Normal Mean Pulmonary Artery Pressure Research Articles

S46 Outcome after pulmonary endarterectomy (PEA): Long term follow-up of the UK national cohort

IntroductionChronic thromboembolic pulmonary hypertension (CTEPH) is a life threatening condition that historically has a poor outcome with supportive medical treatment. Pulmonary endarterectomy (PEA) is the treatment of choice and offers...

Pulmonary hypertension in obesity-hypoventilation syndrome

Pulmonary hypertension (PH) is considered a clinically important feature of Obesity-Hypoventilation Syndrome (OHS). We aimed to determine prevalence, characteristics and severity of PH including associations with clinical outcomes after established non-invasive positive pressure ventilation (NPPV). In a prospective cross-sectional study, clinically stable OHS-patients (NPPV duration ≥ 3 months) were consecutively assessed using echocardiography, serum markers and right-heart catheterization (RHC). NPPV use was quantified via ventilator counters. Blood gases, lung function, Epworth-Sleepiness Scale (ESS), sleep-quality, WHO-functional class (WHO-FC), 6-min walk distance, and health-related quality of life (HRQL) via Severe Respiratory Insufficiency (SRI) questionnaire were assessed. Of 177 patients considered, 64 fulfilled inclusion criteria. Among these, 21 patients (10 female/11 male; BMI 45 [40; 53] kg/m(2), PaCO2 39.6 [37.8; 45.5] mmHg (median [quartiles])) gave consent for RHC. Four patients (19%) had normal mean pulmonary artery pressure (mPAP < 20 mmHg), 8 (38.1%) mPAP 20-24 mmHg and 9 (42.9%) manifest PH (mPAP ≥ 25 mmHg), 3 of them with combined pre- and/or postcapillary PH. mPAP was negatively correlated to NPPV use, vital capacity and lung diffusing capacity (p < 0.01 each), and positively to BMI (p < 0.05). NPPV use and vital capacity independently predicted mPAP. In patients with PH, ESS, WHO-FC, and some SRI-items were worse (p < 0.05 each) compared to patients without PH. Multivariate analyses revealed mPAP as the only independent predictor of the SRI-physical functioning domain. Mild to moderate PH is frequent in patients with OHS despite NPPV, mPAP being inversely related to NPPV adherence. PH is associated with impairments in daytime-sleepiness, WHO-FC, HRQL and physical functioning.

Baseline characteristics and follow-up in patients with normal haemodynamics versus borderline mean pulmonary arterial pressure in systemic sclerosis: results from the PHAROS registry

BackgroundPatients with normal (mean pulmonary arterial pressure (mPAP) ≤20 mm Hg) and borderline mean pulmonary pressures (21–24 mm Hg) are “at risk” of developing pulmonary hypertension (PH). The objectives of...

Severe Pulmonary Hypertension in Idiopathic Nonspecific Interstitial Pneumonia

Pulmonary hypertension (PH) is a common complication of interstitial lung disease (ILD), particularly in idiopathic pulmonary fibrosis (IPF) and ILD associated with connective tissue disease, where the underlying pathology is often a nonspecific interstitial pneumonia (NSIP) pattern. The degree of PH in ILD is typically mild to moderate and radiographic changes of ILD are usually prominent. We describe four patients with idiopathic NSIP and severe PH (mPAP > 40 mmHg). The average mean pulmonary artery pressure was 51±7 mmHg and pulmonary vascular resistance was 13±4 Wood's units. Pulmonary function was characterized by mild restriction (total lung capacity 63–94% predicted) and profound reductions in DLCO (19–53% predicted). Computed tomographic imaging revealed minimal to moderate interstitial thickening without honeycombing. In two of the cases, an initial clinical diagnosis of idiopathic pulmonary arterial hypertension was made. Both were treated with intravenous epoprostenol, which was associated with worsening of hypoxemia. All four patients died or underwent lung transplant within 4 years of PH diagnonsis. Lung pathology in all four demonstrated fibrotic NSIP with medial thickening of the small and medium pulmonary arteries, and proliferative intimal lesions that stained negative for endothelial markers (CD31 and CD34) and positive for smooth muscle actin. There were no plexiform lesions. Severe pulmonary hypertension can therefore occur in idiopathic NSIP, even in the absence of advanced radiographic changes. Clinicians should suspect underlying ILD as the basis for PH when DLCO is severely reduced or gas exchange deteriorates with pulmonary vasodilator therapy.

