Pulmonary Branches Research Articles

The neuranatomical basis of central control of cardiorespiratory interactions in vertebrates.

The neuranatomical basis of central control of cardiorespiratory interactions in vertebrates.

Pulmonary Wedge Pressures Confirm Pulmonary Hypertension in Broilers Is Initiated by an Excessive Pulmonary Arterial (Precapillary) Resistance

High retrograde pressure through the pulmonary venous system caused by failure of the left ventricle or left atrio-ventricular valve may result in the elevated pulmonary arterial pressure and right ventricular hypertrophy associated with pulmonary hypertension syndrome (PHS; ascites) in broiler chickens. In the present study, unanaesthetized male broilers from an ascites-resistant line, the base population from which the resistant line was derived, and a separate unselected line were used to determine whether changes in wedge pressure (thought to be similar to left atrial pressure) are predictive of differences in the pulmonary arterial pressure of clinically healthy and pre-ascitic broilers. Venous, right atrial, right ventricular, pulmonary arterial, and wedge pressures were obtained by inserting a catheter into a wing vein and progressively advancing the catheter into a pulmonary branch artery until the catheter tip became wedged in and occluded the flow through a terminal artery. Mean right ventricular and pulmonary arterial pressures were lower in the resistant line than in the base population, but wedge pressures did not differ between the resistant, base, and unselected lines. Right:total ventricular weight ratios (RV:TV) and the percentage saturation of hemoglobin with oxygen in arterial blood ranged in value from 0.18 to 0.44 and 65 to 96%, respectively. Wedge pressure, however, remained similar when pre-ascitic broilers with high RV:TV values and low oximetry values were compared with clinically healthy broilers. In all birds, whether healthy or showing pre-ascitic characteristics, the wedge pressure was slightly higher than the right atrial pressure but substantially lower than pulmonary arterial pressure. These observations provide definitive proof that pulmonary hypertension is initiated as a consequence of excessive pulmonary arterial or arteriole resistance. Pulmonary venous pressure is estimated by measuring the pulmonary arterial wedge pressure, and high wedge pressures would be evident if pulmonary hypertension was caused by the elevated downstream resistances associated with left-sided heart failure.

La operación de Glenn bidireccional en 100 casos con cardiopatías congénitas complejas: factores determinantes del resultado quirúrgico

The bidirectional Glenn shunt is a well established surgical technique in children with complex congenital heart disease. The present study is a retrospective analysis of patients undergoing this operation in order to assess the influence of different variables in the outcome. From December 1990 to June 2000, 100 patients received a bidirectional Glenn shunt. Two groups were defined, based on the outcome. Group A (n = 15, unsuccessfully result) including death and need to reoperate, and Group B (n = 85, patients with good outcome). The mortality was 8%. Eight patients were reoperated at follow-up. The survivors were followed for a mean of 3.5 years. Mean pulmonary artery pressure 7 mmHg was a factor associated with poor clinical progress. Other variables (age less than 1 year, excessive pulmonary blood flow, double Glenn operation, significant anatomic anomalies, and arrythmias), were also associated with outcome. Significant variations were observed in the time of by-pass or the need for aortic clamp in cases with simultaneous operative repair of pulmonary branch stenosis. Actuarial survival rate, most more than 1 year was 92%, and freedom from reoperation at 3 years was 90%. The bidirectional Glenn shunt is an excellent palliation in patients with functionally single ventricle. Mean pulmonary artery pressure was the most important variable related with the outcome. We are encouraged to continue with tendency to perform bidirectional Glenn shunt preferably early, avoiding, whenever possible, previous palliative surgery.

Interventional catheterization in surgically treated patients with congenital heart disease.

