Lower Pulmonary Artery Pressure Research Articles

Reconditioning of an injured lung graft with intrabronchial surfactant instillation in an ex vivo lung perfusion system followed by transplantation

BackgroundWe tested whether an injured lung graft from category-3 donation after cardiac death donor could be reconditioned with an ex vivo lung perfusion (EVLP) system by intrabronchial diluted surfactant lavage before transplantation. MethodsIn a pig model, cardiac arrest was induced by deconnecting from the ventilator. Left lung injury was done by intrabronchial instillation of 1 mL/kg pepsin + HCl. After retrieval, the heart–lung block was stored at 4°C for 2 h. In the treated group, transplantation was performed after reconditioning with intrabronchial diluted surfactant lavage in EVLP system. ResultsDuring EVLP, surfactant group showed better oxygenation and lower pulmonary vascular resistance. After transplantation, better oxygenation, lower mean pulmonary artery pressure, and lower lung edema were observed in surfactant group. Lower blood IL-1 beta and IL-6 cytokine levels were measured in the surfactant group. In bronchoalveolar lavage, the percentage of neutrophils, IL-1 beta and IL-6 cytokine levels, amount of protein, and neutrophil infiltration in the lung tissue at the end of the experiment were significantly lower in the surfactant group. ConclusionsOur data demonstrate the feasibility of reconditioning and transplantation of an acutely damaged lung graft due to aspiration from a category-3 DCD donor. Implementation of an EVLP system is an efficacious tool to recondition and assess a questionable graft before transplantation.

Transit of micro-bubbles through the pulmonary circulation of Thoroughbred horses during exercise

It has been observed that microbubbles may pass through the pulmonary circulation of dogs and humans during exercise. In humans, this phenomenon has been associated with lower pulmonary artery pressures, enhanced right ventricular function and greater exercise capacity. In the exercising Thoroughbred horse, extraordinarily high cardiac outputs exert significant pulmonary vascular stresses. The aim of this study was to determine, using contrast echocardiography, whether Thoroughbred horses performing strenuous exercise developed pulmonary transit of agitated contrast microbubbles (PTAC). At rest, agitated contrast was observed in the right ventricle, but not in the left ventricle. However, post-exercise microbubbles were observed in the left ventricle, confirming the occurrence of PTAC with exercise but not at rest. Further investigation is warranted to investigate whether this phenomenon may be associated with superior physiology and performance measures as has been implicated in other species.

PDT Targeting Pulmonary Hypertension: Implications Prevention and Treatment by Photodynamic Therapy

Purpose Pulmonary arterial hypertension (PH) is an unremitting disease defined by progressive increase in pulmonary vascular resistance and vascular remodeling. Currently, little is known about treatments that affect vascular endothelial cell related pathogenic feature of PH. We propose to use photodynamic therapy (PDT) to treat PH, which use vascular specific light sensitive drug (a photosensitizer) and light in the presence of oxygen to irreversibly damage cells. We hypothesize that PDT can reverse vascular remodeling in PH through anti-endothelial proliferative mechanisms. Aim of this study therefore is to evaluate the therapeutic effects of PDT using animal PH model. Methods and Materials To induce PH, Sprague Dawley rats were injected with 60mg/kg monocrotaline (MCT). At day 7, PDT (630nm, 50 J/cm 2 ) using the photosensitizer, aminolevulinic acid (ALA) was administered. Hemodynamic measurements were taken on day 21 and lung and heart samples were dissected for molecular protein analysis. Results Rats treated with PDT using ALA had a significant reduction in right ventricular systolic pressure (RVSP), implying lower pulmonary arterial pressure, and a decreased ratio of RV/LV+S (right ventricle/left ventricle + septum), signifying reduced RV hypertrophy, compared with MCT-PH rats that received solely laser treatment. We observed a significant increase in P21Cip expression and decreased CKD1 and PCNA expression in the rat receiving PDT treatment. Hematoxylin and immunostaining showed PDT partially reverse MCT induced vascular remodeling in the lung treated versus untreated rats. Conclusions The clinical relevance of the findings in animal models will be assessed in human PAH lung tissue after lung transplantation. With these studies, we hope to provide new approaches for the treatment of this devastating disease.

