Catherine N.; Georgiopoulou, Vasiliki V.; Butler, Javed
Background Pulmonary hypertension (PH) in patients with heart failure (HF) is associated with worse outcomes and is rapidly being recognized as a therapeutic target. To facilitate pragmatic research efforts, data regarding the prognostic importance of noninvasively assessed pulmonary artery systolic pressure (PASP) in stable ambulatory patients with HF are needed. Methods and Results We examined the association between echocardiographic PASP and outcomes in 417 outpatients with HF (age, 54±13 years; 60.7% men; 50.4% whites; 24.9% with preserved ejection fraction). Median PASP was 36 mm Hg (interquartile range [IQR]: 29, 46). After a median follow‐up of 2.6 years (IQR: 1.7, 3.9) there were 72 major events (57 deaths; 9 urgent heart transplants; and 6 ventricular assist device implantations) and 431 hospitalizations for HF. In models adjusting for clinical risk factors and therapy, a 10‐mm Hg higher PASP was associated with 37% higher risk (95% CI: 18, 59; P<0.001) for major events, and 11% higher risk (95% CI: 1, 23; P=0.039) for major events or HF hospitalization. The threshold that maximized the likelihood ratio for both endpoints was 48 mm Hg; those with PASP ≥48 mm Hg (N=84; 20.1%) had an adjusted hazard ratio of 3.33 (95% CI: 1.96, 5.65; P<0.001) for major events and 1.47 (95% CI: 1.02, 2.11; P=0.037) for major events or HF hospitalization. Reduced right ventricular systolic function had independent prognostic utility over PASP for adverse outcomes. Right atrial pressure and transtricuspid gradient both contributed to risk. Conclusions Elevated PASP, determined by echocardiography, identifies ambulatory patients with HF at increased risk for adverse events. PMID:24492947
Emerson, Lyska L.; Bull, David A.; Hatton, Nathan; Nativi-Nicolai, Jose; Hildebrandt, Gerhard C.; Ryan, John J.
Abstract Amyloidosis involves extravascular deposition of fibrillar proteins within tissues and organs. Primary light chain amyloidosis represents the most common form of systemic amyloidosis involving deposition of monoclonal immunoglobulin light chains. Although pulmonary amyloid deposition is common in primary amyloidosis, clinically significant pulmonary amyloidosis is uncommon, and elevated pulmonary artery pressures are rarely observed in the absence of other underlying etiologies for pulmonary hypertension, such as elevated filling pressures secondary to cardiac amyloid. In this case report, we present a patient with primary light chain amyloidosis and pulmonary arterial hypertension in the setting of pulmonary vascular and right ventricular myocardial amyloid deposition. PMID:27252852
Rajendran, Ganeshkumar; Astleford, Lindsay; Michael, Mark; Schonfeld, Michael P.; Fields, Timothy; Shay, Sheila; French, Jaketa L.; West, James; Haase, Volker H.
Hypoxia-inducible factors 1 and 2 (HIF-1 and -2) control oxygen supply to tissues by regulating erythropoiesis, angiogenesis and vascular homeostasis. HIFs are regulated in response to oxygen availability by prolyl-4-hydroxylase domain (PHD) proteins, with PHD2 being the main oxygen sensor that controls HIF activity under normoxia. In this study, we used a genetic approach to investigate the endothelial PHD2/HIF axis in the regulation of vascular function. We found that inactivation of Phd2 in endothelial cells specifically resulted in severe pulmonary hypertension (∼118% increase in right ventricular systolic pressure) but not polycythemia and was associated with abnormal muscularization of peripheral pulmonary arteries and right ventricular hypertrophy. Concurrent inactivation of either Hif1a or Hif2a in endothelial cell-specific Phd2 mutants demonstrated that the development of pulmonary hypertension was dependent on HIF-2α but not HIF-1α. Furthermore, endothelial HIF-2α was required for the development of increased pulmonary artery pressures in a model of pulmonary hypertension induced by chronic hypoxia. We propose that these HIF-2-dependent effects are partially due to increased expression of vasoconstrictor molecule endothelin 1 and a concomitant decrease in vasodilatory apelin receptor signaling. Taken together, our data identify endothelial HIF-2 as a key transcription factor in the pathogenesis of pulmonary hypertension. PMID:26976644
Beghetti, Maurice; Tissot, Cecile
Pulmonary hypertension complicates the course of many children and adults with congenital heart diseases (CHDs). The increase in pulmonary pressure associated with CHD is secondary to either increased pulmonary blood flow or increased postcapillary pressures. Pulmonary arterial hypertension is in the vast majority associated with congenital cardiac shunts. Despite major advances in the understanding of the regulation of the pulmonary vascular bed and the pulmonary endothelial lesions leading to pulmonary vascular disease, despite the advances in surgical repair and the discovery of potential therapies in the pre- and postoperative period, pulmonary hypertension still carries a significant mortality and morbidity in patients with CHD. The recent introduction of targeted therapies in other forms of pulmonary arterial hypertension has led to a renewed interest in pulmonary hypertension associated with CHD and this particularly for the most advanced form, the so-called Eisenmenger syndrome (ES). This review summarizes the current knowledge on pulmonary hypertension associated with CHD, focusing on the pathophysiology and treatment of ES.
Yang, Wanjie; Zhao, Xuefeng; Feng, Qingguo; An, Youzhong; Wei, Kai; Wang, Wei; Li, Chang; Cheng, Xiuling
Objective To accurately measure the end-expiratory pulmonary artery wedge pressure (PAWP) with the “expiration holding” function on the ventilator and the “pulmonary artery wedge pressure review” software on the monitor. Materials and methods Fifty prospective measurements were made on 12 patients undergoing pulmonary artery catheter and mechanical ventilation. All measurements were divided into <8 mmHg or ≥8 mmHg subgroups according to respiratory variability, and they were then subdivided into either an airway pressure display measurement group (AM group) or an expiration holding (EH) group for comparison. Results In all measurements, the two groups showed similar levels of accuracy; however, for the time spent for measurement, the EH group was much faster than the airway pressure display measurement group (P<0.001). Additionally, the EH group was associated with lower medical costs. Conclusion The expiration holding approach measured the PAWP more accurately, more quickly, and with reduced costs in comparison to the airway pressure display approach. PMID:24133370
Gan, C.T.; Noordegraaf, A. Vonk; Marques, K.M.J.; Bronzwaer, J.G.F.; Postmus, P.E.; Boonstra, A.
Pulmonary arterial hypertension (PAH) is a disease characterised by an increased pulmonary artery pressure. The precapillary pulmonary arteries show distinct pathobiological changes, i.e. medial hypertrophy, intimal fibrosis, microthrombi and plexiform lesions. Although the pathogenesis is not completely understood, pulmonary vascular proliferation and remodelling, due to a variety of mediators, is believed to play the pathogenetic key role. Genetic research reveals molecular deformities and gene mutations associated with phenotypic PAH. This article covers novel insights into pathobiology, pathogenesis and genes of PAH, which led to a novel classification system and a diagnostic work-up, emanated from the World Health Organisation Symposium on Pulmonary Hypertension in Venice in June 2003. PMID:25696347
Ozkececi, Gulay; Akci, Onder; Bucak, Abdulkadir; Ulu, Sahin; Yalım, Zafer; Aycicek, Abdullah; Onrat, Ersel; Avsar, Alaettin
Nasal septum deviation (NSD) can cause obstruction of the upper airway, which may lead to increased pulmonary artery pressure (PAP) and right ventricle dysfunction. The aim of the present study was to evaluate the effect of septoplasty on right ventricular function and mean PAP of patients with marked NSD. 25 patients with marked NSD (mean age = 31.8 ± 12.3 years) and 27 healthy volunteers (mean age = 34.5 ± 10.8 years) were enrolled. Echocardiography was performed for all subjects and right ventricular function and mean PAP were evaluated before and 3 months after septoplasty. Tricuspid annular plane systolic excursion (TAPSE) and tricuspid annulus early diastolic myocardial velocity (E') were significantly lower in patients with NSD than control subjects, while right ventricle myocardial performance index (RVMPI) and mean PAP were significantly higher (respectively, p = 0.006, 0.037, 0.049, 0.046). When preoperative and postoperative findings were compared, the mean PAP decreased whereas TAPSE increased significantly (respectively, p = 0.007, 0.03). The results of the present study demonstrated that mean PAP increased and right ventricular function worsened in patients with NSD. However, mean PAP decreased and right ventricular function tended to recover after septoplasty.
Austin, Christopher; Alassas, Khadija; Burger, Charles; Safford, Robert; Pagan, Ricardo; Duello, Katherine; Kumar, Preetham; Zeiger, Tonya
BACKGROUND: Elevated mean right atrial pressure (RAP) measured by cardiac catheterization is an independent risk factor for mortality. Prior studies have demonstrated a modest correlation with invasive and noninvasive echocardiographic RAP, but the prognostic impact of estimated right atrial pressure (eRAP) has not been previously evaluated in patients with pulmonary arterial hypertension (PAH). METHODS: A retrospective analysis of 121 consecutive patients with PAH based on right-sided heart catheterization and echocardiography was performed. The eRAP was calculated by inferior vena cava diameter and collapse using 2005 and 2010 American Society of Echocardiography (ASE) definitions. Accuracy and correlation of eRAP to RAP was assessed. Kaplan-Meier survival analysis by eRAP, right atrial area, and Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry) risk criteria as well as univariate and multivariate analysis of echocardiographic findings was performed. RESULTS: Elevation of eRAP was associated with decreased survival time compared with lower eRAP (P < .001, relative risk = 7.94 for eRAP > 15 mm Hg vs eRAP ≤ 5 mm Hg). Univariate analysis of echocardiographic parameters including eRAP > 15 mm Hg, right atrial area > 18 cm2, presence of pericardial effusion, right ventricular fractional area change < 35%, and at least moderate tricuspid regurgitation was predictive of poor survival. However, multivariate analysis revealed that eRAP > 15 mm Hg was the only echocardiographic risk factor that was predictive of mortality (hazard ratio = 2.28, P = .037). CONCLUSIONS: Elevation of eRAP by echocardiography at baseline assessment was strongly associated with increased risk of death or transplant in patients with PAH. This measurement may represent an important prognostic component in the comprehensive echocardiographic evaluation of PAH. PMID:25211049
Celik, Gökhan; Ciledağ, Aydin; Yüksel, Cabir; Yenigün, Bülent Mustafa; Kutlay, Hakan; Yazicıoğlu, Levent; Perçinel, Sibel; Kaya, Akin
A 30 years old male patient was referred to our hospital with a diagnosis of pulmonary thromboembolism due to thorax-computerized tomography (CT) angiography, revealing a thrombus totally occluding left main pulmonary artery. The lesion was evaluated as tumoural mass. Positron emission tomography (PET)-CT revealed pathologic uptake at pulmonary artery mass. Due to localization of tumour, left pneumonectomy was performed. The pathological diagnosis revealed to be pulmonary artery sarcoma. The patient was presented because pulmonary artery sarcomas are very rare tumors and can mimick pulmonary thromboembolism. The true prevalence is underestimated as many pulmonary artery sarcomas are misdiagnosed as pulmonary thromboembolism. PET-CT may help to make a differential diagnosis.
Farsad, Mohsen; Pernter, Patrizia; Triani, Antonio; Osele, Luzian; Wiedermann, Christian J
Pulmonary artery sarcoma, although rare, must be considered in the differential diagnosis of pulmonary thromboembolism. Clinically and radiologically, it may imitate pulmonary embolism, making diagnosis difficult and delaying treatment. Patients often have no symptom resolution despite therapeutic anticoagulation. Visualization of filling defects within a pulmonary artery on contrast-enhanced CT cannot reliably differentiate between pulmonary thromboembolism and malignant lesions like leiomyosarcoma. FDG PET-CT offers the potential for identification of malignant lesions. The authors report a case with pulmonary artery thromboembolism due to thrombi formed on a pulmonary artery leiomyosarcoma. Integrated FDG PET-CT showed no FDG-uptake along the major part of the filling defect within the right main pulmonary artery suggesting blood clot and increased uptake along the posterior wall of the right main pulmonary artery and the left lower lobar artery suggesting malignancy.
Stawicki, Stanislaw P.; Papadimos, Thomas J.; Bahner, David P.; Evans, David C.; Jones, Christian
Introduction: As pulmonary artery catheter (PAC) use declines, search continues for reliable and readily accessible minimally invasive hemodynamic monitoring alternatives. Although the correlation between inferior vena cava collapsibility index (IVC-CI) and central venous pressures (CVP) has been described previously, little information exists regarding the relationship between IVC-CI and pulmonary artery pressures (PAPs). The goal of this study is to bridge this important knowledge gap. We hypothesized that there would be an inverse correlation between IVC-CI and PAPs. Methods: A post hoc analysis of prospectively collected hemodynamic data was performed, examining correlations between IVC-CI and PAPs in a convenience sample of adult Surgical Intensive Care Unit patients. Concurrent measurements of IVC-CI and pulmonary arterial systolic (PAS), pulmonary arterial diastolic (PAD), and pulmonary arterial mean (PAM) pressures were performed. IVC-CI was calculated as ([IVCmax − IVCmin]/IVCmax) × 100%. Vena cava measurements were obtained by ultrasound–credentialed providers. For the purpose of correlative analysis, PAP measurements (PAS, PAD, and PAM) were grouped by terciles while the IVC-CI spectrum was divided into thirds (<33, 33–65, ≥66). Results: Data from 34 patients (12 women, 22 men, with median age of 59.5 years) were analyzed. Median Acute Physiologic Assessment and Chronic Health Evaluation II score was 9. A total of 76 measurement pairs were recorded, with 57% (43/76) obtained in mechanically ventilated patients. Correlations between IVC-CI and PAS (rs = −0.334), PAD (rs = −0.305), and PAM (rs = −0.329) were poor. Correlations were higher between CVP and PAS (R2 = 0.61), PAD (R2 = 0.68), and PAM (R2 = 0.70). High IVC-CI values (≥66%) consistently correlated with measurements in the lowest PAP ranges. Across all PAP groups (PAS, PAD, and PAM), there were no differences between the mean measurement values for the lower and middle IVC
Lai, Yen-Chun; Potoka, Karin C.; Champion, Hunter C.; Mora, Ana L.; Gladwin, Mark T.
Pulmonary arterial hypertension (PAH) is a progressive disorder in which endothelial dysfunction and vascular remodeling obstruct small pulmonary arteries, resulting in increased pulmonary vascular resistance and pulmonary pressures. This leads to reduced cardiac output, right heart failure, and ultimately death. In this review, we attempt to answer some important questions commonly asked by patients diagnosed with PAH pertaining to the disease, and aim to provide an explanation in terms of classification, diagnosis, pathophysiology, genetic etiologies, demographics, and prognostic factors. Furthermore, important molecular pathways that are central to the pathogenesis of PAH are reviewed, including nitric oxide, prostacyclin, endothelin-1, reactive oxygen species, and endothelial and smooth muscle proliferation. PMID:24951762
Akagi, Satoshi; Nakamura, Kazufumi; Matsubara, Hiromi; Ogawa, Aiko; Sarashina, Toshihiro; Ejiri, Kentaro; Ito, Hiroshi
Pulmonary arterial hypertension (PAH) is characterized by elevation of pulmonary artery pressure caused by pulmonary vasoconstriction and vascular remodeling, which leads to right heart failure and death. Epoprostenol (prostaglandin I2) has a potent short-acting vasodilator property, and intravenous continuous epoprostenol is therefore used for treatment of PAH. Here we review evidence for the usefulness of intravenous continuous epoprostenol therapy in patients with PAH. Epoprostenol therapy is effective in idiopathic PAH patients and in patients with PAH associated with connective tissue disease, portal hypertension or congenital heart diseases, but it is not effective in patients with pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis. High-dose epoprostenol therapy markedly improved hemodynamics in some patients with PAH, possibly due to reverse remodeling of pulmonary arteries. This therapy has several side effects and complications such as headache, hypotension and catheter-related infections. Intravenous continuous epoprostenol is an effective treatment, but there are still some problems to be resolved.
Soria, Rodrigo; Egger, Matthias; Scherrer, Urs; Bender, Nicole; Rimoldi, Stefano F
More than 140 million people are living at high altitude worldwide. An increase of pulmonary artery pressure (PAP) is a hallmark of high-altitude exposure and, if pronounced, may be associated with important morbidity and mortality. Surprisingly, there is little information on the usual PAP in high-altitude populations. We, therefore, conducted a systematic review (MEDLINE and EMBASE) and meta-analysis of studies published (in English or Spanish) between 2000 and 2015 on echocardiographic estimations of PAP and measurements of arterial oxygen saturation in apparently healthy participants from general populations of high-altitude dwellers (>2,500 m). For comparison, we similarly analyzed data published on these variables during the same period for populations living at low altitude. Twelve high-altitude studies comprising 834 participants and 18 low-altitude studies (710 participants) fulfilled the inclusion criteria. All but one high-altitude studies were performed between 3,600 and 4,350 m. The combined mean systolic PAP (right ventricular-to-right atrial pressure gradient) at high altitude [25.3 mmHg, 95% confidence interval (CI) 24.0, 26.7], as expected was significantly (P < 0.001) higher than at low altitude (18.4 mmHg, 95% CI 17.1,19.7), and arterial oxygen saturation was significantly lower (90.4%, 95% CI 89.3, 91.5) than at low altitude (98.1%; 95% CI 97.7, 98.4). These findings indicate that at an altitude where the very large majority of high-altitude populations are living, pulmonary hypertension appears to be rare. The reference values and distributions for PAP and arterial oxygen saturation in apparently healthy high-altitude dwellers provided by this meta-analysis will be useful to future studies on the adjustments to high altitude in humans.
Xu, Da; Olivier, N Bari; Mukkamala, Ramakrishna
We developed a technique to continuously (i.e., automatically) monitor cardiac output (CO) and left atrial pressure (LAP) by mathematical analysis of the pulmonary artery pressure (PAP) waveform. The technique is unique to the few previous related techniques in that it jointly estimates the two hemodynamic variables and analyzes the PAP waveform over time scales greater than a cardiac cycle wherein wave reflections and inertial effects cease to be major factors. First, a 6-min PAP waveform segment is analyzed so as to determine the pure exponential decay and equilibrium pressure that would eventually result if cardiac activity suddenly ceased (i.e., after the confounding wave reflections and inertial effects vanish). Then, the time constant of this exponential decay is computed and assumed to be proportional to the average pulmonary arterial resistance according to a Windkessel model, while the equilibrium pressure is regarded as average LAP. Finally, average proportional CO is determined similar to invoking Ohm's law and readily calibrated with one thermodilution measurement. To evaluate the technique, we performed experiments in five dogs in which the PAP waveform and accurate, but highly invasive, aortic flow probe CO and LAP catheter measurements were simultaneously recorded during common hemodynamic interventions. Our results showed overall calibrated CO and absolute LAP root-mean-squared errors of 15.2% and 1.7 mmHg, respectively. For comparison, the root-mean-squared error of classic end-diastolic PAP estimates of LAP was 4.7 mmHg. On future successful human testing, the technique may potentially be employed for continuous hemodynamic monitoring in critically ill patients with pulmonary artery catheters.
Leopold, Jane A.; Maron, Bradley A.
Pulmonary arterial hypertension (PAH) is a devastating disease that is precipitated by hypertrophic pulmonary vascular remodeling of distal arterioles to increase pulmonary artery pressure and pulmonary vascular resistance in the absence of left heart, lung parenchymal, or thromboembolic disease. Despite available medical therapy, pulmonary artery remodeling and its attendant hemodynamic consequences result in right ventricular dysfunction, failure, and early death. To limit morbidity and mortality, attention has focused on identifying the cellular and molecular mechanisms underlying aberrant pulmonary artery remodeling to identify pathways for intervention. While there is a well-recognized heritable genetic component to PAH, there is also evidence of other genetic perturbations, including pulmonary vascular cell DNA damage, activation of the DNA damage response, and variations in microRNA expression. These findings likely contribute, in part, to dysregulation of proliferation and apoptosis signaling pathways akin to what is observed in cancer; changes in cellular metabolism, metabolic flux, and mitochondrial function; and endothelial-to-mesenchymal transition as key signaling pathways that promote pulmonary vascular remodeling. This review will highlight recent advances in the field with an emphasis on the aforementioned molecular mechanisms as contributors to the pulmonary vascular disease pathophenotype. PMID:27213345
Gialafos, Elias J.; Moyssakis, Ioannis; Psaltopoulou, Theodora; Papadopoulos, Dimitrios P.; Perea, Despoina; Vlasis, Kostantinos; Kostopoulos, Charalampos; Votteas, Vassilios; Sfikakis, Petros P.
Decreased levels of matrix metalloproteinases (MMPs) or excess levels of their tissue inhibitors (TIMPs) may contribute to dysregulation of extracellular matrix turnover in systemic sclerosis (SSc). In a cross-sectional study of 106 SSc patients, we measured serum levels of TIMP-4 which is preferentially expressed in cardiovascular structures and searched for correlations with simultaneously performed echocardiography measurements of pulmonary artery systolic pressure (PASP), myocardial performance, and pulmonary function tests. TIMP-4, but not MMP-9, levels were significantly raised in patients with SSc than controls. However, in the subgroup of patients with PASP measurements lower to 40 mmHg (n = 69), TIMP-4 levels were comparable to controls irrespective of the presence of diffuse or limited skin involvement, or lung fibrosis. Individual PASP measurements suggestive of pulmonary hypertension were associated with increased TIMP-4 serum levels (P = .03), independently of age, extent of skin sclerosis, or lung fibrosis, suggesting a cardiopulmonary vasculature-specific role of TIMP-4 activation in SSc. PMID:19190762
Presbitero, P; Bull, C; Haworth, S G; de Leval, M R
Of 12 patients with angiographically absent pulmonary artery, 11 were investigated surgically. The previously occult pulmonary artery was found in 10 patients, in five of whom a vestige of an intrapericardial artery was present and in five the artery was patent only at the hilus, a gap existing between the main pulmonary artery and the hilar vessel, and no artery was found in one. All patients with an intrapericardial artery had right ventricular outflow tract obstruction and a ductus descending vertically from underneath the aortic arch. In those without an intrapericardial vessel the occult artery was on the side opposite the aortic arch, and there was evidence of a ductus coming from the innominate artery on the side of the interruption. The occult pulmonary artery, where identified at operation, was usually joined initially to the systemic circulation. Ultimately, continuity between the hilar and main pulmonary artery may be established surgically. Where no intrapericardial vessel exists, however, a conduit may be required to bridge the gap. It seems advisable to search for the occult artery as early in life as is feasible in the hope that providing a blood supply will ensure development of the vessel and normal lung growth. Images PMID:6743435
Jeong, Nari; Seol, Sang-Hoon; Kim, Il Hwan; Kim, Ji Yeon
Pulmonary artery sarcoma (PAS) is a rare and fatal disease. PAS can often be misdiagnosed as pulmonary thromboembolism. Moreover, the correct diagnosis is frequently delayed due to nonspecific signs and symptoms. The prognosis of patients with PAS is poor. We report a case of a woman with a primary PAS who was initially diagnosed with pulmonary thromboembolism.
Jeong, Nari; Seol, Sang-Hoon; Kim, Il Hwan; Kim, Ji Yeon
Pulmonary artery sarcoma (PAS) is a rare and fatal disease. PAS can often be misdiagnosed as pulmonary thromboembolism. Moreover, the correct diagnosis is frequently delayed due to nonspecific signs and symptoms. The prognosis of patients with PAS is poor. We report a case of a woman with a primary PAS who was initially diagnosed with pulmonary thromboembolism. PMID:27833785
Terra, Ricardo M; Fernandez, Angelo; Bammann, Ricardo H; Junqueira, Jader J M; Capelozzi, Vera L
Pulmonary artery sarcoma is an uncommon neoplasm, and its clinical and radiological presentation usually simulates chronic thromboembolic disease. We present the case of a 77-year-old woman admitted with dyspnea, chest pain, and hemoptysis. A chest computed tomographic scan showed moderate right-sided pleural effusion and a saccular dilatation of the interlobar portion of the right pulmonary artery, which was filled with contrast and surrounded by an irregular soft-tissue attenuation mass, suggesting a ruptured pulmonary artery aneurysm. The patient was operated on. Intraoperatively, a pseudoaneurysm and a solid mass were identified within the oblique fissure around the interlobar artery. Therefore, a right pneumonectomy was performed. Definitive pathologic examination was consistent with pulmonary artery sarcoma. The patient had a good outcome and is free of disease 2 years after surgery.
Gehlen, H; Groner, U; Rohn, K; Stadler, P
In 18 horses, the pulmonary artery wedge pressure and the heart rate were measured during pharmacological stress load. 12 horses were healthy (4 trained, 8 untrained) and 6 horses had a heart disease (3 trained, 3 untrained). Pharmacological stress induction was carried out with the sympathomimetic drug dobutamine at a dosage rate of 7.5 microg/kg/min over 10 minutes of infusion. At the fourth minute, the parasympatholytic drug atropine was administered (5 microg/kg bw), and the heart rate and the pulmonary artery wedge pressure were continuously measured over 26 minutes. During sole dobutamine infusion, a significant decrease in heart rate and a significant increase in pulmonary artery wedge pressure were observed. After the application of atropine in the fourth minute, a significant increase in heart rate (from 35.7 +/- 6 up to 106 +/- 38/ min) and in pulmonary artery wedge pressure (from 15.7 +/- 3 up to 24 +/- 8.6 mmHg) were visible in the group of healthy horses. The horses with heart diseases had a significantly higher increase in both parameters (heart rate and pulmonary artery wedge pressure) with a significantly positive correlation (r = 0.7). The heart rate increased in the horses with heart diseases from 35.2 +/- 2,8 beats/min up to 132 +/- 45.7 beats/min and the pulmonary artery wedge pressure increased from 17.3 +/- 3,2 mmHg up to 32.7 +/- 13 mmHg. The cardiac status (healthy or heart disease) as well as the training level of the horses (untrained or trained) had a significant influence on the heart rate and the pulmonary artery wedge pressure. The untrained horses (healthy and heart disease) showed significantly higher values over a longer period of time than did the trained horses with the same cardiac status. Additionally the influence of pharmacological stress induction on echocardiographic parameters was investigated. The left atrial size (p = 0.015) and left ventricular diameter were significanly different in the systole (p = 0.008) and in the
Boos, C J; Hodkinson, P; Mellor, A; Green, N P; Woods, D R
This study investigated, for the first time, the effects of simulated high altitude, following acute hypobaric hypoxia (HH), on simultaneous assessment of large artery stiffness and endothelial function and its inter-relationship to left ventricular (LV) diastolic function, pulmonary artery systolic pressure (PASP), and estimated PA vascular resistance (PVR). Ten healthy subjects were studied at baseline pre and following acute HH to 4800 m for a total of 180 minutes. Assessments of LV diastolic function, mitral inflow, estimated LV filling pressure (E/e'), PVR, and PASP were undertaken using transthoracic echocardiography. Simultaneous assessments of arterial stiffness index (SI), systemic vascular resistance (SVR), vascular tone, and endothelial function (reflective index [RI]) were performed using pulse contour analysis of the digital arterial waveform. Acute hypoxia led to a fall in SpO₂ (98.1±0.7 vs. 71.8±7.1%; p=0.0002), SVR (1589.1±191.2 vs. 1187.8±248.7; p=0.004), and RI (50.8±10.3 vs. 33.0±6.5%; p=0.0008) with an increase in PASP (24.3±2.2 to 35.0±5.3 mmHg; p=0.0001) and estimated PVR (116.40±19.0 vs. 144.6±21.5; p<0.001). There was no rise in either SI (p=0.13), mitral early annular early e' filling velocity or E/e'. There was a significant inverse correlation between SpO₂ and PASP (r=-0.77; p<0.0001), PVR (r=-0.57; p=0.008) and between the fall in SpO₂ and change (Δ) in RI (baseline vs. 150 min, r=-0.52; p<0.001). There was a modest inverse correlation between ΔRI (lower ΔRI=worsening endothelial function) and ΔPAP (r=-0.55; p=0.10) and a strong inverse correlation between ΔRI and ΔPVR (r=-0.89; p=0.0007). Acute hypobaric hypoxia does not significantly alter large artery stiffness or cause overt LV diastolic function. However, the degree of hypoxia influences both the systemic endothelial and pulmonary vascular responses. This noted association is intriguing and requires further investigation.
Acar, Onur Çağlar; Üner, Abdurrahman; Garça, Mehmet Fatih; Ece, İbrahim; Epçaçan, Serdar; Turan, Mahfuz; Kalkan, Ferhat
Objectives The purpose of the present study is to emphasize the efficacy of the myocardial performance index and tricuspid annular plane systolic excursion (TAPSE) in the determination of impaired cardiac functions and recovery period following the treatment in children with adenoid and/or tonsillar hypertrophy. Methods Fifty-three healthy children after routine laboratory, imaging and clinical examinations, with adenoid and/or tonsillar hypertrophy were evaluated before and 3 months after adenotonsillectomy for cardiac functions using M mode and Doppler echocardiography. Results The mean age of cases was 6.4±3.0 years, 34 (65%) were male, and 19 (35%) were female. Pulmonary hypertension was observed to be mild in 3 patients and moderate in 1 patient preoperatively. When the preoperative and postoperative echocardiographic measurements of the patients were compared, the tricuspid valve E wave velocity, the E/A ratio (E, early diastolic flow rate; A, late diastolic flow rate), and the TAPSE values were determined to be significantly higher postoperatively (P<0.05). The tricuspid valve deceleration time, the isovolumetric relaxation time and the systolic pulmonary artery pressure were found to be significantly lower compared to the preoperative values (P<0.05). Conclusion Adenoidectomy and/or tonsillectomy may prevent cardiac dysfunctions that can develop in the later periods due to adenoid and/or tonsil hypertrophy in children, before the appearance of the clinical findings of cardiac failure. PMID:27090272
Martínez-Guerra, M L; Fernández-Bonetti, P; Peraza, C; Lupi-Herrera, E
Eighteen patients with ventricular septal defect or patent ductus arteriosus were studied to investigate the effects of an increase of pulmonary hypertension. In general group II showed similar results as previously reported in patients with atrial septal defect without pulmonary hypertension. In group I, we found an increased frequency of functional abnormalities in the small airways. We do not have a definitive explanation for the origin of these differences.
Shehatha, Jaffar; Saxena, Pankaj; Clarke, Belinda; Dunning, John; Konstantinov, Igor E
Primary pulmonary artery sarcoma is a rare tumor that can be misdiagnosed as acute or chronic pulmonary thromboembolic disease. This article reports a patient with a preoperative diagnosis of pulmonary embolism who was found to have an extensive pulmonary artery tumor. Surgical resection of the primary pulmonary artery sarcoma and reconstruction of the central pulmonary arteries, followed by adjuvant chemoradiotherapy, provided significant improvement in his clinical symptoms.
Sandhu, A; Yates, T J; Kuriakose, P
Sarcomas involving the lung are a rare occurrence, often a result of metastatic disease from primary malignancies involving the skin, liver, breast or heart. Primary pulmonary artery sarcomas are rarer still, with limited cases reported world-wide and consequently data regarding treatment modalities are sparse and largely experimental. These tumors are often mistaken for a pulmonary embolism and seemingly supported by radiological findings. Patients will often present without symptom resolution despite therapeutic anticoagulation. The following case illustrates how a soft tissue sarcoma of the pulmonary artery can mimic a pulmonary embolism, thus, resulting in both a diagnostic and therapeutic dilemma. A positron emission tomography scan was an invaluable tool in this case, showing increased radiotracer uptake and placing neoplasm at the top of the differential diagnosis. This ultimately led to a biopsy that was vimentin positive, cytokeratin negative and CD117 negative, thus consistent with soft tissue sarcoma.
Stacher, Elvira; Graham, Brian B.; Hunt, James M.; Gandjeva, Aneta; Groshong, Steve D.; McLaughlin, Vallerie V.; Jessup, Marsha; Grizzle, William E.; Aldred, Michaela A.; Cool, Carlyne D.
Rationale: The impact of modern treatments of pulmonary arterial hypertension (PAH) on pulmonary vascular pathology remains unknown. Objectives: To assess the spectrum of pulmonary vascular remodeling in the modern era of PAH medication. Methods: Assessment of pulmonary vascular remodeling and inflammation in 62 PAH and 28 control explanted lungs systematically sampled. Measurements and Main Results: Intima and intima plus media fractional thicknesses of pulmonary arteries were increased in the PAH group versus the control lungs and correlated with pulmonary hemodynamic measurements. Despite a high variability of morphological measurements within a given PAH lung and among all PAH lungs, distinct pathological subphenotypes were detected in cohorts of PAH lungs. These included a subset of lungs lacking intima or, most prominently, media remodeling, which had similar numbers of profiles of plexiform lesions as those in lungs with more pronounced remodeling. Marked perivascular inflammation was present in a high number of PAH lungs and correlated with intima plus media remodeling. The number of profiles of plexiform lesions was significantly lower in lungs of male patients and those never treated with prostacyclin or its analogs. Conclusions: Our results indicate that multiple features of pulmonary vascular remodeling are present in patients treated with modern PAH therapies. Perivascular inflammation may have an important role in the processes of vascular remodeling, all of which may ultimately lead to increased pulmonary artery pressure. Moreover, our study provides a framework to interpret and design translational studies in PAH. PMID:22679007
Alsoufi, Bahaaldin; Slater, Matthew; Smith, Pamela P; Karamlou, Tara; Mansoor, Atiya; Ravichandran, Pasala
Intimal sarcomas of the pulmonary artery are rare tumors that are often difficult to distinguish from pulmonary thromboembolic disease, complicating accurate diagnosis and timely therapy. We report the case of a gentleman with a primary pulmonary artery sarcoma who presented with a massive pulmonary embolism and complete right ventricular outflow tract obstruction. The patient's condition was successfully managed with urgent pulmonary artery thromboendarterectomy, pulmonary valve replacement, and tricuspid valve annuloplasty.
El-Sayed Ahmed, Magdy M; Aftab, Muhammad; Al-Najjar, Raed M; de la Cruz, Kim I; Benjamin, Robert S; Hallman, Charles H
Primary sarcomas that arise from major blood vessels are exceedingly rare, and some of the published cases have been autopsy reports. Most patients are adults. We report a case of pulmonary artery sarcoma in a 77-year-old man who presented with acute onset of dyspnea. Magnetic resonance imaging of the chest revealed a large mass within the pulmonary trunk and its main branches. Because massive pulmonary embolism was suspected, both anticoagulant and thrombolytic therapies were initiated. The patient responded poorly to these therapies, which then necessitated resection of both the mass and the pulmonary valve. A bioprosthetic porcine valve replaced the native valve, and we reconstructed the right ventricular outflow tract with a Dacron patch. Histopathologic examination revealed a high-grade sarcoma with focal myogenic and chondrogenic differentiation. The patient tolerated the procedure well and was discharged from the hospital on postoperative day 7. He was subsequently treated with chemotherapy and radiation and continued to show no evidence of disease. The diagnosis of pulmonary artery sarcoma should be suspected in patients who present with manifestations of pulmonary embolism, especially when there is no evidence of deep venous thrombosis and poor response to anticoagulant therapy. Multimodal therapy can provide prolonged survival.
Aftab, Muhammad; Al-Najjar, Raed M.; de la Cruz, Kim I.; Benjamin, Robert S.; Hallman, Charles H.
Primary sarcomas that arise from major blood vessels are exceedingly rare, and some of the published cases have been autopsy reports. Most patients are adults. We report a case of pulmonary artery sarcoma in a 77-year-old man who presented with acute onset of dyspnea. Magnetic resonance imaging of the chest revealed a large mass within the pulmonary trunk and its main branches. Because massive pulmonary embolism was suspected, both anticoagulant and thrombolytic therapies were initiated. The patient responded poorly to these therapies, which then necessitated resection of both the mass and the pulmonary valve. A bioprosthetic porcine valve replaced the native valve, and we reconstructed the right ventricular outflow tract with a Dacron patch. Histopathologic examination revealed a high-grade sarcoma with focal myogenic and chondrogenic differentiation. The patient tolerated the procedure well and was discharged from the hospital on postoperative day 7. He was subsequently treated with chemotherapy and radiation and continued to show no evidence of disease. The diagnosis of pulmonary artery sarcoma should be suspected in patients who present with manifestations of pulmonary embolism, especially when there is no evidence of deep venous thrombosis and poor response to anticoagulant therapy. Multimodal therapy can provide prolonged survival. PMID:25425986
Rubin, Lewis J; Badesch, David B
Increased pressure in the pulmonary circulation, or pulmonary hypertension, is a common disorder that may complicate various cardiopulmonary conditions, including severe obstructive airways disease and left ventricular dysfunction. An increase in pulmonary arterial pressure that is not due to coexistent cardiopulmonary disease, known as pulmonary arterial hypertension, may occur in the absence of a demonstrable cause (idiopathic or familial); as a complication of systemic conditions, such as connective tissue disease, HIV infection, or chronic liver disease; or as a result of the use of fenfluramine anorexigens, amphetamines, or cocaine. The development of disease-specific therapies for pulmonary arterial hypertension over the past decade underscores the importance of diagnosing pulmonary hypertension early in the course of the condition and implementing a treatment strategy that is based on the condition's cause and severity. In this review, the authors present approaches to the diagnosis and management of pulmonary arterial hypertension, using a hypothetical case to highlight the key management points.
Blackmon, Shanda H; Reardon, Michael J
Primary heart tumors are rare, and malignant primary heart tumors are only a small subset of these. Most primary malignant tumors are sarcomas arising from the cells of the structural elements of the heart such as blood vessels, muscle, connective tissue, fat and even bone. Unlike most malignancies, where cell type often dictates treatment choices and prognosis and is used for classification, the histology in primary cardiac sarcoma plays little role in determining therapeutic options or prognosis. We have found that anatomic location within the heart is the major determining factor in clinical presentation, treatment options and prognosis in cardiac sarcoma. Therefore, we accordingly classify primary cardiac sarcomas into right heart sarcomas, left heart sarcomas and pulmonary artery (PA) sarcomas. Since the first autopsy report of a primary PA sarcoma in 1923, there have been fewer than 250 cases reported in the English literature. Most of these reports have been single autopsy or case reports, and patient prognosis has generally been dismal. Since few institutions and even fewer individual physicians acquire much exposure to this disease, the diagnostic and treatment approaches have remained unresolved. Our cardiac sarcoma group working at the Methodist DeBakey Heart & Vascular Center and the MD Anderson Cancer Center has undertaken a systematic study of this disease, and operated on 9 patients using a radical resection with curative intent and multimodality approach. Based on this work, we have suggested a diagnostic strategy, treatment approach and staging system for primary PA sarcoma. A substantial improvement in patient survival over historical controls has also been demonstrated and will be discussed in this review.
Neary, Joseph M; Gould, Daniel H; Garry, Franklyn B; Knight, Anthony P; Dargatz, David A; Holt, Timothy N
Producer reports from ranches over 2,438 meters in southwest Colorado suggest that the mortality of preweaned beef calves may be substantially higher than the national average despite the selection of low pulmonary pressure herd sires for over 20 years. Diagnostic investigations of this death loss problem have been limited due to the extensive mountainous terrain over which these calves are grazed with their dams. The objective of the current study was to determine the causes of calf mortality on 5 high-altitude ranches in Colorado that have been selectively breeding sires with low pulmonary pressure (<45 mmHg) for over 20 years. Calves were followed from branding (6 weeks of age) in the spring to weaning in the fall (7 months of age). Clinical signs were recorded, and blood samples were taken from sick calves. Postmortem examinations were performed, and select tissue samples were submitted for aerobic culture and/or histopathology. On the principal study ranch, 9.6% (59/612) of the calves that were branded in the spring either died or were presumed dead by weaning in the fall. In total, 28 necropsies were performed: 14 calves (50%) had lesions consistent with pulmonary hypertension and right-sided heart failure, and 14 calves (50%) died from bronchopneumonia. Remodeling of the pulmonary arterial system, indicative of pulmonary hypertension, was evident in the former and to varying degrees in the latter. There is a need to better characterize the additional risk factors that complicate pulmonary arterial pressure testing of herd sires as a strategy to control pulmonary hypertension.
Darwazah, Ahmad K; Alhaddad, Imad A
Unilateral agenesis of the pulmonary artery is a rare congenital anomaly, which commonly involves the right side. Cases are associated with systemic collaterals, that may also rarely arise from the coronary arteries.Two adult patients are presented with a right pulmonary artery agenesis associated with collaterals from the right coronary artery. The implications of such an anomaly on pulmonary artery pressure and lung pathology differs among both cases. The association of coronary collaterals is rare and its implication is variable among various patients.
Huwer, Hanno; Ozbek, Cem; Waldmann, Rita; Winning, Johannes; Isringhaus, Helmut; Kalweit, Gerhard
We report on a sarcoma of the central pulmonary arteries. Surgical therapy consisted in replacing both main pulmonary arteries and the pulmonary trunk including the pulmonary valve. Six months later a left-sided pneumonectomy had to be performed due to an intravascular tumor. Fifteen months after first resection treatment, recurrent tumors of the right pulmonary artery and the right ventricle were resected. Two years after the first operation the patient has no detectable tumor.
Coskun, Ugur; Sinan, Umit Yasar; Calpar, Ilknur; Yildizeli, Bedrettin; Yanartas, Mehmet; Filinte, Deniz; Kucukoglu, Mehmet Serdar
We describe the case of a 60-year-old woman who presented with pulmonary artery sarcoma, a very rare tumor of the cardiovascular system. Her tumor was initially misdiagnosed as chronic pulmonary thromboembolism, and she underwent pulmonary endarterectomy. Early diagnosis of primary pulmonary artery sarcoma is crucial. That alternative should always be considered before settling on a diagnosis of pulmonary embolism. Suspicion should be aroused by the failure of anticoagulant treatment to alleviate pulmonary perfusion abnormalities and systemic symptoms. Surgical resection of the tumor-preferably by pulmonary endarterectomy, followed by reconstruction as needed-is currently the most promising treatment for pulmonary artery sarcoma.
Coskun, Ugur; Calpar, Ilknur; Yildizeli, Bedrettin; Yanartas, Mehmet; Filinte, Deniz; Kucukoglu, Mehmet Serdar
We describe the case of a 60-year-old woman who presented with pulmonary artery sarcoma, a very rare tumor of the cardiovascular system. Her tumor was initially misdiagnosed as chronic pulmonary thromboembolism, and she underwent pulmonary endarterectomy. Early diagnosis of primary pulmonary artery sarcoma is crucial. That alternative should always be considered before settling on a diagnosis of pulmonary embolism. Suspicion should be aroused by the failure of anticoagulant treatment to alleviate pulmonary perfusion abnormalities and systemic symptoms. Surgical resection of the tumor—preferably by pulmonary endarterectomy, followed by reconstruction as needed—is currently the most promising treatment for pulmonary artery sarcoma. PMID:25425987
Geraads, A; Pirotte, C; Ligeonnet, D; Levy, P; Brambilla, C
A study was made of pulmonary artery pressure in 16 chronic bronchitics with severe respiratory failure, who were treated with continuous oxygen therapy at home. At the beginning of the study these patients presented with a pure and severe obstructive syndrome with marked hypoxaemia at rest (mean PaO2 = 6.8 kPa), had a suitable interval from a recent exacerbation, in a stable clinical and functional respiratory state. The duration of longterm oxygen therapy was controlled, as the efficacy of the blood gases (PaO2 of O2 greater than or equal to 8 kPa). The pulmonary artery pressure was measured using a microcatheter, at the beginning, and for most of the 18 months breathing ambient air in a stable state. At the end of this time a significant diminution of the FEV1 (VEMS) (a mean of 100 ml, p less than 0.01). This was evidence of the deterioration in the ventilatory state which contrasted with the improvement in the diminution of pulmonary artery hypertension (HTAP) from 3.43 to 2.97 kPa (p less than 0.05) without the deterioration in the other values. The good result above in chronic bronchitics contrasts with a stable or deteriorating pulmonary arterial pressure in a group of emphysematous (n = 6) and bronchiectatic subjects (n = 4) with somewhat similar functional characteristics but in whom the effect was too small to allow for any statistical comparison. Our results are compared with those in the literature much of which applies to only a few patients and for the great part revealed only haemodynamic stability of oxygen therapy. Possible reasons for these discordant findings are discussed.
Bhagwat, Krishna; Hallam, Jane; Antippa, Phillip; Larobina, Marco
Primary angiosarcoma of pulmonary artery is a very rare lesion. We present a case of primary angiosarcoma that was initially misdiagnosed as a subacute massive pulmonary thromboembolism in a 30-year-old man. This rare disease is usually indistinguishable from acute or chronic thromboembolic disease of the pulmonary arteries. The clinical and radiological findings of pulmonary artery angiosarcoma are similar to those of pulmonary thromboembolism. Although the incidence of pulmonary artery angiosarcoma is very low, our case demonstrates that this disease entity should be included in the differential diagnosis of pulmonary thromboembolism. Patients with early identification can have curative potential with aggressive surgical intervention.
Pinto-Plata, V M; Pozo-Parilli, J C; Baum-Agay, A; Curiel, C; Sánchez de León, R
To determine the effects of pH changes on Pulmonary Artery Pressure (PAP), 18 isolated rabbit lung preparations, perfused with autologous blood mixture and constant PaCO2 have been studied. Each preparation was studied under 3 conditions: Baseline: 30 minutes equilibration period. Acidosis: pH was decreased by 0.2 N HCl infusion, the ventilatory rate was changed and different CO2 mixtures were used to maintain the PCO2 within the initial parameters. Compensated Acidosis (CA): pH was returned to normal values by 0.7 N NaHCO3 infusion maintaining PCO2 in its initial values. The decrease in pH (acidosis) from 7.36 +/- 0.05 to 7.18 +/- 0.06 at constant PCO2, generated a significant increase in PAP (13.6 +/- 3.2 cm H2O to 18.8 +/- 5.2 cm H2O, p < 0.01). The pH increase (CA) from 7.18 +/- 0.06 to 7.40 +/- 0.09 caused the PAP to decrease (18.8 +/- 5.2 cm H2O to 15.9 +/- 4.2 cm H2O); the fluid filtration rate remained unchanged during the whole experiment. It is concluded that blood pH changes at constant PCO2 result in significant changes of PAP. Acidemia produces pulmonary vasoconstriction, which may be a contributing factor in the genesis of pulmonary hypertension in clinical conditions with increased hydrogen ion concentration [H+].
Adeli, Hassan; Nemati, Bardia; Jandaghi, Mahboubeh; Riahi, Mohammad Mahdi; Salarvand, Fatemeh
BACKGROUND Primary pulmonary artery sarcomas are very rare and their histologic type called leiomyosarcoma is even rarer. These tumors are frequently misdiagnosed as pulmonary thromboembolism in clinical settings. Many patients receive anticoagulant therapy without response, and many are diagnosed postmortem only. Most of the tumors reported in the literature have involved the right ventricular outflow tract and the main pulmonary trunk, often extending into the main pulmonary artery (MPA) branches. CASE REPORT A 64-year-old woman presented with weakness, fatigue, malaise, dyspnea, and marked elevation of pulmonary artery pressure was admitted to our hospital. She was initially diagnosed with chronic pulmonary thromboembolism, and chest computed tomography (CT) scan revealed lobulated heterogeneous left hilar mass extended to precarinal and subcarinal space. Magnetic resonance imaging (MRI) demonstrated a polypoid lesion at the trunk with extension to left MPA and its first branch. The patient was operated, and a yellowish-shiny solid mass in pulmonary trunk was seen intra-operation and pulmonary endarterectomy was performed. Her tumor was pathologically diagnosed as pulmonary artery leiomyosarcoma. CONCLUSION Clinicians must consider pulmonary artery sarcoma when making the differential diagnosis for patients with pulmonary artery masses. The clinical prediction scores and the CT and MRI findings can help identifying patients with pulmonary artery sarcoma. PMID:25161682
Yan, Tao; Zhang, Guan-xin; Li, Bai-lin; Zhong, Keng; Xu, Zhi-yun; Han, Lin
We sought to explore the pulmonary haemodynamic changes in rheumatic mitral stenosis patients with secondary pulmonary hypertension. The pulmonary artery resistance and compliance of 35 patients with rheumatic mitral stenosis and 12 controls without cardiopulmonary vascular disease were evaluated by using an improved method, which is based on making calculations with parameters obtained from right heart catheterisation. The results are as follows: (1) pulmonary artery compliance in patients with secondary pulmonary hypertension was significantly lower than that of the control group (P<0.01); (2) linear correlation analyses showed that preoperative mean pulmonary artery pressure (mPAP) closely correlated with zero-pressure compliance in the mitral stenosis group (r=-0.745, P<0.05); (3) PAP and pulmonary vascular resistance decreased significantly in both groups with mitral stenosis after infusing 0.5 μg kg(-1) min(-1) of sodium nitroprusside (P<0.01). The pulmonary zero pressure compliance and mean pressure compliance increased significantly in the group with mild pulmonary hypertension; whereas in the severe group, the mean compliance changed with significance as the mPAP decreased (1.51 ± 0.59 vs 1.81 ± 0.77 ml/mmHg), however no significant change occurred in the pulmonary zero pressure compliance (2.35 ± 1.24 ml/mmHg vs. 2.24 ± 1.53 ml/mmHg, P>0.05) The walls of pulmonary artery vessels in patients with pulmonary hypertension secondary to rheumatic mitral stenosis appeared to be remodelled by varying degrees as indicated by their haemodynamic properties. Structural remodelling may be a factor affecting preoperative pulmonary artery pressure. Mitral stenosis patients with severe pulmonary hypertension have significantly lower responses to sodium nitroprusside possibly due to aggradation and deposition of collagen in the artery walls, decreasing constriction and dilation, or atrophy of smooth muscle cells.
Weir, E. Kenneth; Archer, Stephen L.; Markowitz, Jeremy; Rose, Lauren; Pritzker, Marc; Madlon-Kay, Richard; Thenappan, Thenappan
Abstract Pulmonary pulse wave transit time (pPTT), defined as the time for the systolic pressure pulse wave to travel from the pulmonary valve to the pulmonary veins, has been reported to be reduced in pulmonary arterial hypertension (PAH); however, the underlying mechanism of reduced pPTT is unknown. Here, we investigate the hypothesis that abbreviated pPTT in PAH results from impaired right ventricular–pulmonary artery (RV-PA) coupling. We quantified pPTT using pulsed-wave Doppler ultrasound from 10 healthy age- and sex-matched controls and 36 patients with PAH. pPTT was reduced in patients with PAH compared with controls. Univariate analysis revealed the following significant predictors of reduced pPTT: age, right ventricular fractional area change (RV FAC), tricuspid annular plane excursion (TAPSE), pulmonary arterial pressures (PAP), diastolic pulmonary gradient, transpulmonary gradient, pulmonary vascular resistance, and RV-PA coupling (defined as RV FAC/mean PAP or TAPSE/mean PAP). Although the correlations between pPTT and invasive markers of pulmonary vascular disease were modest, RV FAC (r = 0.64, P < 0.0001), TAPSE (r = 0.67, P < 0.0001), and RV-PA coupling (RV FAC/mean PAP: r = 0.72, P < 0.0001; TAPSE/mean PAP: r = 0.74, P < 0.0001) had the strongest relationships with pPTT. On multivariable analysis, only RV FAC, TAPSE, and RV-PA coupling were independent predictors of pPTT. We conclude that shortening of pPTT in patients with PAH results from altered RV-PA coupling, probably occurring as a result of reduced pulmonary arterial compliance. Thus, pPTT allows noninvasive determination of the status of both the pulmonary vasculature and the response of the RV in patients with PAH, thereby allowing monitoring of disease progression and regression. PMID:28090301
Tsapenko, Mykola V; Tsapenko, Arseniy V; Comfere, Thomas BO; Mour, Girish K; Mankad, Sunil V; Gajic, Ognjen
Pulmonary artery pressure elevation complicates the course of many complex disorders treated in a noncardiac intensive care unit. Acute pulmonary hypertension, however, remains underdiagnosed and its treatment frequently begins only after serious complications have developed. Significant pathophysiologic differences between acute and chronic pulmonary hypertension make current classification and treatment recommendations for chronic pulmonary hypertension barely applicable to acute pulmonary hypertension. In order to clarify the terminology of acute pulmonary hypertension and distinguish it from chronic pulmonary hypertension, we provide a classification of acute pulmonary hypertension according to underlying pathophysiologic mechanisms, clinical features, natural history, and response to treatment. Based on available data, therapy of acute arterial pulmonary hypertension should generally be aimed at acutely relieving right ventricular (RV) pressure overload and preventing RV dysfunction. Cases of severe acute pulmonary hypertension complicated by RV failure and systemic arterial hypotension are real clinical challenges requiring tight hemodynamic monitoring and aggressive treatment including combinations of pulmonary vasodilators, inotropic agents and systemic arterial vasoconstrictors. The choice of vasopressor and inotropes in patients with acute pulmonary hypertension should take into consideration their effects on vascular resistance and cardiac output when used alone or in combinations with other agents, and must be individualized based on patient response. PMID:19183752
Kriz, Joseph P; Munfakh, Nabil A; King, Gregory S; Carden, Juan O
Pulmonary artery intimal sarcomas are rare and lethal malignant tumors that typically affect larger vessels: the aorta, inferior vena cava, and pulmonary arteries. Since symptoms and imaging of pulmonary arterial intimal sarcomas mimic pulmonary thromboembolism, the differential diagnosis of a patient presenting with chest pain, dyspnea, and filling defect within the pulmonary arteries should include intimal sarcoma. Often right ventricular failure is observed due to pulmonary hypertension caused by the obstructive effect of the tumor and concomitant chronic thromboembolism. We report the case of a 72-year-old African-American male with arterial intimal sarcoma of the left and right pulmonary artery with extension through the right artery into the bronchus and right lung.
Kriz, Joseph P.; Munfakh, Nabil A.; King, Gregory S.; Carden, Juan O.
Pulmonary artery intimal sarcomas are rare and lethal malignant tumors that typically affect larger vessels: the aorta, inferior vena cava, and pulmonary arteries. Since symptoms and imaging of pulmonary arterial intimal sarcomas mimic pulmonary thromboembolism, the differential diagnosis of a patient presenting with chest pain, dyspnea, and filling defect within the pulmonary arteries should include intimal sarcoma. Often right ventricular failure is observed due to pulmonary hypertension caused by the obstructive effect of the tumor and concomitant chronic thromboembolism. We report the case of a 72-year-old African-American male with arterial intimal sarcoma of the left and right pulmonary artery with extension through the right artery into the bronchus and right lung. PMID:27239183
Robinson, Jeffrey C; Pugliese, Steven C; Fox, Daniel L; Badesch, David B
Pulmonary arterial hypertension (PAH) is characterized by molecular and pathologic alteration to the pulmonary circulation, resulting in increased pulmonary vascular resistance, right ventricular failure, and eventual death. Pharmacologic treatment of PAH consists of use of a multitude of pulmonary vasodilators, sometimes in combination. PAH has been associated with increased thrombosis and disrupted coagulation and fibrinolysis, making anticoagulation an attractive and frequently employed therapeutic modality. Observational studies have provided some insight into the therapeutic potential of anticoagulation in idiopathic PAH, but there is a distinct lack of well-controlled prospective trials. Due to the conflicting evidence, there is a large amount of heterogeneity in the application of therapeutic anticoagulation in PAH and further well-controlled prospective trials are needed to clarify its role in treating PAH.
Matsubara, Hiromi; Ogawa, Aiko
Treatment of pulmonary hypertension has progressed by recently developed pulmonary arterial hypertension-targeted drugs. However, long-term survival of the patients with idiopathic/heritable pulmonary arterial hypertension is still suboptimal. To improve the outcomes, treatment goals of pulmonary hypertension were proposed at the 5th World Symposium on Pulmonary Hypertension held at Nice, France in 2013; parameters were obtained from cardiopulmonary exercise test, blood tests, echocardiography, and magnetic resonance imaging. In particular, parameters evaluating right ventricular function have been highlighted because survival of the patients with pulmonary arterial hypertension is closely related to right ventricular function. However, treatment specifically targeted to improve right ventricular function in pulmonary hypertension is not yet established. In this setting, we need to maintain or improve right ventricular function with available vasodilators. In this review, we focus on the following two points: (1) Why can pulmonary arterial hypertension-targeted drugs improve right ventricular function without an apparent decrease in pulmonary artery pressure? (2) Are proposed goals sufficient to improve long-term prognosis of the patients? Further, we will discuss what would be the appropriate goal in treating patients with pulmonary arterial hypertension.
Heusner, A. A.; Tracy, M. L.
Describes a simple hydraulic analog which allows students to explore some physical aspects of the cardiovascular system and provides them with a means to visualize and conceptualize these basic principles. Simulates the behavior of arterial pressure in response to changes in heart rate, stroke volume, arterial compliance, and peripheral…
Koch, Achim; Mechtersheimer, Gunhild; Tochtermann, Ursula; Karck, Matthias
A 64-year-old male developed chest pain while gardening. Aortic dissection and coronary artery disease were excluded but chest computed tomography (CT) scan showed an aneurysmic enlargement of the pulmonary artery and a fluttering structure within. He underwent immediate sternotomy for replacement of the pulmonary artery. Histology showed an intimal sarcoma of both branches of the pulmonary artery. The pulmonary artery was replaced by a T-shaped Gore-Tex-prosthesis.
