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Pulmonary Arterial Pressure (pulmonary + arterial_pressure)
Kinds of Pulmonary Arterial Pressure Selected AbstractsContribution of pulmonary surfactant with inhaled nitric oxide for treatment of pulmonary hypertensionPEDIATRICS INTERNATIONAL, Issue 5 2006SATOSHI KUSUDA Abstract Background: Combined therapy of inhaled nitric oxide (iNO) with pulmonary surfactant replacement was reported to improve oxygenation in patients or animal models of persistent pulmonary hypertension of the newborn with pulmonary surfactant deficiency lung. To evaluate the potential of iNO for the treatment of persistent pulmonary hypertension of the newborn, pulmonary arterial pressure (PAP) was measured during iNO before and after pulmonary surfactant replacement in an animal model of pulmonary hypertension with surfactant deficiency. Methods: Seven newborn piglets were injected with L-nitro-arginine-methylester to produce an animal model of pulmonary hypertension. After PAP increased, iNO (30 p.p.m.) was introduced. Then iNO was stopped, and animals were subjected to lung lavage with saline. After recording the effect of iNO, all animals then received exogenous pulmonary surfactant installation. After surfactant treatment, iNO was again introduced. Results: Pulmonary arterial pressure and systemic arterial pressure were increased significantly by >30% after infusion of L-nitro-arginine-methylester. During iNO only PAP was reduced significantly. Respiratory system compliance decreased significantly after lung lavage, and increased significantly after pulmonary surfactant replacement with concomitant increase of PaO2. In contrast, significant reduction of PAP with iNO before and after pulmonary surfactant replacement were also observed. The reduction ratios of PAP under each condition were 75.2 ± 7.4%, 81.3 ± 3.1%, and 79.1 ± 5.3%, respectively (not significant among conditions). Conclusion: These results suggest that iNO is still a potent pulmonary arterial vasodilator even under pulmonary surfactant deficiency in an animal model of pulmonary hypertension. [source] Transcatheter versus Surgical Closure of Secundum Atrial Septal Defect in Adults: Impact of Age at Intervention.CONGENITAL HEART DISEASE, Issue 3 2007A Concurrent Matched Comparative Study Abstract Objectives., To compare the short- and mid-term outcomes of surgical (SUR) vs. transcatheter closure of secundum atrial septal defect (ASD) using Amplatzer septal occluder (ASO) in adults with a very similar spectrum of the disease; and to identify predictors for the primary end point. Design., Single-center, concurrent comparative study. Surgically treated patients were randomly matched (2:1) by age, sex, date of procedure, ASD size, and hemodynamic profile. Setting., Tertiary referral center. Patients., One hundred sixty-two concurrent patients with ASD submitted to ASO (n = 54) or SUR closure (n = 108) according with their preferences. Main Outcome Measures., Primary end point was a composite index of major events including failure of the procedure, important bleeding, critical arrhythmias, serious infections, embolism, or any major cardiovascular intervention-related complication. Predictors of these major events were investigated. Results., Atrial septal defects were successfully closed in all patients, and there was no mortality. The primary event rate was 13.2% in ASO vs. 25.0% in SUR (P = .001). Multivariate analysis showed that higher rate of events was significantly associated with age >40 years; systemic/pulmonary output ratio <2.1; and systolic pulmonary arterial pressure >50 mm Hg; while in the ASO group the event rate was only associated with the ASD size (>15 cm2/m2; relative risk = 1.75, 95% confidence interval 1.01,8.8). There were no differences in the event-free survival curves in adults with ages <40 years. Conclusions., The efficacy for closure ASD was similar in both groups. The higher morbidity observed in SUR group was observed only in the patients submitted to the procedure with age >40 years. The length of hospital stay was shorter in the ASO group. Surgical closure is a safe and effective treatment, especially in young adults. There is certainly nothing wrong with continuing to do surgery in countries where the resources are limited. [source] Protein kinase C mRNA and protein expressions in hypobaric hypoxia-induced cardiac hypertrophy in ratsACTA PHYSIOLOGICA, Issue 4 2010M. Uenoyama Abstract Aim:, Protein kinase C (PKC), cloned as a serine/threonine kinase, plays key roles in diverse intracellular signalling processes and in cardiovascular remodelling during pressure overload or volume overload. We looked for correlations between changes in PKC isoforms (levels and/or subcellular distributions) and cardiac remodelling during experimental hypobaric hypoxic environment (HHE)-induced pulmonary hypertension. Methods:, To study the PKC system in the heart during HHE, 148 male Wistar rats were housed for up to 21 days in a chamber at the equivalent of 5500 m altitude level (10% O2). Results:, At 14 or more days of exposure to HHE, pulmonary arterial pressure (PAP) was significantly increased. In the right ventricle (RV): (1) the expression of PKC-, protein in the cytosolic and membrane fractions was increased at 3,14 days and at 5,7 days of exposure respectively; (ii) the