Interventional catheterization is an alternative to surgery for some congenital heart defects. For other malformations, the surgeon and the interventionist will join in an effort to obtain an optimal result: the typical example is pulmonary atresia with VSD and aortopulmonary collaterals. In other cases, the cardiologist may be called upon to intervene with catheter techniques to correct sequelae or residual lesions after surgical correction, avoiding redo surgery. Most often, the task consists of opening stenoses by balloon dilatation and/or stenting the main targets being pulmonary artery branch stenoses, venous obstructions after Mustard procedure, and recoarctations. Whereas simple balloon dilatation of recoarctation often brings good results, stents are often needed to obtain optimal results in pulmonary branch stenoses. Stenting of pulmonary veins has been disappointing. Closing unwanted vessels and defects is another task for the interventional cardiologist after cardiac surgery. Here, the most frequent procedure is closing aortopulmonary collaterals in pulmonary atresia and VSD after corrective surgery. Advantages and limitations of these procedures are discussed.

WS15‐06Doppler ultrasonography of the human fetal pulmonary circulation and its role in the prediction of pulmonary hypoplasia

ObjectivesTo determine the value of Doppler flow velocity waveforms from the fetal arterial pulmonary branches relative to fetal biometric indices and clinical correlates in the prenatal prediction of lethal lung hypoplasia (LH) in prolonged oligohydramnios.Study design42 singleton pregnancies with oligohydramnios associated with premature rupture of membranes (PROM, n = 31) or bilateral renal pathology (n = 11) were examined using a combined color coded Doppler and 2d real‐time ultrasound system. Thoracic (TC), cardiac (CC) and abdominal circumference (AC) and the largest vertical amniotic fluid pocket were measured. Pulsed Doppler measurements of the arterial pulmonary branches were made at the level of the cardiac four‐chamber view after visualization with color Doppler. Diagnosis of LH was based on pathological, clinical and radiological criteria.ResultsThe prevalence of lethal LH was 43%. In the PROM‐subset, combination of onset of PROM = 20 weeks; duration of oligohydramnios = 8 weeks and degree of oligohydramnios = 1 cm, presented the highest clinical prediction rate for lethal LH. For both the total group and the PROM‐subset, the highest prediction rate for lethal LH from biometric and Doppler parameters was presented by TC/AC ratio, peak systolic velocity in the proximal branch and time‐averaged and end‐diastolic velocity in the middle branch of the pulmonary artery. In the prom subset, combination of all three clinical, biometric and Doppler parameters revealed the most favorable combination to predict lethal LH (PPV 100%, accuracy 93%, and sensitivity 71%).ConclusionDoppler velocimetry may detect changes in blood velocity waveforms from the arterial branches of the fetal pulmonary circulation in the presence of LH, but fails to be the ultimate test for the prenatal prediction of lethal LH. The best prediction can be achieved by combining clinical, biometric and Doppler parameters.

Human fetal pulmonary artery velocimetry: repeatability and normal values with emphasis on middle and distal pulmonary vessels.

To establish the nature and gestational age dependency of flow velocity waveforms from fetal middle and distal arterial pulmonary branches in the second half of normal pregnancy and to determine repeatability and inter-relationship of flow velocity waveform recordings from proximal, middle and distal arterial pulmonary branches. Cross-sectional study. A total of 111 singleton normal pregnancies between 20 and 40 weeks of gestation were studied using a color-coded Doppler ultrasound system. Pulmonary waveforms were obtained at the level of the fetal cardiac four-chamber view. Repeatability was tested from two recordings at 15 min time-intervals in 25 separate normal pregnancies. Acceptable repeatability of flow velocity waveforms from fetal arterial pulmonary branches was established with coefficients of variation below 15%. The nature of middle arterial pulmonary flow velocity waveforms was similar to that of proximal waveforms and showed a gestational age-related change for diastolic velocity parameters, peak systolic/peak diastolic ratio and pulsatility index. The distal arterial pulmonary branch displayed a monophasic forward flow velocity profile throughout the cardiac cycle. All velocity parameters of the distal branch remained unchanged with advancing gestation, with the exception of the pulsatility index. Significant inter-pulmonary changes were found for all pulmonary arterial waveform parameters. Alteration in pulmonary vascular resistance may play a role in gestational age-related changes, whereas changes in vessel branching/diameter and in the distance between the heart and more distal arterial pulmonary vessels may cause inter-pulmonary differences.