AOKI, Takuma; SUNAHARA, Hiroshi; SUGIMOTO, Keisuke; ITO, Tetsuro; KANAI, Eiichi; FUJII, Yoko
Case 1 involved a 4-month-old intact male Somali cat in which peripheral pulmonary artery stenosis (PPS) was recognized after a cardiac murmur remained following patent ductus arteriosus ligation. Case 2, which involved a 1-year-old neutered male Norwegian Forest cat, and Case 3, which involved a 6-month-old intact female American Curl cat, were referred, because of cardiac murmurs. Grades III to IV/VI systolic heart murmurs were auscultated at the left heart base in all 3 cats. All cases showed bilateral pulmonary artery stenosis, although there were no associated clinical signs. In Cases 1 and 2, the pressure gradient through the stenosis decreased after treatment with atenolol. PMID:25650057
Kanjanauthai, Somsupha; Kanluen, Tony; Ray, Cynthia
Pulmonary artery sarcoma is a highly malignant tumour. Therefore, making the diagnosis is very important. We describe a case which presented with dyspnea on exertion and was initially diagnosed as saddle pulmonary embolism per CT thorax with contrast. Despite adequate anticoagulation, symptoms still progressed. Follow-up CT thorax showed an extension of the presumed filling defect or clots into the left main pulmonary artery with new lung nodules. This prompted suspicion that this may not be a pulmonary embolism. Biopsy of the lung nodule revealed high grade soft tissue sarcoma with primary source from the pulmonary artery. Our case highlights that pulmonary artery sarcoma should always be included in the differential diagnosis of pulmonary embolism especially, if symptoms still progress while on adequate anticoagulation, or any pulmonary nodules develop on follow-up exam.
Suzuki, Chihiro; Takahashi, Masafumi . E-mail: email@example.com; Morimoto, Hajime; Izawa, Atsushi; Ise, Hirohiko; Hongo, Minoru; Hoshikawa, Yasushi; Ito, Takayuki; Miyashita, Hiroshi; Kobayashi, Eiji; Shimada, Kazuyuki; Ikeda, Uichi
Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of smooth muscle cells (SMCs), leading to occlusion of pulmonary arterioles, right ventricular (RV) hypertrophy, and death. We investigated whether mycophenolate mofetil (MMF), a potent immunosuppresssant, prevents the development of monocrotaline (MCT)-induced PAH in rats. MMF effectively decreased RV systolic pressure and RV hypertrophy, and reduced the medial thickness of pulmonary arteries. MMF significantly inhibited the number of proliferating cell nuclear antigen (PCNA)-positive cells, infiltration of macrophages, and expression of P-selectin and interleukin-6 on the endothelium of pulmonary arteries. The infiltration of T cells and mast cells was not affected by MMF. In vitro experiments revealed that mycophenolic acid (MPA), an active metabolite of MMF, dose-dependently inhibited proliferation of human pulmonary arterial SMCs. MMF attenuated the development of PAH through its anti-inflammatory and anti-proliferative properties. These findings provide new insight into the potential role of immunosuppressants in the treatment of PAH.
Perros, Frédéric; Dorfmüller, Peter; Humbert, Marc
Regardless of the initial trigger, the elevated pulmonary arterial pressure and vascular resistance in patients with pulmonary arterial hypertension are primarily caused by remodeling and thrombosis of small- and medium-sized pulmonary arteries and arterioles, as well as sustained vasoconstriction. The process of pulmonary vascular remodeling involves all layers of the vessel wall and is complicated by cellular heterogeneity within each compartment. Indeed, each cell type (endothelial cells, smooth muscle cells, and fibroblasts), as well as inflammatory cells and platelets, may play significant roles in this condition. Recent studies have emphasized the relevance of several mediators in this condition, including prostaglandin-I (2) (prostacyclin), nitric oxide, endothelin-1, angiopoietin-1, 5-hydroxytryptamine (serotonin), cytokines, chemokines, and members of the transforming growth factor beta (TGF-beta) superfamily. Targeting some of these dysfunctional pathways (prostacyclin, nitric oxide, and endothelin-1) has been beneficial in subjects displaying pulmonary arterial hypertension.
Mouratoglou, Sophia-Anastasia; Giannakoulas, George; Deftereos, Spyridon; Giannopoulos, Georgios; Angelidis, Christos; Cleman, Michael W; Vassilikos, Vassilios P
Pulmonary arterial hypertension (PAH) is a serious life threatening disease that leads to right heart failure and death. Elevated pulmonary vascular resistance (PVR) is the main pathophysiological component that leads to elevated pulmonary arterial pressures and increased right ventricular afterload. Increased PVR is related to different mechanisms that include vasoconstriction, proliferative and obstructive remodeling of the pulmonary vessel wall and in situ thrombosis. Numerous molecular, genetic and humoral abnormalities have been proposed to play an important role in pulmonary vasoconstriction and remodeling. Of those, calcium (Ca(+2)) is a well recognized parameter involved in the pathogenetic mechanisms of PAH, because of its twofold role in both vasoconstriction and pulmonary artery smooth muscle cell (PASMC) proliferation. The aim of this review is to focus on Ca(+2) handling and dysregulation in PASMC of PAH patients.
Siordia, Juan A; Garlish, Amanda; Truong, Huong
Primary pulmonary artery sarcoma is a rare disease that has a poor survival prognosis due to misdiagnosis with pulmonary thromboembolism or metastatic embolisation, detailed image findings and complicated surgical procedures. Surgical procedures established for treatment include pneumonectomy and pulmonary endarterectomy. Survival after surgery still remains at 1 year survival of 50%. The following case report demonstrates a patient's status postpneumonectomy for pulmonary artery sarcoma that presented with no complications after 1.5-year follow-up.
Wang, Kai; Ma, Jianfa; Pang, Yusheng; Lao, Jinquan; Pan, Xuanren; Tang, Qiaoyun; Zhang, Feng; Su, Danyan; Qin, Suyuan; Shrestha, Arnav Prasad
Calcium-activated chloride channels (CaCCs) play a vital role in regulating pulmonary artery tone during pulmonary arterial hypertension (PAH) induced by high blood flow. The role of CaCCs inhibitor niflumic acid (NFA) in vivo during this process requires further investigation. We established the PAH model by abdominal shunt surgery and treated with NFA in vivo. Fifty rats were randomly divided into normal, sham, shunt, NFA group 1 (0.2 mg/kg), and NFA group 2 (0.4 mg/kg). Pathological changes, right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter were analyzed. Then contraction reactions of pulmonary arteries were measured. Finally, the electrophysiological characteristics of pulmonary arterial smooth muscle cells were investigated using patch-clamp technology. After 11 weeks of shunting, PAH developed, accompanied with increased right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter. In the NFA treatment groups, the pressure and pathological changes were alleviated. The pulmonary artery tone in the shunt group increased, whereas it decreased after NFA treatment. The current density of CaCC was higher in the shunt group, and it was decreased in the NFA treatment groups. In conclusion, NFA attenuated pulmonary artery tone and structural remodeling in PAH induced by high pulmonary blood flow in vivo. CaCCs were involved and the augmented current density was alleviated by NFA treatment.
Elliott, C Gregory
Painstaking research led to the discovery of gene mutations responsible for heritable forms of pulmonary arterial hypertension (PAH). Mutations in the gene BMPR2, which codes for a cell surface receptor (BMPRII), cause the approximately 80% of heritable cases of PAH. Less commonly mutations in ALK1, CAV1, ENG, and SMAD9, and newly discovered mutations in KCNK3, may cause heritable PAH. Other family members of many patients diagnosed with idiopathic PAH may be diagnosed with PAH. Genetic counseling and testing should be offered to patients diagnosed with heritable or idiopathic PAH.
Yamamoto, Kei; Nozue, Tsuyoshi; Tsuchida, Masayuki; Iwaki, Taku; Nagamine, Hiroshi; Yasuda, Tamotsu; Kawase, Hiroshi; Matsushita, Kazuhiko; Michishita, Ichiro
We herein report the case of a 39-year-old woman with a pulmonary embolism caused by intimal sarcoma of the pulmonary artery. She presented with shortness of breath and leg edema. Computed tomography showed a low density area that extended from the main pulmonary artery to the bilateral pulmonary arteries. We diagnosed her to have a pulmonary thromboembolism. The thrombosis did not decrease after the administration of anti-coagulant therapy, and she underwent resection of the thrombotic tissue. Histopathologically, the surgical specimen was not found to be thrombotic tissue but rather an intimal sarcoma of the pulmonary artery. After undergoing surgery, she received radiation therapy and chemotherapy; however, she died 31 months after being diagnosed.
Hou, Yulong; Shen, Zhenya; Gao, Wei; Ye, Wenxue
A 72-year-old woman with pulmonary artery intimal sarcoma was successfully treated with surgery. With heightened clinical awareness and technological advancement, more and more cases were diagnosed definitely before operation. Computed tomography of the chest showed a mass in right ventricular extending to pulmonary trunk and the left pulmonary artery. The patient underwent complete surgical resection and repair of the pulmonary artery with no evidence of recurrence during the 12-month follow-up, suggesting that early identification and aggressive surgical intervention would improve survival.
Santos-Ribeiro, Diana; Mendes-Ferreira, Pedro; Maia-Rocha, Carolina; Adão, Rui; Leite-Moreira, Adelino F; Brás-Silva, Carmen
Pulmonary arterial hypertension is a progressive syndrome based on diverse aetiologies, which is characterized by a persistent increase in pulmonary vascular resistance and overload of the right ventricle, leading to heart failure and death. Currently, none of the available treatments is able to cure pulmonary arterial hypertension; additional research is therefore needed to unravel the associated pathophysiological mechanisms. This review summarizes current knowledge related to this disorder, and the several experimental animal models that can mimic pulmonary arterial hypertension and are available for translational research.
Serino, G; Giacomazzi, F
Pulmonary Hypertension (PH) is definited by a mean pulmonary artery pressure (PAPm) >25 mmHg at rest. The Dana Point 2008 Revised Classification System represents the most recent classification system update with respect of various etiologies of PH. About 10 % of adolescents or adults with uncorrected congenital heart disease (CHD) with left-to-right shunt and high pulmonary blood flow develop Pulmonary Arterial Hypertension (PAH) . Progressive vascular remodeling and increase in pulmonary vascular resistance (PVR) may ultimately lead to reversal of the shunt (pulmonary to systemic) causing cyanosis and determining the so-called Eisenmenger Syndrome (ES). Recent advances in the early diagnosis and medical targeted treatment of adult patients with CHD-PAH and ES can improve PAP, PVR and exercise tolerance, together with NYHA Class and survival, and may potentially reverse the vascular remodeling process in selected patients.
Naeije, Robert; Manes, Alessandra
Pulmonary arterial hypertension (PAH) is a right heart failure syndrome. In early-stage PAH, the right ventricle tends to remain adapted to afterload with increased contractility and little or no increase in right heart chamber dimensions. However, less than optimal right ventricular (RV)-arterial coupling may already cause a decreased aerobic exercise capacity by limiting maximum cardiac output. In more advanced stages, RV systolic function cannot remain matched to afterload and dilatation of the right heart chamber progressively develops. In addition, diastolic dysfunction occurs due to myocardial fibrosis and sarcomeric stiffening. All these changes lead to limitation of RV flow output, increased right-sided filling pressures and under-filling of the left ventricle, with eventual decrease in systemic blood pressure and altered systolic ventricular interaction. These pathophysiological changes account for exertional dyspnoea and systemic venous congestion typical of PAH. Complete evaluation of RV failure requires echocardiographic or magnetic resonance imaging, and right heart catheterisation measurements. Treatment of RV failure in PAH relies on: decreasing afterload with drugs targeting pulmonary circulation; fluid management to optimise ventricular diastolic interactions; and inotropic interventions to reverse cardiogenic shock. To date, there has been no report of the efficacy of drug treatments that specifically target the right ventricle.
Roman, Antonio; López-Meseguer, Manuel; Domingo, Enric
Treatment of pulmonary arterial hypertension has achieved significant progress over the past 20 years. Currently, 3 groups of drugs have proven useful for the treatment of this disease: endothelin receptor antagonist, phosphodiesterase inhibitors and prostacyclin and its analogues. It is recommended to initiate treatment with one of these drugs, the choice depending on the initial severity of patient disease and the preferences of the treating physician. When the patient does not have a satisfactory response, new drugs acting at a different pathway are most commonly added. At this time, considering referral for lung transplantation could be an alternative. Most experts recommend grouping maximum experience in what is known as expert centers. Treatment has led to better survival in these patients, but there is still a long way to cure this life-threatening disease.
Fedde, M R; Erickson, H H
Blood was taken from 49 Thoroughbred horses before and after racing at the track to determine if frusemide modified the apparent viscosity of the blood and to determine the effects of changes in shear rate and packed cell volume (PCV), associated with strenuous exercise, on apparent and relative viscosities. Small increases in apparent viscosity of the blood (at a specified PCV and shear rate) occurred in horses given frusemide compared to those receiving no frusemide; however, no differences were seen in relative viscosity. Although 2 groups of horses, those receiving frusemide before racing and those not receiving this drug were studied, the results suggest no influence of frusemide on any red blood cell variable that might modify apparent blood viscosity. Apparent viscosity of the blood was slightly (but significantly) higher after racing than before racing at any given PCV and shear rate, but relative viscosity was lower in the post race than in the prerace blood sample. The most important contributing factor to the increase in apparent viscosity in blood during racing is the increase in PCV, because the blood becomes nearly shear rate independent at shear rates likely to exist in the cardiovascular system during exercise. With an increase in PCV from 40 to 65% at shear rates above 225/s, apparent viscosity approximately doubled. However, this increase alone cannot account for the elevated pulmonary vascular pressure in the running horse, and additional factors, especially those causing the high left atrial pressure, must be considered. The cause of the elevated pressure may be multifactorial in nature.
Zhao, Zhi-Min; Liu, Su-Xuan; Zhang, Guan-Xin; Yang, Fan; Wang, Yang; Wu, Feng; Zhao, Xian-Xian; Xu, Zhi-Yun
While the molecular chaperone heat shock protein 90 (HSP90) is involved in a multitude of physiological and pathological processes, its role relating to pulmonary arterial hypertension (PAH) remains unclear. In the present study, we investigated the effect in which HSP90 improves pulmonary arteriole remodeling, and explored the therapeutic utility of targeting HSP90 as therapeutic drug for PAH. By Elisa and immunohistochemistry, HSP90 was found to be increased in both plasma and membrane walls of pulmonary arterioles from PAH patients. Moreover, plasma HSP90 levels positively correlated with mean pulmonary arterial pressure and C-reactive protein. In a monocrotaline-induced rat model of PH, we found that 17-AAG, a HSP90-inhibitor, alleviated the progress of PH, demonstrated by lower pulmonary arterial pressure and absence of right ventricular hypertrophy. Immunohistochemical staining demonstrated that 17-AAG improved pulmonary arteriole remodeling on the basis of reduced wall thickness and wall area. The inflammatory response attributed to PH could be attenuated by 17-AAG through reduction of NF-κB signaling. Moreover, 17-AAG was found to suppress PDGF-stimulated proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) through induction of cell cycle arrest in the G1 phase. In conclusion, HSP90 inhibitor 17-AAG could improve pulmonary arteriole remodeling via inhibiting the excessive proliferation of PASMCs, and inhibition of HSP90 may represent a therapeutic avenue for the treatment of PAH. PMID:27472464
Yang, Ying; Qiao, Jian; Wang, Huiyu; Gao, Mingyu; Ou, Deyuan; Zhang, Jianjun; Sun, Maohong; Yang, Xin; Zhang, Xiaobo; Guo, Yuming
Calcium signaling has been reported to be involved in the pathogenesis of hypertension. Verapamil, one of the calcium antagonists, is used to characterize the role of calcium signaling in the development of pulmonary arterial hypertension syndrome in broilers. The suppression effect of verapamil on pulmonary arterial hypertension and pulmonary vascular remodeling was examined in broilers, from the age of 16 days to 43 days. Our results showed that oral administration of lower dose of verapamil (5 mg/kg body weight every 12 h) prevented the mean pulmonary arterial pressure, the ascites heart index and the erythrocyte packed cell volume of birds at low temperature from increasing, the heart rate from decreasing, and pulmonary arteriole median from thickening, and no pulmonary arteriole remodeling in broilers treated with the two doses of verapamil at low temperature was observed. Our results indicated that calcium signaling was involved in the development of broilers' pulmonary arterial hypertension, which leads to the development of ascites, and we suggest that verapamil may be used as a preventive agent to reduce the occurrence and development of pulmonary arterial hypertension in broilers.
Ahmed, Mostafa; Hamed, Fadi; Prieto, Lourdes R.
Abstract Peripheral pulmonary artery stenosis (PPAS) is an underrecognized condition in the adult population. PPAS can lead to pulmonary hypertension but is likely misdiagnosed as either idiopathic pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. We retrospectively identified adult patients with PPAS either in its isolated form or related to other congenital defects from January 1998 to September 2012. We reviewed the patients’ clinical data by using our hospital electronic medical records and/or their paper charts. We identified 6 adult patients with PPAS with an age range of 16–56 years (1 woman and the rest men). Presenting signs and symptoms were thoracic murmurs, progressive dyspnea, and syncope. Three patients had Williams-Beuren syndrome. Pulmonary angiography showed that PPAS was predominantly located in main branches or lobar pulmonary arteries in 5 patients, while in 1 patient the arterial narrowing was at the level of the segmental pulmonary arteries. Right heart catheterization showed a mean pulmonary artery pressure (PAP) ranging from 35 to 60 mmHg. Balloon dilation was performed in all patients, predominantly in the lobar arteries, and it caused a decrease in mean PAP that ranged from 16% to 46% in 5 patients. In 1 patient the mean PAP did not decrease. All but 1 patient had follow-up echocardiograms at 1 year that showed stable echocardiographic findings. Pulmonary hypertension due to PPAS continues to presents a diagnostic challenge. Therefore, a high index of suspicion during the initial evaluation of pulmonary hypertension is essential for its prompt diagnosis and adequate treatment. PMID:25992283
Hall, J E; Guyton, A C; Coleman, T G; Mizelle, H L; Woods, L L
The importance of the renal pressure natriuresis and diuresis mechanisms in long-term control of body fluid volumes and arterial pressure has been controversial and difficult to quantitate experimentally. Recent studies, however, have demonstrated that in several forms of chronic hypertension caused by aldosterone, angiotensin II (AngII), vasopressin, or norepinephrine and adrenocorticotropin, increased renal arterial pressure is essential for maintaining normal excretion of sodium and water in the face of reduced renal excretory capability. When renal arterial pressure was servo-controlled in these models of hypertension, sodium and water retention continued unabated, causing ascites, pulmonary edema, or even complete circulatory collapse within a few days. Apparently, other mechanisms for volume homeostasis, such as the various natriuretic and diuretic factors that have been postulated, are not sufficiently powerful to maintain fluid balance in the absence of increased renal arterial pressure when renal excretory function is reduced in these forms of hypertension. The intrarenal mechanisms responsible for pressure natriuresis and diuresis are not entirely clear, but they seem to involve small increases in glomerular filtration rate and filtered load as well as reductions in fractional reabsorption in proximal and distal tubules. During chronic disturbances of arterial pressure additional factors, especially changes in AngII and aldosterone formation, act to amplify the effectiveness of the basic renal pressure natriuresis and diuresis mechanisms in regulating arterial pressure and body fluid volumes.
Yamasaki, Motohisa; Sumi, Yuki; Sakakibara, Yumi; Tamaoka, Meiyo; Miyazaki, Yasunari; Arai, Hirokumi; Kojima, Katsuo; Itoh, Fusahiko; Amano, Tomonari; Yoshizawa, Yasuyuki; Inase, Naohiko
A 63-year-old female presented with abnormal lung shadows but had, apart from this, few symptoms. Computed tomography (CT) revealed multiple nodules and blockage of the pulmonary artery. She was immediately diagnosed with pulmonary artery sarcoma based on a careful differential diagnosis and underwent surgery. Her tumor was pathologically diagnosed as leiomyosarcoma (i.e. intimal sarcoma). Pulmonary artery sarcoma can be easily confounded with thromboembolism in a clinical setting and some cases are diagnosed post mortem only. In our case, clinical prediction scores (Wells score, Geneva score, and revised Geneva score) for the pulmonary embolism showed low probability. Moreover, chest CT showed uncommon findings for pulmonary thromboembolism, as the nodules were too big for thrombi. Because surgical resection can provide the only hope of long-term survival in cases of pulmonary artery sarcoma, clinicians should consider this possibility in the differential diagnosis of pulmonary embolism. Clinical prediction scores and CT findings might help to reach the correct diagnosis of pulmonary artery sarcoma.
Guzeltas, Alper; Ozturk, Erkut; Tanidir, Ibrahim Cansaran; Kasar, Taner; Haydin, Sertac
Objective This study evaluated clinical and diagnostic findings, treatment methods, and follow-up of cases of anomalous coronary arteries from the pulmonary artery. Methods The study included all cases diagnosed with anomalous coronary arteries from the pulmonary artery between January 2012 and January 2016. Data from patients’ demographic characteristics, electrocardiography, echocardiography, angiographic findings, operation, intensive care unit stay, and follow-up were evaluated. Results The study included 12 patients (8 male, 4 female), 10 with anomalous left coronary artery from the pulmonary artery (ALCAPA) and 2 with anomalous right coronary artery from the pulmonary artery (ARCAPA). Median age at diagnosis was 4 months (range, 1 month - 10 years old) and median weight was 5.5 kg (range, 3-30 kg). The most common complaints were murmur (n=7) and respiratory distress (n=5). In 4 cases, the initial diagnosis was dilated cardiomyopathy. Electrocardiographs were pathologic in all cases. Echocardiographic examination revealed medium to severe mitral valve regurgitation in 4 cases and reduced (< 40%) ejection fraction in 6 patients. Of the 12 patients, 8 underwent direct implantation of the left coronary artery into the aorta, 2 underwent implantation of the right coronary artery into the aorta, and the remaining 2 underwent a Takeuchi procedure. There were no early mortalities. Median hospital stay was 20 days (range, 5-35 days). Median follow-up duration was 18 months (range, 5-36 months), and no cases required further surgery during follow-up. Conclusions Anomalous coronary arteries from the pulmonary artery can be successfully repaired providing there is early diagnosis and effective, appropriate intensive care unit follow-up. Therefore, coronary artery origins should be evaluated carefully, especially in cases with dilated cardiomyopathies.
Schiebler, Mark L.; Bhalla, Sanjeev; Runo, James; Jarjour, Nizar; Roldan, Alejandro; Chesler, Naomi; François, Christopher J.
The current Dana Point classification system (2009) divides elevation of pulmonary artery pressure into Pulmonary Arterial Hypertension (PAH) and Pulmonary Hypertension (PH). Fortunately, pulmonary arterial hypertension (PAH) is not a common disease. However, with the aging of the first world’s population, heart failure is now an important cause of pulmonary hypertension with up to 9% of the population involved. PAH is usually asymptomatic until late in the disease process. While there are indirect features of PAH found on noninvasive imaging studies, the diagnosis and management still requires right heart catheterization. Imaging features of PAH include: 1. Enlargement of the pulmonary trunk and main pulmonary arteries, 2. Decreased pulmonary arterial compliance, 3. Tapering of the peripheral pulmonary arteries, 4. Enlargement of the inferior vena cava, and 5. Increased mean transit time. The chronic requirement to generate high pulmonary arterial pressures measurably affects the right heart and main pulmonary artery. This change in physiology causes the following structural and functional alterations that have been shown to have prognostic significance: Relative area change of the pulmonary trunk, RVSVindex, RVSV, RVEDVindex, LVEDVindex, and baseline RVEF <35%. All of these variables can be quantified non-invasively and followed longitudinally in each patient using MRI to modify the treatment regimen. Untreated PAH frequently results in a rapid clinical decline and death within 3 years of diagnosis. Unfortunately, even with treatment, less than 1/2 of these patients are alive at four years. PMID:23612440
Karau, Kelly L.; Molthen, Robert C.; Johnson, Roger H.; Dhyani, Anita H.; Haworth, Steven T.; Dawson, Christopher A.
Animal models and micro-CT imaging are useful for understanding the functional consequences of, and identifying the genes involved in, the remodeling of vascular structures that accompanies pulmonary vascular disease. Using a micro-CT scanner to image contrast-enhanced arteries in excised lungs from fawn hooded rats (a strain genetically susceptible to hypoxia induced pulmonary hypertension), we found that portions of the pulmonary arterial tree downstream from a given diameter were morphometrically indistinguishable. This 'self-consistency' property provided a means for summarizing the pulmonary arterial tree architecture and mechanical properties using a parameter vector obtained from measurements of the contiguous set of vessel segments comprising the longest (principal) pathway and its branches over a range of vascular pressures. This parameter vector was used to characterize the pulmonary vascular remodeling that occurred in rats exposed to a hypoxic (11.5% oxygen) environment and provided the input to a hemodynamic model relating structure to function. The major effect of the remodeling was a longitudinally (pulmonary artery to arterioles) uniform decrease in vessel distensibility that resulted in a 90% increase in arterial resistance. Despite the almost uniform change in vessel distensibility, over 50% of the resistance increase was attributable to vessels with unstressed diameters less than 125 microns.
Bhattacharya, Mallar; Kallet, Richard H; Ware, Lorraine B; Matthay, Michael A
Negative-pressure pulmonary edema (NPPE) or postobstructive pulmonary edema is a well-described cause of acute respiratory failure that occurs after intense inspiratory effort against an obstructed airway, usually from upper airway infection, tumor, or laryngospasm. Patients with NPPE generate very negative airway pressures, which augment transvascular fluid filtration and precipitate interstitial and alveolar edema. Pulmonary edema fluid collected from most patients with NPPE has a low protein concentration, suggesting hydrostatic forces as the primary mechanism for the pathogenesis of NPPE. Supportive care should be directed at relieving the upper airway obstruction by endotracheal intubation or cricothyroidotomy, institution of lung-protective positive-pressure ventilation, and diuresis unless the patient is in shock. Resolution of the pulmonary edema is usually rapid, in part because alveolar fluid clearance mechanisms are intact. In this review, we discuss the clinical presentation, pathophysiology, and management of negative-pressure or postobstructive pulmonary edema.
Weir-McCall, Jonathan R.; Struthers, Allan D.; Lipworth, Brian J.; Houston, J. Graeme
COPD is the second most common cause of pulmonary hypertension, and is a common complication of severe COPD with significant implications for both quality of life and mortality. However, the use of a rigid diagnostic threshold of a mean pulmonary arterial pressure (mPAP) of ≥25mHg when considering the impact of the pulmonary vasculature on symptoms and disease is misleading. Even minimal exertion causes oxygen desaturation and elevations in mPAP, with right ventricular hypertrophy and dilatation present in patients with mild to moderate COPD with pressures below the threshold for diagnosis of pulmonary hypertension. This has significant implications, with right ventricular dysfunction associated with poorer exercise capability and increased mortality independent of pulmonary function tests. The compliance of the pulmonary artery (PA) is a key component in decoupling the right ventricle from the pulmonary bed, allowing the right ventricle to work at maximum efficiency and protecting the microcirculation from large pressure gradients. PA stiffness increases with the severity of COPD, and correlates well with the presence of exercise induced pulmonary hypertension. A curvilinear relationship exists between PA distensibility and mPAP and pulmonary vascular resistance (PVR) with marked loss of distensibility before a rapid rise in mPAP and PVR occurs with resultant right ventricular failure. This combination of features suggests PA stiffness as a promising biomarker for early detection of pulmonary vascular disease, and to play a role in right ventricular failure in COPD. Early detection would open this up as a potential therapeutic target before end stage arterial remodelling occurs. PMID:26095859
Shingaki, Masami; Kobayashi, Yutaka
60-year-old female who complained of severe dyspnea was admitted with a diagnosis of massive pulmonary embolism. An emergency operation was undertaken due to right side heart failure. Under extracorporeal circulation with beating heart, large, white and smooth surface mass which was originated from right pulmonary artery was removed. Pathology of the mass showed low differentiated sarcoma. No evidence of other primary lesion by positron emission tomography-computed tomography (PET-CT) suggested primary pulmonary artery sarcoma. We scheduled total resection of the right lung, however postoperative CT showed large mass occupying from right pulmonary artery to main pulmonary trunk. Palliative chemo radiation therapy was introduced. Pulmonary artery sarcoma mimicking pulmonary thromboembolism is so malignant that the diagnosis and treatment should not be delayed.
Enderby, Cher Y; Burger, Charles
Pulmonary arterial hypertension is a chronic, progressive disease of the pulmonary vasculature resulting in poor outcomes if left untreated. The management of group 1 pulmonary arterial hypertension has included the use of prostanoids, phosphodiesterase-5 inhibitors, and endothelin receptor antagonists targeting the prostacyclin, endothelin-1, and nitric oxide pathways. Three new medications have been approved by the US Food and Drug Administration over the past couple of years. Macitentan is the newest endothelin receptor antagonist, riociguat is a soluble guanylate cyclase stimulator, and treprostinil diolamine is the first oral prostanoid. This review will focus on the key trials leading to their approval, special considerations for each medication, and their potential place in therapy. The use of combination therapy as initial therapy in pulmonary arterial hypertension will also be discussed.
Introduction Disconnected pulmonary arteries are unusual and may result in pulmonary hypertension with acute right heart failure. Case presentation We report a case of a three-month-old Asian girl who presented with heart failure and severe pulmonary hypertension due to a disconnected right pulmonary artery. An epoprostenol (prostacyclin) infusion was instrumental in lowering pulmonary artery pressures and stabilizing the child prior to surgery. Conclusions This is, to the best of our knowledge, the first report of successful prostacyclin usage in such a situation. PMID:20525186
Genetic analysis has uncovered that familial and idiopathic pulmonary arterial hypertension (PAH) is linked to germline mutations in BMP type II receptor (BMPRII). PAH is characterized by enhanced remodeling of pulmonary arteries due to arterial smooth muscle cell proliferation. BMPRII mutations contribute to abnormal mitotic responses to BMP ligands in pulmonary artery smooth muscle cells. Unbalanced Smad signaling induced by BMP and TGFbeta is functionally involved in the pathogenesis of PAH. BMPRII mutations also increase the susceptibility of endothelial cell apoptosis. The combination of increased endothelial injury and impaired suppression of smooth muscle cell proliferation is critical for the cellular pathogenesis of PAH. However, the detailed molecular mechanism leading to severe vascular remodeling caused by BMPRII mutations has yet to be elucidated.
Atkins, C E; Keene, B W; McGuirk, S M; Sato, T
In an effort to better understand the role of vasodilators in the management of pulmonary hypertension associated with chronic heartworm disease (HWD), pulmonary hemodynamic measurements were obtained from 7 experimentally infected, anesthetized dogs before and after hydralazine administration (mean dose, 1.96 mg/kg of body weight). Five dogs were maintained on room air, while 2 were maintained on 100% oxygen during the hydralazine study. The hemodynamic effect of hydralazine in dogs with HWD was evaluated, using heart rate, cardiac index, mean pulmonary artery pressure, mean arterial pressure, total pulmonary resistance, total systemic resistance, total systemic resistance/total pulmonary resistance, left ventricular dP/dtmax, left ventricular end diastolic pressure, and left and right ventricular double products ([mean arterial pressure x heart rate] and [mean pulmonary artery pressure x heart rate], respectively). Responders were defined as those in which total pulmonary resistance decreased > or = 20% without an increase in mean pulmonary arterial pressure and in which heart rate increase was < or = 10%. Comparison was also made between maximal hemodynamic effect of hydralazine with that after 100% oxygen administration for 15 minutes to previously normoxemic dogs (n = 5). Significance was determined if P < 0.05, using the paired t-test. Hydralazine induced significant reductions in mean pulmonary and systemic arterial pressures and total pulmonary resistance, with no significant change in heart rate, cardiac index, total systemic resistance, left ventricular dP/dtmax, left ventricular end diastolic pressure, or right and left ventricular double products. Four (57%) of the 7 dogs studied were considered responders. Pretreatment cardiac index, mean pulmonary artery pressure, and total pulmonary resistance did not allow differentiation of responders from nonresponders.(ABSTRACT TRUNCATED AT 250 WORDS)
Boucherat, Olivier; Chabot, Sophie; Antigny, Fabrice; Perros, Frédéric; Provencher, Steeve; Bonnet, Sébastien
Pulmonary arterial hypertension (PAH) is a devastating cardiopulmonary disorder with various origins. All forms of PAH share a common pulmonary arteriopathy characterised by vasoconstriction, remodelling of the pre-capillary pulmonary vessel wall, and in situ thrombosis. Although the pathogenesis of PAH is recognised as a complex and multifactorial process, there is growing evidence that potassium channels dysfunction in pulmonary artery smooth muscle cells is a hallmark of PAH. Besides regulating many physiological functions, reduced potassium channels expression and/or activity have significant effects on PAH establishment and progression. This review describes the molecular mechanisms and physiological consequences of potassium channel modulation. Special emphasis is placed on KCNA5 (Kv1.5) and KCNK3 (TASK1), which are considered to play a central role in determining pulmonary vascular tone and may represent attractive therapeutic targets in the treatment of PAH.
Wideman, R F; Rhoads, D D; Erf, G F; Anthony, N B
Pulmonary arterial hypertension (PAH) syndrome in broilers (also known as ascites syndrome and pulmonary hypertension syndrome) can be attributed to imbalances between cardiac output and the anatomical capacity of the pulmonary vasculature to accommodate ever-increasing rates of blood flow, as well as to an inappropriately elevated tone (degree of constriction) maintained by the pulmonary arterioles. Comparisons of PAH-susceptible and PAH-resistant broilers do not consistently reveal differences in cardiac output, but PAH-susceptible broilers consistently have higher pulmonary arterial pressures and pulmonary vascular resistances compared with PAH-resistant broilers. Efforts clarify the causes of excessive pulmonary vascular resistance have focused on evaluating the roles of chemical mediators of vasoconstriction and vasodilation, as well as on pathological (structural) changes occurring within the pulmonary arterioles (e.g., vascular remodeling and pathology) during the pathogenesis of PAH. The objectives of this review are to (1) summarize the pathophysiological progression initiated by the onset of pulmonary hypertension and culminating in terminal ascites; (2) review recent information regarding the factors contributing to excessively elevated resistance to blood flow through the lungs; (3) assess the role of the immune system during the pathogenesis of PAH; and (4) present new insights into the genetic basis of PAH. The cumulative evidence attributes the elevated pulmonary vascular resistance in PAH-susceptible broilers to an anatomically inadequate pulmonary vascular capacity, to excessive vascular tone reflecting the dominance of pulmonary vasoconstrictors over vasodilators, and to vascular pathology elicited by excessive hemodynamic stress. Emerging evidence also demonstrates that the pathogenesis of PAH includes characteristics of an inflammatory/autoimmune disease involving multifactorial genetic, environmental, and immune system components. Pulmonary
Background The degree of pulmonary hypertension is not independently related to the severity of left ventricular systolic dysfunction but is frequently associated with diastolic filling abnormalities. The aim of this study was to assess diastolic times at increasing heart rates in normal and in patients with and without abnormal exercise-induced increase in pulmonary artery pressure (PASP). Methods. We enrolled 109 patients (78 males, age 62 ± 13 years) referred for exercise stress echocardiography and 16 controls. The PASP was derived from the tricuspid Doppler tracing. A cut-off value of PASP ≥ 50 mmHg at peak stress was considered as indicative of abnormal increase in PASP. Diastolic times and the diastolic/systolic time ratio were recorded by a precordial cutaneous force sensor based on a linear accelerometer. Results At baseline, PASP was 30 ± 5 mmHg in patients and 25 ± 4 in controls. At peak stress the PASP was normal in 95 patients (Group 1); 14 patients (Group 2) showed an abnormal increase in PASP (from 35 ± 4 to 62 ± 12 mmHg; P < 0.01). At 100 bpm, an abnormal (< 1) diastolic/systolic time ratio was found in 0/16 (0%) controls, in 12/93 (13%) Group 1 and 7/14 (50%) Group 2 patients (p < 0.05 between groups). Conclusion The first and second heart sound vibrations non-invasively monitored by a force sensor are useful for continuously assessing diastolic time during exercise. Exercise-induced abnormal PASP was associated with reduced diastolic time at heart rates beyond 100 beats per minute. PMID:22104611
Su, Junjing; Hilberg, Ole; Howard, Luke; Simonsen, Ulf; Hughes, Alun D
Mean pulmonary arterial pressure and pulmonary vascular resistance remain the most common hemodynamic measures to evaluate the severity and prognosis of pulmonary hypertension. However, pulmonary vascular resistance only captures the non-oscillatory component of the right ventricular hydraulic load and neglects the dynamic compliance of the pulmonary arteries and the contribution of wave transmission. Wave intensity analysis offers an alternative way to assess the pulmonary vasculature in health and disease. Wave speed is a measure of arterial stiffness and the magnitude and timing of wave reflection provide information on the degree of impedance mismatch between the proximal and distal circulation. Studies in the pulmonary artery have demonstrated distinct differences in arterial wave propagation between individuals with and without pulmonary vascular disease. Notably, greater wave speed and greater wave reflection are observed in patients with pulmonary hypertension and in animal models exposed to hypoxia. Studying wave propagation makes a valuable contribution to the assessment of the arterial system in pulmonary hypertension and here, we briefly review the current state of knowledge of the methods used to evaluate arterial waves in the pulmonary artery. PMID:27636734
Nakashima, S; Kuwaki, K; Komatsu, K; Tsukamoto, M; Abe, T
A 63-year-old woman who underwent surgical correction of a recurrent pulmonary artery aneurysm associated with pulmonary stenosis and regurgitation is reported. On April 1986, she underwent commissurotomy of pulmonary valve, reconstruction of right ventricle out flow tract using a Polystan monocusp patch and pulmonary aneurysmorrhaphy for pulmonary artery aneurysm. Pathological examination of the resected pulmonary arterial wall revealed mucoid degeneration of media and fragmentation of elastic fiber. Nine years after the operation, recurrence of pulmonary artery aneurysm, pulmonary stenosis and regurgitation were recognized. On September 1995, she underwent redo operation with graft replacement of pulmonary artery and pulmonary valve replacement using woven Dacron prosthesis containing a Carpentier-Edwards bioprosthetic valve. We should choose as an initial procedure with graft replacement for pulmonary artery aneurysm with fragility of the pulmonary arterial wall. She is now doing very well at one year and 5 months after the redo operation.
Presti, B; Berthrong, M; Sherwin, R M
Chronic massive thrombosis of major pulmonary arteries, usually described in 0.1% of autopsies, was found in 68 of 7,753 autopsies (0.9%) in our hospital. For comparison, 201 of the 7,753 autopsies (2.6%) revealed acute-massive pulmonary emboli. The 68 cases of chronic thromboses by definition had the right, left, or main pulmonary artery occluded or severely stenosed by organized thrombi. The average age was 67; males predominated 3 to 2. Dyspnea and right heart failure were the most common clinical features, though a correct antemortem diagnosis was rare. Severe lung disease was present in 34 cases (50%); one patient (1%) had mitral stenosis. In the remaining patients, clinical thrombophlebitis had been present in 20 cases (29%), and 13 cases (19%) had no recognized related disease. When the lung disease had prominent laterality, thrombi were invariably located on the side of the most serious disease, implying propagation of smaller thrombi in diseased lung retrograde to major arteries. In bilateral lung disease or in patients without lung disease, thromboses were randomly distributed between right or left sides, suggesting an embolic origin. Assessment of the severity of pulmonary arteriosclerosis and distal arterial patency indicated that most patients could have potentially benefited from surgical thromboendarterectomy. The reason for the high incidence of chronic pulmonary artery thrombosis in our autopsy service has not been elucidated. The effects of high altitude may be important in the pathogenesis, although polycythemia was not excessive in our cases.
Badesch, David B; Champion, Hunter C; Sanchez, Miguel Angel Gomez; Hoeper, Marius M; Loyd, James E; Manes, Alessandra; McGoon, Michael; Naeije, Robert; Olschewski, Horst; Oudiz, Ronald J; Torbicki, Adam
The diagnosis and assessment of pulmonary arterial hypertension is a rapidly evolving area, with changes occurring in the definition of the disease, screening and diagnostic techniques, and staging and follow-up assessment. The definition of pulmonary hypertension has been simplified, and is now based on currently available evidence. There has been substantial progress in advancing the imaging techniques and biomarkers used to screen patients for the disease and to follow up their response to therapy. The importance of accurate assessment of right ventricular function in following up the clinical course and response to therapy is more fully appreciated. As new therapies are developed for pulmonary arterial hypertension, screening, prompt diagnosis, and accurate assessment of disease severity become increasingly important. A clear definition of pulmonary hypertension and the development of a rational approach to diagnostic assessment and follow-up using both conventional and new tools will be essential to deriving maximal benefit from our expanding therapeutic armamentarium.
Zhou, Guofei; Chen, Tianji
Pulmonary arterial hypertension (PAH) is a devastating disease without effective treatment. Despite decades of research and the development of novel treatments, PAH remains a fatal disease, suggesting an urgent need for better understanding of the pathogenesis of PAH. Recent studies suggest that microRNAs (miRNAs) are dysregulated in patients with PAH and in experimental pulmonary hypertension. Furthermore, normalization of a few miRNAs is reported to inhibit experimental pulmonary hypertension. We have reviewed the current knowledge about miRNA biogenesis, miRNA expression pattern, and their roles in regulation of pulmonary artery smooth muscle cells, endothelial cells, and fibroblasts. We have also identified emerging trends in our understanding of the role of miRNAs in the pathogenesis of PAH and propose future studies that might lead to novel therapeutic strategies for the treatment of PAH. PMID:25192340
Sanal, Shirin; Aronow, Wilbert S; Ravipati, Gautham; Maguire, George P; Belkin, Robert N; Lehrman, Stuart G
We investigated the accuracy of computed tomographic measurements of main pulmonary artery diameter (MPAD) and of MPAD/ascending aorta diameter (AAD) in predicting moderate or severe pulmonary hypertension in 190 patients with acute pulmonary embolism. A pulmonary artery systolic pressure of > or = 50 mm Hg measured by Doppler echocardiography was considered moderate or severe pulmonary hypertension. A MPAD of > 28.6 mm and a MPAD/AAD ratio of > or = 1.00 measured by computed tomography were considered abnormal. A MPAD of > 28.6 mm had a 75% sensitivity and specificity, a 52% positive predictive value, a 89% negative predictive value, a 3.0 likelihood ratio for a positive test, and a 0.33 likelihood ratio for a negative test in predicting moderate or severe pulmonary hypertension. A MPAD/AAD ratio of > or = 1.00 had a 59% sensitivity, a 82% specificity, a 55% positive predictive value, a 84% negative predictive value, a 3.3 likelihood ratio for a positive test, and a 0.50 likelihood ratio for a negative test.
Szenczi, Orsolya; Karlócai, Kristóf; Bucsek, László; Rigó, János
Idiopathic pulmonary arterial hypertension is characterized by progressive increase in pulmonary arterial pressure and pulmonary vascular resistance which lead to right ventricular failure and death. Pregnancy in patients with idiopathic pulmonary arterial hypertension is contraindicated because of the high maternal and fetal mortality. The authors present a case of successful pregnancy and delivery of a patient with idiopathic pulmonary arterial hypertension in Hungary for the first time. The aim of the report was to demonstrate that management and treatment of idiopathic pulmonary arterial hypertension in a pregnant woman is a complex and multidisciplinary task that should involve obstetrician, cardiologist and anesthesiologist. Those patients who become pregnant and do not wish to terminate the pregnancy must be referred to obstetric centers where a multidiciplinary approach is taken.
Slavik, Z; Webber, S A; Lamb, R K; Horvath, P; LeBlanc, J G; Keeton, B R; Monro, J L; Tax, P; Tuma, S; Reich, O
Right-sided BSCA provides for satisfactory pulmonary arterial growth in infants and children with complex congenital heart defects, and it could enhance the growth of a small right pulmonary artery. The growth of the left pulmonary artery, particularly in younger patients, needs close attention to confirm the safe role of BSCA in long-term palliation.
Hako, René; Fedačko, Ján; Morochovič, Radoslav; Kristian, Pavol; Pekárová, Tímea; Tuomainen, Petri; Pella, Daniel
Background. Pulmonary arterial dissection with chronic pulmonary arterial hypertension as its major cause is a very rare but life-threatening condition. In most cases the main pulmonary trunk is the affected site usually without involvement of its branches. Segmental or lobar pulmonary artery dissection is extremely rare. Case Presentation. We report a unique case of left lower lobe pulmonary artery dissection in a 70-year-old male, with confirmed chronic pulmonary hypertension. To confirm dissection MDCT pulmonary angiography was used. Multiplanar reformation (MPR) images in sagittal, coronal, oblique sagittal, and curved projections were generated. This case report presents morphologic CT features of rare chronic left lobar pulmonary artery dissection associated with chronic pulmonary hypertension at a place of localised pulmonary artery calcification. CT pulmonary angiography excluded signs of thromboembolism and potential motion or flow artefacts. Conclusion. To the best of our knowledge, no case of lower lobe pulmonary artery dissection with flap calcification has been reported yet. CT imaging of the chest is a key diagnostic tool that is able to detect an intimal flap and a false lumen within the pulmonary arterial tree and is preferred in differential diagnosis of rare complications of sustained pulmonary arterial hypertension. PMID:28154579
Velebit, V.; Christenson, J. T.; Simonet, F.; Maurice, J.; Schmuziger, M.; Hauser, H.; Didier, D.
A pulmonary artery sarcoma was diagnosed preoperatively by magnetic resonance imaging enhanced with gadolinium and confirmed by percutaneous computed tomographic guided needle biopsy. Accurate preoperative diagnosis allowed planned curative surgery with removal of the right ventricular outflow tract and reconstructive surgery using a cryopreserved homograft. Images PMID:8539663
Zajtchuk, Rustik; Resnekov, Leon; Ranniger, Klaus; Gonzalez-Lavin, Lorenzo
A case of chronic aortic to pulmonary artery traumatic fistula is presented and the surgical repair is detailed. Closure through the aorta is recommended; this approach provides a dry operative field and avoids the need for dissection of adhesions around the fistulous tract. Fistulae of this type are not common and the pertinent literature is reviewed. Images PMID:5576540
Khomaziuk, V A
Echocardiographic evaluation was done of left ventricular functional state in 90 patients with primary and secondary pulmonary arterial hypertension with and without intercavitary shunting. Changes in left ventricular function were identified in 86% cases; they reflected disturbances in both ventricles compensatory interaction. The degree of changes depended on the degree of dilatation of the right ventricle and level of interchamber shunting.
SMA with some globular domains, predominantly colocalizing with GFP endothelial lineage-marked cells in the neointima (Figure 4F). Figure 4. VE...whether the neointima arises from a small population of apoptosis- resistant pulmonary artery endothelial cells that proliferate after injury to produce
Prasad, Rajniti; Srivastava, G N; Mishra, O P; Singh, Utpal Kant
We report a two-and-half–year-old boy who presented with recurrent respiratory tract infections. He had cortriatum of right atrium, spina bifida occulta, hemivertebra and dysplastic right thumb. On CT of chest, he had also unilateral pulmonary artery agenesis. The case is being reported because of common manifestations of rare disease and its associated cardiac and skeletal abnormalities. PMID:23784756
Meyer, F J; Lossnitzer, D; Kristen, A V; Schoene, A M; Kübler, W; Katus, H A; Borst, M M
Idiopathic pulmonary arterial hypertension (IPAH) is a pulmonary vasculopathy of unknown aetiology. Dyspnoea, peripheral airway obstruction and inefficient ventilation are common in IPAH. Data on respiratory muscle function are lacking. This prospective single-centre study included 26 female and 11 male patients with IPAH in World Health Organization functional classes II-IV. Mean+/-SD pulmonary artery pressure was 48.6+/-16.9 in females and 53.1+/-22.9 mmHg in males; cardiac output was 3.7+/-1.3 and 4.2+/-1.7 L x min(-1). Maximal inspiratory pressure (PI,max) was lower in the female patients than in 20 controls (5.3+/-2.0 versus 8.2+/-2.0 kPa). In the male patients, PI,max was lower than in 25 controls (6.8+/-2.2 versus 10.5+/-3.7 kPa). Maximal expiratory pressure (PE,max) was lower in the female patients than in controls (6.2+/-2.6 versus 9.5+/-2.1 kPa), and in male patients as compared to controls (7.1+/-1.6 versus 10.3+/-3.9 kPa). There was no correlation between PI,max or PE,max and parameters of pulmonary haemodynamics or exercise testing. The ratio of mouth occlusion pressure within the first 0.1 s of inspiration and PI,max was higher in IPAH than in controls (females 0.067+/-0.066 versus 0.021+/-0.008; males 0.047+/-0.061 versus 0.023+/-0.016). In conclusion, this study provides the first evidence of inspiratory and expiratory muscle weakness in idiopathic pulmonary arterial hypertension. The pathomechanisms and the prognostic significance should be further investigated.
Jiang, Xinguo; Tamosiuniene, Rasa; Sung, Yon K.; Shuffle, Eric M.; Tu, Allen B.; Valenzuela, Antonia; Jiang, Shirley; Zamanian, Roham T.; Fiorentino, David F.; Voelkel, Norbert F.; Peters-Golden, Marc; Stenmark, Kurt R.; Chung, Lorinda; Rabinovitch, Marlene; Nicolls, Mark R.
A recent study demonstrated a significant role for leukotriene B4 (LTB4) causing pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). LTB4 was found to directly injure luminal endothelial cells and promote growth of the smooth muscle cell layer of pulmonary arterioles. The purpose of the current study was to determine the effects of LTB4 on the pulmonary adventitial layer, largely composed of fibroblasts. Here, we demonstrate that LTB4 enhanced human pulmonary artery adventitial fibroblast (HPAAF) proliferation, migration and differentiation in a dose-dependent manner through its cognate G-protein coupled receptor, BLT1. LTB4 activated HPAAF by up-regulating p38 MAPK as well as Nox4 signaling pathways. In an autoimmune model of PH, inhibition of these pathways blocked perivascular inflammation, decreased Nox4 expression, reduced reactive oxygen species production, reversed arteriolar adventitial fibroblast activation and attenuated PH development. This study uncovers a novel mechanism by which LTB4 further promotes PAH pathogenesis, beyond its established effects on endothelial and smooth muscle cells, by activating adventitial fibroblasts. PMID:26558820
Perros, Frédéric; Humbert, Marc; Cohen-Kaminsky, Sylvia
It is admitted that autoimmunity results from a combination of risks such as genetic background, environmental triggers, and stochastic events. Pulmonary arterial hypertension (PAH) shares with the so-called prototypic autoimmune diseases, genetic risk factors, female predominance and sex hormone influence, association with other chronic inflammatory and autoimmune diseases, defects in regulatory T cells function, and presence of autoantibodies. Case reports have been published indicating the beneficial effect of some immunosuppressive and anti-inflammatory therapies in PAH, supporting the potential role of immune mechanisms in the pathophysiology of the disease. In this review, we discuss the current knowledge on autoimmune mechanisms operating in PAH, especially mounting a local autoimmune response inside the pulmonary tissue, namely pulmonary lymphoid neogenesis. A better understanding of the role of autoimmunity in pulmonary vascular remodelling may help develop targeted immunomodulatory strategies in PAH.
Gan, C.T.; Noordegraaf, A. Vonk; Marques, K.M.J.; Bronzwaer, J.G.F.; Postmus, P.E.; Boonstra, A.
Medical therapy for pulmonary arterial hypertension (PAH) focuses on pulmonary vascular remodelling and smooth muscle cell proliferation. This article covers the drugs which are approved or are in sight and the evidence-based treatment strategies that target the different pathobiological pathways, emanated from the World Health Organisation Symposium on Pulmonary Hypertension in Venice, June 2003. In addition we briefly look at the 'Venice consensus' on surgical treatment. In the past five and a half years more than 360 patients were seen for pulmonary hypertension in the Free University Medical Centre (VUmc). Present-day treatment, research studies and novel treatment strategies in the VUmc will be reviewed. Future treatments will be on the basis of insights into pathobiology, pathogenesis and genes in PAH and should focus on drug combinations, which theoretically target different or similar pathobiological pathways. PMID:25696358
Hao, Mingwen; Li, Miaomiao; Li, Wenjun
Galectin-3 (Gal-3) is a β-galactoside-binding lectin, which is important in inflammation, fibrosis and heart failure. The present study aimed to investigate the role and mechanism of Gal-3 in hypoxia-induced pulmonary arterial hypertension (PAH). Male C57BL/6J and Gal-3−/− mice were exposed to hypoxia, then the right ventricular systolic pressure (RVSP) and Fulton's index were measured, and Gal-3 mRNA and protein expression in the pulmonary arteries was analyzed by reverse transcription-quantitative polymerase chain reaction and western blotting. Compared with the control, hypoxia increased the mRNA and protein expression levels of Gal-3 in wild type murine pulmonary arteries. Gal-3 deletion reduced the hypoxia-induced upregulation of RVSP and Fulton's index. Furthermore, human pulmonary arterial endothelial cells (HPAECs) and human pulmonary arterial smooth muscle cells (HPASMCs) were stimulated by hypoxia in vitro, and Gal-3 expression was inhibited by small interfering RNA. The inflammatory response of HPAECs, and the proliferation and cell cycle distribution of HPASMCs was also analyzed. Gal-3 inhibition alleviated the hypoxia-induced inflammatory response in HPAECs, including tumor necrosis factor-α and interleukin-1 secretion, expression of intercellular adhesion molecule-1 and adhesion of THP-1 monocytes. Gal-3 inhibition also reduced hypoxia-induced proliferation of HPASMCs, partially by reducing cyclin D1 expression and increasing p27 expression. Furthermore, Gal-3 inhibition suppressed HPASMC switching from a ‘contractile’ to a ‘synthetic’ phenotype. In conclusion, Gal-3 serves a fundamental role in hypoxia-induced PAH, and inhibition of Gal-3 may represent a novel therapeutic target for the treatment of hypoxia-induced PAH. PMID:27959409
Lee, Ran; Son, Jae Sung; Park, Yong Mean
Aneurysm of the main pulmonary artery is a rare clinical entity that can be congenital or acquired. Most cases occur in association with other congenital malformations, severe pulmonary hypertension, vasculitides, infectious agents, or collagen vascular disorders. We report here a pediatric case of left pulmonary artery aneurysm associated with valvular pulmonary stenosis and a hypoplastic right pulmonary artery, which we confirmed via multidetector computed tomography angiography.
Ryan, John; Dasgupta, Asish; Huston, Jessica; Chen, Kuang-Huieh; Archer, Stephen L.
Pulmonary arterial hypertension (PAH) is an idiopathic cardiopulmonary disease characterized by obstruction of small pulmonary arteries by excessive proliferation and apoptosis-resistance of vascular cells, as well as inflammation, thrombosis and vasoconstriction. Vascular obstruction increases the afterload faced by the right ventricle (RV), leading to RV failure. The proliferative, obstructive vasculopathy of PAH shares several mitochondrial abnormalities with cancer, notably a shift to aerobic glycolysis and mitochondrial fragmentation. Mitochondria in the pulmonary artery smooth muscle cell (PASMC) normally serve as oxygen sensors. In PAH, acquired mitochondrial abnormalities, including epigenetic silencing of superoxide dismutase (SOD2), disrupt oxygen sensing creating a pseudo-hypoxic environment characterized by normoxic activation of Hypoxia-Inducible Factor-1α (HIF-1α). The resulting metabolic shift to aerobic glycolysis (the Warburg phenomenon) reflects inhibition of pyruvate dehydrogenase by pyruvate dehydrogenase kinases. In addition, altered mitochondrial dynamics result in mitochondrial fragmentation. The molecular basis of this structural change includes upregulation and activation of fission mediators, notably dynamin-related protein 1 (DRP-1), and downregulation of fusion mediators, especially mitofusin-2 (MFN2). These pathogenic mitochondrial abnormalities offer new therapeutic targets. Inhibition of mitotic fission or enhancement of fusion in PAH PASMC slows cell proliferation, causes cell cycle arrest, and induces apoptosis. DRP-1 inhibition or MFN2 gene therapy can regress PAH in experimental models of PAH. This review focuses on the etiology of mitochondrial fragmentation in PAH and explores the therapeutic implications of mitochondrial dynamics in the pulmonary vasculature and RV. PMID:25672499
Geyik, Serdar; Yavuz, Kivilcim; Keller, Frederick S.
Connections between the systemic and pulmonary arterial systems are rare conditions that can be due to either congenital or acquired diseases such as anomalous systemic arterial supply to normal lung, pulmonary sequestration, and systemic supply to pulmonary arteriovenous malformations. Herein, a unique case of systemic artery to pulmonary arterial malformation and its endovascular treatment in a patient with no history of the usual etiologies is reported.