Pulmonary hypertension in critical care

To review the contemporary management of patients with pulmonary hypertension in critical care. The normal mean pulmonary artery pressure (mPAP) at rest is 14±3 mmHg and pulmonary hypertension is considered when mPAP is greater than or equal to 25 mmHg at rest. The classification of pulmonary hypertension has been redefined recently and updated in 2009 and could help to guide the management of patients with pulmonary hypertension in critical care. The management of pulmonary hypertension in ICU is based on expert opinion. Among the diagnostic and monitoring tools available, echocardiography provides useful information noninvasively, although pulmonary artery catheter must be used in case of complicated situations. Calcium sensitizers, a new class of inotrope, have inotropic effects and induce dilatation of the pulmonary, systemic, and coronary vasculature and thus could be useful in case of right ventricular failure (RVF), particularly in patients with acute respiratory distress syndrome (ARDS). By increasing the pulmonary vasodilator response to inhaled nitric oxide and preventing the rebound pulmonary vasoconstriction which occurs following cessation of nitric oxide breathing, selective type 5 isoform of phosphodiesterase inhibitors could be useful in critically ill patients. This article reviews recent and key findings on the management of pulmonary hypertension in critically ill patients.

Relationship Between Reactive Pulmonary Hypertension and Mortality in Patients With Acute Decompensated Heart Failure

In patients with heart failure, pulmonary hypertension (PH) predicts higher risk for morbidity and mortality. However, few data are available on the prognostic implications of reactive (precapillary) PH superimposed on passive (postcapillary) PH. We performed a subgroup analysis of 242 patients with acute decompensated heart failure assigned to pulmonary artery catheter placement in the Vasodilation in the Management of Acute Congestive Heart Failure trial. Patients were classified into 3 groups, using the final (posttreatment) hemodynamic measurements: (1) no PH (mean pulmonary artery pressure ≤ 25 mm Hg; (2) passive PH (mean pulmonary artery pressure > 25, pulmonary capillary wedge pressure >15 mm Hg, and pulmonary vascular resistance ≤ [corrected] Wood units); and (3) reactive PH (mean pulmonary artery pressure > 25, [corrected] pulmonary capillary wedge pressure >15 mm Hg, and pulmonary vascular resistance > 3 Wood units). Fifty-eight patients were classified as normal mean pulmonary artery pressure, 124 with passive PH and 60 with reactive PH. During follow-up of 6 months, 5 (8.6%), 27 (21.8%), and 29 (48.3%) deaths occurred in patients without PH, patients with passive PH, and with reactive PH, respectively (P<0.0001). After multivariable adjustments, reactive PH remained an independent predictor of death, with an adjusted hazard ratio of 4.8 compared with patients without PH, and 2.8 compared with patients with passive PH (95% confidence interval, 1.7 to 4.7, P=0.0001). Similar results were obtained when reactive PH was defined on the basis of transpulmonary gradient. Reactive PH is common among patients with acute decompensated heart failure after initial diuretic and vasodilator therapy. The adverse outcome associated with PH is predominantly due to increased mortality rates in the subgroup of patients with reactive PH.