cytosolic expression of PKC-, protein was increased at 1,5, 14 and 21 days of exposure; (3) the membrane expressions of the proteins were decreased at 14,21 (PKC-,II), 14,21 (PKC-,), and 0.5,5 and 21 (PKC-,) days of exposure; (4) the expression of the active form of PKC-, protein on the plasma membrane was increased at 3 days of exposure (based on semiquantitative analysis of the immunohistochemistry). In the left ventricle, the expressions of the PKC mRNAs, and of their cytosolic and membrane proteins, were almost unchanged. The above changes in PKC-,, which were strongly evident in the RV, occurred alongside the increase in PAP. Conclusion:, PKC-, may help to modulate the right ventricular hypertrophy caused by pulmonary hypertension in HHE. [source] Responses of the bronchial and pulmonary circulations to short-term nitric oxide inhalation before and after endotoxaemia in the pigACTA PHYSIOLOGICA, Issue 1 2002R. J. M. Middelveld ABSTRACT The physiological responses of the bronchial circulation to acute lung injury and endotoxin shock are largely unexplored territory. This study was carried out to study the responsiveness of the bronchial circulation to nitric oxide (NO) inhalation before and after endotoxaemia, in comparison with the pulmonary circulation, as well as to study changes in bronchial blood flow during endotoxaemia. Six anaesthetized pigs (pre-treated with the cortisol-synthesis inhibitor metyrapone) received an infusion of 10 µg/kg endotoxin during 2 h. Absolute bronchial blood flow was measured via an ultrasonic flow probe around the bronchial artery. The pigs received increasing doses of inhaled NO over 5 min each (0, 0.2, 2 and 20 ppm) before and after 4 h of endotoxaemia. The increase in bronchial vascular conductance during 5 min of inhalation of 20 ppm NO before endotoxin shock was significantly higher (area under curve (AUC) 474.2 ± 84.5% change) than after endotoxin shock (AUC 118.2 ± 40.4%, P < 0.05 Mann,Whitney U -test). The reduction of the pulmonary arterial pressure by 20 ppm NO was not different. A short rebound effect of the pulmonary arterial pressure occurred after discontinuation of inhaled NO before endotoxaemia (AUC values above baseline 54.4 ± 19.7% change), and was virtually abolished after endotoxaemia (AUC 6.1 ± 4.0%, P = 0.052, Mann,Whitney U -test). Our results indicate that the responsiveness of the bronchial circulation to inhalation of increasing doses of inhaled NO during endotoxin shock clearly differ from the responsiveness of the pulmonary circulation. The reduced responsiveness of the bronchial circulation is probably related to decreased driving pressure for the bronchial blood flow. The absence of the short rebound effect on pulmonary arterial pressure (PAP) after induction of shock could be related to maximum constriction of the pulmonary vessels at 4 h. [source] The effects of methylene blue on ovine post-pneumonectomy pulmonary oedemaACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2010E. V. SUBOROV Background: We recently reported that post-pneumonectomy pulmonary oedema (PPO) occurs after ventilating the remaining lung with excessive tidal volumes. Studies in small animals have indicated that nitric oxide (NO) release increases in hyper-inflated lungs, but confirmatory evidence from larger animals is still lacking. We hypothesized that PPO could be prevented by methylene blue (MB), an inhibitor of NO synthase. Methods: Sheep were subjected to a right-sided pneumonectomy (PE) and randomly assigned to a protectively ventilated group ((PROTV group, n=7) with tidal volumes of 6 ml/kg at 20 inflations/min and a positive end-expiratory pressure (PEEP) of 2 cmH2O, and two groups undergoing ,injurious ventilation' (INJV) with tidal volumes of 12 ml/kg and zero end-expiratory pressure (ZEEP), a control group (INJV group, n=7) and a treatment group subjected to MB 1 h after PE (INJV+MB group, n=7). Haemodynamic variables, lung mechanics, blood gases and plasma nitrites and nitrates (NOx) were determined. Results: PE reduced pulmonary blood volume, extravascular lung water (EVLWI) and quasistatic lung compliance in all groups, in parallel with a rise in peak airway pressure (P<0.05). In the INJV group, pulmonary arterial pressure, EVLWI and pulmonary vascular permeability index increased and arterial oxygenation decreased towards cessation of the experiments. These changes were not antagonized by MB. Plasma NOx increased in all the groups compared with baseline, but with no intergroup difference. Conclusion: MB did not reduce PPO and accumulation of NOx in sheep subjected to ventilation with excessive tidal volumes and ZEEP. [source] Aldosterone receptor antagonism and heart failure: insights from an outpatient clinicJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 4 2008R. Mariotti Summary Objective:, In randomized clinical trials, aldosterone antagonists have been shown to reduce mortality and morbidity in heart failure (HF). The aim of the present study was to examine the risk-benefit profile of aldosterone antagonists in routine clinical practice. Methods:, A retrospective analysis, extending over a 1-year period, of the clinical, instrumental and laboratory data of 264 HF outpatients was performed. All patients were on a ,-blocker and an ACE-inhibitor (or angiotensin-II receptor-blocker) and 151 were taking an aldosterone