Fujio, Hideki; Nakamura, Kazufumi; Matsubara, Hiromi; Kusano, Kengo Fukushima; Miyaji, Katsumasa; Nagase, Satoshi; Ikeda, Tetsuya; Ogawa, Aiko; Ohta-Ogo, Keiko; Miura, Daiji; Miura, Aya; Miyazaki, Masahiro; Date, Hiroshi; Ohe, Tohru
Idiopathic pulmonary arterial hypertension (IPAH) is associated with proliferation of smooth muscle cells (SMCs) in small pulmonary arteries. Inhibition of proliferation of pulmonary artery smooth muscle cells (PASMCs) may be an effective treatment of patients with idiopathic pulmonary arterial hypertension. Recent studies have shown that carvedilol, an alpha- and beta-blocker with antioxidant and calcium channel blocking properties, inhibits the proliferation of cultured normal human pulmonary artery smooth muscle cells. In this study, we tested the hypothesis that carvedilol has antiproliferative effects on pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension. Pulmonary artery smooth muscle cells from six idiopathic pulmonary arterial hypertension patients who had undergone lung transplantation were cultured. To determine cell proliferation, H-thymidine incorporation was measured. Platelet-derived growth factor-induced proliferation of IPAH-PASMCs was significantly greater than that of normal control pulmonary artery smooth muscle cells. Carvedilol (0.1 microM to 10 microM) inhibited the proliferation of idiopathic pulmonary arterial hypertension-pulmonary artery smooth muscle cells in a concentration-dependent manner. Prazosin (an alpha-blocker) and N-acetyl L cysteine (an antioxidant agent) (0.1 microM to 10 microM) did not inhibit their proliferation, but the high concentration of propranolol (a beta-blocker) and nifedipine (a calcium channel blocker) (10 microM) inhibited the proliferation. The combination of propranolol and nifedipine inhibited the proliferation but only at a high concentration (10 microM) combination. Cell cycle analysis revealed that carvedilol (10 microM) significantly decreased the number of cells in S and G2/M phases. These results indicate that carvedilol inhibits the exaggerated proliferation of pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension
Tanaka, Akiko; Shirasaka, Tomonori; Okada, Kenji; Okita, Yutaka
We describe our experience with a patient who had metastasized pulmonary artery sarcoma, but survived 7 years after diagnosis. A 61-year-old man was diagnosed with pulmonary artery intimal sarcoma after resection of metastatic tumours to the bilateral lungs. The primary lesion in the pulmonary artery trunk extending into the bilateral branches was treated by tumour endoarterectomy followed by chemotherapy. He underwent resections of lung metastases two more times before detection of recurrent obstructive pulmonary artery sarcoma 4 years after the tumour endoarterectomy. En bloc resection of the tumour including the pulmonary artery trunk, valve and interventricular septum was performed, and the right ventricular out flow tract was reconstructed with a stentless pulmonary valve and equine pericardium. He died of the disease soon after an operation for metastatic brain tumour 3 years later. Pulmonary artery sarcoma has a dismal prognosis, but aggressively repeated surgical interventions may lengthen survival.
Chu, YanBiao; XiangLi, XiaoYing; Niu, Hu; Wang, HongChao; Jia, PingDong; Gong, WenBin; Wu, DaWei; Qin, WeiDong; Xing, ChunYan
Hypoxia-induced pulmonary arterial hypertension (HPAH) is a refractory disease characterized by increased proliferation of pulmonary vascular smooth cells and progressive pulmonary vascular remodeling. The level of nitric oxide (NO), a potential therapeutic vasodilator, is low in PAH patients. L-arginine can be converted to either beneficial NO by nitric oxide synthases or to harmful urea by arginase. In the present study, we aimed to investigate whether an arginase inhibitor, S-(2-boronoethyl)-L-cysteine ameliorates HPAH in vivo and vitro. In a HPAH mouse model, we assessed right ventricle systolic pressure (RVSP) by an invasive method, and found that RSVP was elevated under hypoxia, but was attenuated upon arginase inhibition. Human pulmonary artery smooth muscle cells (HPASMCs) were cultured under hypoxic conditions, and their proliferative capacity was determined by cell counting and flow cytometry. The levels of cyclin D1, p27, p-Akt, and p-ERK were detected by RT-PCR or Western blot analysis. Compared to hypoxia group, arginase inhibitor inhibited HPASMCs proliferation and reduced the levels of cyclin D1, p-Akt, p-ERK, while increasing p27 level. Moreover, in mouse models, compared to control group, hypoxia increased cyclin D1 expression but reduced p27 expression, while arginase inhibitor reversed the effects of hypoxia. Taken together, these results suggest that arginase plays an important role in increased proliferation of HPASMCs induced by hypoxia and it is a potential therapeutic target for the treatment of pulmonary hypertensive disorders.
Fukuda, Wakako; Morohashi, Satoko; Fukuda, Ikuo
Pulmonary artery intimal sarcoma is a rare tumour and the diagnosis is often delayed. We report the case of a woman with a primary pulmonary artery intimal sarcoma who presented with massive pulmonary embolism. The definitive diagnosis was elucidated after the patient's death by autopsy specimen. We discuss the diagnosis and lessons learned from this case.
Green, Nicholas J; Rollason, Terence P
Fatal haemopericardium in a 27 year old pregnant woman was caused by rupture of a dissecting aneurysm of the pulmonary artery. She had an uncorrected patent ductus arteriosus and severe pulmonary hypertension. The wall of the pulmonary artery showed atherosclerosis and cystic medionecrosis. PMID:1467058
Hunter, Kendall S.; Feinstein, Jeffrey A.; Ivy, D. Dunbar; Shandas, Robin
The hemodynamic state of the pulmonary arteries is challenging to routinely measure in children due to the vascular circuit's position in the lungs. The resulting relative scarcity of quantitative clinical diagnostic and prognostic information impairs management of diseases such as pulmonary hypertension, or high blood pressure of the pulmonary circuit, and invites new techniques of measurement. Here we examine recent applications of macro-scale computational mechanics methods for fluids and solids – traditionally used by engineers in the design and virtual testing of complex metal and composite structures – applied to study the pulmonary vasculature, both in healthy and diseased states. In four subject areas, we briefly outline advances in computational methodology and provide examples of clinical relevance. PMID:21499523
Khattar, R S; Fox, D J; Alty, J E; Arora, A
Pulmonary arterial dissection is an extremely rare and usually lethal complication of chronic pulmonary hypertension. The condition usually manifests as cardiogenic shock or sudden death and is therefore typically diagnosed at postmortem examination rather than during life. However, recent isolated reports have described pulmonary artery dissection in surviving patients. The first case of pulmonary artery dissection in a surviving patient with cor pulmonale caused by chronic obstructive pulmonary disease is presented. The aetiology, pathophysiology, and clinical presentation of pulmonary artery dissection are reviewed and factors that may aid diagnosis during life are discussed.
Guazzi, M; Bandera, F; Pelissero, G; Castelvecchio, S; Menicanti, L; Ghio, S; Temporelli, P L; Arena, R
Echo-derived pulmonary arterial systolic pressure (PASP) and right ventricular (RV) tricuspid annular plane systolic excursion (TAPSE; from the end of diastole to end-systole) are of basic relevance in the clinical follow-up of heart failure (HF) patients, carrying two- to threefold increase in cardiac risk when increased and reduced, respectively. We hypothesized that the relationship between TAPSE (longitudinal RV fiber shortening) and PASP (force generated by the RV) provides an index of in vivo RV length-force relationship, with their ratio better disclosing prognosis. Two hundred ninety-three HF patients with reduced (HFrEF, n = 247) or with preserved left ventricular (LV) ejection fraction (HFpEF, n = 46) underwent echo-Doppler studies and N-terminal pro-brain-type natriuretic peptide assessment and were tracked for adverse events. The median follow-up duration was 20.8 mo. TAPSE vs. PASP relationship showed a downward regression line shift in nonsurvivors who were more frequently presenting with higher PASP and lower TAPSE. HFrEF and HFpEF patients exhibited a similar distribution along the regression line. Given the TAPSE, PASP, and TAPSE-to-PASP ratio (TAPSE/PASP) collinearity, separate Cox regression and Kaplan-Meier analyses were performed: one with TAPSE and PASP as individual measures, and the other combining them in ratio form. Hazard ratios for variables retained in the multivariate regression were as follows: TAPSE/PASP ≥ 0.36 mm/mmHg [hazard ratio (HR): 10.4, P < 0.001]; TAPSE ≥ 16 mm (HR: 5.1, P < 0.01); New York Heart Association functional class ≥ 3 (HR: 4.4, P < 0.001); E/e' (HR: 4.1, P < 0.001). This study shows that the TAPSE vs. PASP relationship is shifted downward in nonsurvivors with a similar distribution in HFrEF and HFpEF, and their ratio improves prognostic resolution. The TAPSE vs. PASP relationship as a possible index of the length-force relationship may be a step forward for a more efficient RV function evaluation and
Perros, Frédéric; Montani, David; Dorfmüller, Peter; Huertas, Alice; Chaumais, Marie-Camille; Cohen-Kaminsky, Sylvia; Humbert, Marc
Inflammation is important for the initiation and the maintenance of vascular remodeling in the most commun animal models of pulmonary hypertension (PH), and its therapeutical targeting blocks PH development in these models. In human, pulmonary vascular lesions of PH are also the source of an intense chemokine production, linked to inflammatory cell recruitment. However, arteritis is uncommon in PH patients. Of note, current PH treatments have immunomodulatory properties. In addition, some studies have shown a correlation between levels of circulating inflammatory mediators and patients' survival. The study of autoimmunity in the pathophysiology of pulmonary arterial hypertension is becoming an area of intense investigation. New immunopathological approaches to PH should allow the development of innovative treatments for this very severe condition.
Feng, Shasha; Chen, Siyao; Yu, Wen; Zhang, Da; Zhang, Chunyu; Tang, Chaoshu; Du, Junbao; Jin, Hongfang
This study aimed to determine whether hydrogen sulfide (H2S) inhibits pulmonary arterial endothelial inflammation in rats with monocrotaline (MCT)-induced pulmonary hypertension and its possible mechanisms. Twenty-four male Wistar rats were divided randomly into control, MCT, and MCT+H2S treatment groups. Human pulmonary arterial endothelial cells (HPAEC) were cultured and divided into four groups: control, MCT, MCT+H2S, and H2S. Pulmonary artery pressure was determined using a right cardiac catheterization procedure 3 weeks after MCT administration. Pulmonary vascular morphological changes and inflammatory infiltration were measured. Endogenous H2S levels, cystathionine-γ-lyase (CSE) expression, and inflammatory cytokines were determined both in vivo and in vitro. In addition, phosphorylation of NF-κB p65 and IκBα was detected by western blotting, and NF-κB p65 nuclear translocation, as well as its DNA-binding activity, was determined. Pulmonary hypertension and vascular remolding developed 3 wks after MCT administration, with elevated lung tissue inflammatory infiltration and cytokine level associated with activation of the NF-κB pathway, both in vivo and in vitro. However, the endogenous H2S/CSE pathway was downregulated in MCT rats. By contrast, an H2S donor markedly reduced pulmonary artery pressure, pulmonary vascular structural remolding, and increased lung inflammatory infiltration and cytokine levels of MCT-treated rats. Meanwhile, H2S reversed the activation of the NF-κB pathway successfully. The downregulated pulmonary arterial endothelial H2S/CSE pathway is involved in the pulmonary inflammatory response in MCT-treated pulmonary hypertensive rats. H2S attenuated endothelial inflammation by inhibiting the NF-κB pathway.
Ghatnekar, Angela; Chrobak, Izabela; Reese, Charlie; Stawski, Lukasz; Seta, Francesca; Wirrig, Elaine; Paez-Cortez, Jesus; Markiewicz, Margaret; Asano, Yoshihide; Harley, Russell; Silver, Richard; Feghali-Bostwick, Carol; Trojanowska, Maria
Pulmonary arterial hypertension (PAH) is a chronic and progressive disease characterized by pulmonary vasculopathy with elevation of pulmonary artery pressure, often culminating in right ventricular failure. GATA-6, a member of the GATA family of zinc-finger transcription factors, is highly expressed in quiescent vasculature and is frequently lost during vascular injury. We hypothesized that endothelial GATA-6 may play a critical role in the molecular mechanisms underlying endothelial cell (EC) dysfunction in PAH. Here we report that GATA-6 is markedly reduced in pulmonary ECs lining both occluded and nonoccluded vessels in patients with idiopathic and systemic sclerosis-associated PAH. GATA-6 transcripts are also rapidly decreased in rodent PAH models. Endothelial GATA-6 is a direct transcriptional regulator of genes controlling vascular tone [endothelin-1, endothelin-1 receptor type A, and endothelial nitric oxide synthase (eNOS)], pro-inflammatory genes, CX3CL1 (fractalkine), 5-lipoxygenease-activating protein, and markers of vascular remodeling, including PAI-1 and RhoB. Mice with the genetic deletion of GATA-6 in ECs (Gata6-KO) spontaneously develop elevated pulmonary artery pressure and increased vessel muscularization, and these features are further exacerbated in response to hypoxia. Furthermore, innate immune cells including macrophages (CD11b(+)/F4/80(+)), granulocytes (Ly6G(+)/CD45(+)), and dendritic cells (CD11b(+)/CD11c(+)) are significantly increased in normoxic Gata6-KO mice. Together, our findings suggest a critical role of endothelial GATA-6 deficiency in development and disease progression in PAH.
Murtaza, Ghulam; Mermer, Petra; Goldenberg, Anna; Pfeil, Uwe; Paddenberg, Renate; Weissmann, Nobert; Lochnit, Guenter; Kummer, Wolfgang
The two-pore domain potassium channel KCNK3 (TASK-1) is expressed in rat and human pulmonary artery smooth muscle cells. There, it is associated with hypoxia-induced signalling, and its dysfunction is linked to pathogenesis of human pulmonary hypertension. We here aimed to determine its role in hypoxic pulmonary vasoconstriction (HPV) in the mouse, and hence the suitability of this model for further mechanistic investigations, using appropriate inhibitors and TASK-1 knockout (KO) mice. RT-PCR revealed expression of TASK-1 mRNA in murine lungs and pre-acinar pulmonary arteries. Protein localization by immunohistochemistry and western blot was unreliable since all antibodies produced labelling also in TASK-1 KO organs/tissues. HPV was investigated by videomorphometric analysis of intra- (inner diameter: 25–40 μm) and pre-acinar pulmonary arteries (inner diameter: 41–60 μm). HPV persisted in TASK-1 KO intra-acinar arteries. Pre-acinar arteries developed initial HPV, but the response faded earlier (after 30 min) in KO vessels. This HPV pattern was grossly mimicked by the TASK-1 inhibitor anandamide in wild-type vessels. Hypoxia-provoked rise in pulmonary arterial pressure (PAP) in isolated ventilated lungs was affected neither by TASK-1 gene deficiency nor by the TASK-1 inhibitor A293. TASK-1 is dispensable for initiating HPV of murine intra-pulmonary arteries, but participates in sustained HPV specifically in pre-acinar arteries. This does not translate into abnormal rise in PAP. While there is compelling evidence that TASK-1 is involved in the pathogenesis of pulmonary arterial hypertension in humans, the mouse does not appear to serve as a suitable model to study the underlying molecular mechanisms. PMID:28301582
Rahimtoola, S H; Ongley, P A; Swan, H J
Introduction of a cardiac catheter into the pulmonary artery from the right heart is not possible in a substantial proportion of patients with transposition of the great vessels. It is necessary to obtain the pulmonary artery pressure and oxygen saturation value to evaluate the degree of pulmonary stenosis and the pulmonary vascular resistance. Twenty-three patients are described in whom this was accomplished by percutaneous suprasternal puncture. There was no mortality and there were no significant complications. The technique appears to be safe and reliable.
Sheikh, Abdul Q; Lighthouse, Janet K; Greif, Daniel M
Excess smooth muscle accumulation is a key component of many vascular disorders, including atherosclerosis, restenosis, and pulmonary artery hypertension, but the underlying cell biological processes are not well defined. In pulmonary artery hypertension, reduced pulmonary artery compliance is a strong independent predictor of mortality, and pathological distal arteriole muscularization contributes to this reduced compliance. We recently demonstrated that embryonic pulmonary artery wall morphogenesis consists of discrete developmentally regulated steps. In contrast, poor understanding of distal arteriole muscularization in pulmonary artery hypertension severely limits existing therapies that aim to dilate the pulmonary vasculature but have modest clinical benefit and do not prevent hypermuscularization. Here, we show that most pathological distal arteriole smooth muscle cells, but not alveolar myofibroblasts, derive from pre-existing smooth muscle. Furthermore, the program of distal arteriole muscularization encompasses smooth muscle cell dedifferentiation, distal migration, proliferation, and then redifferentiation, thereby recapitulating many facets of arterial wall development.
Tajima, Hiroyuki Murata, Satoru; Kumazaki, Tatsuo; Abe, Yutaka; Takano, Teruo
A distal pulmonary artery perforation was successfully occluded by percutaneous microcoil embolization via a microcatheter. Microcoil embolization is a reasonable alternative therapeutic approach for this rare complication of pulmonary interventional procedures.
Nadler, Samuel T; Edelman, Jeffrey D
Multiple conditions result in development of pulmonary hypertension. Pulmonary arterial hypertension (PAH) is the subclassification of pulmonary hypertension, in which known or unknown underlying conditions lead to similar intrinsic alterations in the pulmonary vasculature. PAH is a progressive condition characterized by restricted blood flow through the pulmonary circulation leading to poor survival in the absence of effective therapy. Over the last two decades, new therapeutic agents have substantially improved the course and prognosis for PAH patients. Three available classes of drugs, ie, prostacyclins, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors provide multiple options for treatment of PAH. Endothelin receptor antagonists and phosphodiesterase-5 inhibitors are administered orally, whereas prostacyclin therapies are delivered by continuous intravenous or subcutaneous infusion, or as aerosols by nebulization. Because of the risks and inconveniences associated with administration, prostacyclins are typically reserved for patients with more advanced disease or progression despite oral therapy. Inhaled administration may be a safer and easier route for prostacyclin administration. Treprostinil is a prostacyclin analog that has been demonstrated to be effective when administered by continuous subcutaneous or intravenous infusion, and more recently by nebulization. PMID:21191432
Kluess, H A; Stafford, J; Evanson, K W; Stone, A J; Worley, J; Wideman, R F
This study examined factors contributing to increased vascular resistance and plexiform lesion formation in broiler chickens susceptible to idiopathic pulmonary arterial hypertension (IPAH). A diet supplemented with excess tryptophan (high-Trp diet), the precursor for serotonin, was used to accelerate the development of IPAH. Broilers fed the high-Trp diet had higher pulmonary arterial pressures than broilers fed the control diet, and plexiform lesion incidences tended to be higher (P = 0.11) in the high-Trp group than in the control group at 30 d of age. The intrapulmonary arteries were assessed for vasoconstriction in response to serotonin and adenosine triphosphate (ATP) and for activities of key metabolic enzymes for serotonin and ATP. The pulmonary artery (defined as the first major branch of the pulmonary artery inside the lung) and the primary pulmonary arterial rami (defined as the second major branch of the pulmonary artery inside the lung) both exhibited vasoconstriction in response to serotonin and ATP. This is the first study to demonstrate purinergic-mediated vasoconstriction in intrapulmonary arteries from broilers. Arteriole responsiveness did not differ between broilers fed the control diet or the high-Trp diet. Therefore, the high-Trp diet enhanced the development of IPAH but did not affect the artery's sensitivity to serotonin or ATP. Monoamine oxidase activity, responsible for the breakdown of serotonin, was severely impaired in pulmonary arteries from broilers in the high-Trp group. Accordingly, serotonin may persist longer and elicit an amplified response in broilers fed the high-Trp diet.
Araki, Y; Tajima, K; Yoshikawa, M; Abe, T; Suenaga, Y
We report the pulmonary intimal sarcoma of the pulmonary artery which is encountered infrequently. The patient, a 67-year-old man, was admitted with right heart failure. Diagnosis was not established completely by computed tomography of the thorax, pulmonary angiogram and pulmonary scintigram, therefore chronic pulmonary thromboembolism was suspected. Palliative resection was performed with cardiopulmonary bypass and total circulatory arrest. Pathologic examination of the resected tumor revealed pulmonary intimal sarcoma, which originated from the pulmonary artery. The patient died four months postoperatively. The cause of death was determined by autopsy to be recurrent pulmonary intimal sarcoma invading the left atrium and multiple metastasis of the brain, pancreas, adrenal glands and right lung.
Betkier-Lipińska, Katarzyna; Czarkowski, Sebastian; Hendzel, Piotr; Cwetsch, Andrzej
Idiopathic dilatation of the pulmonary artery (IDPA) is a rare congenital heart disease. It has been described for almost one hundred years, and numerous definitions have been proposed. The IDPA diagnostic criteria have not been updated for years. Secondary to primary disease, pulmonary artery aneurism was recognised as a lethal defect; however, long-term follow-up of patients with IDPA has not been well researched. Thus, indications to medical or surgical treatment are not evidence based. Here, we present a rare case of a 54-year-old patient with IDPA, who remained under observation for 36 years without surgical intervention. PMID:26855651
Wideman, R F; Eanes, M L; Hamal, K R; Anthony, N B
Broilers that are susceptible to pulmonary hypertension syndrome (PHS, ascites) have an elevated pulmonary arterial pressure (PAP) when compared with PHS-resistant broilers. Two distinctly different syndromes, pulmonary arterial hypertension and pulmonary venous hypertension (PVH), both are associated with increases in PAP. Pulmonary arterial hypertension occurs when the right ventricle must elevate the PAP to overcome increased resistance to flow through restrictive pulmonary arterioles upstream from the pulmonary capillaries. In contrast, PVH is commonly caused by increased downstream (postcapillary) resistance. The sites of resistance to pulmonary blood flow are deduced by making contemporaneous measurements of the PAP and the wedge pressure (WP) and calculating the transpulmonary pressure gradient (TPG) (TPG = PAP - WP). We obtained PAP and WP values from 8-, 12-, 16-, 20-, and 24-wk-old anesthetized male and female broilers from a PHS-susceptible line. Pressures were recorded as a catheter was advanced through a wing vein to the pulmonary artery and onward until the WP was obtained. In addition to sex and age comparisons of vascular pressure gradients, the data also were pooled to obtain 3 cohorts for broilers having the lowest PAP values (n = 52; range: 12 to 22.9 mmHg), intermediate PAP values (n = 63; range: 23 to 32.9 mmHg), and highest PAP values (n = 62; range: 33 to 62 mmHg) independent of age or sex. Within each of the age, sex, and PAP cohort comparisons, broilers with elevated PAP consistently exhibited the hemodynamic characteristics of pulmonary arterial hypertension (elevated PAP and TPG combined with a normal WP) and not PVH (elevated PAP and WP combined with a normal or reduced TPG). Susceptibility to PHS can be attributed primarily to pulmonary arterial hypertension associated with increased precapillary (arteriole) resistance.
Johnson, Roger H.; Karau, Kelly L.; Molthen, Robert C.; Dawson, Christopher A.
Stiffening, or loss of distensibility, of arterial vessel walls is among the manifestations of a number of vascular diseases including pulmonary arterial hypertension. We are attempting to quantify the mechanical properties of vessel walls of the pulmonary arterial tree using parameters derived from high-resolution volumetric x-ray CT images of rat lungs. The pulmonary arterial trees of the excised lungs are filled with a contrast agent. The lungs are imaged with arterial pressures spanning the physiological range. Vessel segment diameters are measured from the inlet to the periphery, and distensibilities calculated from diameters as a function of pressure. The method shows promise as an adjunct to other morphometric techniques such as histology and corrosion casting. It possesses the advantages of being nondestructive, characterizing the vascular structures while the lungs are imaged rapidly and in a near-physiological state, and providing the ability to associate mechanical properties with vessel location in the intact tree hierarchy.
Hirata, Naoyuki; Kanaya, Noriaki; Yamazaki, Yutaka; Sonoda, Hajime; Namiki, Akiyoshi
We report a rare case of pulmonary embolism (PE) caused by a carbon dioxide (CO2) blower during off-pump coronary artery bypass grafting (OPCAB). When the anastomosis of the right internal thoracic artery to left anterior descending artery was performed, the operator tore the right ventricle outflow track (RVOT) that was adjacent to the left anterior descending artery. Immediately after the anastomosis and repair of the torn RVOT with CO2 blower, the systolic pulmonary artery pressure (PAP) increased from 28 to 64 mmHg, and end-tidal CO2 decreased from 32 to 12 mmHg. Because transesophageal echocardiograph (TEE) showed numerous gas bubbles in the main pulmonary artery, we diagnosed PE caused by invasion of CO2 gas bubbles via the torn RVOT. Although a CO2 blower is useful to enhance visualization of the anastomosis during OPCAB, it should not be used for the venous system because it may cause CO2 embolism.
Dornas, Ana Paula Alves Valle; Campos, Frederico Thadeu Assis Figueiredo; Rezende, Cláudia Juliana; Ribeiro, Carlos Alberto; Amaral, Nilson Figueiredo; Corrêa, Ricardo de Amorim
Intimal sarcoma of the pulmonary artery is a rare and potentially lethal tumor, the diagnosis of which is difficult and therefore frequently delayed. The clinical signs and symptoms are nonspecific, often mimicking chronic pulmonary thromboembolism (CPTE). We report the case of a 45-year-old male under treatment for CPTE associated with pulmonary arterial hypertension and chronic cor pulmonale. There was no response to treatment with anticoagulants and sildenafil. We emphasize the difficulties in diagnosing intimal sarcoma of the pulmonary artery, the need to investigate this neoplasm in the differential diagnosis of CPTE and the systematic use of criteria for the appropriate prescription of new medications for pulmonary artery hypertension.
Gutiérrez, Alejandra; Sauler, Maor; Mitchell, James M; Siegel, Mark D; Trow, Terence K; Bacchetta, Matthew; Fares, Wassim H
Pulmonary artery sarcomas (PAS) are rare tumors with a poor prognosis. They are often misdiagnosed as pulmonary embolism (PE) leading to futile anticoagulation treatment and delay in proper diagnosis. We present a case of a patient who was initially misdiagnosed and anticoagulated for presumed pulmonary embolism. Progressive symptoms and additional imaging led to the diagnosis of intimal pulmonary artery sarcoma for which he underwent surgical resection. This case serves as a reminder to consider pulmonary artery sarcoma in the differential diagnosis of patients with dyspnea and filling defects on CT pulmonary angiogram offering the potential for resection prior to metastasis.
Min, Daniel; Lee, Ji-Hyun; Jeong, Hye-Cheol; Kim, Jung-Hyun; Shin, Suk-Pyo; Kim, Hong-Min; Han, Kyu Hyun; Jeong, Hye Yun; Kim, Eun-Kyung
Pulmonary artery sarcoma (PAS) is a rare, poorly differentiated malignancy arising from the intimal layer of the pulmonary artery. Contrast-enhanced chest computed tomography (CT) is a good diagnostic modality that shows a low-attenuation filling defect of the pulmonary artery in PAS patients. An 18-year-old man was referred to our hospital for the evaluation and management of cavitary pulmonary lesions that did not respond to treatment. A contrast-enhanced CT of the chest was performed, which showed a filling defect within the right interlobar pulmonary artery. The patient underwent a curative right pneumonectomy after confirmation of PAS. Although lung parenchymal lesions of PAS are generally nonspecific, it can be presented as cavities indicate pulmonary infarcts. Clinicians must consider the possibility of PAS as well as pulmonary thromboembolism in patients with pulmonary infarcts. So, we report the case with PAS that was diagnosed during the evaluation of cavitary pulmonary lesions and reviewed the literatures.
Min, Daniel; Lee, Ji-Hyun; Jeong, Hye-Cheol; Kim, Jung-Hyun; Shin, Suk-Pyo; Kim, Hong-Min; Han, Kyu Hyun; Jeong, Hye Yun
Pulmonary artery sarcoma (PAS) is a rare, poorly differentiated malignancy arising from the intimal layer of the pulmonary artery. Contrast-enhanced chest computed tomography (CT) is a good diagnostic modality that shows a low-attenuation filling defect of the pulmonary artery in PAS patients. An 18-year-old man was referred to our hospital for the evaluation and management of cavitary pulmonary lesions that did not respond to treatment. A contrast-enhanced CT of the chest was performed, which showed a filling defect within the right interlobar pulmonary artery. The patient underwent a curative right pneumonectomy after confirmation of PAS. Although lung parenchymal lesions of PAS are generally nonspecific, it can be presented as cavities indicate pulmonary infarcts. Clinicians must consider the possibility of PAS as well as pulmonary thromboembolism in patients with pulmonary infarcts. So, we report the case with PAS that was diagnosed during the evaluation of cavitary pulmonary lesions and reviewed the literatures. PMID:24734102
Schulze-Neick, I.; Hausdorf, G.; Lange, P. E.
In a patient with pulmonary valve atresia with hypoplastic main pulmonary artery selective angiography showed absence of the central left pulmonary artery and a right pulmonary artery originating from the ascending aorta close to the left coronary artery. This unusual anatomical arrangement complicates interventional and surgical treatment. Images PMID:8297705
Mori, Shohei; Uehara, Hirofumi; Motoi, Noriko; Okumura, Sakae
We report a very rare case of pulmonary artery sarcoma that presented as an isolated lung mass, which we attempted to resect via lobectomy, although this resulted in incomplete resection due to unnoticed latent proximal presentations. A 54-year-old man complained of a dry cough that had persisted for 2 months. Enhanced chest computed tomography revealed a lobular mass in his left lower lobe. Therefore, left lower lobectomy was performed as a radical surgery, and the tumor was ultimately diagnosed as pulmonary artery sarcoma. However, follow-up computed tomography at 16 months revealed proximal presentations in the pulmonary trunk and right pulmonary artery, which we retrospectively discovered were present before the surgery. This case highlights the importance of evaluating the lumen of the pulmonary artery, to accurately determine the required extent of any radical surgery, even in cases of pulmonary artery sarcoma that presents as an isolated lung mass.
Guntheroth, W; Miyaki-Hull, C
The Coanda effect (the tendency of a jet stream to adhere to a boundary wall), and the relevant anatomy, may explain the location of ductal jets within the main pulmonary artery. With the usual insertion of the duct close to the left pulmonary artery, during right ventricular ejection, the ductal jet adheres to the left wall of the main pulmonary artery. When right ventricular ejection is absent in pulmonary atresia, the ductal jet streams down the right wall of the pulmonary artery to the pulmonary valve, reverses, and maintains a parallel column back toward the bifurcation. If the reversed flow is mistaken for ejection from the right ventricle, the diagnosis of pulmonary atresia may be missed.
Zhang, Yun; Chen, Weijie; Xu, Yanping; Liu, Hang; Chen, Yunlin; Yang, Hanxuan; Yin, Yuehui
Sympathetic activation plays an important pathophysiological role in the progression of pulmonary artery hypertension. Although adrenergic vasomotor fibers are present in the adventitia of pulmonary arteries, the anatomy of the peri-arterial pulmonary nerves is still poorly understood. The aim of the current study was to determine the sympathetic nerve distribution in canine pulmonary arteries. A total of 2160 sympathetic nerves were identified in six Chinese Kunming canines. Nerve counts were greatest in the proximal segment, with a slight decrease in the distal segment; the middle segment showed the least number of nerves. In the left and right pulmonary arteries, 77.61% and 78.97% of the nerves were located within a 1-3-mm range, respectively. The number of nerves in the posterior region of the bifurcation and pulmonary trunk outnumbered those in the anterior region. Furthermore, 65.33% of the nerves were located in the first 2-mm range of the posterior region of bifurcation, and 89.62% of the nerves were located within the 1-3-mm range of the posterior region of the pulmonary trunk. In conclusion, a great abundance of sympathetic nerves occurred in the proximal and distal segments of the bilateral pulmonary arteries. There is a clear predominance of sympathetic nerve distribution in the posterior region of the bifurcation and pulmonary trunk. This anatomic distribution may have implications for the future development of percutaneous pulmonary artery denervation. PMID:27158332
Sugimoto, Koichi; Yoshihisa, Akiomi; Nakazato, Kazuhiko; Jin, Yuichiro; Suzuki, Satoshi; Yokokawa, Tetsuro; Misaka, Tomofumi; Yamaki, Takayoshi; Kunii, Hiroyuki; Suzuki, Hitoshi; Saitoh, Shu-ichi; Takeishi, Yasuchika
Background Although pulmonary hypertension due to left heart disease (LHD-PH) accounts for the largest proportion of pulmonary hypertension, few reports on the epidemiological analysis of LHD-PH exist. Recently, pulmonary arterial capacitance (PAC) has attracted attention as a possible factor of right ventricular afterload along with pulmonary vascular resistance. We therefore investigated the clinical significance of PAC in LHD-PH. Methods The subject consisted of 252 LHD-PH patients (145 men, mean age 63.4 ± 14.7 years) diagnosed by right heart catheterization. PAC was estimated by the ratio between stroke volume and pulmonary arterial pulse pressure. Patients were classified into four groups according to the PAC (1st quartile was 0.74 to 1.76 ml/mmHg, the 2nd quartile 1.77 to 2.53 ml/mmHg, the 3rd quartile 2.54 to 3.59 ml/mmHg, and the 4th quartile 3.61 to 12.14 ml/mmHg). The end-points were defined as rehospitalization due to worsening heart failure and/or cardiac death. The Cox proportional hazard regression model was used to determine what variables were associated with cardiac events. Results The patients in the 1st quartile had the lowest cardiac index and stroke volume index, and the highest mean pulmonary arterial pressure, mean pulmonary capillary wedge pressure, and pulmonary vascular resistance compared with the 2nd, 3rd, and 4th quartiles. Fifty-four patients experienced cardiac events during the follow-up period (median 943 days). The event-free rate of the 1st quartile was significantly lower than that of the 3rd and 4th quartiles (66.7% vs 82.5% [3rd quartile], P = 0.008; and 92.1% [4th quartile], P < 0.001). The Cox hazard analysis revealed that PAC was significantly associated with cardiac events (HR 0.556, 95% CI 0.424–0.730, P < 0.001). Conclusion PAC is useful in the prediction of cardiac event risk in LHD-PH patients. PMID:27875533
Ricci, Silvia; Fainardi, Valentina; Spaziani, Gaia; Favilli, Silvia; Chiappa, Enrico
We describe a rare case of right aortic arch (RAA) and nonconfluent pulmonary arteries. RAA and a right-sided arterial duct (AD) were identified on the prenatal scan, but a second left-sided AD and disconnection of the left pulmonary artery were missed. The missed diagnosis in fetal life adversely affected postnatal management. We suggest that fetuses with a prenatal diagnosis of RAA and right-sided AD be delivered in tertiary care centres to rule out an association with bilateral AD and nonconfluent pulmonary arteries after birth. Prompt postnatal diagnosis will enable preservation of flow in the disconnected pulmonary artery through prostaglandin E1 infusion until surgical reconstruction.
Wilkins, Martin R.
Developing new treatments for pulmonary arterial hypertension (PAH) is a challenge. We have enjoyed success with regulatory approvals for three drug classes—prostanoids, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors. But we have also seen some disappointing results, for example, from studies with vasoactive intestinal polypeptide, statins and tergolide. Animal models are an unreliable predictor of efficacy in humans. The best model for the disease is the patient. This review discusses three major issues facing the evaluation of drugs in PAH patients—target validation, choosing the right dose, and early trial design. PMID:23662193
Izzo, Anthony; McSweeney, Julia; Kulik, Thomas; Khatwa, Umakanth; Kothare, Sanjeev V
The usual differential diagnoses of nocturnal events in children include parasomnias, nocturnal seizures, nocturnal reflux (Sandifer syndrome), hypnic jerks, periodic limb movements of sleep, and sleep disordered breathing. We report a previously healthy young girl who presented to the sleep clinic for evaluation of nocturnal events which were diagnosed as medically refractory nocturnal seizures. It was not until a syncopal event occurred in the daytime, which prompted referral for cardiac evaluation, the diagnosis of idiopathic pulmonary arterial hyper-tension (IPAH) was made. Sleep physicians should consider IPAH in the differential diagnosis of nocturnal events in children.
Parshin, V D; Motus, I Ya; Belov, Yu V; Chernyavsky, A M; Neretin, A V; Rusinov, V V
Sarcoma of the pulmonary artery is a rare tumor. At present the literature describes single cases. However the number of publications increases in recent time due to improved diagnostics. There are appeared papers, which provide a series of observations of surgical treatment for this kind of tumor exceeded more than 10 cases. It can be assumed that today the number of these cases in the literature contains several hundreds. Thus despite the rarity of this tumor there is a certain understanding of the clinical picture of this disease and treatment that we tried to do in this paper being studied the available literature and bringing four of our observation.
Akagi, Satoshi; Kusano, Kengo Fukushima
Vascular thrombosis implicates in the pathogenesis of pulmonary arterial hypertension (PAH). Anticoagulation therapy (warfarin) has been recommended by many experts in the treatment of PAH. However, the long-term effectiveness of anticoagulation therapy remains controversial. Because of the various drugs, such as epoprostenol, bosentan, and sildenafil, for the treatment of PAH recently, warfarin alone is not a realistic therapy for PAH. Accordingly we reviewed the previous manuscript regarding anticoagulation therapy for PAH, and looked at the current role of anticoagulation therapy in Japan.
Nunley, J A; Goldner, R D; Koman, L A; Gelberman, R; Urbaniak, J R
Twenty-seven patients with acute injuries to the radial or ulnar arteries had arterial repairs using microvascular techniques. No patient had an ischemic hand secondary to his arterial injury. The overall patency rate for all repaired vessels was 56%. For sharp, clean lacerations, the success rate for repairs was 55%. Repairs of acute, sharp lacerations yielded no better results than delayed reconstructions. The average distal end arterial stump pressure for patent arteries was 66% of mean, while for thrombosed vessels it was 76% of mean; this was not a statistically significant difference (p = 0.9). There was no statistical correlation between forearm arterial patency, age, sex, vessel injured, mechanism of injury, time of repair, or clinically measured distal arterial stump pressure. At the present time, it does not appear to be possible to predict arterial patency by measuring arterial stump pressure at the time of definitive repair.
Khan, Asaad Akbar; McFadden, Eugene Patrick
Flash pulmonary edema is characteristically sudden in onset with rapid resolution once appropriate therapy has been instituted (Messerli et al., 2011). Acute increase of left ventricular (LV) end diastolic pressure is the usual cause of sudden decompensated cardiac failure in this patient population. Presence of bilateral renal artery stenosis or unilateral stenosis in combination with a single functional kidney in the susceptible cohort is usually blamed for this condition. We describe a patient who presented with flash pulmonary edema in the setting of normal coronary arteries. Our case is distinct as our patient developed flash pulmonary edema secondary to unilateral renal artery stenosis in the presence of bilateral functioning kidneys. Percutaneous stent implantation in the affected renal artery resulted in rapid resolution of pulmonary edema. PMID:25793128
Samánek, M; Fiser, B; Ruth, C; Tůma, S; Hucín, B
Radioisotope lung scanning was used to investigate the distribution of pulmonary blood flow after banding of the pulmonary artery in children with a left-to-right shunt and pulmonary hypertension. An abnormal distribution of blood flow in the lung on the side of the operation approach was observed in all patients in the first three weeks following surgery. Abnormalities were still observed in 17 of 21 children 10 months to more than 8 years after the banding operation. There was no significant relation between the occurrence of these abnormalities and time after surgery. Diminished flow to the zones of the right lung was observed less frequently. The incidence of abnormalities in flow distribution was also high preoperatively. Respiratory complications in infants with large left-to-right shunts were considered to be responsible for most of the abnormal blood flow distributions observed. Radioactive lung scanning was found to be a valuable diagnostic method in the early and late postoperative period in infants and small children. It was more sensitive than the other techniques used in revealing deviation of blood flow from one lung in those cases with shifting of the applied band. Images PMID:1111558
Kheyfets, Vitaly O.; Schroeder, Joyce D.; Dunning, Jamie; Shandas, Robin; Buckner, J. Kern; Browning, James; Hertzberg, Jean; Hunter, Kendall S.; Fenster, Brett E.
Abstract Pulmonary hypertension (PH) is associated with proximal pulmonary arterial remodeling characterized by increased vessel diameter, wall thickening, and stiffness. In vivo assessment of wall shear stress (WSS) may provide insights into the relationships between pulmonary hemodynamics and vascular remodeling. We investigated the relationship between main pulmonary artery (MPA) WSS and pulmonary hemodynamics as well as markers of stiffness. As part of a prospective study, 17 PH patients and 5 controls underwent same-day four-dimensional flow cardiac magnetic resonance imaging (4-D CMR) and right heart catheterization. Streamwise velocity profiles were generated in the cross-sectional MPA in 45° increments from velocity vector fields determined by 4-D CMR. WSS was calculated as the product of hematocrit-dependent viscosity and shear rate generated from the spatial gradient of the velocity profiles. In-plane average MPA WSS was significantly decreased in the PH cohort compared with that in controls (0.18 ± 0.07 vs. 0.32 ± 0.08 N/m2; P = 0.01). In-plane MPA WSS showed strong inverse correlations with multiple hemodynamic indices, including pulmonary resistance (ρ = −0.74, P < 0.001), mean pulmonary pressure (ρ = −0.64, P = 0.006), and elastance (ρ = −0.70, P < 0.001). In addition, MPA WSS had significant associations with markers of stiffness, including capacitance (ρ = 0.67, P < 0.001), distensibility (ρ = 0.52, P = 0.013), and elastic modulus (ρ = −0.54, P = 0.01). In conclusion, MPA WSS is decreased in PH and is significantly associated with invasive hemodynamic indices and markers of stiffness. 4-D CMR–based assessment of WSS may represent a novel methodology to study blood-vessel wall interactions in PH. PMID:27076906
Lee, Pilhwa; Carlson, Brian E; Chesler, Naomi; Olufsen, Mette S; Qureshi, M Umar; Smith, Nicolas P; Sochi, Taha; Beard, Daniel A
Individualized modeling and simulation of blood flow mechanics find applications in both animal research and patient care. Individual animal or patient models for blood vessel mechanics are based on combining measured vascular geometry with a fluid structure model coupling formulations describing dynamics of the fluid and mechanics of the wall. For example, one-dimensional fluid flow modeling requires a constitutive law relating vessel cross-sectional deformation to pressure in the lumen. To investigate means of identifying appropriate constitutive relationships, an automated segmentation algorithm was applied to micro-computerized tomography images from a mouse lung obtained at four different static pressures to identify the static pressure-radius relationship for four generations of vessels in the pulmonary arterial network. A shape-fitting function was parameterized for each vessel in the network to characterize the nonlinear and heterogeneous nature of vessel distensibility in the pulmonary arteries. These data on morphometric and mechanical properties were used to simulate pressure and flow velocity propagation in the network using one-dimensional representations of fluid and vessel wall mechanics. Moreover, wave intensity analysis was used to study effects of wall mechanics on generation and propagation of pressure wave reflections. Simulations were conducted to investigate the role of linear versus nonlinear formulations of wall elasticity and homogeneous versus heterogeneous treatments of vessel wall properties. Accounting for heterogeneity, by parameterizing the pressure/distention equation of state individually for each vessel segment, was found to have little effect on the predicted pressure profiles and wave propagation compared to a homogeneous parameterization based on average behavior. However, substantially different results were obtained using a linear elastic thin-shell model than were obtained using a nonlinear model that has a more
Jaijee, Shareen K; Ariff, Ben; Howard, Luke; O'Regan, Declan P; Gin-Sing, Wendy; Davies, Rachel; Gibbs, J Simon R
Pulmonary arterial dilatation associated with pulmonary hypertension may result in significant compression of local structures. Left main coronary artery and left recurrent laryngeal nerve compression have been described. Tracheobronchial compression from pulmonary arterial dilatation is rare in adults, and there are no reports in the literature of its occurrence in idiopathic pulmonary arterial hypertension. Compression in infants with congenital heart disease has been well described. We report 2 cases of tracheobronchial compression: first, an adult patient with idiopathic pulmonary arterial hypertension who presents with symptomatic left main bronchus compression, and second, an adult patient with Eisenmenger ventricular septal defect and right-sided aortic arch, with progressive intermedius and right middle lobe bronchi compression in association with enlarged pulmonary arteries.
Peterson, B.T.; Grauer, S.E.; Hyde, R.W.; Ortiz, C.; Moosavi, H.; Utell, M.J.
To see whether air emboli to the lungs rather than brain compression caused these findings, anesthetized dogs received intravenous air infusions, subdural air infusions, or brain compression from balloons inflated in the subdural space. Subdural air and intravenous air resulted in similar vascular responses. Pulmonary artery pressure (Ppa) increased 160% (P < 0.01) and pulmonary venous pressure transiently rose 13 +- 5 Torr (P < 0.05) without an increase in left atrial pressure or cardiac output (Q). The end-tidal PCP/sub 2/ fell 55% (P < 0.01) and the postmortem weight of the lungs increased 55% (P < 0.05). Brain compression with a subdural balloon instead of air only caused a 20% rise in Ppa and Q without pulmonary edema. Thus, pulmonary air emboli rather than brain compression accounts for the edema and pulmonary hypertension caused by subdural air. Catheters in pulmonary veins and the left atrium showed that air emboli cause transient pulmonary venous hypertension as well as a reproducible form of noncardiogenic pulmonary edema.
Xing, Ai-ping; Hu, Xiao-yun; Shi, Yi-wei; Du, Yong-cheng
Pulmonary artery hypertension (PAH) is a severe disease characterized with progressive increase of pulmonary vascular resistance that finally causes right ventricular failure and premature death. Cigarette smoke (CS) is a major factor of Chronic Obstructive Pulmonary Disease (COPD) that can lead to PAH. However, the mechanism of CS-induced PAH is poorly understood. Mounting evidence supports that pulmonary vascular remodeling play an important role in the development of PAH. PDGF signaling has been demonstrated to be a major mediator of vascular remodeling implicated in PAH. However, the association of PDGF signaling with CS-induced PAH has not been documented. In this study, we investigated CS-induced PAH in rats and the expression of platelet derived growth factor (PDGF) and PDGF receptor (PDGFR) in pulmonary artery. Forty male rats were randomly divided into control group and three experimental groups that were exposed to CS for 1, 2, and 3 months, respectively. CS significantly increased right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI). Histology staining demonstrated that CS significantly increased the thickness of pulmonary artery wall and collagen deposition. The expression of PDGF isoform B (PDGF-B) and PDGF receptor beta (PDGFRβ) were significantly increased at both protein and mRNA levels in pulmonary artery of rats with CS exposure. Furthermore, Cigarette smoke extract (CSE) significantly increased rat pulmonary artery smooth muscle cell (PASMC) proliferation, which was inhibited by PDGFR inhibitor Imatinib. Thus, our data suggest PDGF signaling is implicated in CS-induced PAH.
Wang, Xiaobing; Ren, Weidong; Yang, Jun
Pulmonary artery sarcoma (PAS) is an extremely rare malignancy. It is usually found after it grows large enough to occupy almost the entire lumen of the pulmonary artery and causes serious clinical symptoms. Thus, it is usually difficult to distinguish PAS from pulmonary thromboembolism based on imaging examinations. Few case reports had shown the attachment of PAS to pulmonary artery, a key characteristic for diagnosis, and differential diagnosis of PAS. In this case, we found a PAS, which did not cause local obstruction and some tumor emboli, which obstructed the branches of the pulmonary arteries and caused pulmonary hypertension and clinical symptoms. Transthoracic echocardiography (TTE) revealed a part of the tumor attached to the intima of the main pulmonary artery with a peduncle and had obvious mobility, which was suggestive of PAS and differentiated it from the pulmonary thromboembolism. To our knowledge, this is the first case report of a pedunculated PAS suggested by TTE. Combined with pulmonary artery computed tomography angiography, the diagnosis of PAS is strongly suggested before the operation. This case indicates that TTE could reveal the attachment and mobility of PAS in the main pulmonary and may provide useful information for the diagnosis and differential diagnosis of PAS, especially a pedunculated PAS.
de Carvalho, Adriana Castro; Hovnanian, André Luiz; Fernandes, Caio Julio César dos Santos; Lapa, Mônica; Jardim, Carlos; Souza, Rogério
Phosphodiesterase inhibitors like sildenafil have already been shown to improve functional capacity and hemodynamics in the treatment of pulmonary arterial hypertension. Few studies address the effects of new phosphodiesterase inhibitors as tadalafil. We report a case of a patient with idiopathic pulmonary arterial hypertension in functional class IV (New York Heart Association) with significant response to treatment with tadalafil.
Sunavala, A J; Thacker, H P; Khann, J N
Agenesis or hypoplasia of the right or left pulmonary arteries are among the rarest pulmonary artery anomalies with left sided anomalies being reported even less frequently. Pulmonary artery agenesis should be suspected in asymptomatic patients if a plain chest X-ray shows asymmetric lung fields, lung hypoplasia, or hyperinflation of the contralateral lung. It must be considered as a rare cause of recurrent lower respiratory tract infections in childhood and in subjects with a low threshold for or recurrent "High Altitude Pulmonary Edema".
Vitiello, Renato; Pisanti, Chiara; Pisanti, Antonello; Silberbach, Michael
Pulmonary artery agenesis and hypoplasia of the homolateral lung occasionally occurs as an isolated lesion, but more often has associated congenital cardiac anomalies. We present a case where pulmonary artery agenesis was the sole lesion in an asymptomatic child. Pulmonary artery agenesis should be suspected in asymptomatic patients if a plain chest X-ray shows asymmetric lung fields, lung hypoplasia, or hyperinflation of the contralateral lung. Echocardiography is the best tool to establish the diagnosis. In our opinion, invasive procedures, such as cardiac catheterization, may be postponed if there is no echocardiographic evidence of pulmonary hypertension.
Mikaberidze, Nino; Goldberg, Ythan; Khosraviani, Khashayar; Taub, Cynthia
Unilateral pulmonary artery agenesis (UPAA) with pulmonary hypoplasia is a rare congenital anomaly. We describe a 71-year old male who was incidentally diagnosed with the right UPAA and a hypoplastic right lung supplied by collateralized right coronary.
Orun, Utku Arman; Yilmaz, Osman; Bilici, Meki; Karademir, Selmin; Uner, Cigdem; Senocak, Filiz; Dogan, Vehbi
Unilateral pulmonary artery agenesis is a rare congenital anomaly caused by a backward displacement of the conical artery of the truncus arteriosus. It is commonly associated with additional cardiovascular abnormalities. A 7-year-old girl was admitted to our clinic with the complaint of shortness of breath upon exertion. Chest radiography revealed a hypoplastic right lung. Absence of the right pulmonary artery with atrial septal defect and pulmonary hypertension was demonstrated by echocardiography, computed tomography, and cardiac catheterization. Bosentan is effectively used to treat pulmonary arterial hypertension.
Pousada, Guillermo; Baloira, Adolfo; Valverde, Diana
Pulmonary Arterial Hypertension (PAH) is a rare and progressive disease with low incidence and prevalence, and elevated mortality. PAH is characterized by increased mean pulmonary artery pressure. The aim of this study was to analyse patients with combined mutations in BMPR2, ACVRL1, ENG and KCNA5 genes and to establish a genotype-phenotype correlation. Major genes were analysed by polymerase chain reaction (PCR) and direct sequencing. Genotype-phenotype correlation was performed. Fifty-seven (28 idiopathic PAH, 29 associated PAH group I) were included. Several mutations in different genes, classified as pathogenic by in silico analysis, were present in 26% of PAH patients. The most commonly involved gene was BMPR2 (12 patients) followed by ENG gene (9 patients). ACVRL1 and KCNA5 genes showed very low incidence of mutations (5 and 1 patients, respectively). Genotype-phenotype correlation showed statistically significant differences for gender (p = 0.045), age at diagnosis (p = 0.035), pulmonary vascular resistance (p = 0.030), cardiac index (p = 0.035) and absence of response to treatment (p = 0.011). PAH is consequence of a heterogeneous constellation of genetic arrangements. Patients with several pathogenic mutations seem to display a more severe phenotype. PMID:27630060
Fernandez-Bonetti, P; Lupi-Herrera, E; Martinez-Guerra, M L; Barrios, R; Seoane, M; Sandoval, J
The mechanical properties of the lung were studied in ten nonsmokers with idiopathic pulmonary artery hypertension (IPAH) (mean pulmonary artery pressure 65.7 +/- 30 mm Hg). In the routine lung test, residual volume was found to be abnormal (greater than 120 percent of the predicted) in seven patients, and measured airway resistance was normal in eight out of the ten patients. A decreased FEF 75-85 percent, abnormal values for the helium-air flow ratios and increased closing capacities were documented in eight of ten patients in whom lung elastic recoil was normal (six of ten) or increased (four of ten). These features suggest peripheral airways obstruction (PAO) which was also supported by histopathologic findings in three cases (one biopsy and two necropsies). The observed changes in lung compliance could be related to the behavior of the coupling of the air-space and vascular compartments. The etiology of PAO in IPAH patients is not known, but our results indicate that both the peripheral airways and the pulmonary circulation are affected. The knowledge of PAO in IPAH patients could help to better understand the observed V/Q inequality in this entity.
Takatsuki, Shinichi; Calderbank, Michelle; Ivy, David Dunbar
This study aimed to investigate the safety, tolerability, and effects of tadalafil on children with pulmonary arterial hypertension (PAH) after transition from sildenafil or after tadalafil received as initial therapy. A total of 33 pediatric patients with PAH were retrospectively evaluated. Of the 33 patients, 29 were switched from sildenafil to tadalafil. The main reason for the change from sildenafil was once-daily dosing. The average dose of sildenafil was 3.4 ± 1.1 mg/kg/day, and that of tadalafil was 1.0 ± 0.4 mg/kg/day. For 14 of the 29 patients undergoing repeat catheterization, statistically significant improvements were observed after transition from sildenafil to tadalafil in terms of mean pulmonary arterial pressure (53.2 ± 18.3 vs. 47.4 ± 13.7 mmHg; p < 0.05) and pulmonary vascular resistance index (12.2 ± 7.0 vs 10.6 ± 7.2 Units/m(2); p < 0.05). Clinical improvement was noted for four patients treated with tadalafil as initial therapy. The side effect profiles were similar for the patients who had transitioned from sildenafil to tadalafil including headache, nausea, myalgia, nasal congestion, flushing, and allergic reaction. Two patients discontinued tadalafil due to migraine or allergic reaction. One patient receiving sildenafil had no breakthrough syncope after transition to tadalafil. Tadalafil can be safely used for pediatric patients with PAH and may prevent disease progression.
LeVarge, Barbara L
Prostacyclin is an endogenous eicosanoid produced by endothelial cells; through actions on vascular smooth-muscle cells, it promotes vasodilation. Pulmonary arterial hypertension (PAH) is characterized by elevated mean pulmonary artery pressure due to a high pulmonary vascular resistance state. A relative decrease in prostacyclin presence has been associated with PAH; this pathway has thus become a therapeutic target. Epoprostenol, the synthetic equivalent of prostacyclin, was first utilized as short-term or bridging therapy in the 1980s. Further refinement of its long-term use via continuous intravenous infusion followed. A randomized controlled trial by Barst et al in 1996 demonstrated functional, hemodynamic, and mortality benefits of epoprostenol use. This work was a groundbreaking achievement in the management of PAH and initiated a wave of research that markedly altered the dismal prognosis previously associated with PAH. Analogs of prostacyclin, including iloprost and treprostinil, exhibit increased stability and allow for an extended array of parenteral and non-parenteral (inhaled and oral) therapeutic options. This review further examines the pharmacology and clinical use of epoprostenol and its analogs in PAH. PMID:25848300
Pan, Jun-Yen; Lin, Chu-Chuan; Chang, Jen-Ping
Assessment of the pulmonary circulation status including pressure, resistance, size, and absence of anatomical distortion, is crucial to the successful Fontan operation. Most patients are found to have acceptable pulmonary arteries after previous palliation, although some degree of distortion is not uncommon. However, in rare instances, some patients have only one functioning lung with another pulmonary artery seriously hypoplastic or atretic. For theses patients, completion of a Fontan operation will be challenging. We reported a 17-year-old girl with a single ventricle and heterotaxy syndrome and only her left lung functioning, who underwent one-lung Fontan operation with a satisfactory result. PMID:27713611
Zhang, Yun-yun; Xu, Fan; Chu, Ming; Bi, Li-qing
Objective: To assess the incidence, possible risk factors and prognosis of pulmonary arterial hypertension (PAH) in critically ill elderly patients. Methods: We selected 122 cases admitted to the ICU, ages 60–93 years old. An echocardiography examination was performed within four days after admission to the ICU. PAH is usually suspected if the patient’s pulmonary artery systolic pressure ≥ 40 mmHg. We collected echocardiography data, relevant clinical data and routine laboratory data; we then used a statistical method to analyze the risk factors for PAH in critically ill elderly patients and examined its impact on the prognosis. Results: Total 51 patients were diagnosed with PAH. The prevalence of critically ill elderly patients with PAH was 41.8%. The ANOVA analysis showed that if patients had COPD (P = 0.031) and/or respiratory failure (P = 0.021), they were more prone to PAH. An enlarged left atrium (P = 0.038) and/or right ventricle (P = 0.029), a declining left ventricle fractional shortening rate (P = 0.038), and an elevated amount of the brain natriuretic peptides (P = 0.046) were all associated with the occurrence of PAH. Multivariate regression analysis showed that the left atrial diameter (P = 0.045) was the risk factor in critically ill elderly patients with PAH. The 30-day mortality rate was 33.3% for elderly patients with PAH, which is statistically significant (P = 0.035) when compared with the mortality rate of patients with normal pulmonary artery pressure. Our multivariate regression analysis also showed that, for critically ill elderly patients admitted in the ICU, PAH (P = 0.039) is risk factor for increased mortality. Conclusions: A higher incidence of PAH occurs in critically ill elderly patients. PAH is more likely to occur in patients with an enlarged left atrium, and these problems adversely impact the prognosis. PMID:28367167
Ginghina, Carmen; Popescu, Bogdan A; Enache, Roxana; Ungureanu, Catalina; Deleanu, Dan; Platon, Pavel
Dilatation of the pulmonary artery may lead to the compression of adjacent structures. Of those, the extrinsic compression of the left main coronary artery is the most worrisome. We present the case of a 48-year-old woman who was diagnosed with pulmonary artery dilatation due to severe, thromboembolic pulmonary hypertension. She also had angina and coronary angiography revealed a 70% ostial stenosis of the left main coronary artery. The presence of this isolated lesion in a young woman without risk factors for atherosclerosis suggests extrinsic compression of the left main coronary artery by the dilated pulmonary artery as the likely mechanism. The patient underwent direct stenting of the left main coronary stenosis with a good result.