Hémodynamique de repos et d’effort dans l’hypertension artérielle pulmonaire

The normal mean pulmonary artery pressure (PAP) is 14 ± 3 mmHg. Precapillary pulmonary hypertension is defined as a mean PAP ≥ 25 mmHg at rest and a pulmonary capillary wedge pressure ≤ 15 mmHg as assessed by right heart catheterization. When performed in experienced centers, right heart catheter procedures in patients with pulmonary hypertension are associated with low morbidity and mortality rates. Right heart catheterization remains essential for the management of pulmonary arterial hypertension (PAH) as it confirms the diagnosis, determines the type of pulmonary hypertension, its severity, its vasoreactivity as well as response to therapeutic interventions. The hemodynamic severity largely influences patients' management including the choice of initial and subsequent therapies. Hemodynamic evaluation during exercise allows a precise characterization of the true resistive properties of pulmonary vessels through the assessment of the pressure-flow relationship. The significance of isolated pulmonary hypertension during exercise remains unknown. Indeed, roughly 50% of healthy subjects > 50 years old exhibit mean PAP > 30 mmHg during mild exercise. Isolated exercise-induced increases in mean PAP > 30 mmHg during exercise is thus no longer used to define pulmonary hypertension. More complex hemodynamic parameters allow partitioning of arterial and venous vascular resistance, as well as a better characterization of pulmonary artery compliance, right ventricle function and right ventriculo-arterial coupling. The clinical relevance of these subtle markers of pulmonary vascular abnormalities remains unknown.

Prevalence of Acute Vasoresponsiveness in Patients With Pulmonary Hypertension: Treatment Implications

Pulmonary hypertension (PH) is a serious and often progressive disorder that results in right ventricular dysfunction. The general reported rate of patients who are responders is 10%-26%. More recently, using the current criteria, the rate of acute vasodilator response was as low as 6%. This study used the most current guidelines to assess the prevalence of acute vasoresponsiveness in patients with PH. A retrospective chart review of 618 patients seen in the PH clinic at the Mayo Clinic Jacksonville from 1991 to June 2008 was conducted. We assessed the prevalence of acute vasoresponsiveness in patients with PH who had undergone vasodilator trial with epoprostenol or nitric oxide, using the current accepted criteria. One hundred and seventy-six patients who underwent a vasodilator trial that had complete hemodynamic data were identified. The average age was 61 +/- 14 years and most were women (67%). The PH was severe with most patients in the World Health Organization (WHO) functional class III-IV (82%), and an average mean pulmonary artery pressure of 48 +/- 11 mm Hg. Although the study group included all WHO diagnostic groups, 69% were diagnosed as Group I pulmonary arterial hypertension. We found an overall prevalence of response to acute vasodilator therapy to be 26%. Using the most current criteria to identify acute responders to vasodilator therapy in PH patients, we found a slightly higher rate of "responders" than previously reported. Acute vasodilator testing identifies a clinically important group who may benefit from calcium channel blockers (CCBs), and this study confirms that a significant percentage of PH patients are acutely vasoresponsive.

Exercise-induced Pulmonary Arterial Hypertension Is Associated With An Attenuated Increase In Cardiac Output During Exercise