Congenital Heart Surgery Nomenclature and Database Project: right ventricular outflow tract obstruction–intact ventricular septum

The extant nomenclature for pulmonary atresia/stenosis with intact ventricular septum, pulmonary artery and/or pulmonary branch stenosis, double chambered right ventricle, absent pulmonary valve with intact ventricular septum, and ventricular to pulmonary artery conduit failure is reviewed for the purpose of establishing a unified reporting system. The subject was debated and reviewed by members of the STS-Congenital Heart Surgery Database Committee and representatives from the European Association for Cardiothoracic Surgery. All efforts were made to include all relevant nomenclature categories using synonyms where appropriate. Multiple risk factors were considered such as coronary artery fistulas/sinusoids, tricuspid annular size and location of peripheral pulmonary artery stenoses. A comprehensive database set is presented which is based on a hierarchical scheme. Data are entered at various levels of complexity and detail which can be determined by the clinician. These data can lay the foundation for comprehensive risk stratification analyses. A minimum database set is also presented which will allow for data sharing and would lend itself to basic interpretation of trends. Potential diagnostic related risk factors for each lesion are presented.

Cardiac and smooth muscle cell contribution to the formation of the murine pulmonary veins.

Previous studies have demonstrated that the primordial pulmonary veins originate as an outgrowth of the atrial cells and anastomosis with the pulmonary venous plexus. As a consequence of this embryologic origin the tunica media of these vessels is composed of cardiac cells that express atrial specific markers (Lyons et al. [1990] J Cell Biol 111:2427-2436; Jones et al. [1994] Dev Dyn 200:117-128). We used transgenic mice for the cardiac troponin I (cTNI) gene and smooth muscle (SM) myosin heavy chain as differentiation markers, to analyze how cardiac and SM cells contribute to the formation and structural remodeling of the pulmonary veins during development. We show here that the tunica media of the adult mouse pulmonary veins contains an outer layer of cardiac cells and an intermediate SM cell compartment lining down on the inner endothelium. This structural organization is well expressed in the intrapulmonary veins from the beginning of vasculogenesis, with cardiac cells accumulating over preexisting roots of endothelial and SM cells and extending to the third bifurcation of the pulmonary branches without reaching the more distal tips of the vessels. On the other hand, SM cells, which are widely distributed in the intrapulmonary veins from the embryonic stage E16, accumulate also in the extrapulmonary branches and reach the posterior wall of the left atrium, including the orifices of the pulmonary veins. This event takes place around birth when the pulmonary blood flow starts to function properly. A model for the development of the pulmonary veins is presented, based upon our analysis.

The role of the pulmonary afferent receptors in producing hemodynamic changes during hyperinflation and endotracheal suctioning in an oleic acid-injured animal model of acute respiratory failure.

The purpose of this study was to examine the role of the pulmonary afferent receptors in producing hemodynamic changes during hyperinflation and endotracheal suctioning (ETS) in an oleic acid-injured animal model of acute respiratory failure. Previous investigations of hyperinflation as a method to prevent hypoxia-induced sequelae of ETS have demonstrated unrecognized hemodynamic consequences. In this within-subject, repeated-measures study, instrumented, oleic acid-injured dogs had continuous measurements of heart rate (HR), mean aortic blood pressure (MAP), left ventricular pressure (Plv), pulmonary artery pressure (Ppa), right ventricular afterload (Ppa(tm)), right atrial pressure (Pra), and right ventricular filling pressure (Pra(tm)) during hyperinflation and ETS when the vagi were intact and after the pulmonary branches of the vagus nerves had been severed. After severing the vagi, MAP and Plv were decreased and HR and Ppa were increased. With the vagi severed, there was less variation in MAP and Ppa but increased variation in HR. These findings suggest that vagally mediated reflexes from the lungs produce some, but not all, of the hemodynamic effects associated with hyperinflation and ETS. Continued research is necessary to discover a method of hyperoxygenation and suctioning that does not produce potentially harmful hemodynamic effects.