Kim, Hae Jin
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular remodeling of pulmonary arteries (PAs) and increased vascular resistance in the lung. Monocrotaline (MCT), a toxic alkaloid, is widely used for developing rat models of PAH caused by injury to pulmonary endothelial cells; however, characteristics of vascular functions in MCT-induced PAH vary and are not fully understood. Here, we investigated hypoxic pulmonary vasoconstriction (HPV) responses and effects of various vasoconstrictors with isolated/perfused lungs of MCT-induced PAH (PAH-MCT) rats. Using hematoxylin and eosin staining, we confirmed vascular remodeling (i.e., medial thickening of PA) and right ventricle hypertrophy in PAH-MCT rats. The basal pulmonary arterial pressure (PAP) and PAP increase by a raised flow rate (40 mL/min) were higher in the PAH-MCT than in the control rats. In addition, both high K+ (40 mM KCl)- and angiotensin II-induced PAP increases were higher in the PAH-MCT than in the control rats. Surprisingly, application of a nitric oxide synthase inhibitor, L-NG-Nitroarginine methyl ester (L-NAME), induced a marked PAP increase in the PAH-MCT rats, suggesting that endothelial functions were recovered in the three-week PAH-MCT rats. In addition, the medial thickening of the PA was similar to that in chronic hypoxia-induced PAH (PAH-CH) rats. However, the HPV response (i.e., PAP increased by acute hypoxia) was not affected in the MCT rats, whereas HPV disappeared in the PAH-CH rats. These results showed that vascular contractility and HPV remain robust in the MCT-induced PAH rat model with vascular remodeling. PMID:27847441
PULMONARY HYPERTENSION , *PULMONARY BLOOD CIRCULATION, BLOOD CIRCULATION, LUNG, PATHOLOGY, VASCULAR DISEASES, ARTERIES, OBSTRUCTION(PHYSIOLOGY...EMBOLISM, HISTOLOGY, DOGS, LABORATORY ANIMALS, BLOOD PRESSURE , EXPERIMENTAL DATA, PHYSIOLOGY.
Becker, Eva Maria; Stasch, Johannes-Peter; Bechem, Martin; Keldenich, Jörg; Klipp, Alexandra; Schaefer, Katja; Ulbrich, Hannes-Friedrich; Truebel, Hubert
Background Approved therapies for pulmonary arterial hypertension can induce oxygen desaturation when administered to patients with secondary forms of pulmonary hypertension (PH), probably due to an increase in ventilation/perfusion mismatch. Thus, so far these treatments have largely failed in secondary forms of PH. Methods We established an animal model of heterogeneous lung ventilation to evaluate the desaturation potential of mechanistically distinct vasoactive drugs launched or currently in clinical development for the treatment of PH. Single-lung ventilation was induced in five groups (N = 6) of anesthetized minipigs (7 weeks, 4 to 5 kg BW), and their hemodynamic parameters were monitored before and after intravenous injection of control (vehicle only), endothelin antagonist (bosentan; 0.3, 1, 3, 10 mg/kg), phosphodiesterase type 5 inhibitor (sildenafil; 3, 10, 30, 100 µg/kg), and soluble guanylate cyclase stimulators (BAY 41–8543 and riociguat; 1, 3, 10, 30 µg/kg). Cumulative doses were administered before successive unilateral ventilation cycles. The doses were chosen to achieve equal effect on blood pressure by the different pharmacologic principles. Results Single-lung ventilation resulted in transient increases in mean pulmonary artery pressure (mPAP) and desaturation. In contrast to control, all drugs dose-dependently decreased hypoxic mPAP (a positive treatment effect) and increased area under the arterial hemoglobin saturation curve (unwanted desaturation effect). Riociguat and bosentan reduced hypoxic mPAP to the greatest extent, while the soluble guanylate cyclase stimulators riociguat and BAY 41–8543 lowered arterial oxygen saturation of hemoglobin the least. Conclusions Future investigations will be required to confirm these findings in clinical settings. PMID:24015306
Gupta, Nilesh; Ibrahim, Hany M; Ahsan, Fakhrul
This study investigates the respirability and efficacy of peptide-micelle hybrid nanoparticles as carriers for inhalational therapy of pulmonary arterial hypertension (PAH). CARSKNKDC (CAR), a cell-penetrating and lung-homing peptide, conjugated polyethylene glycol-distearoyl-phosphoethanolamine micelles containing fasudil, an investigational anti-PAH drug, were prepared by solvent evaporation method and characterized for various physicochemical properties. The pharmacokinetics and pharmacological efficacy of hybrid particles containing fasudil were evaluated in healthy rats and monocrotaline-induced PAH rats. CAR micelles containing fasudil had an entrapment efficiency of approximately 58%, showed controlled release of the drug, and were monodispersed with an average size of approximately 14 nm. Nuclear magnetic resonance scan confirmed the drug's presence in the core of peptide-micelle hybrid particles. Compared with plain micelles, CAR peptide increased the cellular uptake by approximately 1.7-fold and extended the drug half-life by approximately fivefold. The formulations were more prone to accumulate in the pulmonary vasculature than in the peripheral blood, which is evident from the ratio of the extent of reduction of pulmonary and systemic arterial pressures. On the whole, this study demonstrates that peptide-polymer hybrid micelles can serve as inhalational carriers for PAH therapy.
Papathanasiou, Athanasios; Nakos, George
Pulmonary hypertension (PH) is a condition characterized by the elevation of the mean pulmonary artery pressure above 25 mmHg and the pulmonary vascular resistance above 3 wood units. Pulmonary arterial hypertension (PAH) is an uncommon condition with severe morbidity and mortality, needing early recognition and appropriate and specific treatment. PH is frequently associated with hypoxemia, mainly chronic obstructive pulmonary disease and DPLD and/or left heart diseases (LHD), mainly heart failure with reduced or preserved ejection fraction. Although in the majority of patients with PH the cause is not PAH, a significant number of published studies are still in regard to group I PH, leading to a logical assumption that PH due to other causes is not such an important issue. So, is there a reason to discuss PH other than PAH? Chronic lung diseases, mainly chronic obstructive lung disease and DPLD, are associated with a high incidence of PH which is linked to exercise limitations and a worse prognosis. Although pathophysiological studies suggest that specific PAH therapy may benefit such patients, the results presented from small studies in regard to the safety and effectiveness of the specific PAH therapy are discouraging. PH is a common complication of left heart disease and is related to disease severity, especially in patients with reduced ejection fraction. There are two types of PH related to LHD based on diastolic pressure difference (DPD, deﬁned as diastolic pulmonary artery pressure - mean PAWP): Isolated post-capillary PH, defined as PAWP > 15 mmHg and DPD < 7 mmHg, and combined post-capillary PH and pre-capillary PH, defined as PAWP > 15 mmHg and DPD ≥ 7 mmHg. The potential use of PAH therapies in patients with PH related to left heart disease is based on a logical pathobiological rationale. In patients with heart failure, endothelial dysfunction has been proposed as a cause of PH and hence as a target for treatment, supported by the presence of
Drexler, E. S; Bischoff, J. E; Slifka, A. J; McCowan, C. N; Quinn, T. P; Shandas, R; Ivy, D. D; Stenmark, K. R
Changes in the compliance properties of large blood vessels are critical determinants of ventricular afterload and ultimately dysfunction. Little is known of the mechanical properties of large vessels exhibiting pulmonary hypertension, particularly the trunk and right main artery. We initiated a study to investigate the influence of chronic hypoxic pulmonary hypertension on the mechanical properties of the extrapulmonary arteries of rats. One group of animals was housed at the equivalent of 5000 m elevation for three weeks and the other held at ambient conditions of ~1600 m. The two groups were matched in age and gender. The animals exposed to hypobaric hypoxia exhibited signs of pulmonary hypertension, as evidenced by an increase in the RV/(LV+S) heart weight ratio. The extrapulmonary arteries of the hypoxic animals were also thicker than those of the control population. Histological examination revealed increased thickness of the media and additional deposits of collagen in the adventitia. The mechanical properties of the trunk, and the right and left main pulmonary arteries were assessed; at a representative pressure (7 kPa), the two populations exhibited different quantities of stretch for each section. At higher pressures we noted less deformation among the arteries from hypoxic animals as compared with controls. A four-parameter constitutive model was employed to fit and analyze the data. We conclude that chronic hypoxic pulmonary hypertension is associated with a stiffening of all the extrapulmonary arteries. PMID:27096124
Nair, Krishna Kumar Mohanan; Pillai, Harikrishnan Sivadasan; Titus, Thomas; Varaparambil, Ajitkumar; Sivasankaran, Sivasubramonian; Krishnamoorthy, Kavassery Mahadevan; Namboodiri, Narayanan; Sasidharan, Bijulal; Thajudeen, Anees; Ganapathy, Sanjay; Tharakan, Jaganmohan
Pulmonary artery pressure (PAP) is known to regress after successful balloon mitral valvotomy (BMV). Data of persistent pulmonary artery hypertension (PPAH) following BMV is scarce. We analyzed the clinical, echocardiographic, and hemodynamic data of 701 consecutive patients who have undergone successful BMV in our institute from 1997 to 2003. Data of 287 patients who had PPAH (defined by pulmonary artery systolic pressure [PASP] of ≥ 40 mmHg at one year following BMV) were compared to the data of 414 patients who did not have PPAH. Patients who had PPAH were older (39.9 ± 9.9 years vs. 29.4 ± 10.1; P < 0.001). They had higher prevalence of atrial fibrillation (AF; 21.9 vs. 12.1%, P < 0.05), moderate or severe pulmonary artery hypertension (PAH) defined as PASP more than 50 mmHg (43.5 vs. 33.8%, P = 0.00), anatomically advanced mitral valve disease as assessed by Wilkin's echocardiographic score > 8 (33.7 vs. 23.2%, P < 0.001), and coexistent aortic valve disease (45.6 vs. 37.9%, P < 0.001) at the baseline. Those patients with PPAH had comparatively lower immediate postprocedural mitral valve area (MVA). On follow-up of more than five years, the occurrence of restenosis (39.3 vs. 10.1%, P = 0.000), new onset heart failure (14% vs. 4%, P < 0.05) and need for reinterventions (9.5% vs. 2.8%, P < 0.05) were higher in the PPAH group. Patients with PPAH were older, sicker, and had advanced rheumatic mitral valve disease. They had higher incidence of restenosis, new onset heart failure, and need for reinterventions on long term follow-up. PPAH represents an advanced stage of rheumatic valve disease and indicates chronicity of the disease, which may be the reason for the poorer prognosis of these patients. Patients with PPAH requires intense and more frequent follow-up. PMID:24015345
Liu, Qin; Han, Hai-Chao
Tortuosity that often occurs in carotid and other arteries has been shown to be associated with high blood pressure, atherosclerosis, and other diseases. However the mechanisms of tortuosity development are not clear. Our previous studies have suggested that arteries buckling could be a possible mechanism for the initiation of tortuous shape but artery buckling under pulsatile flow condition has not been fully studied. The objectives of this study were to determine the artery critical buckling pressure under pulsatile pressure both experimentally and theoretically, and to elucidate the relationship of critical pressures under pulsatile flow, steady flow, and static pressure. We first tested the buckling pressures of porcine carotid arteries under these loading conditions, and then proposed a nonlinear elastic artery model to examine the buckling pressures under pulsatile pressure conditions. Experimental results showed that under pulsatile pressure arteries buckled when the peak pressures were approximately equal to the critical buckling pressures under static pressure. This was also confirmed by model simulations at low pulse frequencies. Our results provide an effective tool to predict artery buckling pressure under pulsatile pressure.
Canavan, Jane L; Kaliaraju, Djeya; Nolan, Claire M; Clark, Amy L; Jones, Sarah E; Kon, Samantha S C; Polkey, Michael I; Man, William D-C
Pulmonary rehabilitation (PR) can improve aerobic exercise capacity, health-related quality of life and dyspnoea in patients with chronic obstructive pulmonary disease (COPD). Recent studies have suggested that exercise training may improve blood pressure and arterial stiffness, albeit in small highly selected cohorts. The aim of the study was to establish whether supervised outpatient or unsupervised home PR can reduce peripheral blood pressure. Resting blood pressure was measured in 418 patients with COPD before and after outpatient PR, supervised by a hospital-based team (HOSP). Seventy-four patients with COPD undergoing an unsupervised home-based programme acted as a comparator group (HOME). Despite significant improvements in mean (95% confidence interval) exercise capacity in the HOSP group (56 (50-60) m, p < 0.001) and HOME group (30 (17-42) m, p < 0.001) systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) did not change in either the HOSP (SBP: p = 0.47; DBP: p = 0.06; MAP: p = 0.38) or HOME group (SBP: p = 0.67; DBP: p = 0.38; MAP: p = 0.76). Planned subgroup analysis of HOSP patients with known hypertension and/or cardiovascular disease showed no impact of PR upon blood pressure. PR is unlikely to reduce blood pressure, and by implication, makes a mechanism of action in which arterial stiffness is reduced, less likely.
Pérez del Río, M J; Molina Suárez, R; Fresno Forcelledo, M F; Veiga González, M; Madrigal Rubiales, B; González González, M; Herrero Zapatero, A
Pulmonary artery intimal sarcomas tend to be presented with symptoms of pulmonary thromboembolism and grow regionally, with little capacity to metastasize. They probably originate from subendothelial cells, that become myofibroblasts. Knowledge of it is important to establish a presurgery diagnosis, with the possibility of a total resection, the only useful treatment until now. We report a case of a pulmonary artery primary sarcoma, in a 73 year old woman, admitted with hemoptysis and pleuritic chest pain, who died ten days after. Autopsy revealed an intraluminal mass at the pulmonary artery trunk, without regional nor distance involvement. Microscopic study showed a pleomorphic tumor with spindle and epithelioid cells, positive for actin, desmin and vimentin. All these data support the diagnosis of primary intimal sarcoma of the pulmonary artery. We want to emphasize the myogenic differentiation of the tumor, uncommon in previously reported cases.
Chaachoui, Najia; Haik, William; Tournoux, François
A 72-year-old woman with no significant medical history presented to the emergency room for severe dyspnoea. The initial clinical diagnosis was acute pulmonary embolism. Heparin infusion was initiated while awaiting a computed tomographic scan but the patient's condition deteriorated dramatically and stat echocardiogram showed tamponade. Post-evacuation echo showed a dilated right ventricle with pulmonary hypertension and obstruction of the right pulmonary artery by a homogeneous mass attached to the pulmonary artery, suggesting a tumour rather than a thrombus. Computed tomographic scan confirmed the presence of an obstructive mass with almost no perfusion of the right lung. The patient was referred to cardiac surgery and the mass was removed, with anatomo-pathological diagnosis of a typical pulmonary artery sarcoma. Unfortunately, the patient died a few days after surgery. Primary pulmonary artery sarcoma is a rare tumour that arises in the central pulmonary arteries. Clinical presentation is often attributed to other causes of pulmonary hypertension, like pulmonary embolism. Magnetic resonance imaging could help to distinguish a soft tissue mass from a thrombus but definitive diagnosis is almost always made at surgery or autopsy since patients usually present in acute and unstable situations. Prognosis is poor, from several months to a few years, and depends on how early the diagnosis is made, the presence of recurrence or metastasis after surgical resection, and the use of adjuvant therapy like radiation and chemotherapy.
Among connective tissue diseases, pulmonary arterial hypertension (PAH) is frequently associated with systemic sclerosis and systemic lupus erythematosus. PAH is less common in mixed connective tissue diseases and Sjögren's syndrome, and rare in rheumatoid arthritis. PAH in systemic sclerosis may be either isolated (prevalence about 8%) or associated with interstitial lung disease. Echocardiographic screening for PAH is worthwhile in patients with systemic sclerosis, especially as treatments for idiopathic PAH (endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostanoids) are effective in this setting. The prevalence of PAH among patients with systemic lupus erythematosus is poorly known; immunosuppressive treatment is sometimes effective by itself but most patients benefit from PAH treatment. PAH associated with connective tissue diseases has a worse prognosis than idiopathic PAH.
D’Andrilli, Antonio; Venuta, Federico; Rendina, Erino Angelo
Bronchovascular reconstructive procedures employed in order to avoid pneumonectomy (PN) in patients functionally unsuitable have provided, over time, excellent results, similar or even better than those obtained by PN. In recent years, new successful techniques have been developed that pertain in particular the prevention of major complications and the reconstruction of the pulmonary artery (PA). Encouraging data from increasing number of published experiences support the choice of parenchymal sparing procedures for lung cancer also in patients with good functional reserve. This is even more true if considering trials published in the last 10 years, thus indicating that improved outcome can be achieved with increased experience in reconstructive techniques and perioperative management. This article discusses the main technical aspects and results of literature. PMID:26981268
Dhariwal, AK; Bavdekar, SB
Pulmonary arterial hypertension (PAH) is a life-threatening disease of varied etiologies. Although PAH has no curative treatment, a greater understanding of pathophysiology, technological advances resulting in early diagnosis, and the availability of several newer drugs have improved the outlook for patients with PAH. Sildenafil is one of the therapeutic agents used extensively in the treatment of PAH in children, as an off-label drug. In 2012, the United States Food and Drug Administration (USFDA) issued a warning regarding the of use high-dose sildenafil in children with PAH. This has led to a peculiar situation where there is a paucity of approved therapies for the management of PAH in children and the use of the most extensively used drug being discouraged by the regulator. This article provides a review of the use of sildenafil in the treatment of PAH in children. PMID:26119438
Sidorenko, B A; Preobrazhenskiĭ, D V; Batyraliev, T A; Belenkov, Iu N
The review is devoted to different aspects of pulmonary arterial hypertension (PAH); new classification of PAH is published in 2010. There are idiopathic PAH and PAH associated with other diseases. Current guidelines recommend to treat PAH only after the verification of diagnosis with right heart catheterization and acute tests with vasodilators. Patients-reactors should be treated with calcium antagonists. The following drugs related to one of three categories should be used in PAH: (1) prostanoids (epoprostenol, iloprost et al.); (2) blockers of endothelin receptors (bosentan, ambrisentan, sitaxsentan); (3) phosphodiesterase 5 type inhibitors (sildenafil, tadalafil et al.) In majority of cases the combined treatment is used, usually the combination of bosentan and sildenafil is used.
Murphy, Glenn S; Nitsun, Martin; Vender, Jeffery S
In the United States more than 1.5 million pulmonary artery catheters (PACs) are inserted each year. Of these, approximately 55% are placed in high-risk surgical and trauma patients. Most clinicians believe that PAC use is beneficial in guiding therapy and may improve outcome. Despite these beliefs and hundreds of published articles related to PACs, appropriate use and impact on outcome remain unclear. A review of the current literature reveals conflicting data and significant flaws in most study designs. Inadequate sample size, lack of randomization, lack of standardization of therapies to PAC data, and deficiencies in user knowledge all significantly limit interpretation of clinical trials. Despite these deficiencies and the need for better-designed investigations, it is the opinion of the authors that access to hemodynamic data provided by the PAC, coupled with accurate interpretation of the data, may lead to reduced perioperative morbidity and mortality.
Dhariwal, A K; Bavdekar, S B
Pulmonary arterial hypertension (PAH) is a life-threatening disease of varied etiologies. Although PAH has no curative treatment, a greater understanding of pathophysiology, technological advances resulting in early diagnosis, and the availability of several newer drugs have improved the outlook for patients with PAH. Sildenafil is one of the therapeutic agents used extensively in the treatment of PAH in children, as an off-label drug. In 2012, the United States Food and Drug Administration (USFDA) issued a warning regarding the of use high-dose sildenafil in children with PAH. This has led to a peculiar situation where there is a paucity of approved therapies for the management of PAH in children and the use of the most extensively used drug being discouraged by the regulator. This article provides a review of the use of sildenafil in the treatment of PAH in children.
LIU, PANPAN; YAN, SHUANGQUAN; CHEN, MAYUN; CHEN, ALI; YAO, DAN; XU, XIAOMEI; CAI, XUEDING; WANG, LIANGXING; HUANG, XIAOYING
The synthesis and accumulation of collagen play an important role in the formation and progression of hypoxic pulmonary hypertension. Baicalin has been reported to prevent bleomycin-induced pulmonary fibrosis. However, the role of baicalin in the treatment of pulmonary hypertension remains unknown. A disintegrin and metalloprotease with thrombospondin type-1 motif (ADAMTS-1) is a secreted enzyme that acts on a wide variety of extracellular matrix (ECM) substrates associated with vascular diseases. In this study, we aimed to investigate the effects of baicalin on the synthesis of collagen I in rats with pulmonary hypertension induced by hypoxia and the changes in ADAMTS-1 expression. A total of 24 Sprague Dawley rats were randomly assigned to 3 groups as follows: the control group (C), the hypoxia group (H) and the hypoxia + baicalin group (B). The rats in groups H and B were kept in a normobaric hypoxic chamber for 4 weeks, and the rats in group C were exposed to room air. We measured the hemodynamic indexes, including mean pulmonary artery pressure (mPAP), mean systemic (carotid) artery pressure (mSAP), and then calculated the mass ratio of right ventricle to left ventricle plus septum [RV/(LV + S)] to reflect the extent of right ventricular hypertrophy. We measured the mRNA and protein expression levels of type I collagen, type III collagen and ADAMTS-1 by hybridization in situ, and immunohistochemistry and western blot analysis, respectively. The results revealed that treatment with baicalin significantly reduced pulmonary artery pressure and attenuated the remodeling of the pulmonary artery under hypoxic conditions by increasing the expression of ADAMTS-1, so that the synthesis of type I collagen and its mRNA expression were inhibited. In conclusion, baicalin effectively inhibits the synthesis of collagen I in pulmonary arteries and this is associated with an increase in the expression of ADAMTS-1. Thus, treatment with baicalin may be an effective method for
Liu, Panpan; Yan, Shuangquan; Chen, Mayun; Chen, Ali; Yao, Dan; Xu, Xiaomei; Cai, Xueding; Wang, Liangxing; Huang, Xiaoying
The synthesis and accumulation of collagen play an important role in the formation and progression of hypoxic pulmonary hypertension. Baicalin has been reported to prevent bleomycin-induced pulmonary fibrosis. However, the role of baicalin in the treatment of pulmonary hypertension remains unknown. A disintegrin and metalloprotease with thrombospondin type-1 motif (ADAMTS-1) is a secreted enzyme that acts on a wide variety of extracellular matrix (ECM) substrates associated with vascular diseases. In this study, we aimed to investigate the effects of baicalin on the synthesis of collagen I in rats with pulmonary hypertension induced by hypoxia and the changes in ADAMTS-1 expression. A total of 24 Sprague Dawley rats were randomly assigned to 3 groups as follows: the control group (C), the hypoxia group (H) and the hypoxia + baicalin group (B). The rats in groups H and B were kept in a normobaric hypoxic chamber for 4 weeks, and the rats in group C were exposed to room air. We measured the hemodynamic indexes, including mean pulmonary artery pressure (mPAP), mean systemic (carotid) artery pressure (mSAP), and then calculated the mass ratio of right ventricle to left ventricle plus septum [RV/(LV + S)] to reflect the extent of right ventricular hypertrophy. We measured the mRNA and protein expression levels of type I collagen, type III collagen and ADAMTS-1 by hybridization in situ, and immunohistochemistry and western blot analysis, respectively. The results revealed that treatment with baicalin significantly reduced pulmonary artery pressure and attenuated the remodeling of the pulmonary artery under hypoxic conditions by increasing the expression of ADAMTS-1, so that the synthesis of type I collagen and its mRNA expression were inhibited. In conclusion, baicalin effectively inhibits the synthesis of collagen I in pulmonary arteries and this is associated with an increase in the expression of ADAMTS-1. Thus, treatment with baicalin may be an effective method for
García de Hombre, Alina M; Cuffini, Alejandro; Bonadeo, Alejandro
Negative pressure pulmonary oedema (NPPO) is an anaesthetic complication due to acute obstruction of the upper airway, whose main cause is laryngospasm. The pathophysiology involves a strong negative intrapleural pressure during inspiration against a closed glottis, which triggers excessive pressure in the pulmonary microvasculature. Although its diagnosis can be difficult, its recognition helps to minimise morbidity and mortality. This article presents a case of NPPO due to postextubation laryngospasm.
Linguraru, Marius George; Mukherjee, Nisha; Van Uitert, Robert L.; Summers, Ronald M.; Gladwin, Mark T.; Machado, Roberto F.; Wood, Bradford J.
Pulmonary arterial hypertension is a known complication associated with sickle-cell disease; roughly 75% of sickle cell disease-afflicted patients have pulmonary arterial hypertension at the time of death. This prospective study investigates the potential of image analysis to act as a surrogate for presence and extent of disease, and whether the size change of the pulmonary arteries of sickle cell patients could be linked to sickle-cell associated pulmonary hypertension. Pulmonary CT-Angiography scans from sickle-cell patients were obtained and retrospectively analyzed. Randomly selected pulmonary CT-Angiography studies from patients without sickle-cell anemia were used as negative controls. First, images were smoothed using anisotropic diffusion. Then, a combination of fast marching and geodesic active contours level sets were employed to segment the pulmonary artery. An algorithm based on fast marching methods was used to compute the centerline of the segmented arteries. From the centerline, the diameters at the pulmonary trunk and first branch of the pulmonary arteries were measured automatically. Arterial diameters were normalized to the width of the thoracic cavity, patient weight and body surface. Results show that the pulmonary trunk and first right and left pulmonary arterial branches at the pulmonary trunk junction are significantly larger in diameter with increased blood flow in sickle-cell anemia patients as compared to controls (p values of 0.0278 for trunk and 0.0007 for branches). CT with image processing shows great potential as a surrogate indicator of pulmonary hemodynamics or response to therapy, which could be an important tool for drug discovery and noninvasive clinical surveillance.
Gangadharan, Venkat; Sivagnanam, Kamesh; Murtaza, Ghulam; Ponders, Michael; Teixeira, Otto; Paul, Timir
A 36-year-old woman was seen with complaints of exertional chest pain and shortness of breath. Her medical history included atrial fibrillation and diabetes. Physical examination was unremarkable except for an irregular cardiac rhythm. Myocardial perfusion imaging revealed the presence of a large area of infarction involving the entire anterior and apical walls and part of the anteroseptal wall with minimal periinfarct ischemia. Computed tomography coronary angiogram revealed an anomalous left main coronary artery arising from the main pulmonary artery. Right and left heart catheterizations demonstrated moderate pulmonary hypertension with a slight step-up in oxygen saturation between the right ventricle and main pulmonary artery. Coronary angiography showed a large tortuous right coronary artery with collaterals to the left anterior descending artery that drained into the main pulmonary artery. She was referred for surgery. This case demonstrates a rare coronary artery anomaly in an adult where survival is dependent on collateral circulation. PMID:28210637
Mun, Da-Na; Park, Chun Soo; Kim, Young-Hwue; Goo, Hyun Woo
A multistage plan and multidisciplinary approach are the keys to successful repair in patients with pulmonary atresia (PA) with ventricular septal defect (VSD) and major aortopulmonary collateral arteries (MAPCAs). In this article, we present a multidisciplinary approach adopted to treat a patient with PA with VSD and MAPCAs associated with left pulmonary artery interruption. PMID:27733998
Manes, Alessandra; Palazzini, Massimiliano; Dardi, Fabio; D'Adamo, Antonio; Rinaldi, Andrea; Galiè, Nazzareno
Pulmonary arterial hypertension (PAH) is a severe clinical condition defined as mean pulmonary artery pressure ≥25 mmHg and normal pulmonary capillary wedge pressure (≤15 mmHg). In PAH the increase in pulmonary pressure is due to an intrinsic disease of the small pulmonary arteries (resistance vessels) characterized by vascular proliferation and remodeling. The increase in pulmonary vascular resistance with subsequent elevation of the right ventricular afterload leads to right ventricular failure after variable periods of time. Although targeted disease therapies have been developed over the last decade that resulted in improved quality of life and outcome for PAH patients, the prognosis is still severe and there remains no cure for this disease. From a clinical standpoint, PAH includes a group of heterogeneous pathological conditions: in idiopathic, heritable and drug- and toxin-induced PAH, since there are no predisposing clinical conditions, the structural changes in pulmonary circulation are "isolated"; on the other hand, PAH may be associated with some predisposing diseases such as connective tissue disease, HIV infection, portal hypertension, congenital heart disease, schistosomiasis, and chronic hemolytic anemia. PAH can affect individuals of all age groups, and mean age at diagnosis is around 50 years. Epidemiological data show a great preponderance of females in PAH; the high prevalence of females is particularly evident in the so-called "isolated" PAH forms, whereas in PAH associated with other diseases the female:male ratio is strongly influenced by the epidemiological features of the specific predisposing condition. The reason for the higher female prevalence in PAH has never been clarified: some hypotheses involve the role of sexual hormones (estrogens), autoimmunity, or an X-linked locus in disease predisposition. Female gender is not associated with a different clinical presentation. However, the age of onset tends to be earlier in females than
Ataya, Ali; Cope, Jessica; Alnuaimat, Hassan
Significant advances in the understanding of the pathophysiology of pulmonary arterial hypertension over the past two decades have led to the development of targeted therapies and improved patient outcomes. Currently, a broad armamentarium of pulmonary arterial hypertension-specific drugs exists to assist in the treatment of this complex disease state. In this manuscript, we provide a comprehensive review of the current Food and Drug Administration (FDA)-approved pulmonary arterial hypertension-specific therapies, and their supporting evidence for adults, targeting the nitric oxide, soluble guanylate cyclase, endothelin, and prostacyclin pathways. PMID:27929408
Ataya, Ali; Cope, Jessica; Alnuaimat, Hassan
Significant advances in the understanding of the pathophysiology of pulmonary arterial hypertension over the past two decades have led to the development of targeted therapies and improved patient outcomes. Currently, a broad armamentarium of pulmonary arterial hypertension-specific drugs exists to assist in the treatment of this complex disease state. In this manuscript, we provide a comprehensive review of the current Food and Drug Administration (FDA)-approved pulmonary arterial hypertension-specific therapies, and their supporting evidence for adults, targeting the nitric oxide, soluble guanylate cyclase, endothelin, and prostacyclin pathways.
Domingo, Enric; Aguilar, Rio; López-Meseguer, Manuel; Teixidó, Gisela; Vazquez, Manuel; Roman, Antonio
Pulmonary arterial hypertension (PAH) is a rare fatal disease defined as a sustained elevation of pulmonary arterial pressure to more than 25 mmHg at rest, with a mean pulmonary-capillary wedge pressure and left ventricular enddiastolic pressure of less than 15 mmHg at rest. Histopathology of PAH is founded on structural modifications on the vascular wall of small pulmonary arteries characterized by thickening of all its layers. These changes, named as vascular remodelling, include vascular proliferation, fibrosis, and vessel obstruction. In clinical practice the diagnosis of PAH relies on measurements of pulmonary vascular pressure and cardiac output, and calculation of pulmonary vascular resistances. Direct evaluation of pulmonary vascular structure is not routinely performed in pulmonary hypertension since current imaging techniques are limited and since little is known about the relationship between structural changes and functional characteristics of the pulmonary vasculature. Intravascular ultrasound studies in patients with pulmonary hypertension have shown a thicker middle layer, increased wall-thickness ratio and diminished pulsatility than in control patients. Optical Coherence Tomography, a new high resolution imaging modality that has proven its superiority over intravascular ultrasound (IVUS) for the detection and characterization of coronary atherosclerotic plaque composition, may potentially be a useful technique for the in vivo study of the pulmonary arterial wall. In addition current progress in Echo Doppler technique will quantify right ventricular function with parameters independent of loading conditions and not requiring volumetric approximations of the complex geometry of the right ventricle. This would allow the in vivo study of right ventricular and pulmonary artery remodelling in PAH. PMID:19452037
Benito, F; Oliver, J M
Stents have been previously used to resolve stenoses of branch pulmonary arteries in children. We report 3 patients, with mean age of 22.7 +/- 4.7 years and pulmonary artery stenosis after palliative surgery in whom we implanted seven stents in four procedures. Six P308 Palmaz, overlapped two by two, were implanted by venous femoral approach in two patients, receiving four in the first case and the other two in the third case. In the second case, a NIR type stent was implanted through femoral artery in the right pulmonary artery. Stenosis diameter enlarged from 5.3 +/- 2.3 to 14.4 +/- 4.2 mm and the pressure gradient through stenosis fell from 40.6 +/- 15.3 to 6. 5 +/- 5 mmHg. All stents are well deployed and there are two patients waiting for total correction (previously not feasible) during a follow-up of 30.6 +/- 6.1 months.
Hadinnapola, Charaka; Pepke-Zaba, Joanna
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease characterised by the presence of organised chronic thromboembolic material occluding the proximal pulmonary arteries and a vasculopathy in the distal pulmonary arterial tree. Pulmonary endarterectomy (PEA) is a potential cure for many patients with CTEPH. However, PEA is not suitable for patients with a significant distal distribution of chronic thromboembolic material or with significant comorbidities. Also, a proportion of patients are left with residual CTEPH post PEA. Until recently, pulmonary arterial hypertension-targeted therapies have been used off licence to treat patients with inoperable or residual CTEPH. The CHEST1 study investigated the use of riociguat and was the first randomised controlled trial to show efficacy in inoperable or residual CTEPH. In this review, we explore the pathophysiology of CTEPH and review the current trial evidence for pulmonary arterial hypertension-targeted therapies. We also include a discussion of physiological considerations that require further investigation.
Wen, Shusheng; Cen, Jianzheng; Chen, Jimei; Xu, Gang; He, Biaochuan; Teng, Yun
Background In the patients with longer-segment aortic arch hypoplasia or interruption with ventricular septal defect, surgery with homograft vessel or autologous pericardial patch to augment descending aortic arch will not result in adverse reactions caused by end-to-end anastomosis. In this study, we retrospectively analyzed primary experience of surgical correction of complicated aortic arch anomaly with autologous main pulmonary artery. Methods From July 2010 to March 2016, the twenty-one cases of aortic arch complex anomalies were reconstructed with autologous main pulmonary artery. There were 5 patients with interrupted aortic arch and 16 patients with coarctation of aorta. In patients with interrupted aortic arch, anterior wall of main pulmonary artery was excised to form a conduit whose diameter varied according to the area of patient’s body surface. Both ends of the conduit were anastomosed to aortic arch and descending aorta, respectively. In other patients with coarctation of aorta, aortic arch was augmented with tailored pulmonary artery patch in oval shape. The defect of main pulmonary artery was repaired with autologous pericardial patch. Results There was only one patient died of multiple organ failure postoperatively. The other twenty patients survived without any neurologic complications. Differences of blood pressure between upper and lower limbs were not significant in all cases. During follow-up period, the echocardiography for all patients in the third, sixth, twelfth, and twenty-fourth months showed that blood flow in the descending aortic arch was fluent and there was no obvious blood pressure gradient. Conclusions Autologous main pulmonary artery can be used to repair complicated aortic arch anomalies completely without any anastomotic tension or bronchial obstruction postoperatively. This procedure is feasible and possesses predominant early and mid-term effects, and autologous main pulmonary artery can retain growth capacity during follow
Ventetuolo, Corey E.; Gabler, Nicole B.; Fritz, Jason S.; Smith, K. Akaya; Palevsky, Harold I.; Klinger, James R.; Halpern, Scott D.; Kawut, Steven M.
Background While frequently assessed in trials and clinical practice, hemodynamic response to therapy has never been validated as a surrogate endpoint for clinical events in pulmonary arterial hypertension (PAH). Methods and Results We performed a patient-level pooled analysis of four randomized placebo-controlled trials to determine if treatment-induced changes in hemodynamic values at 12 weeks accounted for the relationship between treatment assignment and the probability of early clinical events (death, lung transplantation, atrial septostomy, PAH hospitalization, withdrawal for clinical worsening, escalation in PAH therapy). We included 1119 subjects with PAH. The median (interquartile range) age was 48 (37 – 59), and 23% were men. 656 (59%) received active therapy (101 [15%] iloprost, 118 [18%] sitaxsentan, 204 [31%] sildenafil, and 233 [36%] subcutaneous treprostinil). Active treatment significantly lowered right atrial pressure (RAP), mean pulmonary artery pressure (mPAP), and pulmonary vascular resistance and increased cardiac output and index (p < 0.01 for all). Changes in hemodynamic values (except for RAP and mPAP) were significantly associated with the risk of a clinical event (p ≤ 0.01 for all). While active treatment approximately halved the odds of a clinical event compared to placebo (p < 0.001), changes in hemodynamics accounted for only 1.2 – 13.9% of the overall treatment effect. Conclusions Treatment-induced changes in hemodynamics at 12 weeks only partially explain the impact of therapy on the probability of early clinical events in PAH. These findings suggest that resting hemodynamics are not valid surrogate endpoints for short-term events in PAH clinical trials. PMID:24951771
Hiraki, T. Kanazawa, S.; Mimura, H.; Yasui, K.; Okumura, Y.; Dendo, S.; Yoshimura, K.; Takahara, M.; Hiraki, Y.
A 29-year-old woman with primary pulmonary hypertension presented with recurrent hemoptysis. Contrast-enhanced CT of the chest demonstrated the enhanced mass surrounded by consolidation related to parenchymal hemorrhage. Pulmonary angiography suggested that the mass was a pulmonary artery false aneurysm. After a microcatheter was superselectively inserted into the parent artery of the falseaneurysm, the false aneurysm was successfully treated by transcatheterembolization with coils. Her hemoptysis has never recurred.
Contreras-Arias, Catalina; Duarte, Diana; Ramírez, Luis F; Serrano, Carlos D
Unilateral absence of a pulmonary artery is an uncommon congenital heart disease. It can be related to respiratory symptoms such as asthma, an unusual finding in some of these patients. This paper reports the case of a 4-year-old male with recurrent respiratory infections and asthma symptoms, in who further studies found agenesia of right pulmonary artery with pulmonary hypoplasia of the same side.
Nielson, Jeffery L. Kang, Preet S.
Fistula formation between a coronary artery bypass graft (CABG)and the pulmonary arterial circulation represents a rare cause of recurrent angina in patients following bypass grafting. Therapy has traditionally involved surgical ligation by open thoracotomy. We describe a case of left internal mammary artery-left upper lobe pulmonary artery fistula presenting as early recurrent angina following CABG. The fistula was embolized using platinum coils, resulting in symptomatic relief and improvement in myocardial perfusion on cardiac perfusion scintigraphy. Coil embolization should be considered a therapeutic option in patients with coronary-pulmonary steal syndrome.
Buggeskov, Katrine B; Sundskard, Martin M; Jonassen, Thomas; Andersen, Lars W; Secher, Niels H; Ravn, Hanne B; Steinbrüchel, Daniel A; Jakobsen, Janus C; Wetterslev, Jørn
Introduction Absence of pulmonary perfusion during cardiopulmonary bypass (CPB) may be associated with reduced postoperative oxygenation. Effects of active pulmonary artery perfusion were explored in patients with chronic obstructive pulmonary disease (COPD) undergoing cardiac surgery. Methods 90 patients were randomised to receive pulmonary artery perfusion during CPB with either oxygenated blood (n=30) or histidine-tryptophan-ketoglutarate (HTK) solution (n=29) compared with no pulmonary perfusion (n=31). The coprimary outcomes were the inverse oxygenation index compared at 21 hours after starting CPB and longitudinally in a mixed-effects model (MEM). Secondary outcomes were tracheal intubation time, serious adverse events, mortality, days alive outside the intensive care unit (ICU) and outside the hospital. Results 21 hours after starting CPB patients receiving pulmonary artery perfusion with normothermic oxygenated blood had a higher oxygenation index compared with no pulmonary perfusion (mean difference (MD) 0.94; 95% CI 0.05 to 1.83; p=0.04). The blood group had also a higher oxygenation index both longitudinally (MEM, p=0.009) and at 21 hours (MD 0.99; CI 0.29 to 1.69; p=0.007) compared with the HTK group. The latest result corresponds to a difference in the arterial partial pressure of oxygen of 23 mm Hg with a median fraction of inspired oxygen of 0.32. Yet the blood or HTK groups did not demonstrate a longitudinally higher oxygenation index compared with no pulmonary perfusion (MEM, p=0.57 and 0.17). Similarly, at 21 hours there was no difference in the oxygenation index between the HTK group and those no pulmonary perfusion (MD 0.06; 95% CI −0.73 to 0.86; p=0.87). There were no statistical significant differences between the groups for the secondary outcomes. Discussion Pulmonary artery perfusion with normothermic oxygenated blood during cardiopulmonary bypass appears to improve postoperative oxygenation in patients with COPD undergoing
Golovenko, O S; Prokopovych, L M; Moshkivska, L V; Truba, Ya P; Lazoryshynets, V V
Right ventricle insufficiency due to pulmonary hypertensive crysis or persisting pulmonary arterial hypertension (PAH) in patients after the interventricle septum defect (IVSD) closure with the heightened resistance of pulmonary arteries (RPA) constitutes an actual problem and associates with a high risk for a life-threatening complications and high lethality. Experience of the IVSD plasty conduction in a patient with high PAH, using a patch with a valve for right ventricle decompression while pulmonary hypertensive crysis in early postoperative period and nonreversible PAH in the remote period of observation, was presented. In the clinic 38 children were operated on for big IVSD, complicated by high PAH and heightened RPA, using a patch with a valve in 1996 - 2014 yrs. Hospital lethality have constituted 2.6%. Postoperatively a pressure in pulmonary artery (PA) have lowered trustworthy from (93.4 ? 14.9) to (49.2 ? 22.9) mm Hg. In a remote period of observation all the patients were alive. In 6 (16.2%) patients in terms from 4 mo to 18 yrs postoperatively a PAH have occurred, a pressure in PA was by 50% higher, than a systemic one. The IVSD plasty in patients with high PAH and heightened RPA may appear successful if a patch with a valve are applied.
Kasikcioglu, Erdem; Akhan, Hulya; Cuhadaroglu, Caglar; Erkan, Feyza
The pulmonary artery is the second most common site of arterial involvement in Behcet's disease. A 32-year-old man presented with bilateral ankle edema, abdominal discomfort, and hemoptysis. He had a history of recurrent oral and genital aphthous ulcerations for 1 year. The diagnosis of Behcet's disease was made on the basis of the criteria published by the International Study Group for Behcet's Disease. His chest X-ray revealed left hilar enlargement. A helical computed tomography (CT) scan showed a pulmonary aneurysm with intramural thrombosis in the left pulmonary artery and enlarged hepatic veins. Treatment with colchicine and cyclophosphamide was given for 24 months, and helical thoracic CT was performed again. Helical CT showed that the pulmonary aneurysm was reduced by treatment. Helical CT could be used in Behcet's disease for the diagnosis and follow-up of pulmonary involvement.
Seyahi, Emire; Melikoglu, Melike; Akman, Canan; Hamuryudan, Vedat; Ozer, Harun; Hatemi, Gulen; Yurdakul, Sebahattin; Tuzun, Hasan; Oz, Buge; Yazici, Hasan
involves mostly descending branches of the pulmonary artery. Pulmonary artery involvement may disappear, but arterial stenosis or occlusions usually develop at the same location. After a mean follow-up of 7 years, 12 of 47 (26%) patients were dead; patients with larger aneurysms were more likely to die. Sixteen of 47 (34%) patients were symptom free, and the remaining 40% had mild dyspnea (13/47) and/or small bouts of hemoptysis (8/47).Pulmonary artery pressure may be elevated, and may indicate a poor prognosis. Mediastinal lymphadenopathy and mild pleural and pericardial effusions may also be observed. Corticosteroids and immunosuppressive agents are the mainstays of treatment; however, refractory cases may require embolization, lobectomy, cavitectomy, and decortication.
Hoogma, Danny; Meyns, Bart; Van Raemdonck, Dirk; Van de Velde, Marc; Missant, Carlo; Rex, Steffen
We describe a patient who presented with a bilateral pulmonary artery sarcoma, initially treated as pulmonary embolism, that necessitated concomitant pulmonary endarterectomy and pneumonectomy. We reviewed the anesthetic management used for this procedure, which bears many similarities to the management of patients undergoing pulmonary thromboendarterectomy. Right ventricular failure, pulmonary hemorrhage, and cerebral ischemia due to circulatory arrest are life-threatening perioperative complications. The anesthesiologist can play a key role in the prevention (or timely recognition and treatment) of these perioperative complications by establishing adequate hemodynamic, echocardiographic, and neurologic monitoring and by optimizing cardiopulmonary function and coagulation.
Pulmonary arterial hypertension; Sporadic primary pulmonary hypertension; Familial primary pulmonary hypertension; Idiopathic pulmonary arterial hypertension; Primary pulmonary hypertension; PPH; Secondary pulmonary ...
Rasmussen, Jason T; Thenappan, Thenappan; Benditt, David G; Weir, E Kenneth; Pritzker, Marc R
Pulmonary arterial hypertension is a manifestation of a group of disorders leading to pulmonary vascular remodeling and increased pulmonary pressures. The right ventricular (RV) response to chronic pressure overload consists of myocardial remodeling, which is in many ways similar to that seen in left ventricular (LV) failure. Maladaptive myocardial remodeling often leads to intraventricular and interventricular dyssychrony, an observation that has led to cardiac resynchronization therapy (CRT) for LV failure. CRT has proven to be an effective treatment strategy in subsets of patients with LV failure resulting in improvement in LV function, heart failure symptoms, and survival. Current therapy for pulmonary arterial hypertension is based on decreasing pulmonary vascular resistance, and there is currently no effective therapy targeting the right ventricle or maladaptive ventricular remodeling in these patients. This review focuses on the RV response to chronic pressure overload, its effect on electromechanical coupling and synchrony, and how lessons learned from left ventricular cardiac resynchronization might be applied as therapy for RV dysfunction in the context of pulmonary arterial hypertension.
Reversal of abnormal cardiac parameters following mitral valve replacement for severe mitral stenosis in relation to pulmonary artery pressure: A retrospective study of noninvasive parameters – Early and late pattern
Parvathy, Usha T.; Rajan, Rajesh; Faybushevich, Alexander Georgevich
Background and objectives Although the regression of pulmonary hypertension (PH) in mitral stenosis (MS) has been studied over varying periods postintervention, corresponding studies on the cardiac chamber alterations after surgery are very limited. We sought to determine the degree of reversal of these and the clinical status in connection with that of pulmonary artery pressures (PAPs) in the early and late postoperative periods. Methods The preoperative, early, and 1-year postoperative data – functional class (FC), cardiothoracic ratio (CTR) in chest X-ray (CXR), and echocardiographically left atrium (LA), right atrium (RA), right ventricle (RV), left ventricle (LV), and pulmonary artery (PA) dimensions, PAP, tricuspid regurgitation (TR) – of 50 patients who had mitral valve replacement (MVR) for MS with PH were retrospectively analyzed for correlations with PAP (Pearson’s), and their change (t-test), in relation to that in PAP. PH group-based [Group (Gp)-I PAP ≤60 mmHg, Gp-II PAP >60 mmHg] analysis highlighted the differences. Results All parameters significantly correlated with the baseline PAP (p < 0.05), except LA (r = 0.081, p = 0.577). Postoperatively, there was significant reduction in all parameters (p < 0.001) and increase in LV (p < 0.003). The PAP regression was 39.42%; with the decrease in CTR, LA, and RA related to it, the early changes being significant (p < 0.01). The RV and PA showed lesser reduction (8.61% and 9.42%), late reduction being more conspicuous. The changes were greater and significant in Gp-II (especially PAP, RV, and PA). At 1 year, PAP normalized in only 19 (38%). Residual PH and chamber enlargement prevailed more in Gp-II. Conclusions This study emphasizes the importance of the baseline PAP in MS to which was proportionate the functional disability and the cardiac chamber alterations (except LA). Their postoperative improvement accompanying the PAP regression differed in degree and time frame
Soubrier, Florent; Chung, Wendy K; Machado, Rajiv; Grünig, Ekkehard; Aldred, Micheala; Geraci, Mark; Loyd, James E; Elliott, C Gregory; Trembath, Richard C; Newman, John H; Humbert, Marc
Major discoveries have been obtained within the last decade in the field of hereditary predisposition to pulmonary arterial hypertension (PAH). Among them, the identification of bone morphogenetic protein receptor type 2 (BMPR2) as the major predisposing gene and activin A receptor type II-like kinase-1 (ACVRL1, also known as ALK1) as the major gene when PAH is associated with hereditary hemorrhagic telangiectasia. The mutation detection rate for the known genes is approximately 75% in familial PAH, but the mutation shortfall remains unexplained even after careful molecular investigation of these genes. To identify additional genetic variants predisposing to PAH, investigators harnessed the power of next-generation sequencing to successfully identify additional genes that will be described in this report. Furthermore, common genetic predisposing factors for PAH can be identified by genome-wide association studies and are detailed in this paper. The careful study of families and routine genetic diagnosis facilitated natural history studies based on large registries of PAH patients to be set up in different countries. These longitudinal or cross-sectional studies permitted the clinical characterization of PAH in mutation carriers to be accurately described. The availability of molecular genetic diagnosis has opened up a new field for patient care, including genetic counseling for a severe disease, taking into account that the major predisposing gene has a highly variable penetrance between families. Molecular information can be drawn from the genomic study of affected tissues in PAH, in particular, pulmonary vascular tissues and cells, to gain insight into the mechanisms leading to the development of the disease. High-throughput genomic techniques, on the basis of next-generation sequencing, now allow the accurate quantification and analysis of ribonucleic acid, species, including micro-ribonucleic acids, and allow for a genome-wide investigation of epigenetic or
Badesch, David B; McLaughlin, Vallerie V; Delcroix, Marion; Vizza, Carmine Dario; Olschewski, Horst; Sitbon, Olivier; Barst, Robyn J
Prostanoids have played a prominent role in the treatment of pulmonary arterial hypertension (PAH). Several compounds and methods of administration have been studied: chronic intravenously infused epoprostenol, chronic subcutaneously infused treprostinil, inhaled iloprost, and oral beraprost. Chronic intravenous epoprostenol therapy has had a substantial impact on the clinical management of patients with severe PAH. It improves exercise capacity, hemodynamics, and survival in patients with idiopathic pulmonary arterial hypertension (IPAH). It also improves exercise capacity and hemodynamics in patients with PAH occurring in association with scleroderma. The complexity of epoprostenol therapy (chronic indwelling catheters, reconstitution of the drug, operation of the infusion pump, and others) has led to attempts to develop other prostanoids with simpler modes of delivery. Treprostinil, a stable prostacyclin analogue with a half-life of 3 h, has been developed for subcutaneous delivery. It has beneficial effects on exercise and hemodynamics, which depend somewhat on the dose achieved. This, in turn, is determined by the patient's ability to tolerate the drug's side effects, including pain and erythema at the infusion site. Inhaled iloprost therapy may provide selectivity of the hemodynamic effects to the lung vasculature, thus avoiding systemic side effects. In a randomized and controlled trial, iloprost resulted in improvement in a combined end point incorporating the New York Heart Association functional class, 6-min walk test, and deterioration or death. Beraprost is the first orally active prostacyclin analogue. In the first of two randomized controlled trials, beraprost increased exercise capacity in patients with IPAH, with no significant changes in subjects with associated conditions. Hemodynamics did not change significantly, and no difference in survival was detected between the two treatment groups. The second study showed that beraprost-treated patients
Kissling, Pascal; Brosi, Philippe; Kull, Christof; Toia, Damien; Maurer, Christoph Andreas
In a patient with a huge endothelial sarcoma of the left pulmonary artery, we report successful implantation of a stent graft in the right pulmonary artery, including the pulmonary arterial trunk. This preoperative measure enabled a safe and radical left-sided pneumonectomy, including the tumor and the central parts of the left pulmonary artery. No major blood loss occurred, and neither use of a heart-lung machine nor cardiopulmonary bypass was necessary.
Schäfer, Michal; Myers, Cynthia; Brown, R Dale; Frid, Maria G; Tan, Wei; Hunter, Kendall; Stenmark, Kurt R
Stiffening of the pulmonary arterial bed with the subsequent increased load on the right ventricle is a paramount feature of pulmonary hypertension (PH). The pathophysiology of vascular stiffening is a complex and self-reinforcing function of extracellular matrix remodeling, driven by recruitment of circulating inflammatory cells and their interactions with resident vascular cells, and mechanotransduction of altered hemodynamic forces throughout the ventricular-vascular axis. New approaches to understanding the cell and molecular determinants of the pathophysiology combine novel biopolymer substrates, controlled flow conditions, and defined cell types to recapitulate the biomechanical environment in vitro. Simultaneously, advances are occurring to assess novel parameters of stiffness in vivo. In this comprehensive state-of-art review, we describe clinical hemodynamic markers, together with the newest translational echocardiographic and cardiac magnetic resonance imaging methods, to assess vascular stiffness and ventricular-vascular coupling. Finally, fluid-tissue interactions appear to offer a novel route of investigating the mechanotransduction processes and disease progression.
Li, Mengxi; Zhang, Nuofu; Zhou, Ying; Li, Jinhui; Gu, Yingying; Wang, Jian; Liu, Chunli
Lipoid pneumonia is an uncommon disease caused by the presence of lipid in the alveoli. Here we described a case of a 50-year-old woman with haemoptysis, cough and tachypnea, who was diagnosed with cholesterol pneumonia accompanying with pulmonary artery hypertension. The extremely high pulmonary artery pressure achieved, in this case, is alarming and should alert the physicians that the cholesterol pneumonia may be one of the underlying causes of pulmonary artery hypertension. After a treatment of methylprednisolone, her clinical symptoms were significantly improved, which suggested that steroid might be a promising therapeutic for patients with cholesterol pneumonia.
Farber, Harrison W; Gibbs, Simon
Pulmonary hypertension (PH) associated with left heart disease (PH-LHD) is the most common type of PH, but its natural history is not well understood. PH-LHD is diagnosed by right heart catheterisation with a mean pulmonary arterial pressure ≥25 mmHg and a pulmonary capillary wedge pressure >15 mmHg. The primary causes of PH-LHD are left ventricular dysfunction of systolic and diastolic origin, and valvular disease. Prognosis is poor and survival rates are low. Limited progress has been made towards specific therapies for PH-LHD, and management focuses on addressing the underlying cause of the disease with supportive therapies, surgery and pharmacological treatments. Clinical trials of therapies for pulmonary arterial hypertension in patients with PH-LHD have thus far been limited and have provided disappointing or conflicting results. Robust, long-term clinical studies in appropriate target populations have the potential to improve the outlook for patients with PH-LHD. Herein, we discuss the knowledge gaps in our understanding of PH-LHD, and describe the current unmet needs and challenges that are faced by clinicians when identifying and managing patients with this disease.
Sen, Supratim; Rao, Suresh G; Kulkarni, Snehal
We describe the cases of two patients with tetralogy of Fallot, aged 4 years and 8 months, who were incidentally detected to have concomitant anomalous left coronary artery from pulmonary artery and total anomalous pulmonary venous connection, respectively, on preoperative imaging. They underwent surgical correction with good mid-term outcomes. In this study, we discuss the embryological basis, physiological effects, and review the literature of these two unusual associations. Awareness of these rare associations will avoid missed diagnoses and consequent surgical surprises.
Ortíz-Gómez, J R; Paja Martí, I; Sos-Ortigosa, F; Pérez-Cajaraville, J J; Arteche-Andrés, M A; Bengoechea, C; Lobo-Palanco, J; Ahmad-Al-Ghool, M
Negative pressure pulmonary edema is a complication, described since 1977, caused by upper airway obstruction in both children and adults. Although its aetiopathogeny is multifactorial, especially outstanding is excessive negative intrathoracic pressure caused by the forced spontaneous inspiration of a patient against a closed glottis, that causes high arteriole and capillary fluid pressures that favor transudation into the alveolar space The resulting pulmonary edema can appear a few minutes after the obstruction of the airway or in a deferred way after several hours. The clinical manifestations are potentially serious, but normally respond well to treatment with supplemental oxygen, positive pressure mechanical ventilation and diuretics. Diagnostic suspicion is important for acting promptly. We report three clinical cases with acute negative pressure pulmonary edema.
Dupuis, J; Hoeper, M M
The endothelin (ET) system, especially ET-1 and the ET(A) and ET(B) receptors, has been implicated in the pathogenesis of pulmonary arterial hypertension (PAH). Together with prostanoids and phosphodiesterase 5 inhibitors, ET receptor antagonists have become mainstays in the current treatment of PAH. Three substances are currently available for the treatment of PAH. One of these substances, bosentan, blocks both ET(A) and ET(B) receptors, whereas the two other compounds, sitaxsentan and ambrisentan, are more selective blockers of the ET(A) receptor. There is ongoing debate as to whether selective or nonselective ET receptor blockade is advantageous in the setting of PAH, although there is no clear evidence that receptor selectivity is relevant with regard to the clinical effects of these drugs. For the time being, other features, such as safety profiles and the potential for pharmacokinetic interactions with other drugs used in the treatment of PAH, may be more important than selectivity or nonselectivity when selecting treatments for individual patients.