Pulmonary arterial hypertension (PAH) can be diagnosed at rest (rPAH) or in response to exercise (EIPAH), however the clinical significance of EIPAH is unclear. rPAH is associated with reduced pulmonary artery capacitance (PAC), an attenuated increase in cardiac output (CO) and a rise in pulmonary vascular resistance (PVC) during exercise. The presence of these abnormalities in subjects with EIPAH may reflect early pulmonary vasculopathy. PURPOSE: To determine whether clinically significant hemodynamic and ventilatory abnormalities exist in patients with EIPAH, despite normal mean pulmonary artery pressure (mPAP) at rest, and their impact on aerobic capacity and health related quality of life (HRQoL). METHODS: 39 symptomatic patients, NYHA class II (n = 27) or III (n = 12), at risk for PAH, underwent a cardiopulmonary exercise test (CPET) with a right heart catheter in situ. 21 healthy controls (C), matched for age, gender and BMI with EIPAH subjects, underwent CPET for comparison of aerobic capacity and ventilatory response. HRQoL (SF-36) was assessed in all subjects. RESULTS: Following CPET, patient subjects were stratified using World Health Organization PAH diagnostic criteria: resting PAH (mPAP ≥ 25 mmHg at rest, n = 7), EIPAH (mPAP ≤25 mmHg at rest, ≥30mmHg on exercise, n = 22) or no evidence of PAH (nonPAH) (n = 10). Compared with nonPAH, both rPAH and EIPAH were associated with lower CO (7.4±0.7, 8.6±0.5 vs 11.0±0.8 L/min, p<0.05, mean±SEM), higher PVC (4.6±0.7, 2.5±0.3 vs 1.4±0.2 Woods units, p<0.05) and lower PAC (1.2±0.3, 1.8±0.1 vs 2.4±0.2 ml/mmHg, p<0.05) at peak exercise. Compared with C, subjects with rPAH and EIPAH had lower peak oxygen consumption (12.8±1.8, 18.0±0.8 vs 25.6±1.7 ml/kg/min, p<0.01), lower end tidal carbon dioxide at anaerobic threshold (AT) (30.3±3.1, 34.0±0.8 vs 39.4±0.6 mmHg, p<0.01) and a higher ventilatory equivalent for carbon dioxide at AT (49.0±5.4, 39.2±1.7 vs 30.9±0.7, p<0.01). rPAH and EIPAH subjects had impaired HRQoL compared with C (p<0.05). CONCLUSIONS: EIPAH is associated with hemodynamic and ventilatory abnormalities typical of rPAH and is suggestive of a clinically important pulmonary vasculopathy linked to reduced exercise capacity and HRQoL.

Long-term outcome of palliation with internal pulmonary artery bands after primary heart transplantation for hypoplastic left heart syndrome.

The purpose of this study was to describe the long-term outcome of infants with hypoplastic left heart syndrome (HLHS) who underwent placement of internal pulmonary artery bands as part of a transcatheter palliation procedure followed by primary heart transplantation. Transcatheter palliation included stenting of the ductus arteriosus, decompression of the left atrium by atrial septostomy, and internal pulmonary artery band placement. Cardiac hemodynamics, pulmonary artery architecture, and pulmonary artery growth since transplantation are described. Nine infants with HLHS had internal pulmonary artery bands placed and underwent successful heart transplant. No infant required reconstruction of the pulmonary arteries at the time of transplant. At 1 year after transplant, all of the recipients had normal mean pulmonary artery pressure, pulmonary vascular resistance, and transpulmonary gradient. Pulmonary angiography performed at 1 year after transplant demonstrated no distortion of pulmonary artery anatomy with significant interval growth of the branch pulmonary arteries. There was 100% survival to hospital discharge after transplant in this cohort of infants. Transcatheter placement of internal pulmonary artery bands for HLHS offers protection of the pulmonary vascular bed while preserving pulmonary artery architecture and growth with good long-term outcome.

Pulmonary Hypertension in Patients with Bronchiolitis Obliterans Syndrome Listed for Retransplantation

Bronchiolitis Obliterans Syndrome (BOS) is a major cause of morbidity and mortality post-lung transplantation. Pulmonary hypertension (PH) may complicate the course of patients with advanced lung disease. We sought to characterize the prevalence of PH in patients with BOS. We performed a retrospective analysis of lung transplant recipients with BOS relisted for transplantation with the United Network for Organ Sharing (UNOS). Right heart catheterization (RHC) data were required for analysis. Eighty patients with BOS qualified for the analysis. PH was present in 32.5% of patients with an average mean pulmonary artery pressure (mPAP) of 32.3 mmHg (range: 26-63 mmHg). Of these, 42.3% had an elevated pulmonary capillary wedge pressure. There was no difference in PH prevalence between bilateral (26.5%) and single lung recipients (41.9%), nor did it differ by primary disease. There was no correlation between pulmonary function data and the presence or severity of PH. There was no difference in oxygen requirements or 6-min walk distance between patients with and without PH. This is the first report of PH in patients with BOS. Many of these cases occur in association with diastolic dysfunction. Although no impact on functional status or outcomes was discerned, further studies appear warranted.