antagonist. Results:, At baseline, subjects treated with aldosterone antagonists had a higher NYHA class, a larger left-ventricular end-diastolic volume, a worse ejection fraction and a higher systolic pulmonary arterial pressure (sPAP). During follow-up, a greater reduction in sPAP and a tendency towards improved systolic and diastolic function were observed in subjects treated with aldosterone antagonists. Moreover, clinical and laboratory parameters did not deteriorate in patients taking aldosterone antagonists. Mortality rates were similar in the two groups (8·6% vs. 8·8%, P = NS). Conclusions:, The use of aldosterone antagonists in HF is associated with an improvement in cardiac function and is well tolerated. In the present study, patients administered these agents had a comparable clinical outcome to that of the control group, despite important differences in baseline risk. [source] Retrospective Evaluation of Sildenafil Citrate as a Therapy for Pulmonary Hypertension in DogsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 5 2006Jonathan F. Bach DACVIM (SA-IM) Pulmonary arterial hypertension (PH) is a pathologic condition in dogs characterized by abnormally high pressures in the pulmonary circulation and has been associated with a poor outcome. Sildenafil is a type V phosphodiesterase inhibitor that produces nitric oxide-mediated vasodilatation. Sildenafil treatment decreases pulmonary arterial pressure and pulmonary vascular resistance in people with PH. The purpose of this study was to describe the clinical characteristics and outcome of dogs with PH treated with sildenafil. The cardiology database was searched for dogs with PH treated with sildenafil. PH was defined as systolic pulmonary arterial pressure (PAPS) 25 mmHg at rest. Medical records were reviewed for the following information: signalment, duration and type of clinical signs before treatment, underlying disease, estimated or measured PAPS, dosage and dosing interval of sildenafil, and the effect of treatment on clinical signs and pulmonary arterial pressure and survival time. Thirteen affected dogs were identified. Clinical signs included collapse, syncope, respiratory distress, and cough. Duration of clinical signs before presentation ranged from 3 days to 5 months. An underlying cause was identified in 8 dogs. The median sildenafil dosage was 1.9 mg/kg. Ten dogs received concurrent medications. Median PAPS was 90 mmHg; 8 dogs were reevaluated after therapy, and the median decrease in PAPS was 16.5 mmHg. The median survival time of all dogs was 91 days. Sildenafil appeared to be well tolerated in dogs with PH and was associated with decreased PAPS and amelioration of clinical signs in most. Sildenafil represents a reasonable treatment option for dogs with pulmonary hypertension. [source] Effects of meconium aspiration in isolated perfused rat lungsPEDIATRIC PULMONOLOGY, Issue 4 2005Wlodzimierz M. Wisniewski MD Abstract Our objective was to study meconium-induced lung injury in isolated perfused rat lungs exposed to anoxia. Our working hypothesis was that meconium-induced lung injury is independent of preexisting hypoxia, and that hypoxia will increase severity of lung injury observed after meconium aspiration. We comparde five different groups of animals (n,=,5) for pulmonary arterial pressure (PAP), weight lung changes, and TNF, expression. Group I had lungs instilled with 4 ml of normal saline. Group II had lungs exposed to 5 min of anoxia. Group III had lungs instilled with 4 ml of 30% filtered human meconium. Group IV had lungs exposed to 5 min of anoxia and then instilled with 4 ml of 30% filtered human meconium. Group V had lungs instilled with 4 ml of 30% unfiltered human meconium. Our subjects were adult Sprague-Dawley rats. The isolated rat lung model was prepared according to Levey and Gast (J Appl Physiol 1966;21:313,316). Lungs were ventilated with room air. Anoxia was caused by the use of N2. The pulmonary artery was cannulated, and pulmonary arterial pressure and lung weight were measured. Lung weight and pulmonary arterial pressure were monitored for 120 min, and TNF, levels were measured in effluent at 15, 30, 60, and 120 min. Experiments were done at the Michael Reese Hospital (Chicago, IL). At the end of the experiment, PAP reached its highest values in group V (10.0,±,1.7 mmHg). Final PAPs in groups I,IV were: 4.85,±,0.3, 4.99,±,0.4, 5.93,±,0.3, and 7.25,±,0.51 mmHg, respectively). Lung wet weight increased significantly only in groups IV and V vs. group I; at 120 min, they were: 0.96,±,0.3 g, P,<,0.01, and 1.5 g,±,0.2 g, P,<,0.01, respectively. TNF, levels did not change significantly over time in group I. TNF, is a marker as well as proprietor of pulmonary inflammatory response. TNF, reached its highest levels in groups IV and V: 595 and 753 pg/ml at 120 min, respectively. In conclusion, a short episode of anoxia prior to meconium aspiration may increase lung sensitivity to meconium-induced lung injury. This effect may be moderated by the TNF, present in the pulmonary circulation. Pediatr Pulmonol. 