Ewert, Ralf; Gläser, Sven; Bollmann, Tom; Schäper, Christoph
Iloprost (Ventavis, Bayer Schering Pharma, Germany) is a synthetic prostacyclin that is used in its inhalative form for the therapy of pulmonary arterial hypertension. Long-term therapy can increase exercise capacity and quality of life. The use of modern nebulizers especially designed for the administration of iloprost guarantees the pulmonary deposition of the required doses and systematically minimizes side effects. Regarding existing data, inhalative iloprost acts in effective and safe combination with other classes of medication; indeed, such combination therapy is frequently necessary in pulmonary arterial hypertension.
Grignola, Juan C; Domingo, Enric; Devera, Lucía; Ginés, Fernando
AIM: To characterize hydraulic right ventricle (RV) afterload by pulmonary arterial pressure waveform analysis in an acute pulmonary hypertension (PH) model. METHODS: Pulmonary artery (PA) flow and pressure were recorded in six anesthetized sheep. Acute isobaric PH was induced by phenylephrine (active) and PA mechanical constriction (passive). We estimated the amplitude of the forward and reflected pressure waves according to the inflection point. In most cases the inflection pressure was smooth, thus the inflection point was defined as the time at which the first derivative of pulmonary arterial pressure reached its first minimum. We calculated the input and characteristic (ZC, time-domain Li method) impedances, the capacitance index (stroke volume/pulse pressure), the augmentation index (AI) (reflected pressure/pulse pressure), the fractional pulse pressure (pulse pressure/mean pressure) and the wasted energy generated by the RV due to wave reflection during ejection (EW). RESULTS: Pulse pressure, fractional pulse pressure, AI and ZC increased and capacitance index decreased during passive PH with respect to control (P < 0.05). In contrast, ZC and the capacitance index did not change and EW and the AI decreased during active PH. Pulse pressure correlated with EW and ZC and the AI was correlated with EW (r > 0.6, P < 0.05). CONCLUSION: PA pressure waveform analysis allows the quantification of the dynamic RV afterload. Prospective clinical studies will be necessary to validate this time-domain approach to evaluate the dynamic RV afterload in chronic PH. PMID:22053220
Ali, M M; Royse, A G; Connelly, K; Royse, C F
The objective of this study was to identify whether pulmonary capillary wedge pressure can be estimated in anaesthetised patients receiving mechanical ventilation, using transoesophageal echocardiography. A retrospective validation study investigated a 10-patient cohort with variable haemodynamic conditions, and a 102-patient series in which a single measurement was made during stable haemodynamic conditions. Concurrent echocardiographic Doppler and pulmonary artery catheter wedge pressure measurements were performed. In the 10-patient cohort, the systolic fraction of Doppler measurements in the pulmonary vein (r = -0.32, p = 0.035) and the E/A ratio (r = 0.56, p = 0.0009) were correlated with the wedge pressure. In all cases, the limits of agreement exceeded 10 mmHg, and sensitivity or specificity for detecting wedge pressure ≥ 15 mmHg was poor. This study demonstrates proof of concept that using transoesophageal echocardiography for estimating the pulmonary artery wedge pressure may not be sufficiently accurate for clinical use.
Yu, Lunyin; Hales, Charles A.
Background Hypoxia results in pulmonary hypertension and vascular remodeling due to induction of pulmonary artery cell proliferation. Besides pulmonary artery smooth muscle cells, pulmonary artery endothelial cells (PAECs) are also involved in the development of pulmonary hypertension, but the effect of hypoxia on PAEC proliferation has not been completely understood. Methods We investigated PAEC proliferation in mice and rats with hypoxia-induced pulmonary hypertension and vascular remodeling as well as in human PAECs under hypoxia. Results and Conclusion We did not find significant PAEC proliferation in chronically hypoxic rats or mice. There was a slight decrease in proliferation in mice and rats with pulmonary hypertension and vascular remodeling. We also did not find significant human PAEC proliferation and cell cycle progression under different levels of oxygen (1, 2, 3, 5 and 10%) for one day, although the same conditions of hypoxia induced significant proliferation and cell cycle progression in pulmonary artery smooth muscle cells and pulmonary artery fibroblasts. Exposure to hypoxia for 7 days also did not increase PAEC proliferation. These results demonstrated that hypoxia alone is not a stimulus to PAEC proliferation in vivo and in vitro. The present study provides a novel role for PAECs in hypoxia-induced pulmonary hypertension and vascular remodeling. PMID:21691120
Yilmaz, Sema; Cimen, Kadriye Akar
Behçet's disease is the most common cause of pulmonary artery aneurysms. Pulmonary artery aneurysms are rare, but they are life-threatening because of their high tendency to rupture. However, there is also a chance that the aneurysms may completely resolve with immunosuppressive therapy. A 30-year-old man was admitted with chest pain, painful oral and genital ulcers, skin rash, weakness, and intermittent hemoptysis. He had a history of Behçet's disease for 6 years. The chest radiography showed a round opacity superior part of hilus on right. The helical thoracic computed tomography (CT) angiography demonstrated pulmonary aneurysms associated with Behçet's disease. The patient was successfully treated with colchicine, corticosteroids, and cyclophosphamide. A discussion about pulmonary artery aneurysms associated with Behçet's disease is provided in this case.
Mathai, Stephen C.; Hassoun, Paul M.
Purpose of review Systemic sclerosis is commonly complicated by pulmonary arterial hypertension (PAH-SSc) and is a leading cause of death in this population. We will review existing challenges and recent advances in the treatment of this disease. Recent findings Traditionally employed outcome measures in pulmonary arterial hypertension research may not be applicable in PAH-SSc. Importantly, new therapies that target abnormal cellular proliferation in the pulmonary vasculature are currently under investigation and may be particularly relevant to PAH-SSc. Summary Pulmonary arterial hypertension complicating systemic sclerosis occurs commonly and portends a poor prognosis. However, recent advances in our understanding of the disease in the context of systemic sclerosis may lead to novel diagnostic and therapeutic strategies that will ultimately improve quality of life and survival in this population. PMID:19667994
Molina, J. Ernesto
A consecutive series of 12 patients between the ages of 6½ and 37 years underwent implantation of venous ventricle-pulmonary artery conduits. GORE-TEX material without prosthetic valves was used. Four patients had L-transposition of the great vessels with ventricular septal defect (VSD) and pulmonary stenosis; four had tetralogy of Fallot with pulmonary atresia; and one had double outlet right ventricle, pulmonary stenosis, and a complete form of A-V canal. Two patients had D-transposition of the great arteries, VSD, and pulmonary stenosis; and one patient had L-transposition of the great arteries and isolated pulmonary stenosis. All patients had low pulmonary resistance and pressures. The technique for implanting this noncrimped type of prosthesis is described in detail. Follow-up ranged from 2 months to 5½ years. GORE-TEX offers a good choice of material for the construction of this type of conduit to prevent pseudointima formation and obstruction, which is often observed in woven Dacron grafts. PMID:15226844
Flick, M R; Moody, L E; Block, A J
Twenty patients with mild to severe chronic obstructive pulmonary disease received ultrasonic nebulization to assess the danger of short-term changes in blood gas levels during this therapy. The status of arterial oxygenation was monitored during 20 minutes of therapy and for 20 minutes following therapy. In nine patients with periodic studies of arterial blood, the mean change in arterial oxygen pressure from base line was a decrease of 0.8 mm Hg at ten minutes into therapy, 2.8 mm Hg at the conclusion of therapy, and 2.9 mm Hg 20 minutes after therapy. In all 20 patients, ear oximetric studies showed only a small mean change at ten minutes into therapy, at the end of therapy, and at 20 minutes after therapy. Changes in the status of arterial oxygenation during and after therapy with ultrasonic nebulization in a group of patients with chronic obstructive pulmonary disease are generally small and of no statistical and limited clinical significance; however, alarming falls in arterial oxygenation can occur and cannot be predicted by base-line testing of pulmonary function or studies of arterial blood. It would be prudent to monitor patients with chronic obstructive pulmonary disease during therapy with ultrasonic nebulization or to withhold therapy altogether.
Perros, Frédéric; Humbert, Marc
The combined effects of vasoconstriction, remodelling of the pulmonary vessel walls and in situ thrombosis contribute to the increase in pulmonary vascular resistance during pulmonary arterial hypertension. Vascular remodelling involves all the sheaths of the vessel wall and all the cell types of which it is composed (endothelial cells, smooth muscle cells, fibroblasts, inflammatory cells and platelets). Excessive vasoconstriction has been related to a defect in the function of expression of the potassium channels and endothelial dysfunction. This leads to chronic insufficiency in the production of vasodilators, notably nitrogen monoxide and prostacyclin and the excessive production of vasoconstrictors such as endotheline-1. These defects contribute to the increase in vascular tonus and pulmonary vascular remodelling and represent pertinent pharmacological targets. Certain growth factors, including those of the super-family of transforming growth factor beta, angiopoietine-1 and serotonin, may play a part in the pathogenesis of pulmonary arterial hypertension.
Behringer, Arnica; Trappiel, Manuela; Berghausen, Eva Maria; Ten Freyhaus, Henrik; Wellnhofer, Ernst; Odenthal, Margarete; Blaschke, Florian; Er, Fikret; Gassanov, Natig; Rosenkranz, Stephan; Baldus, Stephan; Kappert, Kai; Caglayan, Evren
Pulmonary arterial hypertension (PAH) is a fatal disease with limited therapeutic options. Pathophysiological changes comprise obliterative vascular remodelling of small pulmonary arteries, elevated mean pulmonary arterial systolic pressure (PASP) due to elevated resistance of pulmonary vasculature, adverse right ventricular remodelling, and heart failure. Recent findings also indicate a role of increased inflammation and insulin resistance underlying the development of PAH. We hypothesized that treatment of this condition with the peroxisome proliferator-activated receptor-γ (PPARγ) activator pioglitazone, known to regulate the expression of different genes addressing insulin resistance, inflammatory changes, and vascular remodelling, could be a beneficial approach. PAH was induced in adult rats by a single subcutaneous injection of monocrotaline (MCT). Pioglitazone was administered for 2 weeks starting 3 weeks after MCT-injection. At day 35, hemodynamics, organ weights, and -indices were measured. We performed morphological and molecular characterization of the pulmonary vasculature, including analysis of the degree of muscularization, proliferation rates, and medial wall thickness of the small pulmonary arteries. Furthermore, markers of cardiac injury, collagen content, and cardiomyocyte size were analyzed. Survival rates were monitored throughout the experimental period. Pioglitazone treatment improved survival, reduced PASP, muscularization of small pulmonary arteries, and medial wall thickness. Further, MCT-induced right ventricular hypertrophy and fibrosis were attenuated. This was accompanied with reduced cardiac expression of brain natriuretic peptide, as well as decreased cardiomyocyte size. Finally, pulmonary macrophage content and osteopontin gene expression were attenuated. Based on the beneficial impact of pioglitazone, activation of PPARγ might be a promising treatment option in PAH.
heart to the blood pressure . We conclude that when the heart hypertrophies, as a result of the hypertension , the changed cardiac behavior, in turn...Plenary Talks Cardiac and Arterial Contribution to Blood Pressure N.Westerhof, Lab. for Physiology, Institute for Cardiovascular Research...Vrije Universiteit of Amsterdam Blood pressure and blood flow result from the interaction of the heart, the pump, and the arterial system, the load
Sanges, Sébastien; Yelnik, Cécile M.; Sitbon, Olivier; Benveniste, Olivier; Mariampillai, Kuberaka; Phillips-Houlbracq, Mathilde; Pison, Christophe; Deligny, Christophe; Inamo, Jocelyn; Cottin, Vincent; Mouthon, Luc; Launay, David; Lambert, Marc; Hatron, Pierre-Yves; Rottat, Laurence; Humbert, Marc; Hachulla, Eric
Abstract Occurrence of pulmonary arterial hypertension (PAH) in idiopathic inflammatory myopathies (IIMs) without extensive interstitial lung disease (ILD) has rarely been described in the medical literature. This study aimed to report all cases with association of PAH and IIM in the French Pulmonary Hypertension (PH) Registry, to identify IIM features associated with the presence of PAH, and to describe treatment modalities of these patients. All cases of IIM-PAH were retrieved from the French PH Registry, which gathers PH patients prospectively enrolled by 27 referral hospital centers across France. Patients were excluded if they had an extensive ILD or overlap syndrome. Characteristics of IIM-PAH patients were compared with a control group of IIM patients without PH. Among the 5223 PH patients in the Registry, 34 had a diagnosis of IIM. Among them, 3 IIM-PAH patients (2 females and 1 male) had no evidence of extensive ILD or overlap syndrome, and were included in this study. In these 3 patients, dermatomyositis (DM) was the only identified IIM. One patient had autoantibodies classically associated with IIM (anti-Ku). PAH had always developed after IIM onset, was severe in all cases, and led to a marked functional impairment. By pooling our cases with 6 patients previously reported in the literature, and comparing them with a control cohort of 35 IIM patients without PH, we identify several IIM characteristics possibly associated with PAH occurrence, including DM subtype (78% vs 46%; P = 0.02), skin involvement (P = 0.04), anti-SSA antibodies (P = 0.05), and peripheral microangiopathy (P = 0.06). Overall, IIM-PAH patients were managed by corticosteroids and/or immunosuppressants, either alone or combined with PAH therapy. Patients did not seem to respond to IIM treatment alone. Our study reports for the first time the rare but possible association of PAH and IIM in a large prospective PH Registry. In that setting, PAH seems associated with DM, skin involvement
Hsieh, Caleb G; Le, Thomas; Fogelfeld, Keren; Kamangar, Nader
Bronchial artery aneurysm (BAA) is a rare vascular phenomenon. This review highlights a case of a BAA that was complicated by the presence of a bronchial artery to pulmonary artery (BA-PA) fistula, consequently presenting a unique challenge to management. BAAs have a strongly reported risk of rupture resulting in life-threatening hemoptysis. Embolization has thus become routine for the management such severe cases. The management of incidentally found anomalies is less obvious, but prophylactic embolization is a generally accepted practice. In this report, we review some of the risks and benefits associated with BAA embolization with specific consideration of the challenges in cases of co-existing BA-PA fistula. PMID:28217405
Kitajima, Takamasa; Marumo, Satoshi; Shoji, Tsuyoshi; Huang, Cheng-Long; Yuba, Yoshiaki; Fukui, Motonari
Chronic pulmonary arterial obstructions are caused mostly by chronic pulmonary artery thromboembolism and rarely by vasculitis or intimal sarcoma of the pulmonary artery. We herein report an unusual case of a 42-year-old woman with a solitary obstruction of the pulmonary artery in the right lower lobe of her lung. Because we could not exclude the possibility of intimal sarcoma, middle and lower lobectomy was performed. The resected specimens revealed large vessel vasculitis (LVV) and an isolated lesion in the right lower lobe pulmonary artery. LVV should therefore be considered in the differential diagnosis for single pulmonary arterial stenosis or obstruction.
Yang, Y; Zhang, B K; Liu, D; Nie, W; Yuan, J M; Wang, Z; Guo, Y M
1. The aim of the study was to determine if H(2)S is involved in the development of hypoxia-induced pulmonary hypertension in broilers, a condition frequently observed in a variety of cardiac and pulmonary diseases. 2. Two-week-old broilers were reared under normoxic conditions or exposed to normobaric hypoxia (6 h/day) with tissue levels of H(2)S adjusted by administering sodium hydrosulfide (NaHS, 10 µmol/kg body weight/day). Mean pulmonary arterial pressure, right ventricular mass, plasma and tissue H(2)S levels, the expression of cystathionine-β-synthase (CSE) and vascular remodeling were determined at 35 d of age. 3. Exposure to hypoxia-induced pulmonary arterial hypertension was characterized by elevated pulmonary pressure, right ventricular hypertrophy and vascular remodeling. This was accompanied by decreased expression of CSE and decreased concentrations of plasma and tissue H(2)S. 4. Hypoxia-induced pulmonary hypertension was significantly reduced by administration of NaHS but this protective effect was largely abolished by D, L-propargylglycerine, an inhibitor of CSE. 5. The results indicate that H(2)S is involved in the development of hypoxia-induced pulmonary hypertension. Supplementing NaHS or H(2)S could be a strategy for reducing hypoxia-induced hypertension in broilers.
Lever, M.J.; Jay, M.T. )
Experiments have been performed both in vivo and in vitro to measure the steady-state uptake of labeled albumin and Cr-ethylenediaminetetraacetate by various blood vessels of the rabbit: the ascending and descending portions of the thoracic aorta, the carotid artery, the pulmonary artery, and the inferior vena cava. The in vitro experiments indicated that the wall tissues of the pulmonary artery and the vena cava have much greater distribution volumes for albumin than do the systemic arteries. This may in part explain the differences in wall tissue concentrations in vivo and, in turn, the differences between vessels in their susceptibility to atherosclerosis.
Talwar, Sachin; Anderson, Robert H; Keshri, Vikas Kumar; Choudhary, Shiv Kumar; Gulati, Gurpreet Singh; Airan, Balram
Surgical correction of patients with tetralogy of Fallot with pulmonary atresia is now one of the routine procedures performed by pediatric cardiac surgeons. In one variant, the pulmonary arterial supply is derived from a fistulous communication from the coronary arteries. This rare and interesting situation poses a diagnostic and therapeutic dilemma, as well as providing specific management challenges to the surgical team. Here, we discuss important aspects of this rare variant, specifically its morphology, presentation, evaluation and management.
Guo, Haipeng; Zhang, Xin; Cui, Yuqian; Deng, Wei; Xu, Dachun; Han, Hui; Wang, Hao; Chen, Yuguo; Li, Yu; Wu, Dawei
Highlights: • We focus on PASMCs proliferation in the pathogenesis of PAH. • Isorhynchophylline inhibited PASMCs proliferation and alleviated PAH. • IRN blocked PDGF-Rβ phosphorylation and its downstream signal transduction. • IRN regulated cyclins and CDKs to arrest cell cycle in the G0/G1 phase. • We reported IRN has the potential to be a candidate for PAH treatment. - Abstract: Increased pulmonary arterial smooth muscle cells (PASMCs) proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Isorhynchophylline (IRN) is a tetracyclic oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla. It has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether IRN can influence the development of PAH. Here we examined the effect of IRN on monocrotaline (MCT) induced PAH in rats. Our data demonstrated that IRN prevented MCT induced PAH in rats, as assessed by right ventricular (RV) pressure, the weight ratio of RV to (left ventricular + septum) and RV hypertrophy. IRN significantly attenuated the percentage of fully muscularized small arterioles, the medial wall thickness, and the expression of smooth muscle α-actin (α-SMA) and proliferating cell nuclear antigen (PCNA). In vitro studies, IRN concentration-dependently inhibited the platelet-derived growth factor (PDGF)-BB-induced proliferation of PASMCs. Fluorescence-activated cell-sorting analysis showed that IRN caused G0/G1 phase cell cycle arrest. IRN-induced growth inhibition was associated with downregulation of Cyclin D1 and CDK6 as well as an increase in p27Kip1 levels in PDGF-BB-stimulated PASMCs. Moreover, IRN negatively modulated PDGF-BB-induced phosphorylation of PDGF-Rβ, ERK1/2, Akt/GSK3β, and signal transducers and activators of transcription 3 (STAT3). These results demonstrate that IRN could inhibit PASMCs proliferation and
Sakamoto, K; Nishioka, M; Fujimoto, K; Ohta, N; Murata, M; Nakada, T; Sekine, Y; Yokota, M
Unilateral pulmonary arterial hypoplasia and/or pulmonary venous obstruction are serious hazards for Fontan candidates. For these patients, we have started new surgical approach "intrapulmonary septation technic". This consists of 3 components; (A) partial right heart bypass to well-grown side, (B) mandatory pulmonary blood flow to low-capacity side, (aorto-pulmonary shunt or others) and (C) a patch between partial right heart bypass and mandatory pulmonary blood flow. Thirteen patients underwent the approach. The source of partial right heart bypass was brought from superior vena cava (11 patients), inferior vena cava (1 patient) and fenestrated Fontan (1 patient). The mandatory pulmonary blood flow was supplied by aorto-pulmonary shunt (11 patients), pulmonary arterial banding (1 patient) and native pulmonary valve stenosis (1 patient). We added pulmonary artery enlargement (9 patients), release of pulmonary venous obstruction (8 patients) and/or atrio-ventricular valve plasty (5 patients), simultaneously. No hospital death. Early post-operative course was uneventful in all cases except 1, as pulmonary blood flow to low-capacity side had increased gradually after this intervention. Eight patients had reached Fontan operation. In this approach, nearly whole pulmonary artery can grow without any affect of volume overload through well-grown side from collateral arteries of low-capacity side. All procedures of "intrapulmonary septation technic" and reconstruction of pulmonary artery in Fontan operation can be easily performed in larger pulmonary artery of well-grown side, eliminating need for extensive dissection.
Bishop, Bryan M; Mauro, Vincent F; Khouri, Samer J
Pulmonary arterial hypertension is a devastating disease. Before the 1990s, when pharmacologic treatment was finally approved, only supportive therapy was available, consisting of anticoagulation, digoxin, diuretics, and supplemental oxygen. Calcium channel blocker therapy was also an option, but only a small percentage of patients respond to it. However, starting with epoprostenol in 1996, the number of drugs approved to treat pulmonary arterial hypertension increased. Three distinct classes of drugs were developed based on the pathophysiology of the disease: the prostanoids, endothelin-1 receptor antagonists, and phosphodiesterase type 5 inhibitors. The prostanoids are administered either parenterally or by inhalation to replace the lack of prostacyclin within the pulmonary arterial vasculature. The endothelin-1 receptor antagonists were the first class of oral drugs to be developed, but drug interactions and adverse effects are prominent with this class. The phosphodiesterase type 5 inhibitors increase the second messenger cyclic guanosine monophosphate (GMP) that is induced by nitric oxide stimulation. All of the drugs within these three classes are distinct in and of themselves, and their clinical use requires in-depth knowledge of pulmonary arterial hypertension and its pathophysiology. Because these drugs have different mechanisms of action, combination therapy has shown promise in patients with severe disease, although data are still lacking. This article should serve as a practical guide for clinicians who encounter patients with pulmonary arterial hypertension and the drugs used for the treatment of this devastating disease.
de Jesus Perez, Vinicio
Over the past 20 years, there has been an explosion in the development of therapeutics to treat pulmonary arterial hypertension (PAH), a rare but life-threatening disorder associated with progressive elevation of pulmonary pressures and severe right heart failure. Recently, the field has seen the introduction of riociguat, a soluble guanylate cyclase stimulator, a new endothelin receptor antagonist (macitentan), and oral prostanoids (treprostinil and selexipag). Besides new drugs, there have been significant advances in defining the role of upfront combination therapy in treatment-naïve patients as well as proposed methods to deliver systemic prostanoids by use of implantable pumps. In this review, we will touch upon the most important developments in PAH therapeutics over the last three years and how these have changed the guidelines for the treatment of PAH. These exciting developments herald a new era in the treatment of PAH which will be punctuated by the use of more clinically relevant endpoints in clinical research trials and a novel treatment paradigm that may involve upfront double- or triple-combination therapy. We anticipate that the future will make use of these strategies to test the efficacy of upcoming new drugs that aspire to reduce disease progression and improve survival in patients afflicted with this devastating disease. PMID:27990270
Murat, Gurbuz; Cellier, François; Leobon, Bertand; Boudou, Nicolas
Anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital disease responsible for a high mortality rate in childhood. Here, we report for the first time the case of an asymptomatic 61-year old patient showing a combination of anomalous origin of the left anterior descending artery from pulmonary artery and atherosclerotic stenosis in both the right coronary artery and the left circumflex artery without anomalous origin.
Al Jabbari, Odeaa; Abu Saleh, Walid K.; Ramchandani, Mahesh; Scheinin, Scott
Unilateral agenesis of the pulmonary artery (UAPA) is a rare congenital anomaly. This report describes a 52-year-old female who gave a long history of chronic, recurrent, left-sided pulmonary infections related to UAPA. For many years, she was managed medically but the infection continued to recur. She eventually underwent left pneumonectomy and made a good recovery. PMID:27127564
Al Jabbari, Odeaa; Abu Saleh, Walid K; Ramchandani, Mahesh; Scheinin, Scott
Unilateral agenesis of the pulmonary artery (UAPA) is a rare congenital anomaly. This report describes a 52-year-old female who gave a long history of chronic, recurrent, left-sided pulmonary infections related to UAPA. For many years, she was managed medically but the infection continued to recur. She eventually underwent left pneumonectomy and made a good recovery.
Kitami, Akihiko; Sano, Fumitoshi; Hayashi, Shoko; Suzuki, Kosuke; Uematsu, Shugo; Suzuki, Takashi; Saeki, Noriyuki
We present a surgical case of bronchial artery aneurysm (BAA) connecting pulmonary artery accompanied with racemose hemangioma. This is a third surgical case report of BAA directly connecting pulmonary artery in the English literature. A 63-year-old female was found a BAA, 2 cm in diameter, connecting right A4 pulmonary artery. The patient underwent two attempts for embolization. However, due to extensive collaterals, there was persistent flow in the aneurysm. Standard lateral thoracotomy was performed. A BAA was located between A4 and A5 PA. A small branch of A4 PA was separated, and the small vessel connecting to the BAA could be ligated. A5 PA was separated similarly, however BAA was ruptured not to identify the other small vessel connecting to the BAA. After a clamp of the BAA, middle lobe lobectomy was performed. We removed the aneurysm with dilated bronchial artery connecting to the aneurysm. The postoperative course was uneventful.
Pulmonary arterial hypertension (PAH) is defined as an intractable disease characterized by a progressive elevation of pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP), leading to right heart failure and premature death. The five-year survival rate after diagnosis is approximately 57%. Although extensive research has identified some factors associated with the cause of PAH, the etiology and pathogenesis remain unclear. In addition to Ca(2+) channel blockers (nifedipine, diltiazem), three categories of drug have been developed for the treatment of PAH based on the pathological mechanisms: prostacyclin and its analogues (epoprostenol, treprostinil, iloprost), endothelin receptor antagonists (bosentan, ambrisentan), and phosphodiesterase type 5 inhibitors (sildenafil, tadalafil). However, screening of novel types of drug acting on the signal pathway associated with the pathological mechanism underlying PAH is ongoing. We recently found that the extracellular Ca(2+)-sensing receptor (CaSR), which belongs to family C of the G protein-coupled receptor (GPCR) superfamily, is upregulated in pulmonary arterial smooth muscle cells (PASMCs) from patients with idiopathic PAH (IPAH). The upregulated CaSR is necessary for the enhanced Ca(2+) signaling and the augmented cell proliferation in PASMCs from IPAH patients. Most importantly, blockage of CaSR with an antagonist, NPS2143, prevents the development of pulmonary hypertension and right ventricular hypertrophy in animal models of pulmonary hypertension. The use of calcilytics, antagonists of CaSR, may be a novel therapeutic approach for PAH patients.
Qureshi, Athar M; Krasuski, Richard A; Prieto, Lourdes R
Percutaneous pulmonary valve technology has had a great impact on patients with congenital and acquired heart disease. In some patients, implantation of a percutaneous pulmonary valve may not be possible due to the morphology of the existing right ventricular outflow tract. In this report, we describe implantation of a Melody transcatheter pulmonary valve in the left pulmonary artery in a patient with acquired right pulmonary artery occlusion and a large right ventricular outflow tract.
Allen, Roblee P; Schelegle, Edward S; Bennett, Stephen H
Pulmonary hypertension (PH) is associated with progressive changes in arterial network complexity. An allometric model is derived that integrates diameter branching complexity between pulmonary arterioles of generation n and the main pulmonary artery (MPA) via a power-law exponent (X) in dn = dMPA2(-n/X) and the arterial area ratio β = 2(1-2/X). Our hypothesis is that diverse forms of PH demonstrate early decrements in X independent of etiology and pathogenesis, which alters the arteriolar shear stress load from a low-shear stress (X > 2, β > 1) to a high-shear stress phenotype (X < 2, β < 1). Model assessment was accomplished by comparing theoretical predictions to retrospective morphometric and hemodynamic measurements made available from a total of 221 PH-free and PH subjects diagnosed with diverse forms (World Health Organization; WHO groups I-IV) of PH: mitral stenosis, congenital heart disease, chronic obstructive pulmonary lung disease, chronic thromboembolism, idiopathic pulmonary arterial hypertension (IPAH), familial (FPAH), collagen vascular disease, and methamphetamine exposure. X was calculated from pulmonary artery pressure (PPA), cardiac output (Q) and body weight (M), utilizing an allometric power-law prediction of X relative to a PH-free state. Comparisons of X between PAH-free and PAH subjects indicates a characteristic reduction in area that elevates arteriolar shear stress, which may contribute to mechanisms of endothelial dysfunction and injury before clinically defined thresholds of pulmonary vascular resistance and PH. We conclude that the evaluation of X may be of use in identifying reversible and irreversible phases of PH in the early course of the disease process.
Pfister, Sandra L.
Pulmonary arterial hypertension is characterized by elevated pulmonary artery pressure and vascular resistance. In women the incidence is 4 fold greater than that in men. Studies suggest sustained vasoconstriction is a factor in increased vascular resistance. Possible vasoconstrictor mediators include arachidonic acid-derived lipoxygenase metabolites. Our studies in rabbits showed enhanced endothelium-dependent contractions to arachidonic acid in pulmonary arteries from females compared to males. Because treatment with a non-specific lipoxygenase inhibitor reduced contractions in females but not males, the present study identified which lipoxygenase isoform contributes to sex-specific pulmonary artery vasoconstriction. 15- and 5- but not 12-lipoxygenase protein expression was greater in females. Basal and A23187-stimulated release of 15-, 5- and 12-hydroxyeicosatetraenoic acid from females and males was measured by liquid chromatography/mass spectrometry. Only 15-hydroxyeicosatetraenoic acid synthesis was greater in females compared to males under both basal and stimulated conditions. Vascular contractions to 15-hydroxyeicosatetraenoic acid were enhanced in females compared to males (maximal contraction; 44 ± 6% vs 25 ± 3%). The specific 15-lipoxygenase inhibitor PD146176 (12 μmol/L) decreased arachidonic acid-induced contractions in females (maximal contraction; 93 ± 4% vs 57 ± 10%). If male pulmonary arteries were incubated with estrogen (1 μmol/L, 18 hrs), protein expression of 15-lipoxygenase, and 15-hydroxyeicosatetraenoic acid production increased. Mechanisms to explain the increased incidence of pulmonary hypertension in women are not known. Results suggest the 15-lipoxygenase pathway is different between females and males and is regulated by estrogen. Understanding this novel sex-specific mechanism may provide insight into the increased incidence of pulmonary hypertension in females. PMID:21300669
Mungan, Carl E.
Consider the following ConcepTest. A platelet is drifting with the blood flowing through a horizontal artery. As the platelet enters a constriction, does the blood pressure increase, decrease, or stay the same?
Mungan, Carl E.
Consider the following ConcepTest. A platelet is drifting with the blood flowing through a horizontal artery. As the platelet enters a constriction, does the blood pressure increase, decrease, or stay the same?
Nara, Akina; Nagai, Hisashi; Shintani-Ishida, Kaori; Ogura, Sayoko; Shimosawa, Tatsuo; Kuwahira, Ichiro; Shirai, Mikiyasu; Yoshida, Ken-ichi
Pulmonary arterial hypertension (PAH) is prevalent in patients with obstructive sleep apnea syndrome (OSAS). Aging induces arginase activation and reduces nitric oxide (NO) production in the arteries. Intermittent hypoxia (IH), conferred by cycles of brief hypoxia and normoxia, contributes to OSAS pathogenesis. Here, we studied the role of arginase and aging in the pathogenesis of PAH in adult (9-mo-old) and young (2-mo-old) male Sprague-Dawley rats subjected to IH or normoxia for 4 weeks and analyzed them with a pressure-volume catheter inserted into the right ventricle (RV) and by pulsed Doppler echocardiography. Western blot analysis was conducted on arginase, NO synthase isoforms, and nitrotyrosine. IH induced PAH, as shown by increased RV systolic pressure and RV hypertrophy, in adult rats but not in young rats. IH increased expression levels of arginase I and II proteins in the adult rats. IH also increased arginase I expression in the pulmonary artery endothelium and arginase II in the pulmonary artery adventitia. Furthermore, IH reduced pulmonary levels of nitrate and nitrite but increased nitrotyrosine levels in adult rats. An arginase inhibitor (N(ω)-hydroxy-nor-1-arginine) prevented IH-induced PAH and normalized nitrite and nitrate levels in adult rats. IH induced arginase up-regulation and PAH in adult rats, but not in young rats, through reduced NO production. Our findings suggest that arginase inhibition prevents or reverses PAH.
Jones, Blaise; Hirsch, Russel
Case Report. Isolated carotid artery originating from the pulmonary trunk is an exceedingly rare anomalous origin of head and neck vessels. We present this finding, along with a persistent embryonic trigeminal artery, in a male infant with multiple cardiac defects and other congenital anomalies associated with CHARGE syndrome. After extensive investigations, cardiac catheterization revealed the anomalous left common carotid artery arising from the cranial aspect of the main pulmonary artery. There was retrograde flow in this vessel, resulting from the lower pulmonary pressure, essentially stealing arterial supply from the left anterior cerebral circulation. The persistent left-sided trigeminal artery provided collateral flow from the posterior circulation to the left internal carotid artery territory, allowing for safe ligation of the anomalous origin of the left common carotid artery, thereby reversing the steal of arterial blood flow into the pulmonary circulation and resulting in a net improvement of cerebral perfusion. Conclusion. The possibility of this vascular anomaly should be considered in all infants with CHARGE syndrome. Surgical repair or ligation should be tailored to the specific patient circumstances, following a careful delineation of all sources of cerebral perfusion. PMID:27974985
Kagioka, Hitoshi; Ishitoko, Manabu; Itotani, Ryo; Suzuki, Shinko; Aihara, Kensaku; Matsumoto, Masataka; Oguma, Tsuyoshi; Takemura, Masaya; Tokuhisa, Hidetoshi; Fukui, Motonari
A 77-year-old woman presented with hoarseness and hemoptysis. Chest CT scan revealed a mediastinal tumor in the lumen of the left pulmonary artery. A definitive diagnosis could not be made based on mediastinoscopy and thoracotomy. Eight months later, multiple nodular shadows appeared in both lung fields.Video-assisted lung biopsy showed that these nodules were lung metastases of a spindle cell sarcoma. Based on the pathological and radiological findings, a pulmonary artery sarcoma was eventually diagnosed. Interestingly, on immunohistological staining, the tumor cells were diffusely positive for KIT, which is an immunohistochemical marker of gastrointestinal stromal tumors. The patient was treated with imatinib, a KIT tyrosine kinase inhibitor; however, the tumors progressed. The relationship between pulmonary artery sarcoma and KIT requires further study.
Hou, Xiaomeng; Li, Ji; Li, Jing; Cai, Baiqiang
OBJECTIVES: This study described the characteristics of the systemic arterial supply of pulmonary sequestration (PS) in an attempt to better distinguish PS from other acquired lesions. METHODS: We identified 25 patients hospitalized at the Peking Union Medical College Hospital during January 2013 to December 2015 with the assistance of medical catalogers. Twenty-three patients with a definite diagnosis of “pulmonary sequestration” clinically or pathologically were included in the study. The medical records, imaging information, and pathological data were reviewed retrospectively. The general characteristics of the patients and the features of the anomalous arteries were summarized. RESULTS: Aberrant arterial supply of PS was found in all 23 (100%) cases. Among them, twenty patients received surgery, including 14 (70%) with aberrant arterial supply found before surgery, and the other 6 (30%) found during surgery. Nineteen (82.6%) patients had a single systematic arterial supply, with a median diameter of 8 mm. More than one arterial supplies were found in four (17.4%) cases. In 21 (91.3%) cases, the anomalous systemic artery originated from the descending thoracic aorta just adjacent to the sequestrated lung which it supplied, without the presence of accompanying bronchi. In twenty (87.0%) patients who received the surgical intervention, samples of 12 (85.7%) were proved to have elastic vessel walls, out of the 14 samples in which the anomalous systemic arteries were available for analysis. CONCLUSIONS: There are no certain pathology diagnostic criteria for the diagnosis of PS. The detecting of the aberrant systematic artery and distinguishing it from the bronchial arteries corresponded to certain lung abnormalities are the keys to the accurate diagnosis of pulmonary sequestration in adult patients. We propose that the characteristic features of the anomalous arteries include: Originating from aorta and its main branches, adjacent to the sequestrated area
Dykes, John C; Torres, Marilyn; Alexander, Plato J
This report describes the case of a neonate with d-transposition of the great arteries and severe pulmonary arterial hypertension stabilised in the post-operative period with continuous iloprost nebulisation. To our knowledge, this is the first documented method of treating post-operative severe pulmonary arterial hypertension with continuous inhaled iloprost in a patient with complex CHD. We found this method of delivering the drug very effective in stabilising haemodynamic swings in the setting of severe pulmonary arterial hypertension.
Nhu, Quan M; Knowles, Harry; Pockros, Paul J; Frenette, Catherine T
Transarterial chemoembolization (TACE) is an effective palliative intervention that is widely accepted for the management of hepatocellular carcinoma (HCC). Post-TACE pulmonary complications resulting in acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) are rare events. Pulmonary complications after TACE are thought to be related to chemical injury subsequent to the migration of the infused ethiodized oil or chemotherapeutic agent to the lung vasculature, facilitated by arteriovenous (AV) shunts within the hyper-vascular HCC. We review herein the literature on pulmonary complications related to TACE for HCC. Post-TACE pulmonary complications have included pulmonary oil embolism, interstitial pneumonitis, chemical pneumonitis, ALI, ARDS, lipoid pneumonia, acute eosinophilic and neutrophilic pneumonia, bilious pleuritis, pulmonary abscess, pulmonary tumor embolism, and possibly pulmonary metastasis with HCC. The risk factors associated with post-TACE pulmonary complications identified in the literature include large hyper-vascular HCC with AV shunts, large-volume Lipiodol infusion, and embolization via the right inferior phrenic artery. However, the absence of known risk factors is not a guarantee against serious complications. An astute awareness of the potential post-TACE pulmonary complications should expedite appropriate therapeutic interventions and increase potential for early recovery. PMID:27904836
Luo, Xiaoju; Huang, Yuanyuan; He, Yun; Li, Zhixian
The continuous changes in pulmonary hemodynamic properties and right ventricular (RV) function in pulmonary arterial hypertension (PAH) have not been fully characterized in large animal model of PAH induced by a carotid artery–jugular vein shunt. A minipig model of PAH was induced by a surgical anastomosis between the left common carotid artery and the left jugular vein. The model was validated by catheter examination and pathologic analyses, and the hemodynamic features and right-ventricle functional characteristics of the model were continuously observed by Doppler echocardiography. Of the 45 minipigs who received the surgery, 27 survived and were validated as models of PAH, reflected by mean pulmonary artery pressure ≥25 mmHg, and typical pathologic changes of pulmonary arterial remodeling and RV fibrosis. Non-invasive indices of pulmonary hemodynamics (pulmonary artery accelerating time and its ratio to RV ventricular ejection time) were temporarily increased, then reduced later, similar to changes in tricuspid annular displacement. The Tei index of the RV was elevated, indicating a progressive impairment in RV function. Surgical anastomosis between carotid artery and jugular vein in a minipig is effective to establish PAH, and non-invasive hemodynamic and right-ventricle functional indices measured by Doppler echocardiography may be used as early indicators of PAH. PMID:25595189
... on Twitter. What Is Pulmonary Hypertension? Pulmonary hypertension (PULL-mun-ary HI-per-TEN-shun), or PH, is increased pressure in the pulmonary arteries. These arteries carry blood from your heart to your lungs to pick up oxygen. PH causes symptoms such as shortness of ...
Furest, I; Marín, M; Escribano, P; Gómez, M A; Cortinac, J; Blanquer, R
Intimal sarcoma of the pulmonary artery is a rare tumor that is usually diagnosed during surgery or autopsy. Such tumors are characterized by local growth, with only slight ability to metastasize. Diagnosis is difficult and often delayed owing to the nonspecific nature of the symptoms. Since intimal sarcoma of the pulmonary artery is so rare and insidious it is often confused with pulmonary thromboembolism and is therefore treated inappropriately with prolonged anticoagulation or thrombolysis. With a mean survival of 12 months from the onset of symptoms, the prognosis is poor. We present the case of a woman who was preoperatively diagnosed with intimal sarcoma of the pulmonary artery and who underwent surgical resection with no apparent recurrence at long term follow-up. A review of the literature is also included.
McLaughlin, Vallerie V; Badesch, David B; Delcroix, Marion; Fleming, Thomas R; Gaine, Sean P; Galiè, Nazzareno; Gibbs, J Simon R; Kim, Nick H; Oudiz, Ronald J; Peacock, Andrew; Provencher, Steeve; Sitbon, Olivier; Tapson, Victor F; Seeger, Werner
New and emerging therapies might provide benefit in patients with pulmonary arterial hypertension. Their efficacy and safety will be compared with existing combination therapies in randomized clinical trials. Appropriate end points for these trials need to be identified: these will include exercise testing, the composite end point of time to clinical worsening, and hemodynamic markers, including advanced imaging modalities and biomarkers. Quality-of-life questionnaires are useful and important secondary end points; pulmonary arterial hypertension-specific questionnaires are currently being developed. Advantages and disadvantages of various trial designs, including placebo-controlled monotherapy or add-on trials, noninferiority studies, and withdrawal trials are also discussed.
Funatsu, Yohei; Hirayama, Miwa; Shiraishi, Junichi; Asakura, Takanori; Wakaki, Misa; Yamada, Erina; Fujimoto, Kazuyuki; Satomi, Ryosuke; Inaki, Shunsuke; Murata, Yuya; Oyamada, Yoshitaka
Intimal sarcoma is a rare disease with a poor prognosis. We herein report the case of a 71-year-old man with intimal sarcoma of the pulmonary artery treated with pazopanib. The tumor showed regression after 1 month of treatment. Hand-foot syndrome led to cessation of pazopanib, which triggered a disease flare. Pazopanib should be considered in patients with intimal sarcoma of the pulmonary artery that is unresectable or recurrent after surgery or cytotoxic chemotherapy. We must be careful about drug cessation, as it can lead to a disease flare.
Ventetuolo, Corey E; Benza, Raymond L; Peacock, Andrew J; Zamanian, Roham T; Badesch, David B; Kawut, Steven M
Pulmonary arterial hypertension is a rare and often devastating disease, although various effective therapies are now available. Clinical trials have used hemodynamic, cardiac imaging, laboratory, and exercise measurements as surrogate and intermediate end points in pulmonary arterial hypertension. Yet, based on the current literature, it is difficult to surmise which of these (if any) have been definitively validated. In addition, investigators have advocated the use of combined clinical end points in future clinical trials. The dependence of clinical trials and clinical management on such end points warrants a review of their use.
Tian, Lian; Wang, Zhijie; Lakes, Roderic S; Chesler, Naomi C
Large conduit arteries are not purely elastic, but viscoelastic, which affects not only the mechanical behavior but also the ventricular afterload. Different hysteresis loops such as pressure-diameter, pressure-luminal cross-sectional area (LCSA), and stress-strain have been used to estimate damping capacity, which is associated with the ratio of the dissipated energy to the stored energy. Typically, linearized methods are used to calculate the damping capacity of arteries despite the fact that arteries are nonlinearly viscoelastic. The differences in the calculated damping capacity between these hysteresis loops and the most common linear and correct nonlinear methods have not been fully examined. The purpose of this study was thus to examine these differences and to determine a preferred approach for arterial damping capacity estimation. Pressurization tests were performed on mouse extralobar pulmonary and carotid arteries in their physiological pressure ranges with pressure (P) and outer diameter (OD) measured. The P-inner diameter (ID), P-stretch, P-Almansi strain, P-Green strain, P-LCSA, and stress-strain loops (including the Cauchy and Piola-Kirchhoff stresses and Almansi and Green strains) were calculated using the P-OD data and arterial geometry. Then, the damping capacity was calculated from these loops with both linear and nonlinear methods. Our results demonstrate that the linear approach provides a reasonable approximation of damping capacity for all of the loops except the Cauchy stress-Almansi strain, for which the estimate of damping capacity was significantly smaller (22 ± 8% with the nonlinear method and 31 ± 10% with the linear method). Between healthy and diseased extralobar pulmonary arteries, both methods detected significant differences. However, the estimate of damping capacity provided by the linear method was significantly smaller (27 ± 11%) than that of the nonlinear method. We conclude that all loops except the Cauchy stress
Nair, Kiron K S; Zisman, Lawrence S; Lader, Ellis; Dimova, Aneta; Canver, Charles C
Anomalous origin of the left coronary artery from the pulmonary artery is a congenital coronary artery malformation most commonly present in infancy. A variety of surgical procedures have been described to achieve physiological correction of the coronary flow abnormalities. These techniques are effective as long as there is potential for myocardial recovery. However the sequelae of chronic myocardial ischemia that characterize this entity often irreversibly damage the heart and preclude correction and palliation of the native anomaly. In this type of setting, heart transplantation is a realistic option. Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) occasionally presents in adulthood. Anatomic repair with a two coronary artery system may not be optimal in patients presenting with ischemic cardiomyopathy. We report an adult patient with platelet factor 4 (PF4) antibodies who underwent orthotopic heart transplantation (OHT) for ALCAPA.
Kaderli, Aysel Aydin; Baran, Ibrahim; Sağ, Saim; Biçer, Murat; Aker, Sibel
Primary sarcoma of the pulmonary artery (PSPA) is an extremely rare tumor of the cardiovascular system. The prognosis is very poor. The clinical symptoms and imaging findings imitate those of pulmonary emboli, causing delays in diagnosis. In this case report, we describe a 73-year-old man with PSPA who initially was admitted with exertional shortness of breath. Transthoracic echocardiographic evaluation revealed 2 masses in the pulmonary artery causing pulmonary hypertension. The patient underwent operation, but he could not be weaned off cardiopulmonary bypass at the end of the operation and died. Pathologic examination of the masses revealed pulmonary sarcoma. Although this patient was admitted to our clinic only 2 weeks after the initial symptoms, he already had distal metastases.
Reesink, Herre J.; Henneman, Onno D. F.; Delden, Otto M. van; Biervliet, Jules D.; Kloek, Jaap J.; Reekers, Jim A.; Bresser, Paul
We report a 38-year-old patient who presented with pulmonary hypertension and right ventricular dysfunction due to pulmonary artery stenoses as a manifestation of Williams syndrome, mimicking chronic thromboembolic pulmonary hypertension. The patient was treated with balloon angioplasty and stent implantation. Short-term follow-up showed a good clinical result with excellent patency of the stents but early restenosis of the segments in which only balloon angioplasty was performed. These stenoses were subsequently also treated successfully by stent implantation. Stent patency was observed 3 years after the first procedure.
Nesme, P; Arnouk, H; Perol, M; Bayle, J Y; Bejui-Thivolet, F; Baulieux, J; Guérin, J C
Intimal sarcomas growing from the pulmonary trunk or branches of the pulmonary artery, are rare tumours in which the diagnosis is most often made at autopsy or during a thoracotomy. Usually the clinical pictures is non specific resembling a severe pulmonary embolus which is resistant of all treatment. With the help of new imaging techniques, a pre-operative diagnosis is made in more than half the cases. When there is a tumour which is relatively localised and without endoluminal invasion, as in the observation reported here, the diagnosis rests on the histology from the operative specimen.
Tselios, Konstantinos; Gladman, Dafna D; Urowitz, Murray B
Systemic lupus erythematosus (SLE) is characterized by the second highest prevalence of pulmonary arterial hypertension (PAH), after systemic sclerosis, among the connective tissue diseases. SLE-associated PAH is hemodynamically defined by increased mean pulmonary artery pressure at rest (≥25 mmHg) with normal pulmonary capillary wedge pressure (≤15 mmHg) and increased pulmonary vascular resistance. Estimated prevalence ranges from 0.5% to 17.5% depending on the diagnostic method used and the threshold of right ventricular systolic pressure in studies using transthoracic echocardiogram. Its pathogenesis is multifactorial with vasoconstriction, due to imbalance of vasoactive mediators, leading to hypoxia and impaired vascular remodeling, collagen deposition, and thrombosis of the pulmonary circulation. Multiple predictive factors have been recognized, such as Raynaud’s phenomenon, pleuritis, pericarditis, anti-ribonuclear protein, and antiphospholipid antibodies. Secure diagnosis is based on right heart catheterization, although transthoracic echocardiogram has been shown to be reliable for patient screening and follow-up. Data on treatment mostly come from uncontrolled observational studies and consist of immunosuppressive drugs, mainly corticosteroids and cyclophosphamide, as well as PAH-targeted approaches with endothelin receptor antagonists (bosentan), phosphodiesterase type 5 inhibitors (sildenafil), and vasodilators (epoprostenol). Prognosis is significantly affected, with 1- and 5-year survival estimated at 88% and 68%, respectively. PMID:28053559
Tselios, Konstantinos; Gladman, Dafna D; Urowitz, Murray B
Systemic lupus erythematosus (SLE) is characterized by the second highest prevalence of pulmonary arterial hypertension (PAH), after systemic sclerosis, among the connective tissue diseases. SLE-associated PAH is hemodynamically defined by increased mean pulmonary artery pressure at rest (≥25 mmHg) with normal pulmonary capillary wedge pressure (≤15 mmHg) and increased pulmonary vascular resistance. Estimated prevalence ranges from 0.5% to 17.5% depending on the diagnostic method used and the threshold of right ventricular systolic pressure in studies using transthoracic echocardiogram. Its pathogenesis is multifactorial with vasoconstriction, due to imbalance of vasoactive mediators, leading to hypoxia and impaired vascular remodeling, collagen deposition, and thrombosis of the pulmonary circulation. Multiple predictive factors have been recognized, such as Raynaud's phenomenon, pleuritis, pericarditis, anti-ribonuclear protein, and antiphospholipid antibodies. Secure diagnosis is based on right heart catheterization, although transthoracic echocardiogram has been shown to be reliable for patient screening and follow-up. Data on treatment mostly come from uncontrolled observational studies and consist of immunosuppressive drugs, mainly corticosteroids and cyclophosphamide, as well as PAH-targeted approaches with endothelin receptor antagonists (bosentan), phosphodiesterase type 5 inhibitors (sildenafil), and vasodilators (epoprostenol). Prognosis is significantly affected, with 1- and 5-year survival estimated at 88% and 68%, respectively.
Anand, Girija Lewanski, Conrad R.; Cowman, Steven A.; Jackson, James E.
Migration of superior vena cava (SVC) stents is a well-recognised complication of their deployment, and numerous strategies exist for their retrieval. To our knowledge, only three cases of migration of an SVC stent to the pulmonary vasculature have previously been reported. None of these patients developed complications that resulted in death. We report a case of SVC stent migration to the pulmonary vasculature with delayed pulmonary artery thrombosis and death from pulmonary infarction. We conclude that early retrieval of migrated stents should be performed to decrease the risk of serious complications.
Grint, K A; Kellihan, H B
A 3-month-old, 9.9 kg, male pit bull cross was referred for evaluation of collapse. A left basilar systolic heart murmur graded V/VI and a grade IV/VI right basilar systolic heart murmur were ausculted. Echocardiography showed severe pulmonic stenosis characterized by annular hypoplasia, leaflet thickening, and leaflet fusion. After 1 month of atenolol therapy, a pulmonic valve balloon valvuloplasty procedure was performed, and the intra-operative right ventricular pressure was reduced by 43%. Echocardiography, performed the following day, showed apparent rupture of a pulmonary valve leaflet and a membranous structure within the pulmonary artery consistent with a dissecting membrane. Short-term follow-up has shown no apparent progression of the pulmonary artery dissection and the patient remains free of clinical signs.
Ghorishi, Zahra; Milstein, Jay M; Poulain, Francis R; Moon-Grady, Anita; Tacy, Theresa; Bennett, Stephen H; Fineman, Jeffery R; Eldridge, Marlowe W
Congenital heart disease with increased blood flow commonly leads to the development of increased pulmonary vascular reactivity and pulmonary arterial hypertension by mechanisms that remain unclear. We hypothesized a shear stress paradigm of hemodynamic reactivity and network remodeling via the persistence and/or exacerbation of a fetal diameter bifurcation phenotype [parent diameter d(0) and daughters d(1) >or= d(2) with alpha < 2 in (d(1)/d(0))(alpha) + (d(2)/d(0))(alpha) and area ratio beta < 1 in beta = (d(1)(2)+ d(2)(2))/ d(0)(2)] that mechanically acts as a high resistance magnifier/shear stress amplifier to blood flow. Evidence of a hemodynamic influence on network remodeling was assessed with a lamb model of high-flow-induced secondary pulmonary hypertension in which an aortopulmonary graft was surgically placed in one twin in utero (Shunt twin) but not in the other (Control twin). Eight weeks after birth arterial casts were made of the left pulmonary arterial circulation. Bifurcation diameter measurements down to 0.010 mm in the Shunt and Control twins were then compared with those of an unoperated fetal cast. Network organization, cumulative resistance, and pressure/shear stress distributions were evaluated via a fractal model whose dimension D(0) approximately alpha delineates hemodynamic reactivity. Fetus and Control twin D(0) differed: fetus D(0)=1.72, a high-resistance/shear stress amplifying condition; control twin D(0) = 2.02, an area-preserving transport configuration. The Shunt twin (D(0)=1.72) maintained a fetal design but paradoxically remodeled diameter geometry to decrease cumulative resistance relative to the Control twin. Our results indicate that fetal/neonatal pulmonary hemodynamic reactivity remodels in response to shear stress, but the response to elevated blood flow and pulmonary hypertension involves the persistence and exacerbation of a fetal diameter bifurcation phenotype that facilitates endothelial dysfunction/injury.
Garg, Ashok; Mooney, John; Amado Escañuela, Maximiliano German; Mathur, Alok; Goyal, Vikram; Nanda, Navin C
In this report, we present a case of spindle cell sarcoma of the pulmonary artery diagnosed by transthoracic echocardiography. To the best of our knowledge, this case is the youngest reported case of pulmonary artery sarcoma (PAS) to date. PAS is frequently confused for pulmonary embolism; in this case, echocardiographic findings allowed for differentiation between pulmonary embolism and solid tumor.
Sekiguchi, Fumiko; Yamamoto, Kazuo; Matsuda, Kyoko; Kawata, Kyoko; Negishi, Maki; Shinomiya, Kazuaki; Shimamur, Keiichi; Sunano, Satoru
To evaluate whether the elevated blood pressure induced by chronic treatment with N(omega)-nitro-L-arginine methyl ester (L-NAME) contributes to an impairment of endothelium-dependent relaxation (EDR), the effects of chronic treatment of Wistar rats with L-NAME on systolic blood pressure, pulmonary arterial blood pressure and EDR of the pulmonary arteries were studied and compared with those of stroke-prone spontaneously hypertensive rats (SHRSP). While the systolic blood pressure (SBP) of Wistar rats was increased above that of controls by chronic treatment with L-NAME, it was still significantly lower than that of SHRSP. Chronic treatment with L-NAME did not affect pulmonary arterial blood pressure. On the other hand, the pulmonary arterial blood pressure of SHRSP was slightly but significantly higher than that of the control normotensive Wistar Kyoto rats (WKY). EDR in response to acetylcholine in the pulmonary artery of L-NAME-treated rats was significantly smaller than that in control Wistar rats. The EDR markedly increased in the presence of L-arginine and completely disappeared in the presence of N(omega)-nitro-L-arginine. Indomethacin hardly affected EDR. In preparations from SHRSP, the EDR was not different from that in those from WKY. Relaxation induced by sodium nitroprusside was identical in all preparations. Elevation of SBP and the impairment of EDR observed in L-NAME-treated rats recovered two weeks following cessation of treatment. These results suggest that the impaired EDR in the pulmonary artery of L-NAME-treated rats is not due to an L-NAME-induced increase in blood pressure but due to the inhibition of nitric oxide synthase by the drug remaining in the endothelium.