Portopulmonary Hypertension and Liver Transplantation: Hemodynamic Consequences at Reperfusion

Background The absence of portopulmonary hypertension (PH) upon preoperative evaluation for liver transplantation (OLT) does not exclude the occasional occurrence of an acquired PH while awaiting a graft. We sought to estimate hemodynamic changes and right ventriculoarterial coupling during reperfusion. Methods We studied 11 cirrhotic patients diagnosed with mild PH, according to the current classification: mean pulmonary artery pressure (MPAP)-25 to 34 mm Hg. These patients underwent OLT, using the piggyback technique (group PH). None of them had exhibited criteria for PH on preoperative echocardiography. This cohort was compared with 20 consecutive cirrhotic patients with normal MPAP at OLT. We performed a complete hemodynamic profile using a pulmonary artery catheter (RVEF, Baxter-Edwards, Calif, USA) before and 5 minutes after reperfusion. The variables were MPAP and right ventricular (RV) end-diastolic volume index (RVEDVI). Using standard formulas we calculated RV stroke work index (RVSWI), RV end-systolic elastance (Ees), pulmonary effective elastance (Ea), and RV-arterial coupling efficiency as the Ees/Ea ratio. Systolic ventricular function was expressed as RVSWI versus RVEDVI. Results During the anhepatic phase, MPAP, Ees, Ea, and RVSWI were higher in the PH group; but RVEDVI was lower. After reperfusion the pressure (MPAP), contractility (RVSWI) and preload (RVEDVI) increased in both groups. However, afterload (Ea) decreased in the non-PH group; accordingly, Es/Ea increased only in these patients. Discussion At reperfusion, the expansion in preload and cardiac output, without a similar afterload decrease, is responsible for the steady increase in pressure. Our results have shown that in the PH patient group, systolic ventricular function improves during reperfusion by a Frank-Starling mechanism; however, ventricular-arterial uncoupling is maintained (Ees/Ea < 1) because ventricular contractility is not appropriately balanced by simultaneous declines in afterload.

Effects of Dobutamine on Right Ventricular Function and Pulmonary Circulation in Pulmonary Hypertension During Liver Transplantation

Introduction In the setting of orthotopic liver transplantation (OLT), pulmonary hypertension (PH) affects right ventricular (RV) function. When RV failure occurs, reducing RV afterload, optimizing RV preload, and preserving coronary perfusion through maintenance of systemic blood pressure are the primary goals of intraoperative treatment. Patients and methods To verify the effect of dobutamine on RV function and RV-arterial coupling, we compared a group of 9 cirrhotic patients with mild PH treated with OLT to a group of 20 patients with normal mean pulmonary artery pressure (MPAP). All patients received dobutamine (5–10 μg/kg/min) to maintain a cardiac index (CI) >3 L/min/m 2, during the anhepatic phase. Hemodynamic profile, using a pulmonary artery catheter, was performed before and during dobutamine infusion, studying MPAP, CI, and RV end-diastolic volume index (RVEDVI). RV stroke work index (RVSWI), RV end-systolic elastance (Ees), pulmonary effective elastance (Ea), and RV-arterial coupling efficiency as the Ees/Ea ratio were also calculated. Results RV contractility (Ees and RVSWI) and afterload (Ea) were significantly higher among the PH group. In both groups, all the studied variables improved with dobutamine: RV contractility increased, afterload decreased, and thus Ees/Ea coupling markedly increased. Conclusion Cirrhotic patients with mild PH who were undergoing OLT still have a reserve of RV contractile performance and pulmonary vasodilation.