2005; 39:368,373. © 2005 Wiley-Liss, Inc. [source] Changes in pulmonary arterial pressure in term-infants with hypoxic,ischemic encephalopathyPEDIATRICS INTERNATIONAL, Issue 6 2009Jing Liu Abstract Background:, Hypoxic,ischemic encephalopathy (HIE) is an important complication that results from birth asphyxia or some other adverse conditions and has a high risk of neonatal morbidity and mortality. It is unclear, however, whether the elevated pulmonary arterial pressure (PAP) can aggravate the condition and prognosis of HIE. The purpose of the present study was to investigate the relationship between the changes of PAP and HIE in term infants after birth asphyxia. Methods:, The left/right ventricle pre-ejection phase (LPEP/RPEP), left/right ventricle ejection time (LVET/RVET) and the ratios of LPEP/LVET and RPET/RVET were evaluated in 40 term infants with HIE and 40 healthy controls on days 1, 3, 7, and 12,14 after birth using echocardiogram. PAP such as pulmonary arterial diastolic pressure (PADP, mmHg), pulmonary arterial resistance (PAR, mmHg), and pulmonary arterial resistance/systemic resistance ratio (PAR/RS) was calculated using these indexes. Patient mortality was also evaluated. Results:, PADP, PAR, and PAR/RS were significantly higher in HIE patients than in healthy controls during the first week after birth, particularly in severe-degree HIE patients. And until the end of the first week of life, these indexes may return to the levels of healthy controls. Persistent fetal circulation (PFC) was found in nine patients (7/16 severe, 2/12 moderate HIE patients), and non-PFC was found in mild HIE patients. Two patients with PFC died. No patients without PFC died. The course of HIE was longer in patients with pulmonary hypertension than in those without. Conclusion:, Increased PAP is an important pathophysiological process that may influence the course and prognoses of HIE in infants after birth asphyxia, particular in severe HIE patients who often have PFC. Thus it is important to assess changes in PAP using echocardiography. [source] Contribution of pulmonary surfactant with inhaled nitric oxide for treatment of pulmonary hypertensionPEDIATRICS INTERNATIONAL, Issue 5 2006SATOSHI KUSUDA Abstract Background: Combined therapy of inhaled nitric oxide (iNO) with pulmonary surfactant replacement was reported to improve oxygenation in patients or animal models of persistent pulmonary hypertension of the newborn with pulmonary surfactant deficiency lung. To evaluate the potential of iNO for the treatment of persistent pulmonary hypertension of the newborn, pulmonary arterial pressure (PAP) was measured during iNO before and after pulmonary surfactant replacement in an animal model of pulmonary hypertension with surfactant deficiency. Methods: Seven newborn piglets were injected with L-nitro-arginine-methylester to produce an animal model of pulmonary hypertension. After PAP increased, iNO (30 p.p.m.) was introduced. Then iNO was stopped, and animals were subjected to lung lavage with saline. After recording the effect of iNO, all animals then received exogenous pulmonary surfactant installation. After surfactant treatment, iNO was again introduced. Results: Pulmonary arterial pressure and systemic arterial pressure were increased significantly by >30% after infusion of L-nitro-arginine-methylester. During iNO only PAP was reduced significantly. Respiratory system compliance decreased significantly after lung lavage, and increased significantly after pulmonary surfactant replacement with concomitant increase of PaO2. In contrast, significant reduction of PAP with iNO before and after pulmonary surfactant replacement were also observed. The reduction ratios of PAP under each condition were 75.2 ± 7.4%, 81.3 ± 3.1%, and 79.1 ± 5.3%, respectively (not significant among conditions). Conclusion: These results suggest that iNO is still a potent pulmonary arterial vasodilator even under pulmonary surfactant deficiency in an animal model of pulmonary hypertension. [source] Intravascular ultrasound imaging of the pulmonary arteries in primary pulmonary hypertensionRESPIROLOGY, Issue 1 2000Takaaki Nakamoto Objective: Intravascular ultrasound has the unique ability to provide cross-sectional images of the arterial wall. This study examined intravascular ultrasound (IVUS) images of the proximal pulmonary arteries in primary pulmonary hypertension (PPH). Methodology: Study 1: Specimens from four patients who had died of PPH (in vitro PPH group) were compared with those of three patients who had died of subarachnoid haemorrhage but had no evidence of cardiopulmonary disease (in vitro control group). Three-centimetre segments of the following levels were examined by IVUS: pulmonary trunk, eight secondary branch arteries of the upper, middle, and lower lobes of both lungs, and the thoracic descending aorta. Study 2: Four patients with PPH (in vivo PPH group) and five patients without pulmonary hypertension and no evidence of cardiopulmonary disease (in vivo control group) were examined. The IVUS images of the apical segmental artery of the right upper lobe and the descending branch of the right pulmonary artery were studied. Results: Echographic examination of formalin-fixed preparations of secondary branch sections of the pulmonary artery failed to show a clear three-layer structure in the in vitro control group (24 preparations), but a distinct three-layer structure and increased vessel wall thickness were observed in the in vitro PPH group (32 preparations). Similar findings were obtained in the in vivo study. The mean echo density of the proximal pulmonary arterial wall correlated