Clarke, Shanelle; Baumgardt, Shelley; Molthen, Robert
Microfocal CT was used to image the pulmonary arterial (PA) tree in rodent models of pulmonary hypertension (PH). CT images were used to measure the arterial tree diameter along the main arterial trunk at several hydrostatic intravascular pressures and calculate distensibility. High-resolution planar angiographic imaging was also used to examine distal PA microstructure. Data on pulmonary artery tree morphology improves our understanding of vascular remodeling and response to treatments. Angiotensin II (ATII) has been identified as a mediator of vasoconstriction and proliferative mitotic function. ATII has been shown to promote vascular smooth muscle cell hypertrophy and hyperplasia as well as stimulate synthesis of extracellular matrix proteins. Available ATII is targeted through angiotensin converting enzyme inhibitors (ACEIs), a method that has been used in animal models of PH to attenuate vascular remodeling and decrease pulmonary vascular resistance. In this study, we used rat models of chronic hypoxia to induce PH combined with partial left pulmonary artery occlusion (arterial banding, PLPAO) to evaluate effects of the ACEI, captopril, on pulmonary vascular hemodynamic and morphology. Male Sprague Dawley rats were placed in hypoxia (FiO2 0.1), with one group having underwent PLPAO three days prior to the chronic hypoxia. After the twenty-first day of hypoxia exposure, treatment was started with captopril (20 mg/kg/day) for an additional twenty-one days. At the endpoint, lungs were excised and isolated to examine: pulmonary vascular resistance, ACE activity, pulmonary vessel morphology and biomechanics. Hematocrit and RV/LV+septum ratio was also measured. CT planar images showed less vessel dropout in rats treated with captopril versus the non-treatment lungs. Distensibility data shows no change in rats treated with captopril in both chronic hypoxia (CH) and CH with PLPAO (CH+PLPAO) models. Hemodynamic measurements also show no change in the pulmonary vascular
De Dominicis, Florence; Leborgne, Laurent; Raymond, Alexandre; Berna, Pascal
Isolated unilateral pulmonary artery agenesis is a rare congenital anomaly that may be complicated with hemoptysis, recurrent pulmonary infections or pulmonary hypertension. To our knowledge the occurrence of a coronary syndrome associated with a coronary-to-bronchial artery saccular aneurysmal collateralization has never been described before. A 44-year-old female presented a congenital right pulmonary artery agenesis associated with a hypotrophic and multicystic right lung complicated with recurrent bronchitis. This patient had a coronary syndrome for which the coronary artery imaging showed a coronary-to-bronchial artery collateralization with an aneurysm at this level. It gives rise to a coronary syndrome by coronary steal. Two bronchial collaterals arising from a diaphragmatic artery and the subclavian artery were also found on the computed tomography (CT)-scan. This last collateral also showed another saccular aneurysm. We first performed an embolization of those two aneurysms in order to decrease the risk of hemorrhage and coronary steal, before performing a right pneumonectomy. In this case, the surgery was indicated because of the pathological lung and the risk of postembolization ischaemia. The postoperative course was uneventful and the patient was doing well six months later.
Sondheimer, H.M.; Oliphant, M.; Schneider, B.; Kavey, R.E.W.; Blackman, M.S.; Parker, F.B. Jr.
To expand the search for central pulmonary arteries in six patients with absence of cardiac-pulmonary continuity, computerized axial tomography (CAT) of the chest was performed. The CAT scans were compared with previous arteriograms and pulmonary vein wedge angiograms. Three patients with type IV truncus arteriosus were studied, and none had a central, right or left pulmonary artery on CAT scan. However, two patients with tetralogy of Fallot with pulmonary atresia and a patent ductus arteriosus to the right lung demonstrated the presence of a left pulmonary artery. In addition, one child with truncus arteriosus with ''absent'' left pulmonary artery demonstrated a left pulmonary artery on the CAT scan. The CAT scan may therefore enhance our ability to search for disconnected pulmonary arteries in children with complex cyanotic congenital heart disease.
Badlam, Jessica B.; Bull, Todd M.
Pulmonary arterial hypertension (PAH) is a chronic disease that results in narrowing of the small pre-capillary pulmonary arteries leading to elevation of pulmonary artery pressure and pulmonary vascular resistance, subsequent right ventricular failure, and if unchecked, death. Advances in the treatment of PAH over the last two decades have markedly improved survival. These improvements reflect a combination of changes in treatments, improved patient care strategies, and varying disease phenotypes in the PAH population. Currently approved therapies for PAH are directed at the recognized abnormalities within the pulmonary vasculature and include endothelin receptor antagonists, phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators, and prostacyclin pathway agents. Most of these drugs have been approved on the basis of short-term trials that mainly demonstrated improvements in exercise capacity. More recently, long-term, event-driven trials of novel drugs have been performed, demonstrating new efficacy parameters. There have also been exciting advances in the understanding of right heart failure pathophysiology in PAH that have the potential to inspire the development of right ventricular targeted therapy and continued discoveries in the heterogeneity of disease and response to treatment has great potential for developing more ‘personalized’ therapeutic options. In this article, we review the current available data regarding the management of PAH, with an emphasis on the pharmacologic therapies and discussion of novel therapeutic directions for the treatment of this fatal disease. PMID:28348727
Santos-Martínez, Luis Efren; Moreno-Ruiz, Luis Antonio; Jiménez-Santos, Moisés; Olmos-Temois, Sergio Gabriel; Bojorquez-Guerrero, Luis Armando; Baranda-Tovar, Francisco Martín
Inhaled iloprost is a drug from the group of prostacyclins used in the treatment of pulmonary arterial hypertension. Its efficacy and safety have allowed its use as monotherapy and combination therapy. This review describes the product characteristics, amenable to treatment groups, and updated clinical evidence of drug use.
Sandoval-Gutiérrez, José Luis; Santos-Martínez, Luis Efren; Rodríguez-Silverio, Juan; Baranda-Tovar, Francisco Martín; Rivera-Rosales, Rosa María; Flores-Murrieta, Francisco Javier
From the advent of the highly effective antiretroviral treatment, the life expectancy of patients with human immunodeficiency virus has increased significantly. At present, the causes of death are non-infectious complications. Between them, the pulmonary arterial hypertension has a special importance. It is important early detection to establish the therapeutic, with the objective of preventing a fatal outcome to future.
Yamanari, Mauricio Gustavo Ieiri; Mansur, Maria Clara Dias; Kay, Fernando Uliana; Silverio, Paulo Rogerio Barboza; Jayanthi, Shri Krishna; Funari, Marcelo Buarque de Gusmão
The authors report the case of a patient victim of gunshots, with a very rare complication: venous bullet embolism from the left external iliac vein to the lingular segment of the left pulmonary artery. Diagnosis is made with whole-body radiography or computed tomography. Digital angiography is reserved for supplementary diagnosis or to be used as a therapeutic procedure.
Pankey, Edward A; Epps, Matthew; Nossaman, Bobby D; Hyman, Albert L; Kadowitz, Philip J
Pulmonary arterial hypertension (PAH) is a devastating disease with limited therapeutic options. Moreover, when PAH occurs in patients diagnosed with systemic sclerosis, worse outcomes are observed. The purpose of this review is to discuss the etiologies of PAH found in the systemic sclerosis patient, limitations of current medical therapies, and, finally, potential therapies for patients with this combination. PMID:23626904
Leiomyoma of the lung is extremely rare. The entity is not described in WHO blue book. Less than 100 cases of leiomyoma of the lung have been reported in the literature. However, vascular leiomyoma has not been reported in the literature, to the author's best knowledge. Herein reported is the first case of vascular leiomyoma of the lung arising from smooth muscles of the pulmonary artery. A 62-year-old woman (non-smoker) was found to have a small tumor in the upper lobe in the right lung in routine check. Imaging modalities including CT demonstrated no metastatic lesions. Although clinical cytology and biopsy revealed no malignant cell, right upper lobectomy was performed under the clinical diagnosis of lung carcinoma. Grossly, a white tumor of 1 x 0.8 cm was recognized in the lung. Microscopically, the tumor was connected to the pulmonary arteries. The tumor was composed of mature smooth muscles. Small pulmonary arteries are embedded in the tumor. No lymphatics were seen. Immunohistochemically, the tumor cells were poisitive for alpha-smooth muscle actin, vimentin and Ki-67 (labeling 2%). However, they were negative for cytokeratin (CK) AE1/3, CK CAM5.2, desmin, S100 protein, p53, CD34, KIT, HMB45, estrogen receptor, progesterone receptor, and myoglobin. A pathological diagnosis of primary vascular leiomyoma arising from the smooth muscle of pulmonary artery was made. The patient is now free from tumor, and is now alive 10 year after the operation.
... is a heart defect. The left coronary artery (LCA), which carries blood to the heart muscle, begins ... not attach correctly. In the normal heart, the LCA originates from the aorta. It supplies oxygen-rich ...
Nawa, Nobutoshi; Ishida, Hidekazu; Katsuragi, Shinichi; Baden, Hiroki; Takahashi, Kunihiko; Higeno, Ryota; Torigoe, Fumiko; Mihara, Seiko; Narita, Jun; Miura, Kohji; Nakamura, Kazufumi; Kogaki, Shigetoyo; Ozono, Keiichi
We recently found a constitutively active mutant of natriuretic peptide receptor 2 (caNPR2; V883M), which synthesizes larger amounts of cyclic guanosine monophosphate (cGMP) intracellularly without any ligand stimulation than existing drugs. The aim of this study was to investigate the therapeutic effects of gene transduction using caNPR2 for pulmonary arterial hypertension (PAH). In vitro gene transduction into human pulmonary arterial smooth muscle cells using Sendai virus (SeV) vectors carrying caNPR2 induced 10,000-fold increases in the synthesis of cGMP without ligand stimulation, and the proliferation of caNPR2-expressing cells was significantly attenuated. The PAH model rats generated by hypoxia and the administration of SU5416 were then treated with SeV vectors through a direct injection into the left pulmonary artery. Right ventricular systolic pressure was significantly decreased 2 weeks after the treatment, while systemic blood pressure remained unchanged. Histological analyses revealed that the medial wall thickness and occlusion rate of pulmonary arterioles were significantly improved in caNPR2-treated lungs. Neither the systemic integration of virus vectors nor side effects were observed. The massive stimulation of cGMP synthesis by gene therapy with caNPR2 was safe and effective in a PAH rat model and, thus, has potential as a novel therapy for patients with severe progressive PAH. PMID:27419193
Nawa, Nobutoshi; Ishida, Hidekazu; Katsuragi, Shinichi; Baden, Hiroki; Takahashi, Kunihiko; Higeno, Ryota; Torigoe, Fumiko; Mihara, Seiko; Narita, Jun; Miura, Kohji; Nakamura, Kazufumi; Kogaki, Shigetoyo; Ozono, Keiichi
We recently found a constitutively active mutant of natriuretic peptide receptor 2 (caNPR2; V883M), which synthesizes larger amounts of cyclic guanosine monophosphate (cGMP) intracellularly without any ligand stimulation than existing drugs. The aim of this study was to investigate the therapeutic effects of gene transduction using caNPR2 for pulmonary arterial hypertension (PAH). In vitro gene transduction into human pulmonary arterial smooth muscle cells using Sendai virus (SeV) vectors carrying caNPR2 induced 10,000-fold increases in the synthesis of cGMP without ligand stimulation, and the proliferation of caNPR2-expressing cells was significantly attenuated. The PAH model rats generated by hypoxia and the administration of SU5416 were then treated with SeV vectors through a direct injection into the left pulmonary artery. Right ventricular systolic pressure was significantly decreased 2 weeks after the treatment, while systemic blood pressure remained unchanged. Histological analyses revealed that the medial wall thickness and occlusion rate of pulmonary arterioles were significantly improved in caNPR2-treated lungs. Neither the systemic integration of virus vectors nor side effects were observed. The massive stimulation of cGMP synthesis by gene therapy with caNPR2 was safe and effective in a PAH rat model and, thus, has potential as a novel therapy for patients with severe progressive PAH.
Hamoda, Haitham; Tait, P.; Edmonds, D. K.
We report a 44-year-old woman who developed a fatal pulmonary embolus after uterine artery fibroid embolisation (UAE). Bilateral UAE was carried out through a single right-femoral artery puncture. The largest fibroid in the anterior fundal wall measured 4.5 cm, and the largest fibroid in the posterior fundal wall measured 6 cm. The appearances after UAE were satisfactory, and the procedure was apparently uneventful. No immediate complications were noted. The patient developed sudden-onset shortness of breath and went into cardiac arrest 19 h after the procedure. Postmortem autopsy confirmed that the cause of a death was a pulmonary embolism. To our knowledge this is the first reported case in the United Kingdom in which death occurred from a pulmonary embolus after UAE.
Kingman, Martha S; Thompson, Brenda S; Newkirk, Trixie; Torres, Fernando
Pulmonary arterial hypertension complicated by decompensated cor pulmonale is a challenging clinical problem with few effective therapeutic options. B-type natriuretic peptide is a pluripotent hormone that promotes diuresis and natriuresis, vasodilates systemic and pulmonary vessels, and reduces circulating levels of endothelin and aldosterone. It may represent a possible therapeutic strategy for decompensated cor pulmonale in the same manner that it is used to treat decompensated left heart failure. The authors report their experience with B-type natriuretic peptide as adjunctive therapy for pulmonary arterial hypertension complicated by decompensated cor pulmonale. A detailed case report is presented followed by the evaluation of a series of 11 cases occurring in eight patients from December 2002 through April 2004.
Right Pulmonary Artery Distensibility Index (RPAD Index). A field study of an echocardiographic method to detect early development of pulmonary hypertension and its severity even in the absence of regurgitant jets for Doppler evaluation in heartworm-infected dogs.
Venco, Luigi; Mihaylova, Liliya; Boon, June A
Despite the term "heartworm disease" Dirofilaria immitis infection in dogs should be considered a pulmonary arterial disease that might only involve the right heart structures in its late stage. Chronic infection by adult heartworms in dogs results in proliferative endoarteritis leading to progressively increasing pulmonary artery pressure due to reduced elasticity. Elasticity allows the pulmonary arteries to stretch in response to each pulse and helps maintain a relatively constant pressure in the arteries despite the pulsating nature of the blood flow. Pulmonary artery distensibility for both acute and chronic pulmonary hypertension has been investigated in humans using MRI and has been correlated with the severity of hypertension and its outcome and treatment response. The aim of the present study was to investigate whether echocardiographic measurement of the percentage change in diameter of the right pulmonary artery in systole and diastole (distensibility) may be of value in assessing the presence and severity of pulmonary hypertension in heartworm-infected dogs. The Right Pulmonary Artery Distensibility Index (RPAD Index) (which is calculated as the difference in diameter of the right pulmonary artery in systole and diastole) was calculated in healthy and naturally infected heartworm-positive dogs. The right pulmonary artery was chosen because it is usually affected earlier and to a greater degree. Data were obtained from healthy heartworm-free dogs without any clinical, radiographic, or echocardiographic signs of pulmonary hypertension; naturally infected heartworm-positive dogs in different stages of the disease in which pulmonary pressure could be measured by Doppler echocardiography (using tricuspid and or pulmonary regurgitation velocity and pressure gradient); and naturally infected heartworm-positive dogs in different stages of the disease (with or without tricuspid and or pulmonary regurgitation) in which the pulmonary pressure was measured
Erlij, Daniel; Michalland, Susana; Neira, Óscar; Fernández, Cristina; Wolff, Verónica
Pulmonary artery sarcoma is an uncommon entity with high mortality. Its clinical presentation is usually indistinguishable from pulmonary embolism, which leads to a significant delay in diagnosis. Hughes-Stovin syndrome is characterized by venous thrombosis and aneurysms of the pulmonary or bronchial artery. We report a 59 year-old female with a history of recurrent pulmonary embolism. In the last thromboembolic episode a pulmonary artery aneurysm was found on a CT scan. The patient was operated performing a left inferior lobectomy. The patient died five days after surgery and the pathological examination of the surgical piece revealed a pulmonary artery sarcoma.
Singla Long, Svati; Johnson, Pamela T; Hruban, Ralph H; Fishman, Elliot K
Pulmonary artery sarcoma is an uncommon and highly malignant neoplasm that presents a diagnostic challenge to radiologists due to its tendency to mimic the more common condition of pulmonary thromboembolism. Presented in this case report is a patient with pulmonary artery sarcoma who was initially diagnosed with saddle pulmonary embolism based upon computed tomography (CT) findings. The case emphasizes the importance of including pulmonary artery sarcoma in the differential diagnosis of a large filling defect in the pulmonary arteries when specific CT findings are identified in the appropriate clinical setting.
Arita, Shinji; Arita, Noboru; Hikasa, Yoshiaki
This was a pilot study to determine the effectiveness of low-dose imatinib therapy for hemodynamic disturbances, including pulmonary arterial hypertension (PAH), and clinical manifestations caused by chronic heart failure in dogs. Six client-owned dogs with PAH were administered imatinib mesylate orally, 3 mg/kg body weight q24h, for 30 d. Physical examination, blood biochemical tests, radiography, and Doppler echocardiography were performed prior to imatinib administration and again 30 days after administration. Clinical scores were significantly reduced after imatinib treatment. Systolic pulmonary arterial pressure, heart rate, maximum tricuspid regurgitation velocity, left atrium/aorta ratio, right and left ventricular Tei indexes, early diastolic transmitral flow wave/mitral annulus velocity ratio, and plasma atrial natriuretic peptide concentration decreased significantly after therapy. Diastolic blood pressure, stroke volume, cardiac output, and left ventricular fractional shortening increased significantly after therapy. These results indicate that low-dose imatinib therapy was effective for heart failure in dogs with PAH.
Saigal, Aparna; Ng, Wai Kiong; Tan, Reginald B H; Chan, Sui Yung
Pulmonary arterial hypertension (PAH) is a chronic ailment of the lungs, exhibiting elevated arterial pressure and vascular resistance; with a mean arterial pressure above 25 mmHg at rest and above 30 mmHg during exercise. It is associated with poor prognosis, and its prevalence is estimated to be 15 cases per one million. The current treatment options for PAH are discussed with the prostanoid class of drugs being the most effective. The latter drugs act by dilating systemic and pulmonary arterial vascular beds and, with sustained long-term usage, altering pulmonary remodelling. They are administered as IV infusions or inhalation solutions. Despite their clinical effectiveness, prostanoids have short half-lives requiring frequent administration of 6-9 times daily and thus suffer from poor compliance. Controlled release inhalation delivery systems for treatment of PAH, ranging from liposomes, biodegradable nano- and microparticles, formation of co-precipitates and complexation with cyclodextrins, are explored. Arising from these formulation strategies, we developed novel polymeric microspheres for inhalation to reduce dosing frequency and improve medication compliance. These microspheres are designed with release modifiers, to reside in the lung which is the site of drug action for a longer duration so as to release the drug slowly and consistently over a prolonged period. This could lead to the development of the first commercially available controlled release inhalation product.
Kim, Young Il; Kang, Hyo Cheol; Lee, Ho Sung; Choi, Jae Sung; Seo, Ki Hyun; Kim, Yong Hoon; Na, Juock
Pulmonary mucormycosis is a rare opportunistic invasive fungal infection involving the pulmonary vasculature in immunocompromised patients. Pseudoaneurysm of pulmonary artery in mucormycosis is a rare fatal complication after invasion and rupture of a pulmonary artery. We report a patient with diabetes mellitus and incidental lung cancer who developed massive hemoptysis because of a huge pseudoaneurysm of the left pulmonary artery by mucormycosis. Although the patient had been managed by amphotericin B followed by left pneumonectomy for persistent hemoptysis, he died from septic shock and multiorgan failure after surgery. Histologic analysis of a surgical specimen revealed concomitant squamous cell lung cancer.
Iwazawa, Jin; Nakamura, Kenji; Hamuro, Masao; Nango, Mineyoshi; Sakai, Yukimasa; Nishida, Norifumi
We present the case of a 60-year-old woman with symptomatic mitral regurgitation caused by a left-to-right shunt via anastomoses consisting of microfistulae, most likely of inflammatory origin, between the right subclavian artery and the right pulmonary artery. The three arteries responsible for fistulous formation, including the internal mammary, thyrocervical, and lateral thoracic arteries, were successfully occluded by transcatheter embolization using superabsorbent polymer microsphere (SAP-MS) particles combined with metallic coils. No complications have been identified following treatment with SAP-MS particles. This approach significantly reduced the patient's mitral regurgitation and she has remained asymptomatic for more than 4 years.
Mittal, Kartik; Dey, Amit K; Gadewar, Rohit; Sharma, Rajaram; Pandit, Nilesh; Rajput, Priya; Hira, Priya
The incidence of congenital heart disease (CHD) is 2.4-3.8/1000 live births. Up to 70.7 % of all cases of CHD are reported to be benign; complex heart anomalies are extremely rare. Our case is extremely rare, as we report three very rare findings-truncus arteriosus, anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA), and unilateral left pulmonary artery agenesis-in a single patient. Congenital complex cardiac abnormalities are very rare, and two-dimensional echocardiography screening should be supported by cardiac computed tomography (CT). We report a case of truncus arteriosus associated with ARCAPA and left pulmonary artery agenesis diagnosed by cardiac computed tomography; we believe that such an unusual case with all three of these entities has never been reported before.
Chen, Yu-cai; Yuan, Tian-yi; Zhang, Hui-fang; Wang, Dan-shu; Yan, Yu; Niu, Zi-ran; Lin, Yi-huang; Fang, Lian-hua; Du, Guan-hua
Aim: The current therapeutic approaches have a limited effect on the dysregulated pulmonary vascular remodeling, which is characteristic of pulmonary arterial hypertension (PAH). In this study we examined whether salvianolic acid A (SAA) extracted from the traditional Chinese medicine 'Dan Shen' attenuated vascular remodeling in a PAH rat model, and elucidated the underlying mechanisms. Methods: PAH was induced in rats by injecting a single dose of monocrotaline (MCT 60 mg/kg, sc). The rats were orally treated with either SAA (0.3, 1, 3 mg·kg−1·d−1) or a positive control bosentan (30 mg·kg−1·d−1) for 4 weeks. Echocardiography and hemodynamic measurements were performed on d 28. Then the hearts and lungs were harvested, the organ indices and pulmonary artery wall thickness were calculated, and biochemical and histochemical analysis were conducted. The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting. Results: Treatment with SAA or bosentan effectively ameliorated MCT-induced pulmonary artery remodeling, pulmonary hemodynamic abnormalities and the subsequent increases of right ventricular systolic pressure (RVSP). Furthermore, the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium, parenchymal injury and collagen deposition in the lungs. Moreover, the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs. The treatments partially restored MCT-induced reductions of bone morphogenetic protein type II receptor (BMPRII) and phosphorylated Smad1/5 in the lungs. Conclusion: SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRII-Smad pathway and inhibiting apoptosis. Thus, SAA may have therapeutic potential for the patients at high risk of PAH. PMID:27180980
Heper, Gulumser Barcin, Cem; Iyisoy, Atila; Tore, Hasan F.
We report a case with an acquired fistula between the left internal mammary artery and the pulmonary artery following coronary bypass surgery treated with a bovine pericardium covered stent. We also reviewed similar cases reported previously.
Burger, Charles D
The possibility that pulmonary hypertension (PH) may develop in patients with chronic obstructive pulmonary disease (COPD) is well established, but prevalence data vary. The current World Health Organization clinical classification includes COPD in diagnostic group III: PH associated with disorders of the respiratory system or hypoxemia. The National Institute of Health defines PH as a mean pulmonary artery pressure of greater than 25 mmHg. Approximately 10% of the patients seen over the last decade in the PH Clinic at Mayo Clinic in Jacksonville, Florida, have PH due to COPD. The pathophysiology is likely complex and involves hypoxic pulmonary vasoconstriction. Ultimately, chronic hypoxia results in vascular remodeling with narrowing of the vascular lumen. The right heart is forced to generate increased driving pressures to overcome the increased vascular resistance. As the disease progresses, cor pulmonale may develop. The mortality in this setting is increased with five-year survival of 20% to 36% and seems to correlate with worsening PH and age. Fortunately, the PH in most cases is mild and occurs primarily in those with severe hypoxemia. Only 1% to 4% of patients have PH seemingly out of proportion to the severity of the COPD. This disproportionate subgroup may represent an important phenotype that requires a different therapeutic approach. Although supplemental oxygen remains the primary treatment for all PH in association with chronic hypoxia, pulmonary arterial vasodilators may have a therapeutic role in this subgroup. Vasodilators may worsen gas exchange, however, and to date, have no proven benefit. Rigorous future study will be required to determine whether there is a role for using pulmonary arterial vasodilators in this setting.
Meloche, Jolyane; Le Guen, Marie; Potus, François; Vinck, Jérôme; Ranchoux, Benoit; Johnson, Ian; Antigny, Fabrice; Tremblay, Eve; Breuils-Bonnet, Sandra; Perros, Frederic; Provencher, Steeve; Bonnet, Sébastien
Pulmonary arterial hypertension (PAH) is a devastating disease affecting lung vasculature. The pulmonary arteries become occluded due to increased proliferation and suppressed apoptosis of the pulmonary artery smooth muscle cells (PASMCs) within the vascular wall. It was recently shown that DNA damage could trigger this phenotype by upregulating poly(ADP-ribose)polymerase 1 (PARP-1) expression, although the exact mechanism remains unclear. In silico analyses and studies in cancer demonstrated that microRNA miR-223 targets PARP-1. We thus hypothesized that miR-223 downregulation triggers PARP-1 overexpression, as well as the proliferation/apoptosis imbalance observed in PAH. We provide evidence that miR-223 is downregulated in human PAH lungs, distal PAs, and isolated PASMCs. Furthermore, using a gain and loss of function approach, we showed that increased hypoxia-inducible factor 1α, which is observed in PAH, triggers this decrease in miR-223 expression and subsequent overexpression of PARP-1 allowing PAH-PASMC proliferation and resistance to apoptosis. Finally, we demonstrated that restoring the expression of miR-223 in lungs of rats with monocrotaline-induced PAH reversed established PAH and provided beneficial effects on vascular remodeling, pulmonary resistance, right ventricle hypertrophy, and survival. We provide evidence that miR-223 downregulation in PAH plays an important role in numerous pathways implicated in the disease and restoring its expression is able to reverse PAH.
Tanabe, Yoshiyuki; Saito-Tanji, Maki; Morikawa, Yuki; Kamataki, Akihisa; Sawai, Takashi; Nakayama, Koichi
Excessive stretching of the vascular wall in accordance with pulmonary arterial hypertension (PAH) induces a variety of pathogenic cellular events in the pulmonary arteries. We previously reported that indoxam, a selective inhibitor for secretory phospholipase A(2) (sPLA(2)), blocked the stretch-induced contraction of rabbit pulmonary arteries by inhibition of untransformed prostaglandin H(2) (PGH(2)) production. The present study was undertaken to investigate involvement of sPLA(2) and untransformed PGH(2) in the enhanced contractility of pulmonary arteries of experimental PAH in rats. Among all the known isoforms of sPLA(2), sPLA(2)-X transcript was most significantly augmented in the pulmonary arteries of rats with monocrotaline-induced pulmonary hypertension (MCT-PHR). The pulmonary arteries of MCT-PHR frequently showed two types of spontaneous contraction in response to stretch; 27% showed rhythmic contraction, which was sensitive to indoxam and SC-560 (selective COX-1 inhibitor), but less sensitive to NS-398 (selective COX-2 inhibitor); and 47% showed sustained incremental tension (tonic contraction), which was insensitive to indoxam and SC-560, but sensitive to NS-398 and was attenuated to 45% of the control. Only the rhythmically contracting pulmonary arteries of MCT-PHR produced a substantial amount of untransformed PGH(2), which was abolished by indoxam. These results suggest that sPLA(2)-mediated PGH(2) synthesis plays an important role in the rhythmic contraction of pulmonary arteries of MCT-PHR.
Corson, Neal; Armato, Samuel G.; Labby, Zacariah E.; Straus, Christopher; Starkey, Adam; Gomberg-Maitland, Mardi
Rationale and Objectives Pulmonary hypertension (PH) is a complex and fatal disease that is difficult to diagnose non-invasively. This study evaluated previously published CT-based vessel measurement criteria and investigated the predictive power and diagnostic ability of the main pulmonary artery diameter (MPAD) and the ratio of MPAD to aorta diameter (rPA). Materials and Methods The database for this study consisted of 175 PH patients (for whom mean pulmonary artery pressure (mPAP) was known), 16 patients without PH but with known mPAP (non-PH patients), and 114 “normal” patients without known mPAP. The performance of previously published criteria, MPAD > 29 mm and rPA > 1, was determined. The relationship between vessel measurements and mPAP was evaluated through correlation and linear regression analysis. The ability of these measurements to discriminate between patients with and without PH was determined by receiver operating characteristic analysis. Results For discriminating between PH and “normal” patients, the sensitivity and specificity of the criterion MPAD>29mm were 0.89 (0.84-0.93) and 0.83 (0.76-0.90), respectively, and the sensitivity and specificity of the criterion rPA>1 were 0.89 (0.85-0.94) and 0.82 (0.74-0.89), respectively. At a specificity of 0.95 in the task of separating PH and “normal” patients, the sensitivity of MPAD was 0.81 (0.72-0.90) and the sensitivity of rPA was 0.76 (0.66-0.85), but the specificity for both decreased when non-PH patients were included. For the combined PH and non-PH patient groups, the correlation between the vessel measurements and mPAP was significant but low, and the ability of the vessel measurements to predict mPAP was limited. Conclusion This study found that the sensitivity of previously published vessel criteria for identifying PH patients is high but the specificity may not be high enough for routine use in a clinical patient population. PMID:24594422
Jain, Pritesh P; Leber, Regina; Nagaraj, Chandran; Leitinger, Gerd; Lehofer, Bernhard; Olschewski, Horst; Olschewski, Andrea; Prassl, Ruth; Marsh, Leigh M
Prostacyclin analogues are standard therapeutic options for vasoconstrictive diseases, including pulmonary hypertension and Raynaud’s phenomenon. Although effective, these treatment strategies are expensive and have several side effects. To improve drug efficiency, we tested liposomal nanoparticles as carrier systems. In this study, we synthesized liposomal nanoparticles tailored for the prostacyclin analogue iloprost and evaluated their pharmacologic efficacy on mouse intrapulmonary arteries, using a wire myograph. The use of cationic lipids, stearylamine, or 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (DOTAP) in liposomes promoted iloprost encapsulation to at least 50%. The addition of cholesterol modestly reduced iloprost encapsulation. The liposomal nanoparticle formulations were tested for toxicity and pharmacologic efficacy in vivo and ex vivo, respectively. The liposomes did not affect the viability of human pulmonary artery smooth muscle cells. Compared with an equivalent concentration of free iloprost, four out of the six polymer-coated liposomal formulations exhibited significantly enhanced vasodilation of mouse pulmonary arteries. Iloprost that was encapsulated in liposomes containing the polymer polyethylene glycol exhibited concentration-dependent relaxation of arteries. Strikingly, half the concentration of iloprost in liposomes elicited similar pharmacologic efficacy as nonencapsulated iloprost. Cationic liposomes can encapsulate iloprost with high efficacy and can serve as potential iloprost carriers to improve its therapeutic efficacy. PMID:25045260
Jain, Pritesh P; Leber, Regina; Nagaraj, Chandran; Leitinger, Gerd; Lehofer, Bernhard; Olschewski, Horst; Olschewski, Andrea; Prassl, Ruth; Marsh, Leigh M
Prostacyclin analogues are standard therapeutic options for vasoconstrictive diseases, including pulmonary hypertension and Raynaud's phenomenon. Although effective, these treatment strategies are expensive and have several side effects. To improve drug efficiency, we tested liposomal nanoparticles as carrier systems. In this study, we synthesized liposomal nanoparticles tailored for the prostacyclin analogue iloprost and evaluated their pharmacologic efficacy on mouse intrapulmonary arteries, using a wire myograph. The use of cationic lipids, stearylamine, or 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (DOTAP) in liposomes promoted iloprost encapsulation to at least 50%. The addition of cholesterol modestly reduced iloprost encapsulation. The liposomal nanoparticle formulations were tested for toxicity and pharmacologic efficacy in vivo and ex vivo, respectively. The liposomes did not affect the viability of human pulmonary artery smooth muscle cells. Compared with an equivalent concentration of free iloprost, four out of the six polymer-coated liposomal formulations exhibited significantly enhanced vasodilation of mouse pulmonary arteries. Iloprost that was encapsulated in liposomes containing the polymer polyethylene glycol exhibited concentration-dependent relaxation of arteries. Strikingly, half the concentration of iloprost in liposomes elicited similar pharmacologic efficacy as nonencapsulated iloprost. Cationic liposomes can encapsulate iloprost with high efficacy and can serve as potential iloprost carriers to improve its therapeutic efficacy.
Chen, Gui-Lan; Jiang, Hongni; Zou, Fangdong
Background Septic shock is a pathologic condition caused by endotoxin-producing bacteria, and often associated with severe pulmonary hypertension. Inflammation is a major systemic response to endotoxin; however, it is unknown whether endotoxin has a direct impact on pulmonary arteries that contributes to pathogenesis of pulmonary hypertension. Material/Methods Rat pulmonary arteries and primary pulmonary arterial smooth muscle cells (PASMCs) were cultured in vitro and treated with lipopolysaccharide (LPS) and blockers of transient receptor potential canonical (TRPC) channels. Neointimal growth and arterial stenosis were observed on cryosections of cultured pulmonary arteries. Proliferation of PASMCs was examined by a WST-1 (water-soluble tetrazolium salt) assay. Expression of TRPC genes in pulmonary arteries and PASMCs were detected and quantified by real-time polymerase chain reaction and Western blotting. Results LPS significantly induced neointimal growth and stenosis of pulmonary arteries and promoted proliferation of PASMCs. TRPC channel blockers 2-aminoethoxydiphenyl borate and SKF-96365 inhibited LPS-induced remodeling of pulmonary arteries and PASMC proliferation. Expression of TRPC1/3/4/6 was detected in pulmonary arteries and PASMCs. LPS treatment dramatically increased the expression of TRPC3 and TRPC4 at both messenger RNA and protein levels. Conclusions LPS stimulates stenosis of pulmonary arteries through enhancement of TRPC-mediated Ca2+ entry into PASMCs, which is caused by upregulation of TRPC3 and TRPC4 channels. PMID:27471122
Ruffenach, Grégoire; Umar, Soban; Motayagheni, Negar; Reddy, Srinivasa T.; Eghbali, Mansoureh
Abstract Pulmonary arterial hypertension (PAH) is a multifactorial disease characterized by interplay of many cellular, molecular, and genetic events that lead to excessive proliferation of pulmonary cells, including smooth muscle and endothelial cells; inflammation; and extracellular matrix remodeling. Abnormal vascular changes and structural remodeling associated with PAH culminate in vasoconstriction and obstruction of pulmonary arteries, contributing to increased pulmonary vascular resistance, pulmonary hypertension, and right ventricular failure. The complex molecular mechanisms involved in the pathobiology of PAH are the limiting factors in the development of potential therapeutic interventions for PAH. Over the years, our group and others have demonstrated the critical implication of lipids in the pathogenesis of PAH. This review specifically focuses on the current understanding of the role of oxidized lipids, lipid metabolism, peroxidation, and oxidative stress in the progression of PAH. This review also discusses the relevance of apolipoprotein A-I mimetic peptides and microRNA-193, which are known to regulate the levels of oxidized lipids, as potential therapeutics in PAH. PMID:27683603
Fraisse, A; Habib, G
Treatment strategies for pulmonary hypertension in children have dramatically evolved. Traditional therapy with calcium channel blockers and pulmonary transplantation is only indicated in selected patients and does not reduce mortality very significantly. New pulmonary vasodilators are emerging from recent trials in the adult population. Their indications are based on the patient's NYHA classification. The epoprostenol (prostacyclin, Flolan) has shown reduction in mortality and improvement in functional symptoms in pediatric patients. The frequent side effects and continuous intravenous infusion limit the indication of prostacyclin in NYHA class IV children. The endothelin receptor blocker bosentan (Tracleer) is an orally given agent. It improves functional symptoms in adults and hemodynamic measures in children. It can be started in children with moderate functional symptoms (NYHA class II and III). The type V phosphodiesterase inhibitor sildenafil (Viagra) is being evaluated and may represent a promising therapy in the future. Invasive strategies like catheter-based atrial septostomy may be useful in particular cases. Randomized-controlled studies are urgently needed to evaluate the safety and efficacy of these new therapies.
Ammari, Chady; Campisi, Alessio; D’Andrea, Rocco
Peripheral vein catheterization is generally considered a harmless procedure. Venous catheter rupture associated with pulmonary embolism is an unlikely but potentially serious complication. We report a case of a peripheral venous catheter (PVC) fracture with pulmonary artery embolization in the left lower lobe treated successfully by a surgical approach. The positioning of a PVC is not always a harmless procedure. Every time there are difficulties in positioning or in removal of a catheter device, it should be carefully inspected to verify integrity. The advisability of removal of these small foreign bodies is debated; percutaneous retrieval is preferred, while surgery should be discussed case by case. PMID:28149586
Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and cell proliferation in the pulmonary vasculature. Guideline-driven interventions with infused prostacyclin treatment are the mainstay for patients with advanced symptoms. Infused prostacyclin therapy is complex. It is critical to manage prostacyclin therapy with precision because boluses or interruptions can be fatal. Education of patients and inpatient staff nurses is necessary to prevent negative outcomes. Nurses are an essential part of the multidisciplinary team caring for patients with PAH. The diagnostic evaluation and treatment of PAH are reviewed here, and challenges associated with the care of patients on prostacyclin therapy are discussed.
Hassoun, Paul M
Pulmonary arterial hypertension (PAH), a common complication of systemic sclerosis, carries a very severe prognosis and is one of the leading causes of death in patients who suffer from it. Indeed, response to modern medical therapy has been disappointing in scleroderma-related PAH compared with other forms of PAH from the WHO group 1 classification of diseases, despite similar histological changes involving the pulmonary vasculature. This review discusses specific features of scleroderma-related PAH, currently available and US FDA-approved therapy for this syndrome, as well as potential future therapeutic developments based on newly acquired knowledge of this disorder. PMID:19885388
Lai, Ying-Rong; Hong, Jun-Mou; Liu, Zhen-Guo; Deng, Zhen-Sheng; Yeung, Sai-Ching J; Cheng, Chao
Massive hemoptysis in Behçet disease (BD) is rare but often fatal. This report presents a 28-year-old man with recurrent massive hemoptysis. He was diagnosed with bilateral multiple pulmonary artery aneurysms (PAAs), coronary artery aneurysm, and ventricular pseudoaneurysm from BD. The patient underwent emergency right lower lobectomy with no obvious complications. No hemoptysis recurred during an 18-month follow-up. This report also reviews the occurrence of PAAs in BD, with an emphasis on the treatment approaches.
Gupta, Nilesh; Patel, Brijeshkumar; Nahar, Kamrun; Ahsan, Fakhrul
In this study, we tested the hypothesis that a cell permeable peptide, CARSKNKDC (CAR), conjugated nanoerythrosomes (NERs) containing fasudil, a rho-kinase (ROCK) inhibitor, produces prolonged pulmonary preferential vasodilation. CAR conjugated NERs containing fasudil were prepared by hypotonic lysis and extrusion method, optimized for various physicochemical properties in-vitro. The formulations were then used to study the hemodynamic efficacy in a monocrotaline-induced rodent model of pulmonary arterial hypertension (PAH). CAR-NERs-Fasudil was spherical in shape with an average vesicle size and entrapment efficiency of 161.3±1.37nm and 48.81±1.96%, respectively. Formulations were stable for ~3 weeks when stored at 4°C and the drug was released in a controlled fashion for >48 hrs. The uptake of CAR-NERs-Fasudil by TGF-β activated pulmonary arterial smooth muscle cell was ~1.5 fold greater than the uptake of NERs-Fasudil. CAR-NERs-Fasudil inhibited ROCK activity and 5-hydroxytryptamine induced cell proliferation. In terms of reduction of pulmonary arterial pressure, intratracheal administration of CAR-NERs-Fasudil was ~2-fold more specific to the lungs compared with plain fasudil. Overall, CAR peptide grafted nanoerythrosomes offers a new platform for improving the therapeutic efficacy of a rho-kinase inhibitor, fasudil, without affecting peripheral vasodilation. PMID:25460151
Nomori, Hiroaki; Cong, Yue; Sugimura, Hiroshi
It is often difficult to expose the pulmonary artery buried in a scar tissue, especially in lung cancer patients that responded well to neoadjuvant chemoradiotherapy. Difficulty to access pulmonary artery branches may lead to potentially unnecessary pneumonectomy. To complete lobectomy in such cases, a technique with preceding bronchial cutting for exposure of the pulmonary artery is presented. After dissecting the pulmonary vein, the lobar bronchus is cut from the opposite side of the pulmonary artery with scissors. The back wall of the lobar bronchus is cut using a surgical knife from the luminal face, which can expose the pulmonary artery behind the bronchial stump and then complete lobectomy. Fourteen patients have been treated using the present technique, enabling complete resection by lobectomy (including sleeve lobectomy in 3 patients) without major bleeding. The present procedure can expose pulmonary artery buried in scar tissue, resulting in making the lobectomy safer.
Talavera, María L; Diez, Mirta; Cáneva, Jorge O; Boughen, Roberto P; Valdivieso, León; Mendiz, Oscar
Chest pain is a frequent symptom in patients with pulmonary hypertension of any etiology. Its pathophysiology has not been clearly established, the proposed causes are ischemia due to increased right ventricle wall stress, transient increased pulmonary hypertension resulting in acute pulmonary artery dilatation and external compression of the left main coronary artery (LMCA) by a dilated pulmonary artery. We report and discuss here three cases where the association between chest pain and compression of the LMCA by a dilated pulmonary artery could be shown, and they were treated with coronary stenting.
Ooi, Masaya; Omoto, T; Ishikawa, N; Mouri, M; Okayama, T; Fukusumi, M; Ono, M; Tedoriya, T
Primary sarcoma of the pulmonary artery is rare. Diagnosis is difficult and often delayed; pulmonary embolism is part of the differential diagnosis. We treated a 46-year-old woman with progressive dyspnea. Computed tomography showed a lesion occupying the main pulmonary artery and peripheral branches on both sides. The pulmonary artery tumor, resected under cardiopulmonary bypass, was diagnosed pathologically as intimal sarcoma. Two weeks after the operation, the patient was feeling well and discharged from our hospital. Although the prognosis of pulmonary artery sarcoma is poor, early diagnosis and resection may prolong survival.
Kao, Philip H; Lammers, Steve; Tian, Lian; Hunter, Kendall; Stenmark, Kurt R.; Shandas, Robin; Qi, H. Jerry
A new constitutive model for elastic, proximal pulmonary artery tissue is presented here, called the Total Crimped Fiber Model. This model is based on the material and micro-structural properties of the two main, passive, load-bearing components of the artery wall, elastin and collagen. Elastin matrix proteins are modeled with an orthotropic neo-Hookean material. High stretch behavior is governed by an orthotropic crimped fiber material, modeled as a planar sinusoidal linear elastic beam, which represents collagen fiber deformations. Collagen-dependent artery orthotropy is defined by a structure tensor representing the effective orientation distribution of collagen fiber bundles. Therefore, every parameter of the total crimped fiber model is correlated with either a physiologic structure or geometry or is a mechanically-measured material property of the composite tissue. Further, by incorporating elastin orthotropy, this model better represents the mechanics of arterial tissue deformation. These advancements result in a micro-structural total crimped fiber model of pulmonary artery tissue mechanics which demonstrates good quality of fit and flexibility for modeling varied mechanical behaviors encountered in disease states. PMID:21599093
Mair, K M; Johansen, A K Z; Wright, A F; Wallace, E; MacLean, M R
Pulmonary arterial hypertension (PAH) is a complex disease characterized by elevated pulmonary arterial pressure, pulmonary vascular remodelling and occlusive pulmonary vascular lesions, leading to right heart failure. Evidence from recent epidemiological studies suggests the influence of gender on the development of PAH with an approximate female to male ratio of 4:1, depending on the underlying disease pathology. Overall, the therapeutic strategy for PAH remains suboptimal with poor survival rates observed in both genders. Endogenous sex hormones, in particular 17β oestradiol and its metabolites, have been implicated in the development of the disease; however, the influence of sex hormones on the underlying pathobiology remains controversial. Further understanding of the influence of sex hormones on the normal and diseased pulmonary circulation will be critical to our understanding the pathology of PAH and future therapeutic strategies. In this review, we will discuss the influence of sex hormones on the development of PAH and address recent controversies. Linked Articles This article is part of a themed section on Biological Sex and Cardiovascular Pharmacology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-3 PMID:23802760
Husain-Syed, Faeq; Muciño-Bermejo, María-Jimena; Ronco, Claudio; Seeger, Werner; Birk, Horst-Walter
Pulmonary hypertension is a common finding in patients with advanced liver disease. Similarly, among patients with advanced pulmonary arterial hypertension, right heart failure leads to congestive hepatopathy. Diuretic resistant fluid overload in both advanced pulmonary hypertension and chronic liver disease is a demanding challenge for physicians. Venous congestion and ascites-induced increased intra-abdominal pressure are essential regarding recurrent hospitalization, morbidity and mortality. Due to impaired right-ventricular function, many patients cannot tolerate extracorporeal ultrafiltration. Peritoneal dialysis, a well-established, hemodynamically tolerated treatment for outpatients may be a good alternative to control fluid status. We present a patient with pulmonary arterial hypertension and congestive hepatopathy hospitalized for over 3 months due to ascites induced refractory volume overload treated with peritoneal ultrafiltration. We report the treatment benefits on fluid balance, cardiorenal and pulmonary function, as well as its safety. In conclusion, we report a case in which peritoneal ultrafiltration was an efficient treatment option for refractory ascites in patients with congestive hepatopathy.
Santhosh, M C B; Pai, R B; Rao, R P
Arterial tourniquets are used as one of the methods for reducing blood loss and for allowing blood free surgical field. A 20-year-old, 45 kg healthy female with a sphere shaped pendunculated hemangioma in the popliteal fossa of her left lower limb was applied with arterial tourniquet after exsanguination. The procedure was performed under general anesthesia. Soon after exsanguination and tourniquet inflation, the patient developed pulmonary edema which subsided after deflating the tourniquet. The clinical evolution, treatment and pathophysiology of this complication are described.
Agarwal, Richa; Gomberg-Maitland, Mardi
Pulmonary arterial hypertension (PAH) develops from an abnormal interaction between the endothelium and smooth muscle cells in the pulmonary vasculature and is characterized by a progressive rise in pulmonary vascular resistance resulting from vascular remodeling, vasoconstriction, and cellular proliferation. Currently, 3 classes of drugs are approved for the treatment of PAH based on results from small short-term clinical trials-prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors. The pharmacologic management of PAH is rapidly evolving as newer therapeutic targets that stabilize or reverse pulmonary vascular disease and target right ventricular function are being sought and as clinical practice patterns shift in favor of earlier diagnosis and aggressive treatment. This manuscript will review the practical management aspects of currently approved PAH treatments and briefly discuss combination therapy and novel pharmacologic targets. In addition, the treatment of acute right ventricular failure and evidence (or lack thereof) for therapies in non-PAH pulmonary hypertension, such as pulmonary hypertension from left side of the heart disease, are addressed.
Neves, Paulo; Guerra, Miguel; Mâncio, Jennifer; Ponce, Paulo; Vouga, Luís
Pulmonary artery sarcomas (PAS) are extremely rare and the prognosis of patients seems to be very poor. Their clinical appearance is highly nonspecific and variable, rendering the diagnosis difficult. Surgery remains the mainstay of treatment for PAS since early radical resection could offer the only chance of a potential cure. We describe the case of a 88-year old man who was admitted in the emergency department with syncope. The diagnostic study revealed a mass in the main pulmonary artery, extending into the right and left branches and occupying almost the whole of its size. The patient was successfully submitted to complete surgical excision of the mass, which revealed to be a malignant sarcoma.
Kholdani, Cyrus A; Fares, Wassim H; Trow, Terence K
Macitentan is the most recently approved dual endothelin-receptor antagonist (ERA) for the treatment of symptomatic pulmonary arterial hypertension. Compared to other available ERAs, it demonstrates superior receptor-binding properties, with consequently improved tissue penetration, and a longer duration of action allowing for once-daily dosing. It has a favorable adverse-effect profile, with notably no demonstrable increase in the risk of hepatotoxicity or peripheral edema, but like other ERAs, it is potentially limited by significant anemia. Phase I data have demonstrated a favorable drug–drug interaction profile and no need for dose adjustment with hepatic and renal impairment. In the pivotal SERAPHIN study, treatment of symptomatic pulmonary arterial hypertension patients with macitentan led to statistically significant improvements in functional class, exercise tolerance, and hemodynamic parameters, in addition to a reduction in morbidity in an event-driven long-term trial. PMID:25473292
Kim, Kyu Seon; Jo, Eun Young; Yu, Jae Hyeon
Isolated anomalous right coronary artery originating from the pulmonary artery (ARCAPA) is a rare congenital coronary anomaly that is asymptomatic and discovered incidentally in most cases. ARCAPA is generally not considered a fatal defect in infancy or childhood, although cases of sudden death have been reported. Here, we report a 2-month-old female infant who presented with a prolonged fever that was determined to be caused by rhinovirus infection. Myocardial ischemia of the left ventricular posterior wall was already seen on echocardiography, and ARCAPA was discovered incidentally. The patient underwent successful surgical reimplantation of the right coronary artery to the aortic root to re-establish dual ostial circulation. PMID:28018453
Joshi, Sachindra R.; Bastola, Mrigendra M.; McLendon, Jared M.; Oka, Masahiko; Fagan, Karen A.; McMurtry, Ivan F.
Abstract Despite several advances in the pathobiology of pulmonary arterial hypertension (PAH), its pathogenesis is not completely understood. Current therapy improves symptoms but has disappointing effects on survival. Sphingosine-1-phosphate (S1P) is a lysophospholipid synthesized by sphingosine kinase 1 (SphK1) and SphK2. Considering the regulatory roles of S1P in several tissues leading to vasoconstriction, inflammation, proliferation, and fibrosis, we investigated whether S1P plays a role in the pathogenesis of PAH. To test this hypothesis, we used plasma samples and lung tissue from patients with idiopathic PAH (IPAH) and the Sugen5416/hypoxia/normoxia rat model of occlusive PAH. Our study revealed an increase in the plasma concentration of S1P in patients with IPAH and in early and late stages of PAH in rats. We observed increased expression of both SphK1 and SphK2 in the remodeled pulmonary arteries of patients with IPAH and PAH rats. Exogenous S1P stimulated the proliferation of cultured rat pulmonary arterial endothelial and smooth-muscle cells. We also found that 3 weeks of treatment of late-stage PAH rats with an SphK1 inhibitor reduced the increased plasma levels of S1P and the occlusive pulmonary arteriopathy. Although inhibition of SphK1 improved cardiac index and the total pulmonary artery resistance index, it did not reduce right ventricular systolic pressure or right ventricular hypertrophy. Our study supports that S1P is involved in the pathogenesis of occlusive arteriopathy in PAH and provides further evidence that S1P signaling may be a novel therapeutic target. PMID:27683614
Tsyrlin, V A
The date about long time increase of blood pressure in conditions of excessive salt intake, constriction of renal artery in animals with initial low baroreceptor reflex is presented. Arterial hypertension in this case is accompanied by increase activity of sympathetic nervous system. The supposition that arterial baroreceptor reflex place a role in long time regulation of arterial blood pressure is expressed.
Chan, Christina K.; Eriksson, Inger; Johnson, Pamela Y.; Cao, Xiaofang; Westöö, Christian; Norvik, Christian; Andersson-Sjöland, Annika; Westergren-Thorsson, Gunilla; Johansson, Staffan; Hedin, Ulf; Kjellén, Lena; Wight, Thomas N.; Tran-Lundmark, Karin
Abstract Pulmonary arterial hypertension (PAH) is a lethal condition for which there is no effective curative pharmacotherapy. PAH is characterized by vasoconstriction, wall thickening of pulmonary arteries, and increased vascular resistance. Versican is a chondroitin sulfate proteoglycan in the vascular extracellular matrix that accumulates following vascular injury and promotes smooth-muscle cell proliferation in systemic arteries. Here, we investigated whether versican may play a similar role in PAH. Paraffin-embedded lung sections from patients who underwent lung transplantation to treat PAH were used for immunohistochemistry. The etiologies of PAH in the subjects involved in this study were idiopathic PAH, scleroderma, and congenital heart disease (atrial septal defect) with left-to-right shunt. Independent of the underlying etiology, increased versican immunostaining was observed in areas of medial thickening, in neointima, and in plexiform lesions. Western blot of lung tissue lysates confirmed accumulation of versican in patients with PAH. Double staining for versican and CD45 showed only occasional colocalization in neointima of high-grade lesions and plexiform lesions. In vitro, metabolic labeling with [35S]sulfate showed that human pulmonary artery smooth-muscle cells (hPASMCs) produce mainly chondroitin sulfate glycosaminoglycans. In addition, hypoxia, but not cyclic stretch, was demonstrated to increase both versican messenger RNA expression and protein synthesis by hPASMCs. Versican accumulates in vascular lesions of PAH, and the amount of versican correlates more with lesion severity than with underlying etiology or inflammation. Hypoxia is a possible regulator of versican accumulation, which may promote proliferation of pulmonary smooth-muscle cells and vascular remodeling in PAH. PMID:27683612
Kaya, Seyda Ors; Samancilar, Ozgur; Ceylan, Kenan Can
A 73-year-old man underwent left pneumonectomy for squamous cell lung carcinoma 3 years ago. The postoperative and follow-up periods were uneventful. A thrombus was detected in the left pulmonary artery stump during the last chest computed tomography (CT) scan. Anticoagulant treatment was applied: intravenous heparin for 3 days followed by oral warfarin. The follow-up chest CT examination revealed regression in the size of the thrombus. PMID:27785144
Liu, Min; Luo, Chunhai; Wang, Ying; Guo, Xiaojuan; Ma, Zhanhong; Yang, Yuanhua; Zhang, Tianjing
PURPOSE We aimed to define multiparametric magnetic resonance imaging (MRI) findings to differentiate between pulmonary artery sarcoma (PAS) and pulmonary thromboembolism (PTE). METHODS Eleven patients with suspected PTE were prospectively included to undergo pulmonary MRI before surgery or biopsy. MRI protocol included an unenhanced sequence, diffusion-weighted imaging (DWI, b=800 s/mm2) and a dynamic contrast-enhanced sequence. Morphologic characteristics including distribution, filling defect, and intensity were observed on T1-, T2-, and fat-suppressed T2-weighted imaging, DWI, and contrast-enhanced MRI. Apparent diffusion coefficient (ADC) values were calculated. RESULTS Six patients were pathologically diagnosed as PAS and the other five as chronic PTE. There were no significant differences in age, gender, presenting symptoms, D-dimer, and N-terminal pro-brain natriuretic peptide between the two groups (P > 0.05). Among MRI findings that were tested for their ability to diagnose PAS, area under the curve (AUC) was significantly higher than 0.5 for main pulmonary artery involvement (AUC, 0.83±0.13; P = 0.011), hyperintensity on fat-suppressed T2-weighted imaging (AUC, 0.82±0.14; P = 0.025), hyperintensity on DWI (AUC, 0.88±0.12; P = 0.002), contrast enhancement (AUC, 0.92±0.10; P < 0.001) and pleural effusion (AUC, 0.82±0.14; P = 0.025). Moreover, grape-like appearance in distal pulmonary artery and cardiac invasion had 100% specificity for diagnosis of PAS. However, ADC value of PAS was not significantly different than that of chronic PTE (U, 12.00; P = 0.584). CONCLUSION Hyperintense filling defect in main pulmonary artery on fat-suppressed T2-weighted imaging and DWI and contrast enhancement may help to discriminate PAS from PTE. PMID:27919861
Simsek, Pelin Ozlem; Ozcelik, Ugur; Celiker, Alpay; Yalcin, Ebru; Cobanoglu, Nazan; Pekcan, Sevgi; Alehan, Dursun; Ucar, Canan; Dogru, Deniz; Kiper, Nural
Congenital unilateral absence of a pulmonary artery is a rare anomaly most frequently accompanied by other cardiovascular anomalies. We report a 10-year-old girl presenting with fatigue and recurrent hemoptysis who was initially misdiagnosed with idiopathic pulmonary hemosiderosis. Her symptoms did not resolve despite treatment so she was referred to our center for further evaluation. We carried out an angiography which revealed the absence of the right pulmonary artery and multiple collaterals originating from the right subclavian and right internal mammary arteries supplying the right lung. During the follow-up the patient developed a severe episode of pulmonary infection and pulmonary hypertension which responded well to medical treatment. Physicians should be aware of the congenital absence of the right pulmonary artery especially in patients presenting with recurrent respiratory symptoms. Although this condition is generally considered to have a good prognosis, close observation is mandatory in order to prevent further complications and comorbidities.
El Chami, Hala; Hassoun, Paul M.
Altered immunity and inflammation are increasingly recognized features of pulmonary arterial hypertension (PAH). This is suggested by infiltration of various inflammatory cells (e.g., macrophages, T and B lymphocytes), increased cytokine and growth factor (e.g., VEGF and PDGF) expression in remodeled pulmonary vessels, and the presence of circulating chemokines and cytokines. In certain diseases associated with PAH, increased expression of growth and transcriptional (e.g., Nuclear Factor of Activated T cells or NFAT) factors, and viral protein components (e.g., HIV-1 Nef), appear to contribute directly to recruitment of inflammatory cells in remodeled vessels, and may potentially serve as specific therapeutic targets. This section provides an overview of inflammatory pathways highlighting their potential role in pulmonary vascular remodeling in PAH and the possibility of future targeted therapy. PMID:23009917
Timofeev, Julia; Ruiz, George; Fries, Melissa; Driggers, Rita W.