Current role of therapeutic heart catheterization in pediatric cardiology

OBJECTIVE: Cardiac catheterization has begun to be employed for therapeutic purposes since the middle sixties. In this paper the authors review the current indications, technique and results related to each of the interventional procedures. It also includes a brief sample of the Instituto Dante Pazzanese experience for illustrative purpose. METHODS: The main procedures that are addressed include balloon and blade atrial septostomy (Rashkind and Park procedures), pulmonary valvuloplasty, aortic valvuloplasty, mitral valvuloplasty (for rheumatic mitral stenosis), angioplasty for coarctation of aorta with or without stent implantation, angioplasty for pulmonary artery stenosis with or without stent implantation, percutaneous occlusion of the patent ductus arteriosus, percutaneous occlusion of atrial septal defects and balloon dilation of stenosed Blalock-Taussig shunts. The authors make a review of the most important papers published in the literature about Interventional Pediatric Cardiology, including their own experience. RESULTS: Good or excelent therapeutic results are achieved for pulmonic stenosis, coarctation of aorta, patent ductus arteriosus, atrial septal defects and pulmonary branch stenosis. Satisfactory palliations are obtained for aortic stenosis, rheumatic mitral stenosis and complex congenital heart diseases that require balloon atrial septostomy. CONCLUSIONS: Due to the recent technological development, pediatric therapeutic heart catheterization makes it possible to treat or palliate about 30% of all congenital or acquired heart diseases with encouraging results, sparing some patients from the need of cardiac surgery.

Behavior-State–Dependent Changes in Human Fetal Pulmonary Blood Flow Velocity Waveforms

In Brief Objective To establish the influence of fetal behavior states on venous and arterial pulmonary blood flow velocity waveforms in the normally developing term fetus. Methods The relation between venous and arterial pulmonary blood flow velocity waveforms and fetal behavior states was investigated in 18 normal term fetuses. Recordings of the venous pulmonary blood flow velocity waveforms were obtained just proximal to the entrance in the left atrium, and the arterial pulmonary blood flow velocity waveforms were taken from the most proximal branch of the pulmonary artery in the same lung using color Doppler imaging. Time-averaged peak systolic, peak diastolic, and end-diastolic flow velocity; peak systolic to peak diastolic ratio; pulsatility index; and fetal heart rate were calculated from both venous and arterial Doppler recordings obtained during behavior states 1F (quiet sleep) and 2F (active sleep). Fetal behavior states were determined from combined recordings of fetal eye and body movements. Results Recordings of sufficient quality for analysis were obtained from ten fetuses. Venous pulmonary blood flow velocity waveforms demonstrated a statistically significant increase in time-averaged peak diastolic and end-diastolic velocity during fetal behavior state 2F. No behavior-state-related changes were observed for the arterial pulmonary blood flow velocity waveform. Conclusion The data suggest an increased pressure gradient between the pulmonary venous system and the left atrium during behavior state 2F. Flow velocity waveforms from the proximal arterial pulmonary branch are independent of behavioral state. Doppler velocity waveform analysis demonstrates behavior-state dependency in the venous pulmonary system but not in the arterial pulmonary system in the term fetus.