Pneumonectomy for unilateral destroyed lung with pulmonary hypertension due to systemic blood flow through broncho-pulmonary shunts

Three decades ago, a few patients with pulmonary hypertension and respiratory failure associated with a unilateral destroyed lung were reported to have been treated by a pneumonectomy. In the present study, we investigated the clinical features, operative indications, and results of four cases with pulmonary hypertension that underwent a pneumonectomy for a unilateral destroyed lung. Four patients (three males, one female) with a destroyed lung and pulmonary hypertension (mean pulmonary arterial pressure >25 mmHg) were treated by a pneumonectomy between 1999 and 2002 at our institution. Their mean age was 59 years old (range 42-68 years). The underlying lung disease, Medical Research Council (MRC) dyspnea scale, respiratory function, arterial blood gas analysis, pulmonary arterial pressure, preoperative management, operative procedure, and postoperative course for each were reviewed retrospectively. The underlying lung disease that caused the destroyed lung was bronchiectasis in two patients, chronic empyema with bronchopleural fistula in one, and necrotizing pneumonia in one. The average mean pulmonary artery pressure was 33 mmHg (range 25-42 mmHg), which decreased to 27 mmHg (range 19-36 mmHg) after occlusion of the pulmonary artery in the affected lung. Following the pneumonectomy, the average mean pulmonary artery pressure was decreased to 17 mmHg (range 11-25 mmHg). Chronic inflammatory symptoms and functional impairments (showed by blood gas analysis, pulmonary arterial pressure, or MRC dyspnea scale) improved post-pneumonectomy. There was no operative death, though postoperative cardiorespiratory failure occurred in one patient. All patients were discharged from the hospital. We concluded that a pneumonectomy procedure may be indicated for selected patients with a unilateral destroyed lung and pulmonary hypertension due to systemic blood flow though broncho-pulmonary shunts.

Portopulmonary Hypertension in Pediatric Patients

To investigate the clinical presentation, manifestations, and response to therapy of portopulmonary hypertension (PPHTN) in pediatric patients. This study was a retrospective chart review describing the evaluation and course of 7 patients with PPHTN. Causes of portal hypertension (HTN) included biliary atresia (3 cases), cavernous transformation of the portal vein (2 cases), and primary sclerosing cholangitis and cryptogenic cirrhosis (1 case each). The median interval from the diagnosis of portal HTN to PPHTN was 12.1 years. Four patients presented with a new heart murmur, 4 presented with syncope, and 3 presented with dyspnea. Although electrocardiograms (ECGs) and chest x-rays were normal in 3 and 2 patients, respectively, echocardiograms diagnosed pulmonary HTN in all 7 patients. Five patients had cardiac catheterizations; the average mean pulmonary artery pressure was 65 +/- 20 mm Hg. Response to therapy was variable, and 4 patients died. Postmortem lung tissue examination revealed plexiform lesions and pulmonary arteriopathy. Because symptoms are subtle and may be overlooked, pediatric patients with portal HTN who develop a new heart murmur, dyspnea, syncope, or who are being evaluated for liver transplantation require evaluation for PPHTN. ECG and chest x-ray are insensitive screens for PPHTN. An echocardiogram and cardiology evaluation is essential for the diagnosis.

4328 The imaging spectrum of pulmonary hypertension

Resume Pulmonary Hypertension Pulmonary hypertension exists when the mean pulmonary artery pressure exceeds 25mm of Hg at rest. The normal mean pulmonary artery pressure is 12-16mm of Hg at sea level. Pulmonary hypertension is commonly associated with underlying lung diseases such as emphysema and severe fibrosis. In these cases the diagnosis is not difficult. In more unusual causes the diagnosis is delayed up to 24 months after the onset of symptoms which are non-specific and include fatigue, dyspnea, chest pain and syncope. Pulmonary hypertension has been classified in number of ways including the classic separation between pre-capillary and post-capillary disease. Precapillary Pulmonary Hypertension Primary pulmonary hypertension is a disease primarily of women. There is also known association with collagen-vascular disease, HIV infection, portal hypertension and drug ingestion (anorexigens). Pulmonary embolie disease including: bland emboli, tumor emboli, talc and schistosomiasis. Postcapillary Pulmonary Hypertension Pulmonary veno-occlusive disease Compression of pulmonary veins Atrial tumors Mitral disease Left ventricular dysfunction. The pulmonary capillaries can be directly involved in patients with pulmonary capillary hemangiomatosis. The imaging findings in these disease will be discussed.