Pulmonary oligemia maneuver can alleviate pulmonary artery injury during pulmonary thromboendarterectomy procedure

Background Pulmonary thromboendarterectomy (PTE) has evolved as a treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH). This study aimed to characterize if pulmonary oligemia maneuver (POM) can alleviate pulmonary artery injury during PTE procedure. Methods A total of 112 cases of CTEPH admitted to Beijing Anzhen Hospital from March 2002 to August 2011 received PTE procedure. They were retrospectively classified as non-POM group (group A, n=55) or POM group (group B, n=57). Members from group B received POM during rewarming period, whereas members from group A did not. Results There were three (5.45%) early deaths in group A, no death in group B (0) (Fisher's exact test, P=0.118). Six patients in group A needed extracorporeal membrane oxygenation (ECMO) as life support after the PTE procedure, no patients in group B needed ECMO (Fisher's exact test, P=0.013). The patients in group B had a shorter intubation and ICU stay, lower mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR), higher partial pressure of oxygen in artery (PaO2) and arterial oxygen saturation (SaO2) and less medical expenditure than patients in group A. With a mean follow-up time of (58.3 ± 30.6) months, two patients in group A and one patient in group B died. The difference of the actuarial survival after the procedure between the two groups did not reach statistical significance. Three months post the PTE procedure, the difference of residual occluded pulmonary segment between the two groups did not reach statistical significance (P=0.393). Conclusion POM can alleviate pulmonary artery injury, shorten ICU stay and intubation time, and lower down the rate of ECMO after PTE procedure.

An investigation into beef calf mortality on five high-altitude ranches that selected sires with low pulmonary arterial pressures for over 20 years

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.

Living at Altitude Adversely Affects Survival Among Patients With a Fontan Procedure

This study sought to determine whether survival in this cohort of patients was adversely affected by increased residential altitude. The success of the Fontan procedure depends in large part on low pulmonary vascular resistance (PVR). Factors that increase PVR, including an increase in residential altitude, may adversely affect long-term outcome. Higher altitude has been shown to affect functional well-being in patients with a Fontan circulation. Databases from a tertiary cardiac care center in the Intermountain West (elevation 5,000 feet) were analyzed for patients born with single-ventricle anatomy who would now be of adult age. Complete data were then collected on all identified patients who subsequently underwent the Fontan operation. Correlates of, and time to, adverse outcome, defined as death, cardiac transplantation, or clinical decompensation requiring a move to sea level, were determined. Of 149 patients with single-ventricle anatomy, 103 underwent the Fontan procedure, with 70 surviving to adulthood at moderate altitude. Adverse outcome occurred in 55, with death in 24 (23%), cardiac transplantation in 18 (17%), and clinical decompensation requiring move to sea level in 13 (13%). There was no relationship between type, age at, or era of Fontan procedure and long-term outcome. Correlates of long-term, transplant-free survival at moderate altitude included lower residential altitude (4,296 vs. 4,637 feet, p < 0.001), and lower pulmonary artery pressures before the Fontan procedure (13 vs. 15 mm Hg, p = 0.01), and after (14 vs. 18 mm Hg, p = 0.01). Long-term outcome after the Fontan procedure is adversely impacted by higher residential altitude.

Dexamethasone mimics aspects of physiological acclimatization to 8 hours of hypoxia but suppresses plasma erythropoietin.

Dexamethasone ameliorates the severity of acute mountain sickness (AMS) but it is unknown whether it obtunds normal physiological responses to hypoxia. We studied whether dexamethasone enhanced or inhibited the ventilatory, cardiovascular, and pulmonary vascular responses to sustained (8 h) hypoxia. Eight healthy volunteers were studied, each on four separate occasions, permitting four different protocols. These were: dexamethasone (20 mg orally) beginning 2 h before a control period of 8 h of air breathing; dexamethasone with 8 h of isocapnic hypoxia (end-tidal Po2 = 50 Torr); placebo with 8 h of air breathing; and placebo with 8 h of isocapnic hypoxia. Before and after each protocol, the following were determined under both euoxic and hypoxic conditions: ventilation; pulmonary artery pressure (estimated using echocardiography to assess maximum tricuspid pressure difference); heart rate; and cardiac output. Plasma concentrations of erythropoietin (EPO) were also determined. Dexamethasone had no early (2-h) effect on any variable. Both dexamethasone and 8 h of hypoxia increased euoxic values of ventilation, pulmonary artery pressure, and heart rate, together with the ventilatory sensitivity to acute hypoxia. These effects were independent and additive. Eight hours of hypoxia, but not dexamethasone, increased the sensitivity of pulmonary artery pressure to acute hypoxia. Dexamethasone, but not 8 h of hypoxia, increased both cardiac output and systemic arterial pressure. Dexamethasone abolished the rise in EPO induced by 8 h of hypoxia. In summary, dexamethasone enhances ventilatory acclimatization to hypoxia. Thus, dexamethasone in AMS may improve oxygenation and thereby indirectly lower pulmonary artery pressure.