Behavior-state–dependent changes in human fetal pulmonary blood flow velocity waveforms

Objective: To establish the influence of fetal behavior states on venous and arterial pulmonary blood flow velocity waveforms in the normally developing term fetus. Methods: The relation between venous and arterial pulmonary blood flow velocity waveforms and fetal behavior states was investigated in 18 normal term fetuses. Recordings of the venous pulmonary blood flow velocity waveforms were obtained just proximal to the entrance in the left atrium, and the arterial pulmonary blood flow velocity waveforms were taken from the most proximal branch of the pulmonary artery in the same lung using color Doppler imaging. Time-averaged peak systolic, peak diastolic, and end-diastolic flow velocity; peak systolic to peak diastolic ratio; pulsatility index; and fetal heart rate were calculated from both venous and arterial Doppler recordings obtained during behavior states 1F (quiet sleep) and 2F (active sleep). Fetal behavior states were determined from combined recordings of fetal eye and body movements. Results: Recordings of sufficient quality for analysis were obtained from ten fetuses. Venous pulmonary blood flow velocity waveforms demonstrated a statistically significant increase in time-averaged peak diastolic and end-diastolic velocity during fetal behavior state 2F. No behavior-state-related changes were observed for the arterial pulmonary blood flow velocity waveform. Conclusion: The data suggest an increased pressure gradient between the pulmonary venous system and the left atrium during behavior state 2F. Flow velocity waveforms from the proximal arterial pulmonary branch are independent of behavioral state.

Fgf10 is essential for limb and lung formation.

The interactions between fibroblast growth factors (FGF) and their receptors have important roles in mediating mesenchymal-epithelial cell interactions during embryogenesis. In particular, Fgf10 is predicted to function as a regulator of brain, lung and limb development on the basis of its spatiotemporal expression pattern in the developing embryo. To define the role of Fgf10, we generated Fgf10-deficient mice. Fgf10-/- mice died at birth due to the lack of lung development. Trachea was formed, but subsequent pulmonary branching morphogenesis was disrupted. In addition, mutant mice had complete truncation of the fore- and hindlimbs. In Fgf10-/- embryos, limb bud formation was initiated but outgrowth of the limb buds did not occur; however, formation of the clavicles was not affected. Analysis of the expression of marker genes in the mutant limb buds indicated that the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) did not form. Thus, we show here that Fgf10 serves as an essential regulator of lung and limb formation.

Alteraciones cardiovasculares en el síndrome de cutis laxa congénita

Cutis laxa is a unusual disorder of the connective tissue. It may be hereditary or acquired and from the genetical viewpoint, can be either of the dominant or of the recessive type. The autosomic dominant type, less frequent, has a late beginning and the evolution is usually benign, and it seldom has cardiovascular anomalies. On the contrary, the recessive type usually has an early beginning having frequent cardiovascular anomalies, with the outcome of death early in infancy. We report two siblings with the recessive type of the illness, having peripheral arterial stenosis of pulmonary branches. We review the literature with special attention to the angiohemodynamic findings, as there are few bibliographic reports about this subject, as well as about the different hypothesis on the pathogenesis of this illness.

Fgf-10 is required for both limb and lung development and exhibits striking functional similarity to Drosophila branchless.

Fgf-10-deficient mice (Fgf-10(-/-)) were generated to determine the role(s) of Fgf-10 in vertebrate development. Limb bud initiation was abolished in Fgf-10(-/-) mice. Strikingly, Fgf-10(-/-) fetuses continued to develop until birth, despite the complete absence of both fore- and hindlimbs. Fgf-10 is necessary for apical ectodermal ridge (AER) formation and acts epistatically upstream of Fgf-8, the earliest known AER marker in mice. Fgf-10(-/-) mice exhibited perinatal lethality associated with complete absence of lungs. Although tracheal development was normal, main-stem bronchial formation, as well as all subsequent pulmonary branching morphogenesis, was completely disrupted. The pulmonary phenotype of Fgf-10(-/-) mice is strikingly similar to that of the Drosophila mutant branchless, an Fgf homolog.