well with the mean pulmonary arterial pressure (mPA) in the in vitro PPH, and also correlated with the mPA in the in vivo study (r = 0.960, P < 0.0001). The echo intensity of secondary branch sections of the pulmonary artery was higher in the in vitro PPH group than in the in vitro control group (180.5 ± 27.0 vs 132.5 ± 26.7 counts, P < 0.001); similar results were obtained in the in vivo study (144.7 ± 23.4 vs 85.0 ± 14.3 counts, P < 0.01). Conclusions: These results suggest that the histological changes detected in the pulmonary artery walls in the PPH group were responsible for the increased echo intensity. [source] Hemodynamic Changes in a Model of Chronic Heart Failure Induced by Multiple Sequential Coronary Microembolization in SheepARTIFICIAL ORGANS, Issue 11 2009Jan Dieter Schmitto Abstract Although a large variety of animal models for acute ischemia and acute heart failure exist, valuable models for studies on the effect of ventricular assist devices in chronic heart failure are scarce. We established a stable and reproducible animal model of chronic heart failure in sheep and aimed to investigate the hemodynamic changes of this animal model of chronic heart failure in sheep. In five sheep (n = 5, 77 ± 2 kg), chronic heart failure was induced under flouroscopic guidance by multiple sequential microembolization through bolus injection of polysterol microspheres (90 µm, n = 25.000) into the left main coronary artery. Coronary microembolization (CME) was repeated up to three times in 2 to 3-week intervals until animals started to develop stable signs of heart failure. During each operation, hemodynamic monitoring was performed through implantation of central venous catheter (central venous pressure [CVP]), arterial pressure line (mean arterial pressure [MAP]), implantation of a right heart catheter {Swan-Ganz catheter (mean pulmonary arterial pressure [PAPmean])}, pulmonary capillary wedge pressure (PCWP), and cardiac output [CO]) as well as pre- and postoperative clinical investigations. All animals were followed for 3 months after first microembolization and then sacrificed for histological examination. All animals developed clinical signs of heart failure as indicated by increased heart rate (HR) at rest (68 ± 4 bpm [base] to 93 ± 5 bpm [3 mo][P < 0.05]), increased respiratory rate (RR) at rest (28 ± 5 [base] to 38 ± 7 [3 mo][P < 0.05]), and increased body weight 77 ± 2 kg to 81 ± 2 kg (P < 0.05) due to pleural effusion, peripheral edema, and ascites. Hemodynamic signs of heart failure were revealed as indicated by increase of HR, RR, CVP, PAP, and PCWP as well as a decrease of CO, stroke volume, and MAP 3 months after the first CME. Multiple sequential intracoronary microembolization can effectively induce myocardial dysfunction with clinical and hemodynamic signs of chronic ischemic cardiomyopathy. The present model may be suitable in experimental work on heart failure and left ventricular assist devices, for example, for studying the impact of mechanical unloading, mechanisms of recovery, and reverse remodeling. [source] Protective role of the antidiabetic drug metformin against chronic experimental pulmonary hypertensionBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2009C Agard Background and purpose:, Pulmonary arterial hypertension (PAH) is associated with increased contraction and proliferation of pulmonary vascular smooth muscle cells. The anti-diabetic drug metformin has been shown to have relaxant and anti-proliferation properties. We thus examined the effect of metformin in PAH. Experimental approach:, Metformin effects were analysed in hypoxia- and monocrotaline-induced PAH in rats. Ex vivo and in vitro analyses were performed in lungs, pulmonary artery rings and cells. Key results:, In hypoxia- and monocrotaline-induced PAH, the changes in mean pulmonary arterial pressure and right heart hypertrophy were nearly normalized by metformin treatment (100 mg·kg,1·day,1). Pulmonary arterial remodelling occurring in both experimental models of PAH was also inhibited by metformin treatment. In rats with monocrotaline-induced PAH, treatment with metformin significantly increased survival. Metformin increased endothelial nitric oxide synthase phosphorylation and decreased Rho kinase activity in pulmonary artery from rats with PAH. These effects are associated with an improvement of carbachol-induced relaxation and reduction of phenylephrine-induced contraction of pulmonary artery. In addition, metformin inhibited mitogen-activated protein kinase activation and strongly reduced pulmonary arterial cell proliferation during PAH. In vitro, metformin directly inhibited pulmonary artery smooth muscle cell growth. Conclusions and implications:, Metformin protected against PAH, regardless of the initiating stimulus. This protective effect may be related to its anti-remodelling property involving improvement of endothelial function, vasodilatory and anti-proliferative actions. As metformin is currently prescribed to treat diabetic patients, assessment of its use as a therapy against PAH in humans should be easier. [source] Nitric oxide (NO) modulation of PAF-induced cardiopulmonary action: interaction between NO synthase and cyclo-oxygenase-2 pathwaysBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2001Fulvia Fabi To further investigate into the mechanisms of PAF-induced