Management of moderate secondary mitral regurgitation at the time of aortic valve surgery†

To define the impact of surgical strategy [concomitant mitral valve surgery or isolated aortic valve replacement (AVR)] in patients with moderate secondary mitral regurgitation (MR) at the time of AVR. From January 1999 to December 2009, 3339 patients underwent AVR of whom 255 had secondary MR >2+ and constituted the study population. Patients were stratified into two groups, with (Group A, n = 94, 36.8%) and without concomitant mitral valve surgery (Group B, n = 161, 63.2%). Follow-up up to 12 years (1076 patient-years) was analysed for survival, valve-related events and persistent MR. Predictors of late mortality and persistent MR were further analysed. A case-match analysis [age, gender, New York Heart Association (NYHA) and left ventricular ejection fraction] was performed, excluding patients with coronary artery disease (CAD). The mean age of the population was 67.0 ± 11.7 years, 63.5% male and 64.7% in NYHA III-IV. Group B patients were significantly older and had higher incidence of coronary disease, hypertension and mitral calcification. They also had a higher ejection fraction and transaortic gradients, and lower MR grade (mean MR: 2.8 vs 3.2) and pulmonary artery pressure. Mitral surgery consisted mainly of annuloplasty procedures (96%). Only 2 patients from the entire cohort were reoperated on/for the mitral valve. Thirty-day mortality rate was 0.3%. There was no difference in long-term survival and valve-related complications, even after case-matched analysis. CAD, history of cerebrovascular accident, permanent atrial fibrillation, renal failure and persistence of MR emerged as independent predictors of late mortality (P < 0.05). MR improved in 67.4% of patients from Group B against 82.3% from Group A (P = 0.011). Atrial fibrillation (AF) and higher MR grade at discharge were the only independent predictors for persistent MR (P < 0.05). Patients with persistent MR early after AVR had decreased late survival (hazard ratio: 4.9, P = 0.001). Secondary MR improves after AVR even without mitral surgery. Concomitant mitral surgery was significantly associated with greater improvement of postoperative MR, but had no significant impact on survival. However, patients who did not improve immediately after AVR had compromised survival. Patients in AF should have mitral valve repair at the time of surgery.

Comparison of Acute Hemodynamic Effects of Inhaled Nitric Oxide and Inhaled Epoprostenol in Patients with Pulmonary Hypertension

Inhaled nitric oxide (iNO) is used for acute vasoreactivity testing in pulmonary arterial hypertension (PAH) patients. Inhaled epoprostenol (iPGI2) has pulmonary selectivity and is less costly. We sought to compare acute hemodynamic effects of iNO (20 ppm) and iPGI2 (50 ng/kg/min) and determine whether their combination has additive effects. We conducted a prospective, single center, randomized, cross-over study in 12 patients with PAH and seven with heart failure with preserved ejection fraction (HFpEF). In PAH patients, iNO lowered mean pulmonary artery pressure (mPAP) by 9 ± 12% and pulmonary vascular resistance (PVR) by 14 ± 32% (mean ± SD). iPGI2 decreased mPAP by 10 ± 12% and PVR by 12 ± 36%. Responses to iNO and iPGI2 in mPAP and PVR were directly correlated (r2 = 0.68, 0.70, respectively, P < 0.001). In HFpEF patients, mPAP dropped by 4 ± 7% with each agent, and PVR dropped by 33 ± 23% with iNO, and by 25 ± 29% with iPGI2 (P = NS). Pulmonary artery wedge pressure (PAWP) increased significantly with iPGI2 versus baseline (20 ± 3 vs. 17 ± 2 mmHg, P = 0.02) and trended toward an increase with iNO and the combination (20 ± 2, 19 ± 4 mmHg, respectively). There were no additive effects in either group. In PAH patients, the vasodilator effects of iNO and iPGI2 correlated at the doses used, making iPGI2 a possible alternative for testing acute vasoreactivity, but their combination lacks additive effect. Exposure of HFpEF patients to inhaled vasodilators worsens the PAWP without hemodynamic benefit.