Cavopulmonary anastomosis in staging toward fontan operation: pathologic substrates

Background. A review of the history and practice of cavopulmonary connections in staging toward Fontan operation and the pathologic experience at Padua University is presented. Methods. Gross and histologic assessment of the heart-lung blocks removed at autopsy in the cases in which the cause of death could be related to a dysfunction of the cavopulmonary anastomosis were performed. Results. The main complications were distortion of the intraatrial tunnel and thrombosis of the pulmonary branches of the cavopulmonary anastomosis. Conclusions. The cavopulmonary anastomosis remains a widespread procedure, both as a preliminary step to a Fontan operation and as an integral part of a Fontan or modified Fontan procedure in all those cardiac malformations characterized by a hypoplastic right or left ventricle in which these ventricles are too small to support the whole circulation.

NHLBI: fifty years of achievement in pulmonary biology and medicine.

On June 16, 1948, the National Heart Act (P.L. 80-655) authorized the formation of the National Heart Institute (NHI) to “improve the health of the people of the United States through the conduct of researches, investigations, experiments, and demonstrations relating to the cause, prevention, and method of diagnosis and treatment of diseases of the heart and circulation; assist and foster such researches and other activities by public and private agencies, and promote the coordination of all such researches and activities and the useful application of their results; provide training in matters related to heart diseases, including refresher courses for physicians; and develop, and assist states and other agencies in use of the most effective methods of prevention, diagnosis and treatment of heart diseases.” Although the NHI focused its efforts mainly on heart disease, its programs from the beginning included many projects on cardiopulmonary physiology. Research on topics such as fluid balance, muscle biology, control of breathing, high-altitude physiology, and hyperbaric medicine were part of the grant portfolio. These investigations paved the way for formal recognition of a long-standing need for a national program committed to diseases of the lung when the Secretary of the Department of Health, Education, and Welfare announced in November 1969 an expansion of the NHI to the National Heart and Lung Institute (NHLI). * At that time, the National Institutes of Health (NIH) was providing $11.0 million for support of research and training in respiratory diseases, but these activities were dispersed among various institutes, with little integration and no mechanism for coordination. Shortly after issuance of the new charter, several administrative actions were taken: ( 1 ) the NIH Guidelines for Referral were modified to reflect the expanded role of the NHLI; ( 2 ) the National Heart and Lung Advisory Council was increased from 12 to 16 members (Table 1); ( 3 ) an Office of Lung Programs was established in the NHLI; and ( 4 ) an intramural pulmonary program was initiated with establishment of a Pulmonary Function Laboratory in March 1971 and, shortly thereafter, a Pulmonary Branch for Intramural Research. In September 1972 Congress enlarged the authority of the Institute through the National Heart, Blood Vessel, Lung, and Blood Act (P.L. 92-423), which provided for expanded, intensified, and coordinated Institute activities in lung disease research and training. This action launched the formation of the Division of Lung Diseases and the beginning of intense research efforts in all aspects of pulmonary biology and medicine (with the exception of lung cancer, which remained in the National Cancer Institute, and infectious lung diseases, which remained the responsibility of the National Institute of Allergy and Infectious Diseases). In this report, we highlight some of the administrative steps that were taken and acknowledge the contributions of some individuals and groups that played an important role in guiding the implementation and evaluation of the national pulmonary research effort. As we mark the 50th anniversary of the NHLBI, it is clear that throughout the history of the Institute, a close and valuable collaboration in cardiopulmonary medicine must be recognized as contributing to a vast knowledge base that served as the foundation for many important discoveries made in this last half-century.

MR microscopy of lung airways with hyperpolarized 3He.