cardiopulmonary actions, we examined the effects of the nitric oxide synthase (NOS) inhibitor L -N, -nitro- L -arginine (L -NNA), of the specific cyclooxygenase-2 (COX-2) inhibitor NS 398, and of the combined presence of both COX and NOS inhibitors on the PAF responses in the heart lung preparation of guinea-pig (HLP). In HLPs perfused with homologous blood, dose-response curves for the haemodynamic and bronchial effects of PAF (1 , 32 ng) were carried out in the absence or presence of L -NNA (200 ,M). L -NNA caused an increase in the resting pulmonary arterial pressure (PAP) without affecting the other basal values, and strongly potentiated the bronchoconstriction and pulmonary hypertension elicited by PAF. An enhancement of the PAF-induced actions on right atrial pressure (RAP) and cardiac output (CO) was also observed. All the effects of L -NNA were antagonized by L -arginine (2 mM). The presence of L -NNA in the perfusing blood of HLPs failed to affect the pulmonary hypertensive and bronchoconstrictor responses induced by the thromboxane A2 mimetic U46619 (0.05 , 1.6 ,g), 5-hydroxytryptamine (0.1 , 1.6 ,g), and histamine (0.1 , 1.6 ,g), thus suggesting that these PAF secondary mediators are not responsible for the hyper-responsiveness to PAF induced by L -NNA. Blocking COX-2 pathway with NS 398 (15 , 30 ,M) did not alter the cardiopulmonary resting variables. However, a reduction of the PAF-mediated pulmonary hypertension, but not of bronchoconstriction, was observed. When L -NNA was added to the perfusing medium of HLPs pre-treated with NS 398 or with indomethacin (15 ,M), the basal PAP values were enhanced. However, in the combined presence of COX and NOS inhibitors, only a slight increase in the hypertensive responses to the highest doses of PAF was observed, whereas the PAF mediated actions at bronchial and cardiac level were unaffected. This study indicates that (i) the cardiopulmonary actions induced by PAF are specifically modulated by endogenous NO through the NOS pathway, and (ii) COX-2 isoform is involved in the pulmonary hypertensive, but not bronchoconstrictor, effects of PAF. Furthermore, an interaction between PAF stimulated COX, particularly COX-2, and NOS pathways appears to take a functional role at both bronchial and cardiovascular level. British Journal of Pharmacology (2001) 134, 777,788; doi:10.1038/sj.bjp.0704311 [source] Pulmonary venous wedge pressure provides a safe and accurate estimate of pulmonary arterial pressure in children with shunt-dependent pulmonary blood flow,CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, Issue 5 2009Kevin D. Hill MD Abstract Objectives: To compare two methods of pulmonary arterial pressure measurement in children with shunt-dependent pulmonary blood flow. Background: In children with shunt-dependent pulmonary blood flow, direct assessment of pulmonary arterial pressure requires passage of a catheter across the shunt. This can be technically difficult and dangerous. Use of the pulmonary venous wedge pressure offers an alternative but has not been validated in this patient population. Methods: We prospectively studied 18 children with shunt-dependent pulmonary blood flow. Pulmonary venous wedge pressure and directly measured pulmonary arterial pressures were independently assessed by two blinded cardiologists. Results: Directly measured mean pulmonary arterial pressure and pulmonary venous wedge pressure are closely correlated (R2 = 0.80, P < 0.01). Agreement between the two measures is improved at lower mean pressures with greater differences at higher pressures. For 20 of 24 ipsilateral measurements, pulmonary venous wedge pressure was , directly measured pulmonary arterial pressure. Pulmonary venous wedge pressure never underestimated pulmonary arterial pressure by more than 3 mm Hg. Conclusions: Pulmonary venous wedge pressure provides a safe and accurate means of estimating pulmonary arterial pressure in children with shunt-dependent pulmonary blood flow. The slightly lower pressures seen on direct measurement compared with the reverse pulmonary vein may reflect impairment of flow across the shunt by the catheter. © 2009 Wiley-Liss, Inc. [source] Resuscitation with Na+/H+ exchanger inhibitor in traumatic haemorrhagic shock: Cardiopulmonary performance, oxygen transport and tissue inflammationCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 3 2010Dongmei Wu Summary 1. The aim of the present study was to examine the effects of inhibition of the Na+/H+ exchanger (NHE-1) on cardiopulmonary performance, oxygen carrying capacity and tissue inflammation in a pig model of traumatic haemorrhage,resuscitation. 2. In 12 instrumented anaesthetized pigs, traumatic haemorrhage was modelled by producing tibia fractures, followed by haemorrhage of 25 mL/kg for 20 min, and then a 4 mm hepatic arterial tear with surgical repair after 20 min. Animals then underwent low-volume fluid resuscitation with either Hextend (vehicle; n = 6; Hospira, Lake Forest, IL, USA) or 3 mg/kg BIIB513 (an NHE-1 inhibitor) + Hextend (n = 6). The experiment was terminated 6 h after the beginning of resuscitation. 