317: Could intra-aortic balloon pump in addition to extracorporeal membrane oxygenation improve hemodynamics in patients hospitalized for refractory cardiogenic shock?

Refractory cardiogenic shock may lead to the emergent implantation of an ECMO (ExtraCorporeal Membrane Oxygenation). Previous recent guidelines recommend the use of IABP (Intra-Aortic Balloon Pump) in this situation. Up to now, it still remains a debate whether the combination of both these devices may be usefull. The purpose of this study was to determine the impact of an IABP combined to the ECMO on the basis of general hemodynamic parameters and microcirculation. This monocentric prospective study included all patients hospitalized for refractory cardiogenic shock treated with ECMO and IABP between November 2010 and October 2011 in our Intensive Care Unit at la Pitié-Salpêtrière hospital, Paris, France. General hemodynamic status was assessed using clinical parameters, echocardiography and pulmonary capillary catheter. Microcirculation was evaluated using orthogonal polarized spectroscopy and tissue oxygen saturation in muscle (InSpectra®) as well as in brain (Equanox®). We included 12 consecutive patients aged of 57,3±14,4 yo (75% men). IABP was associated with lower systolic pulomary arterial pressure (23,4±9,4 mmHg vs 28,5±10,5 mmHg, p<0,05), lower mean pulmonary arterial pressure (18,8±7,8 mmHg vs 23,7±0,9 mmHg, p<0,01), lower pulmonary capillary wedge pressure (14,9±7,7 mmHg vs 19,3±9,6 mmHg, p<0,01) and higher left ventricular filling (LV) pressure (E/A ratio at 1,3±0,4 vs 2,0±0,9, p=0,04). IABP significantly reduced LV dimensions (End-diastolic LV diameter 51,8±13,6 mm vs 54,2±13,4 mm, p<0,001 and End-systolic LV diameter 49,6±13,7 mm vs 50,8±13,1 mm, p<0,05). However, no statistical improvement of the microcirculation was observed on the basis of muscular and brain oxymetry. In refractory cardiogenic shock requiring ECMO, the association with an IABP could reduce the incidence of acute pulmonary edema by recreating a pulsatile blood flow but does not significantly improve micro-circulation.

Pharmacology of Milrinone in Neonates With Persistent Pulmonary Hypertension of the Newborn and Suboptimal Response to Inhaled Nitric Oxide*

Persistent pulmonary hypertension of the newborn is a common problem with significant morbidity and mortality. Inhaled nitric oxide is the standard care, but up to 40% of neonates are nonresponders. Milrinone is a phosphodiesterase III inhibitor which increases the bioavailability of cyclic adenosine monophosphate and has been shown to improve pulmonary hemodynamics in animal experimental models. The primary objective was to investigate the pharmacological profile of milrinone in persistent pulmonary hypertension of the newborn. Secondary objectives were to delineate short-term outcomes and safety profile. An open label study of milrinone in neonates with persistent pulmonary hypertension of the newborn was conducted. Patients received an intravenous loading dose of milrinone (50 μg/kg) over 60 mins followed by a maintenance infusion (0.33-0.99 μg/kg/min) for 24-72 hrs. Physiologic indices of cardiorespiratory stability and details of cointerventions were recorded. Serial blood milrinone levels were collected after the bolus, following initiation of the maintenance infusion to determine steady state levels, and following discontinuation of the drug to determine clearance. Echocardiography was performed before and after (1, 12 hrs) milrinone initiation. Milrinone. Eleven neonates with a diagnosis of persistent pulmonary hypertension of the newborn who met eligibility criteria were studied. The median (SD) gestational age and weight at birth were 39.2 ± 1.3 wks and 3481 ± 603 g. The mean (± sd) half-life, total body clearance, volume of distribution, and steady state concentration of milrinone were 4.1 ± 1.1 hrs, 0.11 ± 0.01 L/kg/hr, 0.56 ± 0.19 L/kg, and 290.9 ± 77.7 ng/mL. The initiation of milrinone led to an improvement in PaO2 (p = 0.002) and a sustained reduction in FIO2 (p < 0.001), oxygenation index (p < 0.001), mean airway pressure (p = 0.03), and inhaled nitric oxide dose (p < 0.001). Although a transient reduction in systolic arterial pressure (p < 0.001) was seen following the bolus, there was overall improvement in base deficit (p = 0.01) and plasma lactate (p = 0.04) with a trend towards lower inotrope score. Serial echocardiography revealed lower pulmonary artery pressure, improved right and left ventricular output, and reduced bidirectional or right-left shunting (p < 0.05) after milrinone treatment. The pharmacokinetics of milrinone in persistent pulmonary hypertension of the newborn is consistent with published data. The administration of intravenous milrinone led to better oxygenation and improvements in pulmonary and systemic hemodynamics in patients with suboptimal response to inhaled nitric oxide. These data support the need for a randomized controlled trial in neonates.