Background Pulmonary arterial hypertension carries a high risk of mortality in pregnancy. Recent advances in treatment may improve disease course and allow for successful management of the pregnancy. Case Report We present the case of a 20-year-old gravida 1, para 0 with diagnosis of severe primary pulmonary hypertension. The patient was managed with epoprostenol (prostacyclin) infusion via an indwelling catheter, which was initiated at 23 weeks' gestation. The dose was adjusted to the patient's symptoms and a successful vaginal delivery was achieved at 36 weeks' gestation. Although maternal postpartum course was uncomplicated, unexplained neonatal demise occurred at 11 days of life. Conclusion Successful management of pulmonary hypertension in pregnancy can be accomplished with a multidisciplinary approach and intensive therapy. Long-term effects of epoprostenol on fetal or neonatal well-being are unknown. PMID:24147238
Timofeev, Julia; Ruiz, George; Fries, Melissa; Driggers, Rita W
Background Pulmonary arterial hypertension carries a high risk of mortality in pregnancy. Recent advances in treatment may improve disease course and allow for successful management of the pregnancy. Case Report We present the case of a 20-year-old gravida 1, para 0 with diagnosis of severe primary pulmonary hypertension. The patient was managed with epoprostenol (prostacyclin) infusion via an indwelling catheter, which was initiated at 23 weeks' gestation. The dose was adjusted to the patient's symptoms and a successful vaginal delivery was achieved at 36 weeks' gestation. Although maternal postpartum course was uncomplicated, unexplained neonatal demise occurred at 11 days of life. Conclusion Successful management of pulmonary hypertension in pregnancy can be accomplished with a multidisciplinary approach and intensive therapy. Long-term effects of epoprostenol on fetal or neonatal well-being are unknown.
Kheyfets, Vitaly O; Rios, Lourdes; Smith, Triston; Schroeder, Theodore; Mueller, Jeffrey; Murali, Srinivas; Lasorda, David; Zikos, Anthony; Spotti, Jennifer; Reilly, John J; Finol, Ender A
Computational fluid dynamics (CFD) modeling of the pulmonary vasculature has the potential to reveal continuum metrics associated with the hemodynamic stress acting on the vascular endothelium. It is widely accepted that the endothelium responds to flow-induced stress by releasing vasoactive substances that can dilate and constrict blood vessels locally. The objectives of this study are to examine the extent of patient specificity required to obtain a significant association of CFD output metrics and clinical measures in models of the pulmonary arterial circulation, and to evaluate the potential correlation of wall shear stress (WSS) with established metrics indicative of right ventricular (RV) afterload in pulmonary hypertension (PH). Right Heart Catheterization (RHC) hemodynamic data and contrast-enhanced computed tomography (CT) imaging were retrospectively acquired for 10 PH patients and processed to simulate blood flow in the pulmonary arteries. While conducting CFD modeling of the reconstructed patient-specific vasculatures, we experimented with three different outflow boundary conditions to investigate the potential for using computationally derived spatially averaged wall shear stress (SAWSS) as a metric of RV afterload. SAWSS was correlated with both pulmonary vascular resistance (PVR) (R(2)=0.77, P<0.05) and arterial compliance (C) (R(2)=0.63, P<0.05), but the extent of the correlation was affected by the degree of patient specificity incorporated in the fluid flow boundary conditions. We found that decreasing the distal PVR alters the flow distribution and changes the local velocity profile in the distal vessels, thereby increasing the local WSS. Nevertheless, implementing generic outflow boundary conditions still resulted in statistically significant SAWSS correlations with respect to both metrics of RV afterload, suggesting that the CFD model could be executed without the need for complex outflow boundary conditions that require invasively obtained
Kheyfets, Vitaly O.; Rios, Lourdes; Smith, Triston; Schroeder, Theodore; Mueller, Jeffrey; Murali, Srinivas; Lasorda, David; Zikos, Anthony; Spotti, Jennifer; Reilly, John J.; Finol, Ender A.
Computational fluid dynamics (CFD) modeling of the pulmonary vasculature has the potential to reveal continuum metrics associated with the hemodynamic stress acting on the vascular endothelium. It is widely accepted that the endothelium responds to flow-induced stress by releasing vasoactive substances that can dilate and constrict blood vessels locally. The objectives of this study are to examine the extent of patient specificity required to obtain a significant association of CFD output metrics and clinical measures in models of the pulmonary arterial circulation, and to evaluate the potential correlation of wall shear stress (WSS) with established metrics indicative of right ventricular (RV) afterload in pulmonary hypertension (PH). Right heart catheterization (RHC) hemodynamic data and contrast-enhanced computed tomography (CT) imaging were retrospectively acquired for 10 PH patients and processed to simulate blood flow in the pulmonary arteries. While conducting CFD modeling of the reconstructed patient-specific vasculatures, we experimented with three different outflow boundary conditions to investigate the potential for using computationally derived spatially averaged wall shear Stress (SAWSS) as a metric of RV afterload. SAWSS was correlated with both pulmonary vascular resistance (PVR) (R2 = 0.77, P < 0.05) and arterial compliance (C) (R2 = 0.63, P < 0.05), but the extent of the correlation was affected by the degree of patient specificity incorporated in the fluid flow boundary conditions. We found that decreasing the distal PVR alters the flow distribution and changes the local velocity profile in the distal vessels, thereby increasing the local WSS. Nevertheless, implementing generic outflow boundary conditions still resulted in statistically significant SAWSS correlations with respect to both metrics of RV afterload, suggesting that the CFD model could be executed without the need for complex outflow boundary conditions that require invasively obtained
Ugalde P, Héctor; Rozas A, Sebastián; Sanhueza F, María Ignacia; Yubini L, María Cecilia; García B, Sebastián
Anomalies of the origin of coronary arteries are detected in 0.5-1.5% of all angiographies. Anomalous origin of the left main trunk is the most uncommon and its origin from pulmonary artery in adults is exceptional, usually because it is associated with a short survival. We report a 49-year-old female, presenting with a two months history of angina. The exercise electrocardiogram suggested ischemia. A coronary angiography was performed, showing the absence of the left main trunk in the left coronary sinus, a dilated right coronary artery, with no lesions and extensive collateral circulation to the anterior descending and circumflex arteries, with inverted flow and the left main trunk draining to the pulmonary artery. The left ventricle was mildly dilated with middle and apical anterior hypokinesia. Global systolic function was conserved. A surgical correction was decided, occluding the left main anomalous origin and performing a coronary artery bypass grafting from the left internal thoracic artery. The patient was discharged with no complications. At two years of follow-up she is symptom free and has a normal physical capacity.
Alvarez-Díaz, F.; Brito, J. M.; Cordovilla, G.; De León, J. Pérez; Sanchez, P. A.; Bordiú, C. M.
The results of 180 cases of congenital heart disease with diminished pulmonary flow operated upon with Waterston's technique are presented. It is considered that Waterston's operation is to be preferred in children under 2 years of age and in older children who have had a previous thrombotic or insufficient Blalock operation and in whom total correction is not indicated. The problem of pseudotruncus with hypoplastic pulmonary arteries is discussed. The convenience of the Waterston operation in these cases, and the importance of creating an anastomosis at the pulmonary bifurcation and as far back as possible in the aorta, is emphasized. The need to perform this technique in the correct way is stressed. This will avoid the kinking and pulling of the right pulmonary artery, which are causes of preferential blood flow to the right lung, as we have demonstrated experimentally. The possible complications caused by such a technical failure are discussed. The necessity for previous angiocardiographic study, in order properly to repair the defect during total correction, is also considered. Images PMID:4731106
Kawata, Hiroaki; Kishimoto, H; Iwai, S; Ishimaru, K; Saito, T; Kayatani, F; Inamura, N; Hamamichi, Y; Kawada, Y; Nasuno, S; Maekawa, S
We assessed the effect of reconstructing the pulmonary artery during arterial switch surgery for transposition of the great arteries on late pulmonary stenosis. Sixty-five patients who underwent Lecompte procedure between September 1991 and December 2006 were divided, by the procedure used chronologically to reconstruct the pulmonary artery, into group XP (single pantaloon patch with equine pericardium, n = 11), group P (direct reconstruction, n = 47), and group AP (single pantaloon patch with fresh autopericardium, n = 7). Outcome and pulmonary stenosis on the most recent ultrasound cardiography (UCG) were compared in the 3 groups. The median follow-up was 13, 7.5, and 1.3 years, respectively. Both early and late mortalities were 1.5% (1/65). Although percutaneous trans-pulmonary angioplasty was necessary in 1, 13, and 3 patients, there was 1, 1, and 0 reoperation for pulmonary stenosis in the 3 groups, respectively. Pulmonary stenosis (pulmonary arterial maximum flow velocity > 3 m/sec on UCG) was present in 4 (40%). 14 (30%). and 3 patients (43%). Although there was no significant difference among the 3 procedures in preventing pulmonary stenosis 10 years after arterial switch surgery, direct reconstruction of the pulmonary artery may show a superior outcome, in particular, over 10 years after arterial switch surgery.
Han, Ying; Cho, Young-Eun; Ayon, Ramon; Guo, Rui; Youssef, Katia D.; Pan, Minglin; Dai, Anzhi; Yuan, Jason X.-J.
Inhibitors of sodium-glucose cotransporter (SGLT)2 are a new class of oral drugs for type 2 diabetic patients that reduce plasma glucose levels by inhibiting renal glucose reabsorption. There is increasing evidence showing the beneficial effect of SGLT2 inhibitors on glucose control; however, less information is available regarding the impact of SGLT2 inhibitors on cardiovascular outcomes. The present study was designed to determine whether SGLT inhibitors regulate vascular relaxation in mouse pulmonary and coronary arteries. Phlorizin (a nonspecific SGLT inhibitor) and canagliflozin (a SGLT2-specific inhibitor) relaxed pulmonary arteries in a dose-dependent manner, but they had little or no effect on coronary arteries. Pretreatment with phlorizin or canagliflozin significantly inhibited sodium nitroprusside (SNP; a nitric oxide donor)-induced vascular relaxation in pulmonary arteries but not in coronary arteries. Phlorizin had no effect on cGMP-dependent relaxation in pulmonary arteries. SNP induced membrane hyperpolarization in human pulmonary artery smooth muscle cells, and pretreatment of cells with phlorizin and canagliflozin attenuated SNP-induced membrane hyperpolarization by decreasing K+ activities induced by SNP. Contrary to the result observed in ex vivo experiments with SGLT inhibitors, SNP-dependent relaxation in pulmonary arteries was not altered by chronic administration of canagliflozin. On the other hand, canagliflozin administration significantly enhanced SNP-dependent relaxation in coronary arteries in diabetic mice. These data suggest that SGLT inhibitors differentially regulate vascular relaxation depending on the type of arteries, duration of the treatment, and health condition, such as diabetes. PMID:26361875
Hirose, Takashi; Ishikawa, Noboru; Hamada, Kenji; Inagaki, Tomoko; Kusumoto, Sojiro; Shirai, Takao; Okuda, Kentaro; Ohnishi, Tsukasa; Kadokura, Mitsutaka; Adachi, Mitsuru
We report on a 45-year-old woman with intimal sarcoma of the pulmonary artery. She presented with a chief complaint of shortness of breath. Computed tomography (CT) of the chest showed an intraluminal hypoattenuated area extending from the main pulmonary artery into the right main pulmonary artery and bilateral lobar pulmonary arteries. She underwent resection of the lobulated mass from the pulmonary artery. The tumor was diagnosed as an intimal sarcoma. Although she received chemotherapy with amrubicin and carboplatin when the tumor recurred, the tumor enlarged. After radiotherapy was performed, CT of the chest showed shrinkage of the tumor and the regression of consolidation and ground-glass opacity. Radiotherapy and chemotherapy are treatment option for patients with pulmonary artery sarcoma.
Serov, P G
During prosthetic stomatological reception with the help of portable arterial pressure monitor Kardiotechnika-04AD-01 there were examined patients with normal blood pressure and arterial hypertension. The data were received confirming dependence of arterial pressure lifting with personal anxiety level. Conclusion was drown that close patient's examination was necessary before prosthetic stomatological reception.
Han, Daehee; Lee, Kyung Soo; Franquet, Tomas; Müller, Nestor L; Kim, Tae Sung; Kim, Hojoong; Kwon, O Jung; Byun, Hong Sik
Along with clinical examination and laboratory tests, imaging plays a key role in the diagnosis of pulmonary embolism. Multi-detector row helical computed tomography (CT) is particularly helpful in the diagnosis of acute pulmonary thromboembolism (PTE) owing to its capacity to directly show emboli as intravascular filling defects. Although parenchymal abnormalities at CT are nonspecific for acute PTE, they may contribute to a correct diagnosis of chronic PTE, the characteristic helical CT features of which are similar to its angiographic features and include webs or bands, intimal irregularities, abrupt narrowing or complete obstruction of the pulmonary arteries, and "pouching defect." Nonthrombotic pulmonary embolism is an uncommon condition but is sometimes associated with specific imaging findings, including discrete nodules with cavitation (septic embolism), widespread homogeneous and heterogeneous areas of increased opacity or attenuation that typically appear 12-24 hours after trauma (fat embolism), and fine miliary nodules that subsequently coalesce into large areas of increased opacity or attenuation (talcosis). Knowledge of appropriate imaging methods and familiarity with the specific imaging features of pulmonary embolism should facilitate prompt, effective diagnosis.
Tschudi, M R; Barton, M; Bersinger, N A; Moreau, P; Cosentino, F; Noll, G; Malinski, T; Lüscher, T F
Aging is an important determinant of vascular disease. Endothelium-derived nitric oxide (NO) is protective as a vasodilator and inhibitor of platelet function. This study was designed to directly measure effects of prolonged aging on endotheliai NO release in isolated blood vessels and to delineate differences between the systemic and pulmonary circulation. Aortas and pulmonary arteries from 5-6-mo-old (young), 18-19-mo-old (middle-aged), and 32-33-mo-old (old) normotensive female rats were used. Blood pressure and plasma estradiol-17beta (E2) remained unchanged. In isolated blood vessels, NO release was induced by the receptor-independent agonist calcium ionophore A23187 (10 micromol/liter) and measured in situ on the endothelial surface of vessels using a porphyrinic microsensor. In vessels suspended in organ chambers isometric tension was recorded. In the aorta, the initial rate of NO release and peak NO concentration were reduced in middle-aged and old rats (P < 0.0006 vs. young rats, n = 6). Furthermore, endothelium-dependent relaxations to calcium ionophore and acetylcholine (both 10(-10) - 10(-5) mol/liter) were also reduced in aortas from old as compared with young rats (n = 6, P < 0.05). The initial rate of NO release and peak NO concentration significantly correlated with maximal relaxation to calcium ionophore A23187 (correlation coefficients r - 0.916, P < 0.0018 and r = 0.961, P < 0.0001, respectively, n = 7). In pulmonary arteries, however, the initial rate of NO release as well as peak NO concentration did not decrease with age (n = 6 for each age group, NS). In both blood vessels, the NO release was unaffected by superoxide dismutase in all age groups (n = 6, NS). Thus, aging specifically reduces initial rate and peak concentrations of endothelial NO release from aorta but not pulmonary artery indicating reduced NO production. As arterial pressure did not change with aging, the chronic exposure of the aorta to higher pressure and/or pulsatility than
Timmers, Liesbeth; Bové, Thierry; De Pauw, Michel
Intimal sarcoma of the pulmonary artery (PAS) is a rare but potentially lethal tumour, frequently misdiagnosed as chronic thrombo-embolic pulmonary artery disease. Despite the availability of advanced imaging technologies, its preoperative diagnosis remains difficult. We report on two patients with clinical features mimicking chronic pulmonary thrombo-embolism. Further discussion will focus on the differential diagnosis with more classical causes of obstructive pulmonary vascular disease.
Molthen, Robert; Wu, Qingping; Baumgardt, Shelley; Kohlhepp, Laura; Shingrani, Rahul; Krenz, Gary
Pulmonary hypertension (PH) is an incurable condition inevitably resulting in death because of increased right heart workload and eventual failure. PH causes pulmonary vascular remodeling, including muscularization of the arteries, and a reduction in the typically large vascular compliance of the pulmonary circulation. We used a rat model of monocrotaline (MCT) induced PH to evaluated and compared Captopril (an angiotensin converting enzyme inhibitor with antioxidant capacity) and N-acetylcysteine (NAC, a mucolytic with a large antioxidant capacity) as possible treatments. Twenty-eight days after MCT injection, the rats were sacrificed and heart, blood, and lungs were studied to measure indices such as right ventricular hypertrophy (RVH), hematocrit, pulmonary vascular resistance (PVR), vessel morphology and biomechanics. We implemented microfocal X-ray computed tomography to image the pulmonary arterial tree at intravascular pressures of 30, 21, 12, and 6 mmHg and then used automated vessel detection and measurement algorithms to perform morphological analysis and estimate the distensibility of the arterial tree. The vessel detection and measurement algorithms quickly and effectively mapped and measured the vascular trees at each intravascular pressure. Monocrotaline treatment, and the ensuing PH, resulted in a significantly decreased arterial distensibility, increased PVR, and tended to decrease the length of the main pulmonary trunk. In rats with PH induced by monocrotaline, Captopril treatment significantly increased arterial distensibility and decrease PVR. NAC treatment did not result in an improvement, it did not significantly increase distensibility and resulted in further increase in PVR. Interestingly, NAC tended to increase peripheral vascular density. The results suggest that arterial distensibility may be more important than distal collateral pathways in maintaining PVR at normally low values.
Xie, Xue-Jiao; Tao, Yong-Kang; He, Xiaochen; Roman, Richard J.; Aschner, Judy L.; Chen, Jian-Xiong
Pulmonary arterial hypertension (PAH) is a leading cause of heart failure. Although pulmonary endothelial dysfunction plays a crucial role in the progression of the PAH, the underlying mechanisms are poorly understood. The HIF-α hydroxylase system is a key player in the regulation of vascular remodeling. Knockout of HIF-2α has been reported to cause pulmonary hypertension. The present study examined the role of endothelial cell specific prolyl hydroxylase-2 (PHD2) in the development of PAH and pulmonary vascular remodeling. The PHD2f/f mouse was crossbred with VE-Cadherin-Cre promoter mouse to generate an endothelial specific PHD2 knockout (Cdh5-Cre-PHD2ECKO) mouse. Pulmonary arterial pressure and the size of the right ventricle was significantly elevated in the PHD2ECKO mice relative to the PHD2f/f controls. Knockout of PHD2 in EC was associated with vascular remodeling, as evidenced by an increase in pulmonary arterial media to lumen ratio and number of muscularized arterioles. The pericyte coverage and vascular smooth muscle cells were also significantly increased in the PA. The increase in vascular pericytes was associated with elevated expression of fibroblast specific protein-1 (FSP-1). Moreover, perivascular interstitial fibrosis of pulmonary arteries was significantly increased in the PHD2ECKO mice. Mechanistically, knockout of PHD2 in EC increased the expression of Notch3 and transforming growth factor (TGF-β) in the lung tissue. We conclude that the expression of PHD2 in endothelial cells plays a critical role in preventing pulmonary arterial remodeling in mice. Increased Notch3/TGF-β signaling and excessive pericyte coverage may be contributing to the development of PAH following deletion of endothelial PHD2. PMID:27613846
Pulmonary arterial hypertension associated with bronchopulmonary dysplasia and congenital heart disease in preterm infants. A case report of a preterm infant with recurrent pulmonary hypertension after corrective cardiac surgery and review of the literature.
Muneuchi, Jun; Kuraoka, Ayako; Watanabe, Mamie; Ochiai, Yoshie; Joo, Kunitaka
In preterm infants with congenital heart disease, concomitant bronchopulmonary dysplasia (BPD) is associated with relatively poor clinical outcomes because of the increased pulmonary vascular resistance and adverse effects of inflammation on the damaged lungs, even after surgery. We present herein a 1-year-old female who developed recurrent pulmonary arterial hypertension 6 months after closure of a ventricular septal defect. She was born at 26 weeks of gestation (birth weight, 470 g), and developed BPD requiring oxygen supplementation. Her systemic-to-pulmonary blood flow ratio was 2.1 preoperatively and 1.0 postoperatively, pulmonary arterial pressure was 61/15 (mean 39) mmHg preoperatively and 41/17 (mean 24) mmHg postoperatively, and pulmonary vascular resistance was 4.2 mmHg/L·minute·m(2) preoperatively and 3.6 mmHg/L·minute·m(2) postoperatively. At 1 year of age, echocardiography showed an increase in her estimated right ventricular pressure, indicating worsening pulmonary hypertension. After 3 years of treatment with oxygen supplementation, prostacyclin, and bosentan, her pulmonary arterial pressure improved to the normal range. The pathophysiology of pulmonary arterial hypertension is heterogeneous in preterm infants with congenital heart disease and concomitant BPD. Careful management of these patients is warranted even after corrective cardiac surgery.
Bornak, Arash; Baqai, Atif; Li, Xiaoyi; Rey, Jorge; Tashiro, Jun; Velazquez, Omaida C
Enlarging aneurysms in the thoracic aorta frequently remain asymptomatic. Fistulization of thoracic aortic aneurysms (TAA) to adjacent structures or the presence of a patent ductus arteriosus and TAA may lead to irreversible cardiopulmonary sequelae. This article reports on a large aneurysm of the thoracic aorta with communication to the pulmonary artery causing pulmonary edema and cardiorespiratory failure. The communication was ultimately closed after thoracic endovascular aortic aneurysm repair allowing rapid symptom resolution. Early diagnosis and closure of such communication in the presence of TAA are critical for prevention of permanent cardiopulmonary damage.
Ludwig, J.W.; Verhoeven, L.A.J.; Kersbergen, J.J.; Overtoom, T.T.C.
A comparative study of radionuclide scanning (perfusion studies in all 18 patients and ventilation studies in 9) and digital subtraction angiography (DSA) was performed in 18 patients with suspected pulmonary thromboembolism. In 17 patients good visualization of the arteries was obtained with DSA; 10 of these patients had no pre-existing lung disease, and 7 had chronic obstructive pulmonary disease (COPD). The information provided by DSA in this small group was equal to or better than that of scintigraphy, especially in patients with COPD, and the reliability of DSA was superior to that of the radionuclide scintigraphy. Methods for preventing motion artifacts with DSA are also described.
Ramjee, Vimal; Lewis, Melinda M; Clements, Stephen D
Pulmonary artery sarcomas are exceptionally rare, and they are often misdiagnosed as chronic pulmonary thromboemboli. Early and accurate diagnosis is crucial to the prognosis of patients who have pulmonary artery sarcomas.Herein, we describe the case of a 74-year-old man who presented with dyspnea and was initially thought to have a pulmonary embolus. Anticoagulation with unfractionated heparin was ineffective. Rare angiographic findings during routine cardiac catheterization led to the diagnosis of a high-grade, nonmyogenic, primary pulmonary artery sarcoma. This case illustrates the usefulness of angiographic findings as an adjunct to conventional diagnostic methods in correctly identifying this rare, aggressive malignancy.
Obeso Carillo, Gerardo Andrés; Casais Pampín, Rocío; Legarra Calderón, Juan José; Pradas Montilla, Gonzalo
Primary pulmonary artery sarcoma is an uncommon neoplasm with a grim prognosis. Complete resection is the only treatment that can improve the patient's survival. The role of multimodality treatment is still controversial, although adjuvant chemotherapy possibly could improve outcomes of these patients. Several pulmonary artery reconstructive techniques have been reported in the scientific literature, such as patch reconstruction, end-to-end anastomosis, synthetic prosthesis or biological grafts. In this article, we propose a new surgical option for pulmonary artery reconstruction after radical tumour resection using a self-made stapled bovine pericardial graft conduit in a patient with a mass in the pulmonary trunk and right pulmonary artery. We believe that the use of this technique adds safety and effectiveness, and reduces the surgical time.
Tahara, Masahiro; Shimozono, Saiko; Nitta, Tetsuya; Yamaki, Shigeo
Congestive heart failure is a major cause of early death in patients with trisomy 13 or 18 and congenital heart disease (CHD). Pulmonary artery banding for these patients early in life is preferred to protect the lungs from high pulmonary flow rates and improve survival. We performed open lung biopsies in 11 patients with trisomy 13 or 18 accompanied by CHD and severe pulmonary artery hypertension (PAH) between 2009 and 2011. Two (18.2%) of these 11 patients had medial defects of the small pulmonary arteries. One patient with trisomy 13 and an atrial septal defect developed lung hemorrhage and lung edema at the age of 9 months and died at the age of 13 months. The lumens of the small pulmonary arteries of the other patient with trisomy 18 and a ventricular septal defect became occluded due to the intimal proliferation of fibrous tissues at the age of 2 months. This patient died at the age of 27 months. The deaths of both patients were associated with heart-related factors. Patients with medial defects are vulnerable to intimal proliferation in the small pulmonary arteries. More patients with trisomy 13 or 18 and CHD might have similar pulmonary vascular changes. The small pulmonary arteries of patients with trisomy 13 and 18 should be further analyzed.
Kamalasanan, Anu; Cassidy, Deidre B; Struthers, Allan D; Lipworth, Brian J; Houston, J Graeme
Introduction To compare the reproducibility of pulmonary pulse wave velocity (PWV) techniques, and the effects of age and exercise on these. Methods 10 young healthy volunteers (YHV) and 20 older healthy volunteers (OHV) with no cardiac or lung condition were recruited. High temporal resolution phase contrast sequences were performed through the main pulmonary arteries (MPAs), right pulmonary arteries (RPAs) and left pulmonary arteries (LPAs), while high spatial resolution sequences were obtained through the MPA. YHV underwent 2 MRIs 6 months apart with the sequences repeated during exercise. OHV underwent an MRI scan with on-table repetition. PWV was calculated using the transit time (TT) and flow area techniques (QA). 3 methods for calculating QA PWV were compared. Results PWV did not differ between the two age groups (YHV 2.4±0.3/ms, OHV 2.9±0.2/ms, p=0.1). Using a high temporal resolution sequence through the RPA using the QA accounting for wave reflections yielded consistently better within-scan, interscan, intraobserver and interobserver reproducibility. Exercise did not result in a change in either TT PWV (mean (95% CI) of the differences: −0.42 (−1.2 to 0.4), p=0.24) or QA PWV (mean (95% CI) of the differences: 0.10 (−0.5 to 0.9), p=0.49) despite a significant rise in heart rate (65±2 to 87±3, p<0.0001), blood pressure (113/68 to 130/84, p<0.0001) and cardiac output (5.4±0.4 to 6.7±0.6 L/min, p=0.004). Conclusions QA PWV performed through the RPA using a high temporal resolution sequence accounting for wave reflections yields the most reproducible measurements of pulmonary PWV. PMID:27843548
Kochetkova, Evgenia A; Ugai, Ludmila G; Maistrovskaia, Yuliya V; Nevzorova, Vera A
Osteoporosis is a major comorbidity of cardio-respiratory diseases, but the mechanistic links between pulmonary arterial hypertension and bone remain elusive. The purpose of the stud was to evaluate serum adipokines and endothelin-1 (ET-1) levels in the patients with idiopathic pulmonary arterial hypertension (IPAH) NYHA class III-IV and to determine its associations with bone mineral density (BMD). Pulmonary and hemodynamic parameters, BMD Z-scores at the lumbar spine (LS) and femoral neck (FN), serum leptin, adiponectin, visfatin and endothelin-1 (ET-1), were evaluated in 32 patients with IPAH NYHA class III-IV and 30 healthy volunteers. Leptin, adiponectin and ET-1 were higher in the patients with IPAH than in healthy subjects. Visfatin level showed a tendency to increase compared to that of healthy subjects (p = 0.076). The univariate analysis revealed a positive correlation between BMD Z-scores at both sites and 6-min walk test, and inverse relation with pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP). Adiponectin and visfatin showed positive correlations with PVR (p = 0.009 and p = 0.006). Serum adiponectin, visfatin and leptin were inversely associated with Z-scores. After adjusting for BMI and FMI, such associations persisted between visfatin and adiponectin levels and Z-scores at both sites. ET-1 related to mPAP, cardiac index and PVR. Negative correlation was observed between ET-1 and FN BMD (p = 0.01). Positive correlations have revealed between ET-1 and adiponectin (p = 0.02), visfatin (p = 0.004) in IPAH patients. These results provide further evidence that adipokine and endothelial dysregulation may cause not only a decrease in BMD, but also an increase in hemodynamic disorders of IPAH.
We sought to summarize major recent studies in the field of dietary sodium intake and arterial blood pressure, and discuss the following trials. INTERSALT: Sodium intake correlates with the rise in blood pressure with age, but not with the prevalence of hypertension. The population study identified a minimal impact of sodium intake on blood pressure (0.9 mm Hg/10 mmol difference in salt intake). DASH: This diet induced significant reductions in blood pressure compared with the control diet. Further decreases were observed with DASH and a 50 mmol/day sodium intake. VANGUARD: Blood pressure was inversely related to urinary potassium, calcium and magnesium but not to sodium excretion. TONE: Cardiovascular events were highest in the usual care group (83%) and lowest in the sodium reduction-plus-weight loss group (56%). META-ANALYSIS: A systematic review of 11 long-term controlled randomized trials reported a small decrease (1.1 mm Hg) in median systolic but not diastolic blood pressure with a reduced dietary sodium intake. In conclusion, (1) sodium restriction in hypertensive patients reduces blood pressure, and (2) the long-term impact of reduced salt intake on blood pressure, mortality, and morbidity remains to be defined.
Hu, Bangchuan; Gong, Shijin; Yu, Yihua; Dai, Haiwen
Arterial stiffness contributes to heart failure and is decreased by angiotensin receptor blockers (ARBs). This cross-sectional study aimed to assess associations of lung function and ARB with arterial stiffness in patients with chronic heart failure. 354 outpatients (168 males; 186 females; 68.2 ± 7.2 years old) with chronic heart failure were evaluated. Lung function parameters, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and FEV1 to FVC ratio (FEV1/FVC), were assessed. The cardio-ankle vascular index (CAVI) was used to estimate arterial stiffness. Unadjusted correlation analyses revealed a positive association of CAVI with ARB but not ACEI, and a negative correlation with FEV1 (r = −0.2987, p < 0.0001). Multiple stepwise regression analyses showed that ARB and FEV1 (p < 0.0001) were independent predicting factors for CAVI. These findings suggest that reduced pulmonary function is associated with increased CAVI. Pulmonary function protection could be used to improve the prognosis in heart failure, but additional studies are necessary. PMID:28097138
Causes of pulmonary arterial hypertension (PAH) are similar in adults and children. The main difference is that PAH secondary to congenital heart diseases, is the predominant cause in pediatric patients. Persistent pulmonary hypertension of the newborn shows completely different clinical course and pathophysiological mechanisms. It is usually seen in full term babies with a high morbidity and mortality rate. Improved prognosis has been reported with inhaled nitric oxide (NO) and extracorporeal membrane oxygenation therapy in babies hospitalized in well equipped and experienced newborn centers. Primary pulmonary hypertension and familial pulmonary hypertension are rare in pediatric age group because the diagnosis is initially made in adolescence. The incidence of PAH secondary to congenital heart disease is estimated as 1.6 - 12.5 case/million/year. Eisenmenger syndrome is diagnosed in 1% of patients with PAH. Patients with left to right shunts are the main group who develop pulmonary vascular disease if not treated in the early infancy. Some cyanotic congenital heart diseases are also the causes of PAH. The best treatment of patients at risk for the development of pulmonary vascular disease is prevention by early surgical elimination of defects or repairing the anatomy. Treatment options with vasodilating agents like NO, prostaglandin analogs, phosphodiesterase -5 inhibitors and endothelin receptor antagonists are used to improve survival and quality of life. Heart lung or bilateral lung transplantation is the only surgical option for many of these patients. Results of national and international registries will bring valuable epidemiological and prognostic perspectives to pediatric PAH.
Gopal, Deepa M.; Doldt, Bryan; Finch, Kim; Simms, Robert W.; Farber, Harrison W.; Gokce, Noyan
Objectives Scleroderma (SSc)-associated pulmonary arterial hypertension (PAH) is a major cause of mortality in SSc patients and represents an important diagnostic and therapeutic target. Our aims were to evaluate the relationship between echocardiogram-derived right heart hemodynamics and “gold standard” right heart catheterization (RHC) measurements in a scleroderma population, and investigate whether this relationship is modified by a subset of pulmonary hypertension. Methods We performed right heart catheterization and echocardiography on the same day, with pulmonary function testing in 21 consecutive subjects (age 57 ± 10, 81% female) with scleroderma and pre-capillary pulmonary hypertension. Results RHC measures including PA systolic and mean pressure, and pulmonary vascular resistance (PVR) correlated strongly with echo-derived data. RHC-derived pulmonary vascular resistance was negatively associated with RV systolic performance as measured by tricuspid annular plane systolic excursion (TAPSE, rho −0.70, p < 0.001), tissue Doppler tricuspid s’ velocity (rho −0.68, p 0.002), and RV fractional area change (rho −0.78, p < 0.001). Correlations with TAPSE and s’ velocity were strengthened when FVC%/DLCO% ≥ 1.6 used to identify pure PAH phenotypes in SSc. Bland-Altman analyses demonstrated strong agreement between RHC and echo-derived hemodynamic measures. Conclusions Our findings suggest that echocardiography may play a clinical role in identifying pulmonary hypertension and RV dysfunction non-invasively, particularly in a subset of SSc patients stratified by pulmonary function testing. This method may establish specific disease phenotypes with differential cardiovascular impact and prove useful as a marker of disease progression/risk stratification in SSC patients that warrants further investigation in larger cohorts. PMID:24515598
Mukerjee, D; St, G; Coleiro, B; Knight, C; Denton, C; Davar, J; Black, C; Coghlan, J
Objective: To determine the prevalence of systemic sclerosis associated pulmonary arterial hypertension (SScPAH), evaluate outcome, and identify predictors of mortality in a large patient cohort. Methods: A prospective four year follow up study of 794 patients (722 from our own unit and 72 referrals). All patients screened for PAH using a combination of echocardiography, lung function testing, and clinical assessment. Patients with suspected raised pulmonary artery systolic pressures of >35 mm Hg, carbon monoxide transfer factor (TLCO) <50% predicted, or a precipitous fall in TLCO >20% over a one year period with no pulmonary fibrosis, and patients with SSc with breathlessness with no pulmonary fibrosis found were investigated with right heart catheterisation. All patients with SScPAH were treated in accordance with current best practice. Results: The prevalence of PAH was 12% (89/722) by right heart catheter. The survival was 81%, 63%, and 56% at 1, 2, and 3 years from the diagnosis (in 89 patients from our own cohort and 59/72 referrals). Haemodynamic indices of right ventricular failure—raised mRAP (hazard ratio 21), raised mPAP (hazard ratio 20), and low CI (hazard ratio 11) predicted an adverse outcome There was no significant difference in survival between patients with SScPAH with (n=40) and without (n=108) pulmonary fibrosis (p=0.3). Conclusions: The prevalence of SScPAH in this cohort was similar to that of other catheter based studies and lower than that of previous echo based studies. The 148 patients with SScPAH actively treated had comparable outcomes to those of the cohorts with primary pulmonary hypertension. A high mRAP was the strongest haemodynamic predictor of mortality. To improve prognosis, future treatments need to be implemented at an earlier disease stage to prevent right ventricular decompensation. PMID:14583573
Hsu, Chih-Hsin; Ho, Wan-Jing; Huang, Wei-Chun; Chiu, Yu-Wei; Hsu, Tsu-Shiu; Kuo, Ping-Hung; Hsu, Hsao-Hsun; Chang, Jia-Kan; Cheng, Chin-Chang; Lai, Chao-Lun; Liang, Kae-Woei; Lin, Shoa-Lin; Sung, Hsao-Hsun; Tsai, Wei-Chuan; Weng, Ken-Pen; Hsieh, Kai-Sheng; Yin, Wei-Hsian; Lin, Shing-Jong; Wang, Kuo-Yang
Pulmonary hypertension (PH) is a hemodynamic and pathophysiologic condition, defined as a mean pulmonary arterial pressure exceeding 25 mmHg at rest. According to the recent classifications, it is grouped into pulmonary arterial hypertension (PAH), heart-related, lung-related, thromboembolic, and miscellaneous PH. In the past two decades, tremendous advances have occurred in the field of PH. These include (1) development of clinical diagnostic algorithm and a monitoring strategy dedicated to PAH, (2) defining strong rationales for screening at-risk populations, (3) advent of pulmonary specific drugs which makes PAH manageable, (4) recognition of needs of having proper strategy of combining existing pulmonary specific drugs, and/or potential novel drugs, (5) pursuit of clinical trials with optimal surrogate endpoints and study durations, (6) recognition of critical roles of PH/right ventricular function, as well as interdependence of ventricles in different conditions, especially those with various phenotypes of heart failure, and (7) for rare diseases, putting equal importance on carefully designed observation studies, various registries, etc., besides double blind randomized studies. In addition, ongoing basic and clinical research has led to further understanding of relevant physiology, pathophysiology, epidemiology and genetics of PH/PAH. This guidelines from the working group of Pulmonary Hypertension of the Taiwan Society of Cardiology is to provide updated guidelines based on the most recent international guidelines as well as Taiwan’s domestic research on PH. The guidelines are mainly for the management of PAH (Group 1) ; however the majority of content can be helpful for managing other types of PH. PMID:27122817
Choi, Eui-Young; Yoon, Young-Won; Kwon, Hyuck Moon; Kim, Dongsoo; Park, Byung-Eun; Hong, Yoo-Sun; Koo, Ja-Seung; Kim, Tae-Hoon; Kim, Hyun-Seung
Pulmonary artery intimal sarcoma is a rare highly lethal disease, with additional retrograde extension to pulmonic valve and right ventricle being an extremely rare condition. It is frequently mistaken for pulmonary thromboembolism. We report a case of 64-year-old woman with progressive dyspnea initially suspected and treated for pulmonary thromboembolism. Her helical chest CT scan with 3 dimensional (3D) reconstruction combined with echocardiography revealed a compacting main pulmonary artery mass extending to the right ventricular outflow tract and the right pulmonary artery. After excision of the mass, the patient's condition improved dramatically, and the pathologic findings revealed pulmonary intimal sarcoma. This report emphasizes that helical chest CT with 3D reconstruction can be an important tool to differentiate the characteristics of pulmonary artery lesions, such as intimal sarcoma and thromboembolism.
Schuuring, Mark J.; Bonta, Peter I.; van Vugt, Michele; Smithuis, Frank; van Delden, Otto M.; Annema, Jouke T.; Stijnis, Kees
A 44-year-old woman with a history of pulmonary embolism and abdominal echinococcosis complained of sudden thoracic pain and shortness of breath. A D-dimer of 77.5 mg/l (reference ≤0.5 mg/l) was found. Chest CT scan revealed obstruction of the right lower and middle lobe pulmonary artery (PA). Anticoagulation therapy was initiated for the presumed diagnosis of recurrent pulmonary embolism. However, due to persistent symptoms of dyspnea, follow-up CT angiography of the chest was performed 3 months later. A persistent PA obstruction was found and the presumed diagnosis of embolism was questioned. Subsequently, endobronchial ultrasound (EBUS) imaging was performed to support an alternative diagnosis. EBUS imaging showed an inhomogeneous, sharply demarcated, intravascular lesion with round hypoechoic areas compatible with cysts. The diagnosis of embolism was rejected and treatment with albendazole was initiated for pulmonary echinococcosis. Echinococcosis is a parasitic disease and cystic spread in the PA is exceptional. The patient has remained stable for more than 4 years. In case of disease progression, including progressive PA obstruction or life-threatening hemoptysis, surgical resection will be considered. PMID:27760423
Al-Dairy, Alwaleed; Rezaei, Yousef; Pouraliakbar, Hamidreza; Mahdavi, Mohammad; Bayati, Parvin
Anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is a very rare congenital heart defect. Herein, we describe three cases of ARCAPA in an 8 months old, 18 months old, and 4 year old child. Two cases were incidentally diagnosed using a computed tomographic angiograph, and the other was incidentally diagnosed using a coronary angiograph. These cases underwent a reimplantation technique on diagnosis and resulting in positive clinical outcomes during the follow-up period which was a mean of 1.5 years. PMID:28154604
Silverman, Norman H
In the 1970s, diagnosing anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) was often uncertain using imaging alone; however, with the advances in high-frequency transducers, advanced image processing, and other ultrasound modalities such as Doppler colour flow imaging, tissue Doppler imaging, and speckle tracking to asses regional wall motion abnormalities, modern echocardiography now permits accurate diagnosis of ALCAPA with greater certainty. Although many consider ultrasound to be the only imaging test necessary if there is a question as to the diagnosis, other imaging modalities such as MRI, CT, and cardiac catheterisation with angiography remain valuable complementary tests, especially in older patients.
Pugh, Meredith E; Hemnes, Anna R
Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature, ultimately resulting in right heart failure and death. This disease is strongly predominant in females, although little is known regarding how sex influences disease development. Recent developments highlighting the importance of estrogen metabolites in both animal models and human disease have substantially increased our understanding of PAH in women. This review will focus on general knowledge of PAH, translational and basic science data regarding sex hormones in the pulmonary vasculature and on clinical issues that are particular to women with PAH. Future directions for study include the influence of sex hormones on right ventricular responses, improving the understanding of the influence of estrogen exposure in human disease and the study of dehydroepiandrosterone in basic science and human disease. PMID:20187732
Hussain, Azar; Bennett, Robert T; Chaudhry, Mubarak A; Qadri, Syed S; Cowen, Mike; Morice, Alyn H; Loubani, Mahmoud
AIM To determine the optimum resting tension (ORT) for in vitro human pulmonary artery (PA) ring preparations. METHODS Pulmonary arteries were dissected from disease free sections of the resected lung in the operating theatre and tissue samples were directly sent to the laboratory in Krebs-Henseleit solution (Krebs). The pulmonary arteries were then cut into 2 mm long rings. PA rings were mounted in 25 mL organ baths or 8 mL myograph chambers containing Krebs compound (37 °C, bubbled with 21% O2: 5% CO2) to measure changes in isometric tension. The resting tension was set at 1-gram force (gf) with vessels being left static to equilibrate for duration of one hour. Baseline contractile reactions to 40 mmol/L KCl were obtained from a resting tension of 1 gf. Contractile reactions to 40 mmol/L KCl were then obtained from stepwise increases in resting tension (1.2, 1.4, 1.6, 1.8 and 2.0 gf). RESULTS Twenty PA rings of internal diameter between 2-4 mm were prepared from 4 patients. In human PA rings incrementing the tension during rest stance by 0.6 gf, up to 1.6 gf significantly augmented the 40 mmol/L KCl stimulated tension. Further enhancement of active tension by 0.4 gf, up to 2.0 gf mitigate the 40 mmol/L KCl stimulated reaction. Both Myograph and the organ bath demonstrated identical conclusions, supporting that the radial optimal resting tension for human PA ring was 1.61 g. CONCLUSION The radial optimal resting tension in our experiment is 1.61 gf (15.78 mN) for human PA rings. PMID:27721938
Xiao, Qingyang; Guo, Xiaoquan; Zhuang, Yu; Zhang, Caiying; Wang, Tiancheng; Lin, Huayuan; Song, Yalu; Hu, Guoliang; Liu, Ping
Background Pulmonary arterial hypertension, also known as Ascites syndrome (AS), remains a clinically challenging disease with a large impact on both humans and broiler chickens. Pulmonary arterial remodeling presents a key step in the development of AS. The precise molecular mechanism of pulmonary artery remodeling regulating AS progression remains unclear. Methodology/Principal Findings We obtained pulmonary arteries from two positive AS and two normal broilers for RNA sequencing (RNA-seq) analysis and pathological observation. RNA-seq analysis revealed a total of 895 significantly differentially expressed genes (DEGs) with 437 up-regulated and 458 down-regulated genes, which were significantly enriched to 12 GO (Gene Ontology) terms and 4 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways (Padj<0.05) regulating pulmonary artery remodeling and consequently occurrence of AS. These GO terms and pathways include ribosome, Jak-STAT and NOD-like receptor signaling pathways which regulate pulmonary artery remodeling through vascular smooth cell proliferation, inflammation and vascular smooth cell proliferation together. Some notable DEGs within these pathways included downregulation of genes like RPL 5, 7, 8, 9, 14; upregulation of genes such as IL-6, K60, STAT3, STAT5 Pim1 and SOCS3; IKKα, IkB, P38, five cytokines IL-6, IL8, IL-1β, IL-18, and MIP-1β. Six important regulators of pulmonary artery vascular remodeling and construction like CYP1B1, ALDH7A1, MYLK, CAMK4, BMP7 and INOS were upregulated in the pulmonary artery of AS broilers. The pathology results showed that the pulmonary artery had remodeled and become thicker in the disease group. Conclusions/Significance Our present data suggested some specific components of the complex molecular circuitry regulating pulmonary arterial remodeling underlying AS progression in broilers. We revealed some valuable candidate genes and pathways that involved in pulmonary artery remodeling further contributing to the AS
Huang, Jianfei; Zhou, Xiaoyu; Xie, Hao; Zhu, Qilin; Huang, Minjie
Acute pulmonary thromboembolism (PTE) refers to the obstruction of thrombus in pulmonary artery or its branches. Recent studies have suggested that PTE-induced endothelium injury is the major physiological consequence of PTE. And it is reasonal to use PTE-induced endothelium injury to stratify disease severity. According to the massive morphologic and histologic findings, rabbit models could be applied to closely mimic the human PE. Genomewide gene expression profiling has not been attempted in PTE. In this study, we determined the accuracy of rabbit autologous thrombus PTE model for human PTE disease, then we applied gene expression array to identify gene expression changes in pulmonary arteries under PTE to identify potential molecular biomarkers and signaling pathways for PTE. We detected 1343 genes were upregulated and 923 genes were downregulated in PTE rabbits. The expression of several genes (IL-8, TNF-α, and CXCL5) with functional importance were further confirmed in transcript and protein levels. The most significantly differentially regulated genes were related to inflammation, immune disease, pulmonary disease, and cardiovascular diseases. Totally 87 genes were up-regulated in the inflammatory genes. We conclude that gene expression profiling in rabbit PTE model could extend the understanding of PTE pathogenesis at the molecular level. Our study provides the fundamental framework for future clinical research on human PTE, including identification of potential biomarkers for prognosis or therapeutic targets for PTE. PMID:27798647
Tang, Zhiyuan; Wang, Xudong; Huang, Jianfei; Zhou, Xiaoyu; Xie, Hao; Zhu, Qilin; Huang, Minjie; Ni, Songshi
Acute pulmonary thromboembolism (PTE) refers to the obstruction of thrombus in pulmonary artery or its branches. Recent studies have suggested that PTE-induced endothelium injury is the major physiological consequence of PTE. And it is reasonal to use PTE-induced endothelium injury to stratify disease severity. According to the massive morphologic and histologic findings, rabbit models could be applied to closely mimic the human PE. Genomewide gene expression profiling has not been attempted in PTE. In this study, we determined the accuracy of rabbit autologous thrombus PTE model for human PTE disease, then we applied gene expression array to identify gene expression changes in pulmonary arteries under PTE to identify potential molecular biomarkers and signaling pathways for PTE. We detected 1343 genes were upregulated and 923 genes were downregulated in PTE rabbits. The expression of several genes (IL-8, TNF-α, and CXCL5) with functional importance were further confirmed in transcript and protein levels. The most significantly differentially regulated genes were related to inflammation, immune disease, pulmonary disease, and cardiovascular diseases. Totally 87 genes were up-regulated in the inflammatory genes. We conclude that gene expression profiling in rabbit PTE model could extend the understanding of PTE pathogenesis at the molecular level. Our study provides the fundamental framework for future clinical research on human PTE, including identification of potential biomarkers for prognosis or therapeutic targets for PTE.
Geraci, Mark W.; Bull, Todd M.; Tuder, Rubin M.
Synopsis Pulmonary arterial hypertension remains a vexing clinical disease with no cure. Despite advances and the discovery of a gene (BMPR2) associated with many of the hereditary forms of the disease, and some cases not previously known to be inherited, the reasons for mutations in this gene as a cause remain somewhat elusive. Clearly, a complex interplay exists between genetic alterations, environmental exposures (including infections) and disease development. This article addresses the advances in the genetics of PAH, including the identification of genetic etiologies and modulators, and the role of genetics in predicting disease progression and targeting therapeutics. PMID:19945066
Rubin, Lewis J; Simonneau, Gerald; Badesch, David; Galiè, Nazzareno; Humbert, Marc; Keogh, Anne; Massaro, Joseph; Matucci Cerinic, Marco; Sitbon, Olivier; Kymes, Steven
A growing body of published evidence exists on the risk factors for disease progression in pulmonary arterial hypertension (PAH). The Scientific Steering Committee for the Study of Risk in PAH was established to bring together leading clinical and statistical experts in PAH and risk modelling, for the purpose of advancing the understanding of the risk of development and progression of PAH. Herein, we discuss the impact of this information on three key areas: 1) clinical decision-making; 2) policy and reimbursement; and 3) future trials and research.
Nappi, Francesco; Carotenuto, Angelo Rosario; Di Vito, Donato; Spadaccio, Cristiano; Acar, Cristophe; Fraldi, Massimiliano
Ross operation, i.e., the use of autologous pulmonary artery to replace diseased aortic valve, has been recently at the center of a vivid debate regarding its unjust underuse in the surgical practice. Keystone of the procedure regards the use of an autologous biologically available graft which would preserve the anticoagulative and tissue homeostatic functions normally exerted by the native leaflets and would harmoniously integrate in the vascular system, allowing for progressive somatic growth of aortic structures. With this respect, recently, some of the authors have successfully pioneered a large animal model of transposition of pulmonary artery in systemic pressure load in order to reproduce the clinical scenario in which this procedure might be applied and allow for the development and testing of different devices or techniques to improve the pulmonary autograft (PA) performance, by testing a bioresorbable mesh for PA reinforcement. In the present work, to support and supplement the in vivo animal experimentation, a mathematical model is developed in order to simulate the biomechanical changes in pulmonary artery subjected to systemic pressure load and reinforced with a combination of resorbable and auxetic synthetic materials. The positive biological effects on vessel wall remodeling, the regional somatic growth phenomena and prevention of dilatative degeneration have been analyzed. The theoretical outcomes show that a virtuous biomechanical cooperation between biological and synthetic materials takes place, stress-shielding guiding the physiological arterialization of vessel walls, consequently determining the overall success of the autograft system.
Jernigan, Nikki L; Resta, Thomas C
The pulmonary circulation is a low-pressure, low-resistance vascular bed with little to no resting tone under normal conditions. An increase in the [Ca(2+) ]i in PASMCs is an important determinant of contraction, migration, and proliferation. Both Ca(2+) influx through plasma membrane Ca(2+) channels and Ca(2+) release from the SR contribute to a rise in [Ca(2+) ]i . Additionally important in the pulmonary circulation are several kinase-mediated signaling pathways that act to increase the sensitivity of the contractile apparatus to [Ca(2+) ]i . Similarly, cytoskeletal processes resulting in dynamic remodeling of the actin cytoskeleton can further contribute to contractility in the pulmonary circulation. In addition to endocrine, paracrine, and autocrine factors, alveolar hypoxia is an important stimulus for pulmonary vasoconstriction. However, prolonged hypoxia is a critical pathological stimulus associated with the development of pulmonary hypertension and cor pulmonale. In this review, we will discuss recent advances in our understanding of how Ca(2+) homeostasis and sensitization regulate PASMC contractility under both physiological and pathophysiological conditions.
Pulmonary hypertension (PAH) is abnormally high blood pressure in the arteries of the lungs. With PAH, the right side ... Chin K, Channick RN. Pulmonary hypertension. In: Broaddus VC, Mason ... Textbook of Respiratory Medicine . 6th ed. Philadelphia, PA: ...
Panfeng, Xu; Zheying, Zhang; Jie, Wang; Jianying, Zhou; Xiaodong, Teng
Pulmonary artery sarcoma is a rare tumor of the cardiovascular system. We reported a case of primary pulmonary artery sarcoma. In this case, the patient was misdiagnosed with tuberculosis for nearly 1 year and diagnosed by contrast-enhanced computed tomography and histopathologic examination at last.
Al Amri, Salem Mohammad; Banjar, Ahmad Hassan; Cheema, Ahsan Iqbal
We report a case of an acute episode of massive hemoptysis in a diagnosed patient of Behcet's disease, managed conservatively, using angio-guided vascular plug and coils for occluding the multiple bilateral pulmonary artery aneurysms with thoracic surgery backup. The episode of massive hemoptysis was caused by ruptured Pulmonary Artery Aneurysms (PAA).
Ozbek, Cengiz; Emrecan, Bilgin; Calli, Aylin Orgen; Gurbuz, Ali
We describe the case of a 42-year-old man who presented with dyspnea on exertion and a history of anticoagulation therapy for what was thought to be pulmonary arterial thromboembolism. He underwent surgery for obstruction of the right ventricular outflow tract. This is a very rare case of an intimal sarcoma of the pulmonary artery, which we confirmed by pathologic studies.
Kuo, H.-Cg; Ko, Sheung-Fat; Wu, Yu-Tsun; Huang, Chien-Fu; Chien, Shao-Ju; Tiao, Mao-Meng; Liang, Chi-Di
We report an unusual case of simultaneous obstruction of the left pulmonary artery and descending thoracic aorta after Gianturco coil occlusion in a 15-month-old boy. The diagnosis was made by echocardiography and cardiac angiography. At surgery, thrombi coating on the protruded parts of the Gianturco coil in the pulmonary artery and aorta were found.
Kherbeck, Nada; Tamby, Mathieu C; Bussone, Guillaume; Dib, Hanadi; Perros, Frederic; Humbert, Marc; Mouthon, Luc
Pulmonary arterial hypertension is characterized by a remodeling of pulmonary arteries with endothelial cell, fibroblast, and vascular smooth muscle cell activation and proliferation. Since pulmonary arterial hypertension occurs frequently in autoimmune conditions such as systemic sclerosis, inflammation and autoimmunity have been suspected to play a critical role in both idiopathic pulmonary arterial hypertension and systemic sclerosis-associated pulmonary arterial hypertension. High levels of pro-inflammatory cytokines such as interleukin-1 and interleukin-6, platelet-derived growth factor, or macrophage inflammatory protein 1 have been found in lung samples of patients with pulmonary arterial hypertension, along with inflammatory cell infiltrates mainly composed of macrophages and dendritic cells, T and B lymphocytes. In addition, circulating autoantibodies are found in the peripheral blood of patients. Thus, autoimmunity and inflammation probably play a role in the development of pulmonary arterial hypertension. In this setting, it would be important to set-up new experimental models of pulmonary arterial hypertension, in order to define novel therapeutics that specifically target immune disturbances in this devastating condition.
Li, Juan; Zhao, Qian; He, Lirong; Zhuang, Xiaoqing; Li, Fang
A 59-year-old man presented cough, chest pain, and shortness of breath for 2 weeks and fever for 4 days. A contrast chest CT revealed a large right pulmonary artery filling defect, suggestive of pulmonary embolism that failed to respond to anticoagulation therapy. FDG PET/CT was performed to evaluate possible malignancy, which revealed intense activity in the right main pulmonary artery without any extrathoracic abnormality. The ratio of the SUVmax of this lesion to the liver was significantly increased in the delayed PET images. The pathological examination demonstrated primary pulmonary artery sarcoma.
Gaumann, A; Petrow, P; Mentzel, T; Mayer, E; Dahm, M; Otto, M; Kirkpatrick, C J; Kriegsmann, J
Primary tumors of the great vessels (aorta, pulmonal artery, and inferior vena cava) are rare and represent in most cases vascular leiomyosarcomas. Furthermore, there also exists a group of sarcomas arising from the intima, known as intimal sarcomas, associated with early metastasis and a very poor prognosis. Osteopontin (OPN) is an extracellular matrix protein that binds to alphav integrins, thereby promoting cell attachment, chemotaxis, and signal transduction. The reported association of OPN with malignancy and metastasis prompted us to examine the expression of this protein in seven sarcomas of the pulmonary artery. Strong OPN-specific staining could be detected in tumor cells and the adjacent extracellular matrix. Using a double labeling procedure, proliferating cells showed a strong positive reaction with antibodies against OPN. In addition, this protein could be demonstrated in the cytoplasm of macrophages. CD44, a putative receptor of OPN, was expressed on the cellular surface of tumor-associated lymphocytes. The expression of OPN in macrophages and tumor cells indicates that this molecule could possibly mediate cellular adhesion of both cell types in pulmonary sarcomas. The detection in the extracellular matrix shows that OPN is actively secreted and may interact with the corresponding receptor, CD44, on the surface of lymphocytes. Although the function of OPN is not yet fully understood, our data indicate that strong expression of this molecule in poorly differentiated sarcomas could play a role in the progression of malignancy and metastasis as described previously for carcinomas.