A technique using hyperpolarized (HP) 3He to image the small airways of the lung by using moderate flip angles and a short scanning period during early inspiration is demonstrated. Flip angles (alpha) ranging from 10-90 degrees were used in guinea pig experiments with scanning during the entire inspiration period. A second series acquired data throughout a short window of the ventilatory cycle with alpha = 45 degrees. The success of the animal studies has motivated implementation of similar imaging techniques in the clinical arena. Human studies involved imaging over the total inspiration period with alpha approximately 10 degrees. The first series of guinea pig experiments demonstrated that larger flip angles (50-90 degrees) destroy the magnetization before it reaches the smaller airways. At moderate flip angles (20-40 degrees), airway branching down to the fourth generation was apparent. Fifth-order branchings were seen in the images of the second series. The trachea down to fourth generation pulmonary airway branching, along with some distal air spaces, was seen in the human lung images.

Experiencia con el stent de Palmaz en la estenosis de rama pulmonar

Since 1989, the balloon expandable Palmaz stent (Johnson & Johnson Interventional Systems) has been used for the treatment of congenital heart disease. This study reports the results and the technique used for its implantation in native and post surgical retraction pulmonary branch stenosis. From february 1995 to june 1996, we have performed this technique in 11 symptomatic children/adolescents with pulmonary branch stenosis, the mean age was 11 +/- 2 years. Fourteen procedures were made and 16 stents were implanted. The mean condition of the patients was: 7 with tetralogy of Fallot after a previous complete correction, 1 with Noonan syndrome and a surgically corrected atrial septal defect, 1 with pulmonary trunk aneurysm and a previous surgical correction for pulmonary valve and branch stenosis, 1 with pulmonary atresia and an intact septum who underwent a surgical valvotomy and posterior percutaneous valvuloplasty with a good ventricular development, and final was a tricuspid atresia with a previous Waterston anastomosis which produced a stenosis at the right pulmonary branch who underwent a modified Fontan operation with the result of a severe stenosis at the medial and inferior right pulmonary artery. The branch ostium was affected in five cases, and in one case with diffuse hypoplasia of the right branch, the stenosis was at both sites. The stenosis was native in nine cases and post surgery in the other five (2 Waterston, 1 Blalock-Taussig, 1 Fontan). We used the right and/or left femoral vein in all cases except two, in which we used the internal jugular vein. We followed the technique reported by the Boston-Houston experience, with an extra stiff guide and Mullins sheath towards the site of the stenosis. The procedure was effective in all cases except one. The mean pulmonary branch and balloon diameter was 11 +/- 3 mm and 14 +/- 2 mm, respectively, rate 1.2. The stenosis diameter rose from 4.8 +/- 1 to 11 +/- 2 mm (p < 0.001) with a percentage fall from 63 +/- 5 to 2 +/- 1% (p < 0.001). The pressure gradient fell from 30 +/- 5 to 5 +/- 1 mmHg (p < 0.001) and the right ventricle systolic pressure fell from 77 +/- 6 to 48 +/- 3 mmHg (p < 0.01). The mean followup was 10 +/- 3 months, a symptomatic and pulmonary perfusion improvement was seen. After 8 +/- 4 months, we evaluated six patients/nine stents with angiography, and we excluded thrombosis, aneurysms and occlusion of lobar or segmental branches. One case had a proximal stent re-stenosis as it did not cover the whole stenosis, so a new stent was implanted. Three patients/four stents underwent redilatation getting a slightly higher diameter than previously. One patient had a stent migration and he underwent surgical stent retrieval. Implantation of the Palmaz stent is a useful procedure for the treatment of native or post-operative pulmonary stenosis. It is possible to apply it to hypoplastic and ostial pulmonary stenosis. We confirm the effectiveness of redilatation at mid term.

5-Hydroxytryptamine receptors mediating vasoconstriction in pulmonary arteries from control and pulmonary hypertensive rats.