Pulmonary Valve Preservation Strategies for Tetralogy of Fallot Repair

was affirmed in a significant number of patients who tolerated the persistent effects of right ventricular volume overload for many years. In a significant number of postoperative patients, however, long-term complications of pulmonary regurgitation, residual ventricular septal defects (VSD), distal pulmonary artery stenosis, right ventricular dysfunction, atrial or ventricular arrhythmias, and exercise intolerance 2-5 required further operative intervention to address the residual defects, perform concomitant arrhythmia surgery, and pulmonary valve insertion.

Surfactant Improves Graft Function After Gastric Acid–Induced Lung Damage in Lung Transplantation

The number of available donor lungs is still the limiting factor in lung transplantation. We have recently shown that diluted surfactant lavage during ex vivo lung evaluation improved the graft function after gastric acid aspiration. In the present study, we hypothesized that diluted surfactant administration would recondition and improve the graft function after acid aspiration-induced lung injury in a porcine model of pulmonary transplantation. Left lung injury was induced by intrabronchial administration of 1 mL/kg betaine HCl and pepsin mixture. The animals were subsequently ventilated for 24 hours. After organ retrieval, the donor lungs were stored at 4°C for 4 hours. In the control group, left lung transplantation was performed without any surfactant treatment. In the surfactant group, the recipients received intratracheal diluted surfactant lavage just before reperfusion and ventilation. During 7 hours of reperfusion, the hemodynamic and respiratory variables were recorded on an hourly basis. Surfactant lavage resulted in lower mean pulmonary artery pressure, higher mixed venous oxygen saturation, and better oxygenation compared with the control group (p = 0.001). Bronchoalveolar lavage interleukin-6 level, protein, and neutrophil percentage at the end of the experiment were significantly higher in the control group compared with the surfactant group (p = 0.03). Minimal surface tension was significantly lower in the surfactant group compared with controls (p = 0.03). These results demonstrate that application of diluted surfactant before reperfusion can be used effectively to improve the graft function from donor lungs injured by gastric acid aspiration.

Evolving Epidemiology of Pulmonary Arterial Hypertension

Evolving Epidemiology of Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension in the Elderly-Clinical Characteristics and Long-Term Survival

Recent registries describe a significant prevalence of pulmonary arterial hypertension (PAH) in the elderly, but little is known of their characteristics. We aimed to examine the features and prognostic factors of long-term survival in elderly (≥65 years) PAH patients. Clinical, echocardiographic, angiographic, hemodynamic, treatments, and survival data were reviewed in consecutive patients over the course of 20 years. Elderly PAH patients (n = 47) were compared to younger PAH patients (n = 107). At presentation, elderly patients were more likely to have hypertension, diabetes, dyslipidemia, coronary disease, and PAH associated with scleroderma (42.6 vs. 24.3 %; p = 0.02) than younger patients. Prior to PAH therapy, elderly patients had better right ventricular myocardial performance index (RV-MPI; 0.48 ± 0.20 vs. 0.62 ± 0.23, p = 0.006) and lower mean pulmonary arterial pressure (PAP; 45.0 ± 11.1 vs. 49.2 ± 11.8 mmHg, p = 0.04). Elderly patients were treated less often with epoprostenol (8.5 vs. 29 %, p = 0.006) or trepostinil (8.5 vs. 23.4 %, p = 0.04). The 1, 3, and 5 year survival rates of elderly patients were estimated to be 76.4, 50.5, and 37.6 %, respectively. In comparison, younger patients had survival estimates of 92.2, 74.2 and 64.0 % (p = 0.002). Baseline right atrial pressure, mean PAP, cardiac index, and RV-MPI were associated with survival in elderly patients; however in these patients, survival was not affected by any PAH subgroup or age (per year) by itself. The diagnosis of PAH in elderly patients is associated with poorer survival which is in part explained by a greater vulnerability to the hemodynamic disturbances of PAH.