Acute cardiovascular responses to leg-press resistance exercise in heart transplant recipients

Background: Reduced skeletal muscle strength is characteristic of individuals following heart transplantation. Weight lifting exercise has been demonstrated as an effective means by which to increase muscular strength in other cardiac patients but the appropriateness of this form of exercise in heart transplant patients has not been investigated. The purpose of this study was to describe the cardiovascular responses of heart transplant patients to a single, prolonged bout of weight lifting training. Methods: Twenty-three heart transplant recipients were stratified into early (Early; 3 months; n=6), intermediate (Intermediate; 1–3 years; n=7) and late (Late; 5–14 years; n=10) post transplant groups and studied in four experimental conditions: supine rest, upright rest, single leg-press exercise (28 repetitions over 2 min 20 s at 50% 1 repetition maximum) and recovery. Swan-Ganz catheterization allowed measurement of right heart pressures and cardiac output by thermodilution. Systemic arterial pressures and heart rate were measured continuously using a non-invasive finger cuff. Results: Cardiac output increased by 30, 40 and 54% during exercise in Early, Intermediate and Late, respectively. Heart rate increased by 4.5% in Early compared to 11 and 16% increases in Intermediate and Late. At peak exercise, systolic blood pressures reached average values of 179±9, 180±14 and 176±8 mmHg in Early, Intermediate and Late, respectively. Average mean pulmonary artery pressure did not exceed 30 mmHg and average pulmonary wedge pressure did not exceed 15 mmHg in any group during the exercise. Conclusions: These observations indicate that a lengthened set of single leg-press exercise at a moderate lifting intensity can be performed within safe and acceptable physiological limits in patients following heart transplantation. To better address the specific rehabilitation needs of heart transplant recipients, future research should focus on developing training programs which include weight lifting exercise.

Pulmonary blood flow alters nitric oxide production in patients undergoing device closure of atrial septal defects

OBJECTIVETo determine the effect of pulmonary blood flow (Qp) on nitric oxide (NO) production in patients with increased Qp due to an atrial septal defect (ASD).BACKGROUNDAlterations in pulmonary vascular NO production have been implicated in the development of pulmonary hypertension secondary to increased Qp. In vitro, acute changes in flow or shear stress alter NO production. However, the effect of Qp on lung NO production in vivo is unclear.METHODSNineteen patients (2.4–61 years of age, median 17) with secundum ASD undergoing device closure were studied. Before, and 30 min after ASD closure, exhaled NO and plasma nitrate concentration were measured by chemiluminescence (NOA 280, Sievers, Boulder, Colorado).RESULTSBefore ASD closure, all patients had increased Qp (Qp: systemic blood flow [Qs] of 2.0 ± 0.7) and normal mean pulmonary arterial pressure (13.4 ± 3.1 mm Hg). Atrial septal defect device closure decreased Qp from 6.0 ± 2.5 to 3.6 ± 1.3 L/min/m2(p < 0.05). Mean pulmonary arterial pressure was unchanged. Associated with the decrease in Qp, both exhaled NO (−22.1%, p < 0.05) and plasma nitrate concentrations (−17.9%, p < 0.05) decreased.CONCLUSIONSThese data represent the first demonstration that acute changes in Qp alter pulmonary NO production in vivo in humans. Exhaled NO determinations may provide a noninvasive assessment of pulmonary vascular NO production in patients with congenital heart disease. Potential correlations between exhaled NO, pulmonary vascular reactivity and pulmonary hypertension warrant further study.

Effects of inhaled nitric oxide on platelet-activating factor-induced pulmonary hypertension in dogs.