3. Compared with vehicle-treated controls, the addition of NHE-1 inhibition with BIIB513 significantly improved the left ventricle stroke work index and attenuated increases in pulmonary arterial pressure and pulmonary vascular resistance. Furthermore, BIIB513 treatment significantly increased the oxygenated haemoglobin ratio, blood oxygen content and mixed venous blood oxygen saturation and improved blood oxygen delivery. In addition, BIIB513 treatment reduced lung tissue levels of interleukin-6 by 80%, tumour necrosis factor-, by 37% and myeloperoxidase activity by 38%. Nuclear factor-,B DNA binding activity in the lung was also slightly and significantly attenuated following BIIB513 treatment. 4. In conclusion, the present study shows that NHE-1 inhibition facilitates the response to fluid resuscitation after traumatic haemorrhage by improving cardiac function, pulmonary vascular function and oxygen carrying capacity, which results in reduced tissue inflammatory injury. [source] CONTINUOUS FLUOXETINE ADMINISTRATION PREVENTS RECURRENCE OF PULMONARY ARTERIAL HYPERTENSION AND PROLONGS SURVIVAL IN RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2009Shao-Ping Zhu SUMMARY 1The serotonin transporter (SERT) is strongly implicated in the pathogenesis of pulmonary arterial hypertension (PAH) in patients and animal models. Inhibitors of SERT have been reported to attenuate or reverse experimental PAH, which makes them potential therapeutic options for the treatment of PAH in humans. However, little is known about pathophysiological features after reversal or attenuation of PAH; moreover, the long-term therapeutic effects of SERT inhibitors on PAH remain undetermined. Thus, the aim of the present study was to investigate the short- and long-term effects of fluoxetine on monocrotaline (MCT)-induced PAH and associated pathophysiological changes in PAH models. 2Rats were randomly divided into four groups as follows: (i) an M + F group, in which rats received a single injection of MCT (60 mg/kg, s.c.) and then after 3 weeks were given fluoxetine (10 mg/kg) once daily by gavage from Week 4 to Week 12; (ii) an M/F group, in which 3 weeks after a single MCT (60 mg/kg, s.c.) injection, rats were given fluoxetine (10 mg/kg) by daily gavage from Week 4 to Week 6 and were then given an equivalent volume of saline once daily by gavage from Week 7 to Week 12; (iii) an MCT group, in which 3 weeks after a single MCT (60 mg/kg, s.c.) injection rats were given an equivalent volume of saline by gavage from Week 4 to Week 12; and (iv) a saline group, in which rats received an equivalent volume of saline injection or gavage over the 12 week treatment period. Morphometric changes, pulmonary arterial pressure, percentage wall thickness, right ventricular hypertrophy index and SERT expression were detected at various times during the 12 week treatment period. Survival analysis was performed in each group. 3After 12 weeks treatment, it was found that even through fluoxetine treatment resulted in complete reversal of PAH, PAH recurred after fluoxetine withdrawal. In contrast, continuous administration of fluoxetine prevented the recurrence of PAH and prolonged survival. Analysis of SERT protein levels in rat lung indicated that, compared with values obtained at Week 0, SERT protein increased significantly after discontinuation of fluoxetine but continuous fluoxetine administration inhibited this increase. 4In conclusion, SERT overexpression correlates with the recurrence of PAH after withdrawal of fluoxetine in rats. Continuous fluoxetine administration prevents recurrence of PAH and prolongs survival. [source] EFFECT OF BAY 41-2272 IN THE PULMONARY HYPERTENSION INDUCED BY HEPARIN,PROTAMINE COMPLEX IN ANAESTHETIZED DOGSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2007Cristiane F Freitas SUMMARY 1BAY 41-2272 is a potent activator of the nitric oxide-independent site of soluble guanylate cyclase and has been recently introduced as a new therapeutic agent to treat chronic pulmonary hypertension (PH) in neonatal sheep. Because the in vivo heparin,protamine interaction may lead to severe PH, the aim of the present study was to evaluate the effects of BAY 41-2272 in the PH induced by heparin,protamine interaction in anaesthetized dogs. 2Sixteen male dogs (10 mongrel dogs and six Beagles) were anaesthetized and instrumented for acquisition of mean arterial blood pressure (MABP), mean pulmonary arterial pressure (MPAP), heart rate (HR), pulmonary capillary wedge pressure (PCWP), cardiac index (CI) and indices of systemic and pulmonary vascular resistance (ISVR and IPVR, respectively). Plasma cGMP levels and Spo2 were evaluated. 3Intravenous administration of heparin (500 IU/kg) followed 3 min later by protamine (10 mg/kg) caused marked PH, as evaluated by the increase in MPAP, PCWP and IPVR. This was accompanied by a significant fall in MABP and a transient increase in HR. Infusion of BAY 41-2272 (10 µg/kg per h, starting 10 min before heparin administration) augmented plasma cGMP levels and slightly and significantly increased HR and CI, without affecting the other cardiovascular parameters. The elevation in IPVR, MPAP and PCWP triggered by the heparin,protamine interaction was significantly reduced in animals exposed to BAY 41-2272. 4In vehicle-treated dogs, the Spo2 values decreased significantly at the peak of the PH and this was significantly attenuated by treatment with BAY 41-2272. In addition, BAY 41-2272 (10 µmol/L) had no effect on the activated partial thromboplastin time of citrated plasma after the addition of heparin,protamine. 