Dynamic Patient Counseling: A Novel Concept in Idiopathic Pulmonary Fibrosis

The characteristics of long-term survivors with idiopathic pulmonary fibrosis (IPF) have never been fully elucidated. We sought to illustrate the attenuated mortality and describe the characteristics of patients with IPF who survived at least 5 years beyond their initial presentation. Patients with IPF evaluated between 1997 and 2006 were identified through the clinic database. Patients who survived beyond 5 years from the time of their evaluation were compared with those who died or underwent lung transplantation within 5 years. Survival analyses were performed from the time of initial evaluation and contingent on annualized survival thereafter. Eighty-seven patients who survived at least 5 years formed the comparator group to whom other patients were contrasted. These patients had a higher BMI, FVC % predicted, FEV1 % predicted, total lung capacity % predicted, and diffusing capacity of lung for carbon monoxide % predicted, but a lower FEV1/FVC ratio and lower mean pulmonary artery pressures. More than one-half of these patients had moderate or severe disease at the time of presentation. Our annualized contingent survival analyses revealed a progressively increasing median survival dependent on the duration of the disease. Although we were able to demonstrate differences in our 5-year survivors, rather than being a distinct group, these patients appear to exist within a continuum of improving survival dependent on prior disease duration. This progressively improving time-dependent prognosis mandates the serial reevaluation of an individual patient’s projected outcomes. The implementation of dynamic counseling is an important concept in more accurately predicting life expectancy for patients with IPF who are frequently haunted by the prospects of a dismal survival.

The Physiologic and Pathologic Effects of the Reamer Irrigator Aspirator on Fat Embolism Outcome

Intramedullary reaming of long bones before nail insertion has been known to cause an increase in fat emboli introduction into the bloodstream, which is a potentially fatal phenomenon. The goal of this study was to assess whether the reamer irrigator aspirator (RIA) reamer can reduce fat embolic load compared with the standard AO reamer. Fifteen pigs were prepared using an intravenous catheter inserted into the marginal ear vein for fluid balance and drug administration. One third of the pig's blood volume was withdrawn to simulate hemorrhagic shock. Each animal underwent bilateral retrograde femoral reaming, cementing, and nailing using either an RIA or AO reamer. Assignment of a reamer type to the left or right side was done randomly and allowed for direct comparison of matching femur results. Outcome measures were obtained, namely, pulmonary arterial pressure, mean arterial pressure, partial pressure of arterial oxygen, and cardiac output. Staining techniques were used to ascertain fat emboli counts from lung tissue samples. For mean arterial pressure, partial pressure of arterial oxygen, and cardiac output after cement injection, the RIA reamer group showed statistically higher values than the AO reamer group. In corollary, the RIA showed statistically lower pulmonary arterial pressure levels. No differences were noted at baseline, during hypovolemia, and post resuscitation. With the Student t test, no statistical differences were found between reamers regarding fat emboli counts for both staining methods. With the Mann-Whitney test, the RIA reamer showed statistically fewer emboli (7.0 versus 74.5) (P = 0.02, Z = 2.33) using Oil Red "O" staining. The RIA reamer demonstrated superior results with respect to physiologic measures and fat emboli counts and may provide optimal results compared with the AO reamer.

Differences in the Acute Pulmonary Vascular Effects of Oxygen with Nitric Oxide and Diltiazem: Implications for the Long-term Treatment of Pulmonary Arterial Hypertension

Right heart catheterization is performed in patients with pulmonary arterial hypertension to determine the severity of disease and their pulmonary vascular reactivity. This study sought to determine whether the acute pulmonary vasodilatory effects of diltiazem and oxygen with nitric oxide are similar enough to support the practice of using nitric oxide as a surrogate agent to identify patients to treat with an oral calcium channel blocker alone. Retrospective descriptive study. A tertiary medical center for children. Twenty-four individuals (7 months to 17 years of age) with pulmonary arterial hypertension who met criteria for a favorable acute pulmonary vasodilatory response to oxygen with nitric oxide, and were also evaluated with intravenous diltiazem. Right heart catheterization and an evaluation of pulmonary vascular reactivity. The pulmonary vasodilatory effects of oxygen, oxygen with nitric oxide, and intravenous diltiazem; and the need for medications other than amlodipine to decrease long-term pulmonary arterial pressure. Oxygen, oxygen with nitric oxide, and diltiazem acutely decreased pulmonary arterial pressure. Diltiazem also decreased systemic arterial pressure. A lower mean pulmonary arterial pressure was achieved with oxygen and nitric oxide than with diltiazem (30 ± 2 mm Hg vs. 39 ± 3 mm Hg, P< .05). Half of the patients who were treated long term with amlodipine alone failed to develop a long-term 20% decrease in pulmonary arterial pressure and were treated with additional medications. The combination of oxygen and nitric oxide decreased pulmonary arterial pressure more than a dose of intravenous diltiazem that was large enough to decrease systemic arterial pressure. Oxygen and nitric oxide may identify patients who can be treated safely with a calcium channel blocker; however, they should not be used as surrogates to identify patients to treat with a calcium channel blocker alone.