Varsos, Georgios V; Budohoski, Karol P; Czosnyka, Marek; Kolias, Angelos G; Nasr, Nathalie; Donnelly, Joseph; Liu, Xiuyun; Kim, Dong-Joo; Hutchinson, Peter J; Kirkpatrick, Peter J; Varsos, Vassilis G; Smielewski, Peter
The effect of cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (SAH) on critical closing pressure (CrCP) has not been fully delineated. Using cerebral impedance methodology, we sought to assess the behavior of CrCP during CVS. As CrCP expresses the sum of intracranial pressure (ICP) and vascular wall tension, we also explored its role in reflecting changes in vascular tone occurring in small vessels distal to spasm. This retrospective analysis was performed using recordings from 52 patients, diagnosed with CVS through transcranial Doppler measurements. Critical closing pressure was calculated noninvasively using arterial blood pressure and blood flow velocity. Outcome was assessed at both discharge and 3 months after ictus with the Glasgow Outcome Scale. The onset of CVS caused significant decreases in CrCP (P=0.025), without any observed significant changes in ICP (P=0.134). Vasospasm induced asymmetry, with CrCP ipsilateral to CVS becoming significantly lower than contralateral (P=0.025). Unfavorable outcomes were associated with a significantly lower CrCP after the onset of CVS (discharge: P=0.014; 3 months after SAH: P=0.020). Critical closing pressure is reduced in the presence of CVS in both temporal and spatial assessments. As ICP remained unchanged during CVS, reduced CrCP most probably reflects a lower wall tension in dilated small vessels distal to spasm. PMID:25465041
Hassine, Elyès; Bousnina, Sophia; Marniche, Kamel; Fennira, Hammouda; Ben Khelil, Jalila; Ben Mustapha, Mohamed Ali; Megdiche, Mohamed Lamine; Chabbou, Abdellatif
Pulmonary involvement in Behçet's disease is an uncommon condition (12%). Thromboembolism of the superior vena cava and/or other mediastinal veins, aneurysms of the aorta and pulmonary arteries are the main vascular manifestations in addition to pulmonary infarct and intrathoracic hemorrhage. Despite their scarcity, respiratory symptoms may be life-threatening. The aim of this study was to assess the contribution of thoracic imaging for one of the most serious aspects of the disease: pulmonary artery aneurysm. We report five patients with pulmonary artery aneurysms (mean age: 39.5 years). Hemoptysia revealed Behçet's disease in three. Initially explored by conventional radiography, computed tomography and angiography, pulmonary artery aneurysms are currently investigated well with helicoidal computed tomography, digital angiography, magnetic resonance imaging (MRI) and angio-MRI. These imaging techniques provide helpful information for the diagnosis of Behçet's disease.
Portillo-Sanchez, José; Hessein-Abdou, Yasser; Puga-Alcalde, Eugenio; Perez-Martinez, Maria Angeles; Del Carmen Jimenez-Meneses, Maria; Camacho-Pedrero, Agustín; Valdepeñas-Herrero, Luís Ruíz
Primary pulmonary artery sarcoma is a rare tumor that is highly fatal. It can be misdiagnosed as acute or chronic pulmonary thromboembolic disease. Herein, we report the case of a 22-year-old woman with a preoperative diagnosis of pulmonary embolism and superior vena caval thrombosis. Intraoperatively, an extensive sarcoma was seen to extend retrograde from the pulmonary artery, past the right ventricle and right atrium, and into the superior vena cava. Surgical resection of the tumor and reconstruction of the central pulmonary arteries, followed by adjuvant chemotherapy, relieved the clinical symptoms. The patient remained free of cancer at 14 months postoperatively. We believe that this is the 1st report of a primary pulmonary artery sarcoma that extended retrograde into the superior vena cava.
Ishimaru, Kazuhiko; Araki, Kanta; Nakamura, Tsuneyuki; Sawa, Yoshiki
A 2-month-old patient with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) underwent an alternative repair involving coronary transfer with the bay window technique because of the very short left main coronary trunk. This procedure is a clinically relevant and feasible technique for ALCAPA with such a delicate coronary artery anomaly. PMID:27656197
Marrone, Chiara; Santoro, Giuseppe; Palladino, Maria Teresa; Caianiello, Giuseppe; Russo, Maria Giovanna; Calabrò, Raffaele
A 2 month-old infant with severe congestive heart failure due to unrestrictive ventricular septal defect and absence of the left pulmonary artery was submitted to a hybrid transcatheter-surgical palliation consisting in percutaneous re-canalization of the occluded arterial duct-left pulmonary artery complex and surgical banding of the right pulmonary artery. The post-operative course was uneventful and the baby was discharged in a few days under mild anti-congestive therapy. This hybrid approach was highly effective in stabilizing this critical infant in view of a later and safer surgical repair.
Rol, Nina; Timmer, Esther M; Faes, Theo J C; Noordegraaf, Anton Vonk; Grünberg, Katrien; Bogaard, Harm-Jan; Westerhof, Nico
In idiopathic pulmonary arterial hypertension (PAH), increased pulmonary vascular resistance is associated with structural narrowing of small (resistance) vessels and increased vascular tone. Current information on pulmonary vascular remodeling is mostly limited to averaged increases in wall thickness, but information on number of vessels affected and internal diameter decreases for vessels of different sizes is limited. Our aim was to quantify numbers of affected vessels and their internal diameter decrease for differently sized vessels in PAH in comparison with non-PAH patients. Internal and external diameters of transversally cut vessels were measured in five control subjects and six PAH patients. Resistance vessels were classified in Strahler orders, internal diameters 13 μm (order 1) to 500 μm (order 8). The number fraction, that is, percentage of affected vessels, and the internal diameter fraction, that is, percentage diameter of normal diameter, were calculated. In PAH, not all resistance vessels are affected. The number fraction is about 30%, that is, 70% of vessels have diameters not different from vessels of control subjects. Within each order, the decrease in diameter of affected vessels is variable with an averaged diameter fraction of 50-70%. Narrowing of resistance vessels is heterogeneous: not all vessels are narrowed, and the decrease in internal diameters, even within a single order, vary largely. This heterogeneous narrowing alone cannot explain the large resistance increase in PAH We suggest that rarefaction could be an important contributor to the hemodynamic changes.
Al-Naamani, Nadine; Palevsky, Harold I.; Lederer, David J.; Horn, Evelyn M.; Mathai, Stephen C.; Roberts, Kari E.; Tracy, Russell P.; Hassoun, Paul M.; Girgis, Reda E.; Shimbo, Daichi; Post, Wendy S.
Rationale: Pulmonary arterial hypertension (PAH) is a rare progressive disease of the pulmonary vasculature that is characterized by endothelial dysfunction, inflammation, and right ventricular dysfunction. Objectives: The main objective was to determine whether endothelial, inflammatory, and cardiac biomarkers would be associated with the World Health Organization functional assessment and survival in patients with PAH. Methods: We performed a retrospective cohort study of patients with PAH enrolled in the Randomized Clinical Trial of Aspirin and Simvastatin for Pulmonary Arterial Hypertension (ASA-STAT). Biomarkers (N-terminal fragment of pro-BNP [NT-pro-BNP], von Willebrand factor [vWF], soluble P selectin, C-reactive protein, total and high-density lipoprotein cholesterol, triglycerides, tumor necrosis factor, IL-6, β-thromboglobulin, and thromboxane B2) were measured at baseline. Patients from the study were followed until lung transplantation, death, or August 1, 2013. Ordinal logistic regression and Cox regression analyses were performed. Measurements and Main Results: Sixty-five patients with PAH were enrolled. The mean age was 51 years, and 86% were women. Higher vWF activity, lower high-density lipoprotein cholesterol, and higher thromboxane B2 levels were associated with worse World Health Organization functional class after adjustment for age, sex, and etiology of PAH. Higher NT-pro-BNP levels, lower vWF activity, and lower total cholesterol were associated with an increased risk of death or lung transplant after adjustment for age, sex, etiology of PAH, and 6-minute-walk distance. Conclusions: In patients with PAH, lower vWF activity and cholesterol levels and higher NT-pro-BNP levels at baseline were associated with an increased risk of death or transplantation. Clinical trial registered with www.clinicaltrials.gov (NCT00384865). PMID:26501464
Miranda, Carlos D; Kenny, Damien
We report our experience with stenting a right ductus arteriosus in a neonate with ductal origin of the right pulmonary artery (PA), who subsequently developed severe pulmonary hypertension in the left PA requiring decompression of the right ventricle with stenting of the left ductus. © 2015 Wiley Periodicals, Inc.
Flores, Saul; Daily, Joshua; Pratap, Jayant Nick; Cash, Michelle C; Hirsch, Russel
We describe the course and management of a 12-year-old girl with severe pulmonary arterial hypertension who initially presented with severe systemic hypertension. Successful therapy included pulmonary vasodilators and an atrial septostomy, while ensuring adequate maintenance of her systemic vascular resistance to maintain cardiac output. Clear understanding of the physiology and judicious medical management in patients with severe pulmonary arterial hypertension using extreme compensatory mechanisms is vitally important.
Waters, Kendall R.; Mukdadi, Osama M.
Secondary pediatric pulmonary hypertension is a disease that could benefit from improved ultrasonic diagnostic techniques. We perform high-frequency in vitro ultrasound measurements (25 MHz to 100 MHz) on fresh and fixed pulmonary arterial walls excised from normoxic and hypoxic Long-Evans rat models. Estimates of the elastic stiffness coefficients are determined from measurements of the speed of sound. Preliminary results indicate that hypoxia leads to up to increase of 20 % in stiffening of the pulmonary arterial wall.
Seccombe, Leigh M; Chow, Vincent; Zhao, Wei; Lau, Edmund M T; Rogers, Peter G; Ng, Austin C C; Veitch, Elizabeth M; Peters, Matthew J; Kritharides, Leonard
Objective Patients with pulmonary arterial hypertension (PAH) are often recommended supplemental oxygen for altitude travel due to the possible deleterious effects of hypoxia on pulmonary haemodynamics and right heart function. This includes commercial aircraft travel; however, the direct effects and potential risks are unknown. Methods Doppler echocardiography and gas exchange measures were investigated in group 1 patients with PAH and healthy patients at rest breathing room air and while breathing 15.1% oxygen, at rest for 20 min and during mild exertion. Results The 14 patients with PAH studied were clinically stable on PAH-specific therapy, with functional class II (n=11) and III (n=3) symptoms when tested. Measures of right ventricular size and function were significantly different in the PAH group at baseline as compared to 7 healthy patients (p<0.04). There was no evidence of progressive right ventricular deterioration during hypoxia at rest or under exertion. Pulmonary arterial systolic pressure (PASP) increased in both groups during hypoxia (p<0.01). PASP in hypoxia correlated strongly with baseline PASP (p<0.01). Pressure of arterial oxygen correlated with PASP in hypoxia (p<0.03) but not at baseline, with three patients with PAH experiencing significant desaturation. The duration and extent of hypoxia in this study was tolerated well despite a mild increase in symptoms of breathlessness (p<0.01). Conclusions Non-invasive measures of right heart function in group 1 patients with PAH on vasodilator treatment demonstrated a predictable rise in PASP during short-term simulated hypoxia that was not associated with a deterioration in right heart function. PMID:28123765
Lin, Chien-Heng; Li, Tsai-Chung; Tsai, Po-Pang; Lin, Wei-Ching
The improvement of the resolution of rapid scanning in multidetector computed tomography (CT) has an increased accuracy that allows for the demonstration of the relationship of the pulmonary arteries and lung lesions, even in the peripheral lung. The purpose of this study is to evaluate the relationship between the pulmonary arteries and lung lesions by CT, and to use this relationship to distinguish between benign and malignant lung lesions. The relationships of the lung lesions and the adjacent pulmonary artery were recorded as encasement, displacement, penetration, in the margin, and disconnection. Statistical analyses were then performed to evaluate the relationship of the pulmonary arteries to each lesion with a focus toward the possibility of malignancy and the degree of pulmonary arterial encasement in the lesion. The relationship between the pulmonary arteries and lung lesions had a statistically significant difference between benignancy and malignancy (P < 0.001). Inter-observer agreement was substantial (κ = 0.639; 95% CI: 0.518-0.719). The average degrees of pulmonary arterial encasement in benign and malignant lesions were 52.1% ± 27.3% and 71.8% ± 18.8%, respectively (P = 0.011). The ROC curve showed that the degree of pulmonary arterial encasement had a moderate discriminating ability in diagnosing lung carcinoma, and the area under the curve was 0.738. The best cutoff value was 44.4%. The relationships of the pulmonary arteries to lung lesions and the degree of pulmonary arterial encasement could be used in differentiating benignancy from malignancy not only for central lung lesions but also peripheral lung lesions.
Ooi, Chen Yen; Wang, Zhijie; Tabima, Diana M.; Eickhoff, Jens C.
Hypoxic pulmonary hypertension (HPH) causes extralobar pulmonary artery (PA) stiffening, which potentially impairs right ventricular systolic function. Changes in the extracellular matrix proteins collagen and elastin have been suggested to contribute to this arterial stiffening. We hypothesized that vascular collagen accumulation is a major cause of extralobar PA stiffening in HPH and tested our hypothesis with transgenic mice that synthesize collagen type I resistant to collagenase degradation (Col1a1R/R). These mice and littermate controls that have normal collagen degradation (Col1a1+/+) were exposed to hypoxia for 10 days; some were allowed to recover for 32 days. In vivo PA pressure and isolated PA mechanical properties and collagen and elastin content were measured for all groups. Vasoactive studies were also performed with U-46619, Y-27632, or calcium- and magnesium-free medium. Pulmonary hypertension occurred in both mouse strains due to chronic hypoxia and resolved with recovery. HPH caused significant PA mechanical changes in both mouse strains: circumferential stretch decreased, and mid-to-high-strain circumferential elastic modulus increased (P < 0.05 for both). Impaired collagen type I degradation prevented a return to baseline mechanical properties with recovery and, in fact, led to an increase in the low and mid-to-high-strain moduli compared with hypoxia (P < 0.05 for both). Significant changes in collagen content were found, which tended to follow changes in mid-to-high-strain elastic modulus. No significant changes in elastin content or vasoactivity were observed. Our results demonstrate that collagen content is important to extralobar PA stiffening caused by chronic hypoxia. PMID:20852040
Karimi, Mohsen; Kirshbom, Paul M
Anomalous origins of coronary arteries from the pulmonary artery are rare malformations in which the coronary arteries originate from pulmonary artery sinuses or branches. The consequences are variable although, in most cases, these anomalies lead to severe coronary hypoperfusion and ventricular dysfunction. Surgical correction is indicated once the diagnosis is established due to high early mortality associated with the disease. In nearly all cases, the anomalous artery can be excised from its pulmonary origin, mobilized, and reimplanted directly into the ascending aorta using different surgical techniques. In rare circumstances, technical modifications must be used to restore a normal dual coronary perfusion. The emphasis of this article is to provide a collective review of surgical options published in the literature.
Bogaard, Harm J; Mizuno, Shiro; Guignabert, Christophe; Al Hussaini, Aysar A; Farkas, Daniela; Ruiter, Gerrina; Kraskauskas, Donatas; Fadel, Elie; Allegood, Jeremy C; Humbert, Marc; Vonk Noordegraaf, Anton; Spiegel, Sarah; Farkas, Laszlo; Voelkel, Norbert F
Obliteration of the vascular lumen by endothelial cell growth is a hallmark of many forms of severe pulmonary arterial hypertension. Copper plays a significant role in the control of endothelial cell proliferation in cancer and wound-healing. We sought to determine whether angioproliferation in rats with experimental pulmonary arterial hypertension and pulmonary microvascular endothelial cell proliferation in humans depend on the proangiogenic action of copper. A copper-depleted diet prevented, and copper chelation with tetrathiomolybdate reversed, the development of severe experimental pulmonary arterial hypertension. The copper chelation-induced reopening of obliterated vessels was caused by caspase-independent apoptosis, reduced vessel wall cell proliferation, and a normalization of vessel wall structure. No evidence was found for a role of super oxide-1 inhibition or lysyl-oxidase-1 inhibition in the reversal of angioproliferation. Tetrathiomolybdate inhibited the proliferation of human pulmonary microvascular endothelial cells, isolated from explanted lungs from control subjects and patients with pulmonary arterial hypertension. These data suggest that the inhibition of endothelial cell proliferation by a copper-restricting strategy could be explored as a new therapeutic approach in pulmonary arterial hypertension. It remains to be determined, however, whether potential toxicity to the right ventricle is offset by the beneficial pulmonary vascular effects of antiangiogenic treatment in patients with pulmonary arterial hypertension.
Gavilanes, Francisca; Jr, José Leonidas Alves; Fernandes, Caio; Prada, Luis Felipe Lopes; Jardim, Carlos Viana Poyares; Morinaga, Luciana Tamie Kato; Dias, Bruno Arantes; Hoette, Susana; Souza, Rogerio
OBJECTIVE: To evaluate the role of right heart catheterization in the diagnosis of pulmonary arterial hypertension (PAH). METHODS: We evaluated clinical, functional, and hemodynamic data from all patients who underwent right heart catheterization because of diagnostic suspicion of PAH-in the absence of severe left ventricular dysfunction (LVD), significant changes in pulmonary function tests, and ventilation/perfusion lung scintigraphy findings consistent with chronic pulmonary thromboembolism-between 2008 and 2013 at our facility. RESULTS: During the study period, 384 patients underwent diagnostic cardiac catheterization at our facility. Pulmonary hypertension (PH) was confirmed in 302 patients (78.6%). The mean age of those patients was 48.7 years. The patients without PH showed better hemodynamic profiles and lower levels of B-type natriuretic peptide. Nevertheless, 13.8% of the patients without PH were categorized as New York Heart Association functional class III or IV. Of the 218 patients who met the inclusion criteria, 40 (18.3%) and 178 (81.7%) were diagnosed with PH associated with LVD (PH-LVD) and with PAH, respectively. The patients in the HP-LVD group were significantly older than were those in the PAH group (p < 0.0001). CONCLUSIONS: The proportional difference between the PAH and PH-LVD groups was quite significant, considering the absence of echocardiographic signs suggestive of severe LVD during the pre-catheterization investigation. Our results highlight the fundamental role of cardiac catheterization in the diagnosis of PAH, especially in older patients, in whom the prevalence of LVD that has gone undiagnosed by non-invasive tests is particularly relevant. PMID:25610501
Henderson, A Cortney; Prisk, G Kim; Levin, David L; Hopkins, Susan R; Buxton, Richard B
The arterial spin labeling (ASL) method provides images in which, ideally, the signal intensity of each image voxel is proportional to the local perfusion. For studies of pulmonary perfusion, the relative dispersion (RD, standard deviation/mean) of the ASL signal across a lung section is used as a reliable measure of flow heterogeneity. However, the RD of the ASL signals within the lung may systematically differ from the true RD of perfusion because the ASL image also includes signals from larger vessels, which can reflect the blood volume rather than blood flow if the vessels are filled with tagged blood during the imaging time. Theoretical studies suggest that the pulmonary vasculature exhibits a lognormal distribution for blood flow and thus an appropriate measure of heterogeneity is the geometric standard deviation (GSD). To test whether the ASL signal exhibits a lognormal distribution for pulmonary blood flow, determine whether larger vessels play an important role in the distribution, and extract physiologically relevant measures of heterogeneity from the ASL signal, we quantified the ASL signal before and after an intervention (head-down tilt) in six subjects. The distribution of ASL signal was better characterized by a lognormal distribution than a normal distribution, reducing the mean squared error by 72% (p < 0.005). Head-down tilt significantly reduced the lognormal scale parameter (p = 0.01) but not the shape parameter or GSD. The RD increased post-tilt and remained significantly elevated (by 17%, p < 0.05). Test case results and mathematical simulations suggest that RD is more sensitive than the GSD to ASL signal from tagged blood in larger vessels, a probable explanation of the change in RD without a statistically significant change in GSD. This suggests that the GSD is a useful measure of pulmonary blood flow heterogeneity with the advantage of being less affected by the ASL signal from tagged blood in larger vessels.
Ibarrola, Patricia; German, Alexander J; Stell, Anneliese J; Fox, Richard; Summerfield, Nuala J; Blackwood, Laura
A 13-year-old neutered male Persian cat and an 11-year-old neutered female Persian cat were examined because of an acute onset of lameness. In both cats, conscious proprioception and reflexes were diminished in the affected limb. In 1 cat, no blood flow was detected in the left brachial artery with a Doppler ultrasonic flow detector, whereas blood flow in the right brachial artery was easily documented. In the other cat, the right femoral pulse was not palpable. Neither cat had any echocardiographic evidence of cardiac disease. In both cats, treatment was primarily supportive. One cat died, and the other was euthanatized. At necropsy, lung lobe consolidation was seen. Microscopically, there was multifocal infiltration of the lung parenchyma with cuboidal to columnar neoplastic epithelial cells. Neoplastic epithelial cells of similar morphology were identified in nodular masses in sections of muscle, and intravascular tumor emboli were identified obliterating small and large arterioles. Immunohistochemical staining of pulmonary and muscular tissue for pan-cytokeratin antigen revealed intense cytoplasmic staining of neoplastic cells. Staining for factor VIII-related antigen confirmed that clusters of neoplastic cells represented intravascular emboli. Clinical signs in the cats were attributed to arterial occlusion by tumor emboli.
Pulmonary hypertension (PH) is high blood pressure in the arteries to your lungs. It is a serious condition. If you have ... and you can develop heart failure. Symptoms of PH include Shortness of breath during routine activity, such ...
Negishi, Jun; Funamoto, Seiichi; Kimura, Tsuyoshi; Nam, Kwangoo; Higami, Tetsuya; Kishida, Akio
Many types of decellularized tissues have been studied and some have been commercially used in clinics. In this study, small-diameter vascular grafts were made using HHP to decellularize porcine radial arteries. One decellularization method, high hydrostatic pressure (HHP), has been used to prepare the decellularized porcine tissues. Low-temperature treatment was effective in preserving collagen and collagen structures in decellularized porcine carotid arteries. The collagen and elastin structures and mechanical properties of HHP-decellularized radial arteries were similar to those of untreated radial arteries. Xenogeneic transplantation (into rats) was performed using HHP-decellularized radial arteries and an untreated porcine radial artery. Two weeks after transplantation into rat carotid arteries, the HHP-decellularized radial arteries were patent and without thrombosis. In addition, the luminal surface of each decellularized artery was covered by recipient endothelial cells and the arterial medium was fully infiltrated with recipient cells.
Hu, Weiguo; Jin, Richard; Zhang, Jinyan; You, Tao; Peng, Zhihai; Ge, Xiaowen; Bronson, Roderick T.; Halperin, Jose A.; Loscalzo, Joseph
Pulmonary arterial hypertension (PAH) is suspected to be a strong mortality determinant of hemolytic disorders. However, direct contribution of acute intravascular hemolysis to fatal PAH has not been investigated. The roles of nitric oxide (NO) insufficiency and platelet activation in hemolysis-associated fatal PAH have been suspected but not been experimentally studied. We recently generated a unique intravascular hemolysis mouse model in which the membrane toxin, intermedilysin (ILY), exclusively lyses the erythrocytes of transgenically expressing human CD59 mice (ThCD59RBC), thereby inducing ILY-dose–dependent massive hemolysis. Using this murine hemolysis model, we found that the acute increase in pulmonary arterial pressure leading to right ventricle failure caused sudden death. Reduced NO bioavailability and massive platelet activation/aggregation leading to the formation of massive thrombosis specifically in the pulmonary microvasculature played the critical roles in pathogenesis of acute hemolysis-associated fatal PAH. Therapeutic interventions enhancing NO bioactivity or inhibiting platelet activation prevented sudden death or prolonged survival time via the suppression of the acute increase in pulmonary arterial pressure and improvement of right ventricle function. These findings further highlight the importance of the inhibition of platelet activation and the enhancement of NO bioavailability for the treatment and prevention of hemolysis-associated (fatal) PAH. PMID:20511540
Jeon, Chang-Seok; Shim, Man-shik; Yang, Ji-Hyuk; Jun, Tae-Gook
We report the case of a newborn with a rare anatomic variation: a right aortic arch with a retroesophageal left subclavian artery and an anomalous origin of the pulmonary artery from the aorta. This variation was diagnosed using echocardiography and computed tomography, and we treated the condition surgically. PMID:28180103
Ahmed, Mohamed; VanPatten, Sonya; Lakshminrusimha, Satyan; Patel, Hardik; Coleman, Thomas R; Al-Abed, Yousef
Pulmonary hypertension (PH) is a complex disease comprising a pathologic remodeling and thickening of the pulmonary vessels causing an after load on the right heart ventricle that can result in ventricular failure. Triggered by oxidative stress, episodes of hypoxia, and other undetermined causes, PH is associated with poor outcomes and a high rate of morbidity. In the neonate, this disease has a similar etiology but is further complicated by the transition to breathing after birth, which requires a reduction in vascular resistance. Persistent pulmonary hypertension of the newborn (PPHN) is one form of PH that is frequently unresponsive to current therapies including inhaled nitric oxide (due to lack of proper absorption and diffusion), and other therapeutics targeting signaling mediators in vascular endothelium and smooth muscle. The need for novel agents, which target distinct pathways in pulmonary hypertension, remains. Herein, we investigated the therapeutic effects of novel muscarinic receptor ligand C1213 in models of PH We demonstrated that via M3 muscarinic receptors, C1213 induced activating- eNOS phosphorylation (serine-1177), which is known to lead to nitric oxide (NO) production in endothelial cells. Using signaling pathway inhibitors, we discovered that AKT and calcium signaling contributed to eNOS phosphorylation induced by C1213. As expected for an eNOS-stimulating agent, in ex vivo and in vivo models, C1213 triggered pulmonary vasodilation and induced both pulmonary artery and systemic blood pressure reductions demonstrating its potential value in PH and PPHN In brief, this proof-of-concept study provides evidence that an M3 muscarinic receptor functionally selective ligand stimulates downstream pathways leading to antihypertensive effects using in vitro, ex vivo, and in vivo models of PH.
Xie, Yiting; Liang, Mingzhu; Yankelevitz, David F.; Henschke, Claudia I.; Reeves, Anthony P.
A new measurement of the pulmonary artery diameter is obtained where the artery may be robustly segmented between the heart and the artery bifurcation. An automated algorithm is presented that can make this pulmonary artery measurement in low-dose non-contrast chest CT images. The algorithm uses a cylinder matching method following geometric constraints obtained from other adjacent organs that have been previously segmented. This new measurement and the related ratio of pulmonary artery to aortic artery measurement are compared to traditional manual approaches for pulmonary artery characterization. The algorithm was qualitatively evaluated on 124 low-dose and 223 standard-dose non-contrast chest CT scans from two public datasets; 324 out of the 347 cases had good segmentations and in the other 23 cases there was significant boundary inaccuracy. For quantitative evaluation, the comparison was to manually marked pulmonary artery boundary in an axial slice in 45 cases; the resulting average Dice Similarity Coefficient was 0.88 (max 0.95, min 0.74). For the 45 cases with manual markings, the correlation between the automated pulmonary artery to ascending aorta diameter ratio and manual ratio at pulmonary artery bifurcation level was 0.81. Using Bland-Altman analysis, the mean difference of the two ratios was 0.03 and the limits of agreement was (-0.12, 0.18). This automated measurement may have utility as an alternative to the conventional manual measurement of pulmonary artery diameter at the bifurcation level especially in the context of noisy low-dose CT images.
Stieger-Vanegas, Susanne M; Bottorff, Bryan; Sisson, David; Löhr, Christiane V
Intravascular pulmonary artery sarcomas in combination with myocardial metastasis are rare in dogs. We describe the radiographic, echocardiographic, and electrocardiographic-gated (ECG-gated) computed tomographic angiography (CTA) findings in a dog with pulmonary artery sarcoma. All imaging studies demonstrated severe main pulmonary artery enlargement. Echocardiography and ECG-gated CTA revealed a mass occluding the lumen of the right pulmonary artery. In addition, CTA revealed focal left ventricular myocardial contrast enhancement and parenchymal lung changes. Postmortem examination confirmed the presence of a large thrombus associated with arteriosclerosis and an intravascular sarcoma in the right pulmonary artery with metastases to the myocardium, lungs and brain.
Kage, Hidenori; Goto, Yasushi; Amano, Yosuke; Makita, Kosuke; Isago, Hideaki; Kobayashi, Kouichi; Narumoto, Osamu; Okudaira, Reiko; Tanaka, Goh; Takami, Kazutaka; Ohishi, Nobuya; Nagase, Takahide
We herein describe a patient with Behçet's disease in whom we followed the development and resolution of pulmonary artery aneurysms. He presented with intermittent hemoptysis, pulmonary thromboembolism was initially diagnosed, and anticoagulant therapy was started. Over the next several months, the expansion of pulmonary arteries was noted. Five months after his initial admission, he was readmitted for massive hemoptysis, and further examinations revealed that he had Behçet's disease. Corticosteroids and intravenous cyclophosphamide were started. Over the next five months, the pulmonary artery aneurysms and thrombosis resolved. The development of pulmonary artery aneurysms led to the diagnosis of Behçet's disease, and they resolved after immunosuppressive therapy. PMID:27853079
Chowdhury, Ujjwal Kumar; Kapoor, Poonam Malhotra; Rao, Keerthi; Gharde, Parag; Kumawat, Mukesh; Jagia, Priya
We report a rare complication of massive aneurysm of the proximal ligated end of the main pulmonary artery which occurred in the setting of a patient with a functionally univentricular heart and increased pulmonary blood flow undergoing superior cavopulmonary connection. Awareness of this possibility may guide others to electively transect the pulmonary artery in such a clinical setting. PMID:27397472
Johnson, Roger H.; Karau, Kelly L.; Molthen, Robert C.; Haworth, Steven T.; Dawson, Christopher A.
We developed methods to quantify arterial structural and mechanical properties in excised rat lungs and applied them to investigate the distensibility decrease accompanying chronic hypoxia-induced pulmonary hypertension. Lungs of control and hypertensive (three weeks 11% O2) animals were excised and a contrast agent introduced before micro-CT imaging with a special purpose scanner. For each lung, four 3D image data sets were obtained, each at a different intra-arterial contrast agent pressure. Vessel segment diameters and lengths were measured at all levels in the arterial tree hierarchy, and these data used to generate features sensitive to distensibility changes. Results indicate that measurements obtained from 3D micro-CT images can be used to quantify vessel biomechanical properties in this rat model of pulmonary hypertension and that distensibility is reduced by exposure to chronic hypoxia. Mechanical properties can be assessed in a localized fashion and quantified in a spatially-resolved way or as a single parameter describing the tree as a whole. Micro-CT is a nondestructive way to rapidly assess structural and mechanical properties of arteries in small animal organs maintained in a physiological state. Quantitative features measured by this method may provide valuable insights into the mechanisms causing the elevated pressures in pulmonary hypertension of differing etiologies and should become increasingly valuable tools in the study of complex phenotypes in small-animal models of important diseases such as hypertension.
Delcroix, M; Naeije, R
Pulmonary arterial hypertension (PAH) is a rare and potentially fatal disease whose management is usually restricted to a few specialised centres. As patients do not necessarily live in the neighbourhood of these centres, daily care and emergencies have to be delegated to first and second lines. Treatment guidelines do not usually provide recommendations for acute emergency situations as evidence is scarce. This short review provides a description of our therapeutic protocols based on available data. A model of transmural organisation of care for PAH patients, currently applied in Belgium, is described. Thereafter, based on an analysis of the reasons of death in the PAH population, a review of the main emergencies is provided. Cardiac arrest and resuscitation, decompensated right heart failure, respiratory failure, arrhythmia, pericardial effusion, haemoptysis, surgery and drug-related adverse events will be discussed successively. Case reports showing the precariousness of PAH patients will enforce our thesis of the need for optimal patient management organisation.
Chester, Adrian H.; Yacoub, Magdi H.
Pulmonary arterial hypertension (PAH) is a rare but debilitating disease, which if left untreated rapidly progresses to right ventricular failure and eventually death. In the quest to understand the pathogenesis of this disease differences in the profile, expression and action of vasoactive substances released by the endothelium have been identified in patients with PAH. Of these, endothelin-1 (ET-1) is of particular interest since it is known to be an extremely powerful vasoconstrictor and also involved in vascular remodelling. Identification of ET-1 as a target for pharmacological intervention has lead to the discovery of a number of compounds that can block the receptors via which ET-1 mediates its effects. This review sets out the evidence in support of a role for ET-1 in the onset and progression of the disease and reviews the data from the various clinical trials of ET-1 receptor antagonists for the treatment of PAH. PMID:25405182
Austin, Bethany A; Griffin, Brian P
Primary pulmonary artery intimal sarcomas are often diagnosed only at the time of surgery or autopsy as a result of few specific findings both clinically and on imaging studies. We report two cases of this rare and lethal malignancy, both of which were initially thought to be manifestations of thromboembolic disease. In the case of one man, the diagnosis was delayed several months, at which point attempted surgical resection was not feasible. In the second case the echocardiographic and computed tomographic results generated further evaluation. This led to a more prompt diagnosis and treatment extending the patient's survival. In addition, we describe the echocardiographic findings that lent support to the need for surgical intervention and histologic diagnosis.
Bonnet, Sebastien; Provencher, Steeve; Guignabert, Christophe; Perros, Frédéric; Boucherat, Olivier; Schermuly, Ralph Theo; Hassoun, Paul M; Rabinovitch, Marlene; Nicolls, Mark R; Humbert, Marc
Despite important advances in its therapeutic management, pulmonary arterial hypertension (PAH) remains an incurable disease. Although numerous drugs exhibited beneficial effects in preclinical settings, only few have reached clinical trial phases, highlighting the challenges of translating preclinical investigations into clinical trials. Potential reasons for delayed PAH drug development may include the inherent limitations of the currently available animal and in vitro models, potential lack of appropriate standardization of the experimental design, regulatory agencies requirements, competing clinical trials and insufficient funding. Although this is not unique to PAH, there is urgency for reducing the number of false positive signals in preclinical studies and optimizing the development of innovative therapeutic targets through performance of clinical trials based on more robust experimental data. The current review discusses the challenges and opportunities in preclinical research to foster drug development in PAH.
García Hernández, Francisco José; Castillo Palma, María Jesús; González León, Rocío; Garrido Rasco, Rocío; Ocaña Medina, Celia; Sánchez Román, Julio
Despite advances in the treatment of patients with pulmonary arterial hypertension (PAH), survival has not improved greatly (is still very affected). Imatinib, an antagonist of platelet-derived growth factor with antiproliferative activity, has been effective in experimental models and clinically in several published reports. We report the results of imatinib therapy in 4 patients with PAH (functional class IV) who were refractory to treatment with drug combinations for this condition. The final outcome was favorable in only 1 of the 4 cases. In this case, the patient was in functional class III and his hemodynamic parameters had improved significantly within 5 months after starting therapy. However, the patient died as a result of severe toxic hepatitis in which imatinib may have played a role. The present report adds to the few already in the literature (4 cases) and suggests that care should continue to be shown when using imatinib to treat PAH.
Tefera, Endale; Teodori, Michael
Congenital or acquired aneurysm of the pulmonary artery (PA) is rare. Although aneurysms are described following surgical treatment of patent ductus arteriosus (PDA), occurrence of this lesion in association with PDA without previous surgery is extremely uncommon. An eight-year-old patient with PDA and aneurysm of the main PA is described in this report. Clinical diagnosis of PDA was made upon presentation. Diagnosis of PA aneurysm was suspected on chest x-ray and was confirmed on transthoracic echocardiography. Successful surgical resection of the aneurysm and division of the duct were performed under cardiopulmonary bypass. The patient did well on follow-up both from clinical and echocardiographic point of view.
Abolmaali, Nasreddin D; Hietschold, Volker; Appold, Steffen; Ebert, Wolfgang; Vogl, Thomas J
The goal of this study was visualisation and quality assessment of the pulmonary arteries in pigs with modified navigator-echo magnetic resonance angiography using an intravascular contrast agent. Five sedated pigs were examined in a clinical 1.5-T system with modified three-dimensional navigator-echo magnetic resonance angiography (slice thickness 3 mm, pixel size 2.4x1.8 mm2) to evaluate the pulmonary arteries. Using a phased-array four-element thorax coil the entire thorax was scanned before and after intravenous infusion of a gadolinium-based intravascular contrast agent. Assessment of image quality, enhancement-related contrast-to-noise ratio (CNR) measurements and improvement of visibility of peripheral pulmonary vessels was performed. Improvement of quality using Gadomer-17 was found for smaller vessels; pulmonary trunks and the main pulmonary arteries were sufficiently imaged without enhancement. Mean rise of CNR measured in the pulmonary trunks was 28.64% ( P=0.0002), mean rise of CNR in the main pulmonary arteries and the segmental arteries were 79.6% and 148.2%, respectively. Mean distance between the visible peripheral end of 60 sub-segmental arteries and the inner thoracic wall was 12.2 +/- 0.4 mm, and was significantly ( P=0.00002) reduced after contrast infusion to 8.0 +/- 0.4 mm. The combination of inherent flow sensitivity of navigator-echo angiography and Gadomer-17 proved effective for imaging of the pulmonary arteries. In contrast to standard contrast-enhanced pulmonary MRA studies, breath holding is not required. Further studies and the evaluation of findings of patients suffering from pulmonary embolism are needed to evaluate the possible benefits of a higher spatial resolution which is achievable using navigator-echo techniques in contrast to the higher temporal resolution of ultra-fast pulmonary MRA.
Chida, Ayako; Shintani, Masaki; Matsushita, Yoshihisa; Sato, Hiroki; Eitoku, Takahiro; Nakayama, Tomotaka; Furutani, Yoshiyuki; Hayama, Emiko; Kawamura, Yoichi; Inai, Kei; Ohtsuki, Shinichi; Saji, Tsutomu; Nonoyama, Shigeaki; Nakanishi, Toshio
Mutations of BMPR2 and other TGF-β superfamily genes have been reported in pulmonary arterial hypertension (PAH). However, 60–90% of idiopathic PAH cases have no mutations in these genes. Recently, the expression of NOTCH3 was shown to be increased in the pulmonary artery smooth muscle cells of PAH patients. We sought to investigate NOTCH3 and its target genes in PAH patients and clarify the role of NOTCH3 signaling. We screened for mutations in NOTCH3, HES1, and HES5 in 41 PAH patients who had no mutations in BMPR2, ALK1, endoglin, SMAD1/4/8, BMPR1B, or Caveolin-1. Two novel missense mutations (c.2519 G>A p.G840E, c.2698 A>C p.T900P) in NOTCH3 were identified in two PAH patients. We performed functional analysis using stable cell lines expressing either wild-type or mutant NOTCH3. The protein-folding chaperone GRP78/BiP was colocalized with wild-type NOTCH3 in the endoplasmic reticulum, whereas the majority of GRP78/BiP was translocated into the nuclei of cells expressing mutant NOTCH3. Cell proliferation and viability were higher for cells expressing mutant NOTCH3 than for those expressing wild-type NOTCH3. We identified novel NOTCH3 mutations in PAH patients and revealed that these mutations were involved in cell proliferation and viability. NOTCH3 mutants induced an impairment in NOTCH3-HES5 signaling. The results may contribute to the elucidation of PAH pathogenesis. PMID:24936512
Chung, Wook-Jin; Park, Yong Bum; Jeon, Chan Hong; Jung, Jo Won; Ko, Kwang-Phil; Choi, Sung Jae; Seo, Hye Sun; Lee, Jae Seung; Jung, Hae Ok
Despite recent advances in understanding of the pathobiology and targeted treatments of pulmonary arterial hypertension (PAH), epidemiologic data from large populations have been limited to western countries. The aim of the Korean Registry of Pulmonary Arterial Hypertension (KORPAH) was to examine the epidemiology and prognosis of Korean patients with PAH. KORPAH was designed as a nationwide, multicenter, prospective data collection using an internet webserver from September 2008 to December 2011. A total of 625 patients were enrolled. The patients' mean age was 47.6 ± 15.7 yr, and 503 (80.5%) were women. The diagnostic methods included right heart catheterization (n = 249, 39.8%) and Doppler echocardiography (n = 376, 60.2%). The etiologies, in order of frequency, were connective tissue disease (CTD), congenital heart disease, and idiopathic PAH (IPAH) (49.8%, 25.4%, and 23.2%, respectively). Patients with WHO functional class III or IV at diagnosis were 43.4%. In total, 380 (60.8%) patients received a single PAH-specific treatment at the time of enrollment, but only 72 (18.9%) patients received combination therapy. Incident cases during the registry represented 297 patients; therefore, the incidence rate of PAH was 1.9 patients/yr/million people. The 1st-, 2nd-, and 3rd-yr estimated survival rates were 90.8%, 87.8%, and 84.4%, respectively. Although Korean PAH patients exhibited similar age, gender, and survival rate compared with western registries, they showed relatively more CTD-PAH in the etiology and also systemic lupus erythematosus among CTD-PAH. The data suggest that earlier diagnosis and more specialized therapies should be needed to improve the survival of PAH patients.
Lee, Jin Hwa; Cho, Michael H.; Hersh, Craig P.; McDonald, Merry-Lynn N.; Wells, J. Michael; Dransfield, Mark T.; Bowler, Russell P.; Lynch, David A.; Lomas, David A.; Crapo, James D.
Pulmonary hypertension is associated with advanced chronic obstructive pulmonary disease (COPD), although pulmonary vascular changes occur early in the course of the disease. Pulmonary artery (PA) enlargement (PAE) measured by computed tomography correlates with pulmonary hypertension and COPD exacerbation frequency. Genome-wide association studies of PAE in subjects with COPD have not been reported. To investigate whether genetic variants are associated with PAE within subjects with COPD, we investigated data from current and former smokers from the COPDGene Study and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study. The ratio of the diameter of the PA to the diameter of the aorta (A) was measured using computed tomography. PAE was defined as PA/A greater than 1. A genome-wide association study for COPD with PAE was performed using subjects with COPD without PAE (PA/A ≤ 1) as a control group. A secondary analysis used smokers with normal spirometry as a control group. Genotyping was performed on Illumina platforms. The results were summarized using fixed-effect meta-analysis. Both meta-analyses revealed a genome-wide significant locus on chromosome 15q25.1 in IREB2 (COPD with versus without PAE, rs7181486; odds ratio [OR] = 1.32; P = 2.10 × 10−8; versus smoking control subjects, rs2009746; OR = 1.42; P = 1.32 × 10−9). PAE was also associated with a region on 14q31.3 near the GALC gene (rs7140285; OR = 1.55; P = 3.75 × 10−8). Genetic variants near IREB2 and GALC likely contribute to genetic susceptibility to PAE associated with COPD. This study provides evidence for genetic heterogeneity associated with a clinically important COPD vascular subtype. PMID:25101718
Lee, Jin Hwa; Cho, Michael H; Hersh, Craig P; McDonald, Merry-Lynn N; Wells, J Michael; Dransfield, Mark T; Bowler, Russell P; Lynch, David A; Lomas, David A; Crapo, James D; Silverman, Edwin K
Pulmonary hypertension is associated with advanced chronic obstructive pulmonary disease (COPD), although pulmonary vascular changes occur early in the course of the disease. Pulmonary artery (PA) enlargement (PAE) measured by computed tomography correlates with pulmonary hypertension and COPD exacerbation frequency. Genome-wide association studies of PAE in subjects with COPD have not been reported. To investigate whether genetic variants are associated with PAE within subjects with COPD, we investigated data from current and former smokers from the COPDGene Study and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study. The ratio of the diameter of the PA to the diameter of the aorta (A) was measured using computed tomography. PAE was defined as PA/A greater than 1. A genome-wide association study for COPD with PAE was performed using subjects with COPD without PAE (PA/A ≤ 1) as a control group. A secondary analysis used smokers with normal spirometry as a control group. Genotyping was performed on Illumina platforms. The results were summarized using fixed-effect meta-analysis. Both meta-analyses revealed a genome-wide significant locus on chromosome 15q25.1 in IREB2 (COPD with versus without PAE, rs7181486; odds ratio [OR] = 1.32; P = 2.10 × 10(-8); versus smoking control subjects, rs2009746; OR = 1.42; P = 1.32 × 10(-9)). PAE was also associated with a region on 14q31.3 near the GALC gene (rs7140285; OR = 1.55; P = 3.75 × 10(-8)). Genetic variants near IREB2 and GALC likely contribute to genetic susceptibility to PAE associated with COPD. This study provides evidence for genetic heterogeneity associated with a clinically important COPD vascular subtype.
Coche, Emmanuel; Pawlak, Sebastien; Dechambre, Stéphane; Maldague, Baudouin
Our objective was to analyze the peripheral pulmonary arteries using thin-collimation multi-slice spiral CT. Twenty consecutive patients underwent enhanced-spiral multi-slice CT using 1-mm collimation. Two observers analyzed the pulmonary arteries by consensus on a workstation. Each artery was identified on axial and 3D shaded-surface display reconstruction images. Each subsegmental artery was measured at a mediastinal window setting and compared with anatomical classifications. The location and branching of every subsegmental artery was recorded. The number of well-visualized sub-subsegmental arteries at a mediastinal window setting was compared with those visualized at a lung window setting. Of 800 subsegmental arteries, 769 (96%) were correctly visualized and 123 accessory subsegmental arteries were identified using the mediastinal window setting. One thousand ninety-two of 2019 sub-subsegmental arteries (54%) identified using the lung window setting were correctly visualized using the mediastinal window setting. Enhanced multi-slice spiral CT with thin collimation can be used to analyze precisely the subsegmental pulmonary arteries and may identify even more distal pulmonary arteries.
Beltrán-Gámez, Miguel E; Sandoval-Zárate, Julio; Pulido, Tomás
In experimental and clinical cardiology, phosphodiesterase type 5 (PDE-5) inhibitors have brought scientific interest as a therapeutic tool in pulmonary arterial hypertension (PAH) management in recent years. Phosphodiesterases are a superfamily of enzymes that inactivate cyclic adenosine monophosphate and cyclic guanosine monophosphate, the second messengers of prostacyclin and nitric oxide. The rationale for the use of PDE-5 inhibitors in PAH is based on their capacity to overexpresss the nitric oxide pathway pursued inhibition of cyclic guanosine monophosphate hydrolysis. By increasing cyclic guanosine monophosphate levels it promotes vasodilation, antiproliferative and pro-apoptotic effects that may reverse pulmonary vascular remodeling. There is also evidence that these drugs may directly enhance right ventricular contractility through an increase in cyclic adenosine monophosphate mediated by the inhibition of the cyclic guanosine monophosphate -sensitive PDE-3. Sildenafil, tadalafil and vardenafil are 3 specific PDE-5 inhibitors in current clinical use, which share similar mechanisms of action but present some significant differences regarding potency, selectivity for PDE-5 and pharmacokinetic properties. Sildenafil received approval in 2005 by the Food and Drug Administration and the European Medicines Agency and tadalafil in 2009 by the Food and Drug Administration and the European Medicines Agency for the treatment of PAH in patients classified as NYHA/WHO functional class II and III. In Mexico, sildenafil and tadalafil were approved by Comisión Federal de Protección contra Riesgos Sanitarios for this indication in 2010 and 2011, respectively.
Hinzmann, Barbara; Heinz, Sabina; Gall, Henning; Jenkins, David; Kim, Nick H.; Lang, Irene
Abstract We conducted an international study to evaluate practices in the diagnosis and management of pulmonary arterial hypertension (PAH) globally across different geographic regions. Between July and October 2012, PAH-treating physicians completed a 15-minute online questionnaire and provided patient record data for their 3 or 5 most recent patients with PAH. Overall, 560 physicians (Europe: 278; United States: 160; Argentina: 53; Japan: 69) completed the questionnaire and provided data for 2,618 patients. The proportion of physicians who described themselves as working in or affiliated with a specialized pulmonary hypertension center ranged from 13% in Argentina to 74% in the United States. At the time of diagnosis, patients’ New York Heart Association functional class differed significantly between regions. At the time of last assessment, functional class had improved overall, and differences between regions had largely disappeared. A large proportion of patients did not undergo right heart catheterization for the diagnosis of PAH (Europe: 7%–21%; United States: 21%; Japan: 19%; Argentina: 51%). Variations in management included greater use of phosphodiesterase 5 inhibitors in the United States than in Europe and Japan and greater use of triple or greater combination therapy in Japan than in other regions. Results from this study, which includes a global aspect of PAH care, demonstrate that there are significant differences in PAH management between regions and low adherence to guidelines recommending right heart catheterization for the diagnosis of PAH. PMID:27683611
Gabbay, Eli; Fraser, John; McNeil, Keith
The dual endothelin receptor antagonist, bosentan, is an orally active therapy, which is effective in the treatment of pulmonary arterial hypertension (PAH). This review critically appraises the evidence for the efficacy of bosentan in idiopathic and familial PAH, in PAH associated with connective tissue disease and in PAH which may develop in association with other conditions. Data from the pivotal placebo controlled studies and their open labeled extensions as well as long term survival and quality of life data is presented. Data is also presented on the potential benefit of bosentan in patients with inoperable chronic thromboembolic pulmonary hypertension. The safety and tolerability of bosentan as well as drug interactions are discussed. Dosage recommendations in adults and pediatrics are presented. An algorithm is provided to guide the reader in monitoring potential increases in alanine and aspartate transaminase levels that may occur with bosentan use and the dose adjustments that are recommended as a result of any increase in the levels of these enzymes are shown. Finally, the role of bosentan as part of combination therapy in PAH is examined. PMID:18200808
Dias-Neto, Marina; Luísa-Neves, Ana; Pinho, Sónia; Gonçalves, Nádia; Mendes, Maria; Eloy, Catarina; Lopes, José M; Gonçalves, Daniel; Ferreira-Pinto, Manuel; Leite-Moreira, Adelino F; Henriques-Coelho, Tiago
Pediatric pulmonary arterial hypertension (PAH) presents certain specific features. In this specific age group, experimental models to study the pathophysiology of PAH are lacking. To characterize hemodynamic, morphometric, and histological progression as well as the expression of neurohumoral factors and regulators of cardiac transcription in an infantile model of PAH induced by monocrotaline (MCT), eight-day-old Wistar rats were randomly injected with MCT (30 mg/kg, sc, n = 95) or equal volume of saline solution (n = 92). Animals were instrumented for biventricular hemodynamic recording 7, 14, and 21 days after MCT, whereas samples were collected at 1, 3, 7, 14, and 21 days after MCT. Different time point postinjections were defined for further analysis. Hearts and lungs were collected for morphometric characterization, assessment of right- and left-ventricle (RV and LV) cardiomyocyte diameter and collagen type-I and type-III ratio, RV collagen volume fraction, and pulmonary vessels wall thickness. mRNA quantification was undertaken for brain natriuretic peptide (BNP), endothelin-1 (ET-1), and for cardiac transcription regulators (HOP and Islet1). Animals treated with MCT at the 8th day of life presented RV hypertrophy since day 14 after MCT injection. There were no differences on the RV collagen volume fraction or collagen type-I and type-III ratio. Pulmonary vascular remodelling and PAH were present on day 21, which were accompanied by an increased expression of BNP, ET-1, HOP, and Islet1. The infantile model of MCT-induced PAH can be useful for the study of its pathophysiology and to test new therapeutic targets in pediatric age group.
Gomberg-Maitland, Mardi; Demarco, Teresa; Frost, Adaani E.; Torbicki, Adam; Langleben, David; Pulido, Tomas; Correa-Jaque, Priscilla; Passineau, Michael J.; Wiener, Howard W.; Tamari, Mayumi; Hirota, Tomomitsu; Kubo, Michiaki; Tiwari, Hemant K.
Rationale: Pulmonary arterial hypertension (PAH) is a progressive fatal disease. Variable response and tolerability to PAH therapeutics suggests that genetic differences may influence outcomes. The endothelin pathway is central to pulmonary vascular function, and several polymorphisms and/or mutations in the genes coding for endothelin (ET)-1 and its receptors correlate with the clinical manifestations of other diseases. Objectives: To examine the interaction of ET-1 pathway polymorphisms and treatment responses of patients with PAH treated with ET receptor antagonists (ERAs). Methods: A total of 1,198 patients with PAH were prospectively enrolled from 45 U.S. and Canadian pulmonary hypertension centers or retrospectively from global sites participating in the STRIDE (Sitaxsentan To Relieve Impaired Exercise) trials. Comprehensive objective measures including a 6-minute-walk test, Borg dyspnea score, functional class, and laboratory studies were completed at baseline, before the initiation of ERAs, and repeated serially. Single-nucleotide polymorphisms from ET-1 pathway candidate genes were selected from a completed genome-wide association study performed on the study cohort. Measurements and Main Results: Patient efficacy outcomes were analyzed for a relationship between ET-1 pathway polymorphisms and clinical efficacy using predefined, composite positive and negative outcome measures in 715 European descent samples. A single-nucleotide polymorphism (rs11157866) in the G-protein alpha and gamma subunits gene was significantly associated, accounting for multiple testing, with a combined improvement in functional class and 6-minute-walk distance at 12 and 18 months and marginally significant at 24 months. Conclusions: ET-1 pathway associated polymorphisms may influence the clinical efficacy of ERA therapy for PAH. Further prospective studies are needed. PMID:26252367
Hardin, Elizabeth Ashley; Chin, Kelly M
Pulmonary arterial hypertension is characterized by abnormalities in the small pulmonary arteries including increased vasoconstriction, vascular remodeling, proliferation of smooth muscle cells, and in situ thrombosis. Selexipag, a novel, oral prostacyclin receptor agonist, has been shown to improve hemodynamics in a phase II clinical trial and reduce clinical worsening in a large phase III clinical trial involving patients with pulmonary arterial hypertension. In this paper, we describe the prostacyclin signaling pathway, currently available oral prostanoid medications, and the development and clinical use of selexipag. PMID:27895464
Gottwalles, Yannick; Wunschel-Joseph, Marie-Eve; Hanssen, Michel
Rupture of the pulmonary artery or one of its branches during Swan-Ganz catheterization is a complication that is rare but remains fatal in almost 50% of cases. The risk factors and mechanisms involved in the pathogenesis of this accident have been widely reported. Management is twofold: resuscitation procedures and specific medical or even surgical treatment. We report a case of pulmonary artery rupture occurring during Swan-Ganz catheterization that was treated by coil embolization. This technique, which is quick and simple to use, would appear to be very promising. This is the first case of successful emergency treatment of pulmonary artery rupture using an endovascular technique.
Shingyoji, Masato; Ikebe, Dai; Itakura, Meiji; Nakajima, Takahiro; Itami, Makiko; Kimura, Hideki; Iizasa, Toshihiko
Pulmonary artery sarcoma (PAS) is a rare tumor that is often detected at an advanced stage, when disease is so widespread that a radical surgical procedure is no longer indicated. Therefore, less invasive biopsy techniques are required to establish a definitive preoperative diagnosis. Endobronchial ultrasound (EBUS) is useful for producing real-time images of both lymph nodes and the interior of pulmonary arteries adjacent to the bronchi. We report a case with masslike lesions in the pulmonary artery that were observed by EBUS and from which tissue was obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to establish a diagnosis of PAS.
Chen, Xiaoxia; Ren, Shengxiang; Li, Aiwu; Zhou, Caicun
The incidence rate of pulmonary artery sarcoma is very low, but its prognosis is extremely poor. In this case report, after various initial diagnoses at the early stage, pulmonary artery sarcoma was confirmed by surgery. 1 year later, the tumor recurred. After chemotherapy, the patient showed improvement of the subjective complaint of tightness in the chest, and radiological lesion decreased in size. The survival time was extended by 2.5 years. This is the first case report of pulmonary artery sarcoma with such chemo-sensitivity.
Hardin, Elizabeth Ashley; Chin, Kelly M
Pulmonary arterial hypertension is characterized by abnormalities in the small pulmonary arteries including increased vasoconstriction, vascular remodeling, proliferation of smooth muscle cells, and in situ thrombosis. Selexipag, a novel, oral prostacyclin receptor agonist, has been shown to improve hemodynamics in a phase II clinical trial and reduce clinical worsening in a large phase III clinical trial involving patients with pulmonary arterial hypertension. In this paper, we describe the prostacyclin signaling pathway, currently available oral prostanoid medications, and the development and clinical use of selexipag.
Etemadi, Mozziyar; Heller, J. Alex; Schecter, Samuel C.; Shue, Eveline H.; Miniati, Doug; Roy, Shuvo
Congenital pulmonary hypoplasia is a devastating condition affecting fetal and newborn pulmonary physiology, resulting in great morbidity and mortality. The fetal lung develops in a fluid-filled environment. In this paper, we describe a novel, implantable pressure sensing and recording device which we use to study the pressures present in the fetal pulmonary tree throughout gestation. The system achieves 0.18 cm H2O resolution and can record for 21 days continuously at 256 Hz. Sample tracings of in vivo fetal lamb recordings are shown. PMID:22801521
Taçoy, Gülten; Ekim, Numan Nadir; Cengel, Atiye
Idiopathic pulmonary arterial hypertension (IPAH) is characterized by a progressive increase in pulmonary vascular resistance, which may lead to right ventricular failure and death. Major cardiovascular and pulmonary alterations occur during pregnancy and therefore worsen or increase the complications of pulmonary arterial hypertension (PAH). A patient diagnosed with IPAH after a successful full-term pregnancy and cesarean section with epidural anesthesia is presented. The postoperative course was complicated by progressive dyspnea, and lower limb edema. The outcome of treatment with sildenafil during puerperium was favorable in this patient. The clinical course was complicated by an unexpected spontaneous pregnancy after primary infertility.
Guo, Yuehong; Wang, Tie; Yang, Minfu
A 32-year-old woman, who presented with "sharp pain" in the right chest for more than 1 month and worsening dyspnea and fever for 10 days, was initially thought to have a pulmonary embolism. Cardiac ultrasound showed an ill-defined echogenic mass within the pulmonary trunk. F-FDG PET/CT was performed for further evaluation. PET/CT showed an intense hypermetabolism in the main, bilateral proximal, and the right main pulmonary arteries, suggesting the presence of a malignant lesion. Biopsy confirmed the lesion as a primary pulmonary artery sarcoma.
Munoz, J.J. Garcia, J.A.; Bentabol, M.; Padin, M.I.; Serrano, F.
We report the case of a 29-year-old man with hemoptysis. The patient came to the emergency department, where a laboratory test and chest radiograph were reported as normal. The following day the patient again had hemoptysis, though less than previously. He reported no chest pain, dyspnea, fever, catarrh, changes in urine or feces, contact with patients with bacillus diseas