Platelet-activating factor (PAF), a lipid mediator released during endotoxin shock, induces pulmonary hypertension, systemic hypotension and cardiac dysfunction. In this study, we compared the effect of inhaled nitric oxide (NO) on PAF-induced pulmonary hypertension and NO metabolism with that on pulmonary hypertension induced by a stable thromboxane A2 mimetic, U46619. Since PAF-induced hypotension might be mediated by NO, the effect of inhaled NO combined with an intravenously administered NO synthase inhibitor, NG-nitro-L-arginine (L-NNA), on PAF-induced hemodynamic change was also investigated. In a total of 28 beagles anesthetized with pentobarbital the following substances were intravenously administered: PAF 0.56 +/- 0.30 microgram.kg-1.min-1 (group PAF), L-NNA 10 mg.kg-1 + PAF 0.04 +/- 0.03 microgram.kg-1.min-1 (group L-NNA + PAF), U46619 0.60 +/- 0.11 microgram.kg-1.min-1 (group U46619) or L-NNA 10 mg.kg-1 + U46619 0.61 +/- 0.23 microgram.kg-1.min-1 (group L-NNA + U46619) to obtain a mean pulmonary arterial pressure (MPAP) of 25 mmHg. Nitric oxide was then inhaled at 5, 10, 20 and 40 ppm for 15 min at 15-min intervals in the order of increasing concentration. An additional 7 dogs (control group) inhaled NO at normal MPAP (17 mmHg). Hemodynamic and respiratory parameters, NOHb, NO2- + NO3-, and MetHb levels in blood were measured before and during NO administration. In the control group, hemodynamic and respiratory values did not change significantly during NO administration. In group PAF, NO significantly reversed the PAF-induced pulmonary hypertension. PAF induced a marked systemic hypotension and cardiac output reduction, but these changes were not affected by inhalation of NO. L-NNA pretreatment markedly decreased the dose of PAF required to maintain a MPAP of 25 mmHg, and abolished the PAF-induced hypotension. In group L-NNA + PAF, the diminishing effect of inhaled NO on pulmonary vascular resistance (PVR) was significantly greater than that in group PAF. U46619 induced pulmonary hypertension and increases in blood pressure, intrapulmonary shunt and peak airway pressure. L-NNA pretreatment did not change the dose of U46619 required to maintain a MPAP of 25 mmHg. The effects of inhaled NO on PVR decrease were similar in groups U46619 and L-NNA + U46619. No NOHb was detected in any group. NO2- + NO3- concentration increased during NO administrations. There were no significant differences in NO2- + NO3- concentration among groups. Inhaled NO at the dose of 5-40 ppm effectively reversed PAF-induced pulmonary hypertension, especially following pretreatment with L-NNA. Inhaled NO did not affect PAF-induced hypotension or cardiac dysfunction. These findings indicate that low concentrations of inhaled NO may be useful in reversing pulmonary hypertension in the endotoxemia where PAF may be one mediator.

Lesson of the Week: Adrenocortical failure in intensive care

Diagnosis of acute adrenocortical failure in patients admitted to intensive care units is difficult as the clinical features are non-specific and may mimic those of other conditions. We report on a patient in whom the initial diagnosis of septic shock had to be amended later to acute adrenocortical failure. The criteria for laboratory diagnosis of adrenocortical failure in patients in intensive care may need to be modified as adrenocortical function is altered in patients with severe organ dysfunction. A 45 year old woman with myasthenia gravis was admitted to intensive care breathless and disoriented. She had a fever, with a temperature of 38°C, and had an arterial pressure of 60/40 mm Hg. Her serum concentration of sodium was 131 mmol/l and of potassium was 4.4 mmol/l. A full blood count showed a haemoglobin concentration of 148 g/l and leukocytosis, with a cell count of 18.9 x 109/l. Despite fluid resuscitation with 2000 ml 0.9% saline and 1000 ml gelatin (Haemaccel) she remained hypotensive. A pulmonary artery catheter was inserted, and the haemodynamic profile showed a normal mean pulmonary artery pressure of 15 mm Hg and cardiac index of 3.8 l/min/m2 but a low systemic vascular resistance index of 971 dyne.sec/cm5/m2 and left ventricular stroke work index of 20.7 g/m2/beat. A presumptive diagnosis of septic shock …