1. We investigated 5-hydroxytryptamine (5-HT)-receptor mediated vasoconstriction in the main, first branch and resistance pulmonary arteries removed from control and pulmonary hypertensive rats. Contractile responses to 5-HT, 5-carboxamidotryptamine (5-CT, non-selective 5-HT1 agonist), and sumatriptan (5-HT1D-like receptor agonist) were studied. The effects of methiothepin (non-selective 5-HT1 + 2-receptor antagonist) and ketanserin (5-HT2A receptor antagonist) and GR55562 (a novel selective 5-HT1D receptor antagonist) on 5-HT-mediated responses were also studied. Basal levels of adenosine 3':5'-cyclic monophosphate ([cyclic AMP]i) and guanosine 3':5'-cyclic monophosphate ([cyclic GMP]i) were determined and we assessed the degree of inherent tone in the vessels under study. 2. 5-HT was most potent in the resistance arteries. pEC50 values were 5.6 +/- 0.1, 5.3 +/- 0.1, 5.0 +/- 0.2 in the resistance arteries, pulmonary branch and main pulmonary artery, respectively (n = at least 5 from 5 animals). The sensitivity to, and maximum response of, 5-HT was increased in all the arteries removed from the chronic hypoxic (CH) rats. In CH rats the pEC50 values were 5.9 +/- 0.2, 6.3 +/- 0.2, 6.4 +/- 0.2 and the increase in the maximum response was 35%, 51% and 41% in the resistance arteries, pulmonary branch and main pulmonary artery, respectively. Sumatriptan did not contract any vessel from the control rats whilst 5-CT did contract the resistance arteries. In the CH rats, however, they both contracted the resistance arteries (responses to sumatriptan were small) (pEC50: 5-CT; 5.4 +/- 0.2) and the pulmonary artery branches (pEC50: sumatriptan, 5.4 +/- 0.2; 5-CT, 5.4 +/- 0.2). 5-CT also caused a contraction in the main pulmonary artery (pEC50: 6.0 +/- 0.3). 3. Ketanserin (1 nM-1 microM) caused a competitive antagonism of the 5-HT response in all vessels tested. In control rats, the estimated pKb values for ketanserin in resistance arteries, pulmonary branches and main pulmonary artery were 8.3, 7.8 and 9.2, respectively. Methiothepin (1 nM-1 microM) inhibited responses to 5-HT in the first branch (estimated pKb value: 7.8) and main pulmonary artery. In CH rats, the estimated pKb values for ketanserin in resistance arteries, pulmonary branches and main pulmonary artery were 7.7, 8.3 and 9.6, respectively. Methiothepin also inhibited contractions to 5-HT in the pulmonary artery branch and main pulmonary artery with estimated pKb values of 7 and 9.5, respectively. In control animals, GR55562 had no effect on responses to 5-HT in any of the vessels tested. In the CH rats the estimated pKb values for GR55562 were 6.5, 7.8 and 7.0 in the pulmonary resistance arteries, first branch and main pulmonary artery, respectively. 4. Large pulmonary arteries from controls demonstrated inherent tone and this was increased three fold in the CH rats. The resistance arteries from controls demonstrated little inherent tone though this was enhanced in those from the CH rats. 5. [Cyclic AMP]i was 259 +/- 23 pmol mg-1 protein in the pulmonary artery branches removed from control rats and decreased to 192 +/- 11 pml mg-1 protein in the CH rats (P < 0.01, n = 8). [Cyclic GMP]i also decreased in the pulmonary artery branches (from 550 +/- 15, control to 462 +/- 31 pmol mg-1 protein in CH vessels, n = 8, P < 0.01) and in the main pulmonary arteries (from 566 +/- 33, control to 370 +/- 25 pmol mg-1 protein in CH vessels, n = 8, P < 0.001). No changes in either [cyclic AMP]i or [cyclic GMP]i were observed in the resistance arteries. 6. The results suggest that the increased vasoconstrictor response to 5-HT in CH rat pulmonary arteries is due to an increase in 5-HT2A-receptor mediated contraction combined with an increase in r5-HT1B-like receptor-mediated contraction. An increase in vascular tone and decreased levels of [cyclic GMP]i in the large pulmonary arteries may contribute to the observed increase in activity of r5-HT1B-like receptor