The Estrogen Puzzle in Pulmonary Arterial Hypertension

> New Scientist: What do you think most about during the day? > > Stephen Hawking: Women. They are a complete mystery. > > —Stephen Hawking at 70 – exclusive interview at the New Scientist, Jan 4, 2012 The biology of pulmonary arterial hypertension (PAH) is full of mysteries, and one of its longer-standing ones has also intrigued and inspired both scientists and artists throughout history: the female sex. Although affecting patients of all ages and both sexes, PAH preferentially affects young women, suggesting that the female sex is a risk factor for PAH. Even in heritable PAH associated with autosomal dominant mutations in the gene encoding the bone morphogenetic protein receptor type 2 (BMPR2), women after puberty are ≈2.5 times more likely to develop PAH than males.1 In idiopathic PAH the female/male ratio ranges from 1.7:1 or 1.9:1 to 4.1:1 in 3 published PAH registries (the National Institutes of Health registry in the 80s,2 the French registry,3 and the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL),4 respectively). On the other hand, the disease can be more severe in men. Female animals with PAH tend to have lower pulmonary artery pressures and better outcomes compared with males,5 and similarly, male PAH patients have higher mortality than females.6 The basis for this apparent paradox remains unknown. Article see p 1087 Estrogens exert their effects through both genomic effects, by activating their cytosolic or membrane-bound receptors, and nongenomic effects, by activating membrane G protein–coupled estrogen receptors. For example, via the nongenomic effects, estrogens promote the release of both prostacyclin and nitric oxide while, via the genomic effects, they decrease the expression of endothelin 1 under hypoxia, all promoting vasoconstriction in the pulmonary circulation.5 Yet, the pathology of PAH is driven not by vasoconstriction, but rather by a proproliferative and antiapoptotic diathesis throughout the pulmonary arterial wall. The main circulating estrogen in …

Attenuation of Monocrotaline-induced Pulmonary Arterial Hypertension in Rats by Rosuvastatin

Although the effects of statins on pulmonary arterial hypertension (PAH) have been studied previously, the results remain uncertain. The aim of this study was to confirm the impacts of rosuvastatin on monocrotaline (MCT)-induced PAH and potential mechanisms. Rats were subjected to a single subcutaneous injection of MCT to induce PAH. In the prevention protocol, the rats received different doses of rosuvastatin (2 and 10 mg·kg·d) for 4 weeks since MCT injection, whereas in the treatment protocol, the rats received different doses of rosuvastatin 4 weeks after MCT injection for 4 weeks. At the end of the studies, hemodynamic parameters were measured, and the morphology of small pulmonary arteries (SPAs) and right ventricular hypertrophy were assessed. The expression of proliferating cell nuclear antigen (PCNA) and endothelial nitric oxide synthase (eNOS) in SPAs, and Rho kinase 1 (ROCK-1) and eNOS in lung tissue were determined. Rosuvastatin administration could significantly lower mean pulmonary arterial pressure in both prevention and treatment protocols (P < 0.01, respectively), improve survival after PAH development (P < 0.05), and reduce wall thickening of SPAs and right ventricular hypertrophy (P < 0.01, respectively). At the molecular level, rosuvastatin could inhibit the expression of ROCK-1 (P < 0.05, respectively) and PCNA (P < 0.01, respectively) but restore the expression of eNOS (P < 0.05, respectively). These effects were found in a dose-dependent manner. The present data confirmed and extended the previous data regarding the protective impacts of statins on PAH. The effects of rosuvastatin seemed to be associated with the regulation of ROCK-1, PCNA, and eNOS expression.