5In conclusion, BAY 41-2272 was effective in reducing canine PH induced in vivo by the heparin,protamine interaction, thus indicating its potential in the treatment of this type of disorder. [source] The Lung Is The Major Site That Produces Nitric Oxide To Induce Acute Pulmonary Oedema In Endotoxin ShockCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2001Ru Ping Lee SUMMARY 1. The present study was undertaken to determine the locus of nitric oxide (NO) production that is toxic to the lung and produces acute pulmonary oedema in endotoxin shock, to examine and compare the effects of changes in lung perfusate on endotoxin-induced pulmonary oedema (EPE) and to evaluate the involvement of constitutive and inducible NO synthase (cNOS and iNOS, respectively). 2. Experiments were designed to induce septic shock in anaesthetized rats with the administration of Escherichia coli lipopolysaccharide (LPS). Exhaled NO, lung weight (LW)/bodyweight (BW) ratio, LW gain (LWG) and lung histology were measured and observed to determine the degree of EPE 4 h following LPS. The EPE was compared between groups in which LPS had been injected either into the systemic circulation or into the isolated perfused lung. The lung perfusate was altered from whole blood to physiological saline solution (PSS) with 6% albumin to test whether different lung perfusions affected EPE. Pretreatment with various NOS inhibitors was undertaken 10 min before LPS to investigate the contribution of cNOS and iNOS to the observed effects. 3. Endotoxin caused profound systemic hypotension, but little change in pulmonary arterial pressure. The extent of EPE was not different between that induced by systemic injection and that following administration to isolated lungs preparations. Replacement of whole blood with PSS greatly attenuated (P < 0.05) EPE. In blood-perfused lungs, pretreatment with NOS inhibitors, such as N, -nitro- L -arginine methyl ester, aminoguanidine and dexamethasone, significantly prevented EPE (P < 0.05). 4. The major site of NO production through the whole blood is in the lung. The NO production mediated by the iNOS system is toxic to the endothelium in the pulmonary microvasculature. Inhalation of NO for patients with sepsis may be used with clinical caution. Therapeutic consideration of lung extracorporeal perfusion with PSS and pharmacological pretreatment with iNOS inhibitors may be warranted. [source] Evaluation of Myocardial Performance with Conventional Single-Site Ventricular Pacing and Biventricular Pacing in a Canine Model of Atrioventricular BlockJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 9 2003PATRICIO A. FRIAS M.D. Introduction: The aim of this study was to evaluate epicardial biventricular pacing as a means of maintaining synchronous ventricular activation in an acute canine model of AV block with normal ventricular anatomy and function. Chronic single-site ventricular pacing results in dyssynchronous ventricular activation and may contribute to ventricular dysfunction. Biventricular pacing has been used successfully in adult patients with congestive heart failure. Methods and Results: This was an acute study of open chest mongrel dogs (n = 13). ECG, left ventricular (LV), aortic, and pulmonary arterial pressures were measured. LV impedance catheters were used to assess cardiodynamics using instantaneous LV pressure-volume relations (PVR). Following radiofrequency ablation of the AV node, a temporary pacemaker was programmed 10 beats/min above the intrinsic atrial rate, with an AV interval similar to the baseline intrinsic PR interval. The pacing protocol consisted of 5-minute intervals with the following lead configurations: right atrium-right ventricular apex (RA-RVA), RA-LV apex (LVA), and RA-biventricular using combinations of four ventricular sites (RVA, RV outflow tract [RVOT], LVA, LV base [LVB]). RA-RVA was used as the experimental control. LV systolic mechanics, as measured by the slope of the end-systolic (Ees) PVR (ESPVR, mmHg/cc), was statistically greater (P < 0.05) with all modes of biventricular pacing (RA-RVA/LVA 20.0 ± 2.9, RA-RVA/LVB 18.4 ± 2.9, RA-RVOT/LVA 15.1 ± 1.8, RA-RVOT/LVB 17.6 ± 2.9) compared to single-site ventricular pacing (RA-RVA 12.8 ± 1.6). Concurrent with this improvement in myocardial performance was a shortening of the QRS duration (RA-RVA 97.7 ± 2.9 vs RA-RVA/LVA 75.7 ± 4.9, RA-RVA/LVB 70.3 ± 4.9, RA-RVOT/LVA 65.3 ± 4.4, and RA-RVOT/LVB 76.7 ± 5.9, P < 0.05). Conclusion: In this acute canine model of AV block, QRS duration shortened and LV performance improved with epicardial biventricular pacing compared to standard single-site ventricular pacing. (J Cardiovasc Electrophysiol, Vol. 14, pp. 996-1000, September 2003) [source] Pulmonary venous wedge pressure provides a safe and accurate estimate of pulmonary arterial pressure in children with shunt-dependent pulmonary blood flow,CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, Issue 5 2009Kevin D. Hill MD Abstract Objectives: To compare two methods of pulmonary arterial pressure measurement in children with shunt-dependent pulmonary blood flow. Background: In children with shunt-dependent pulmonary blood flow, direct assessment of pulmonary arterial pressure requires passage of a catheter across the shunt. This can be technically difficult and dangerous. Use of the pulmonary venous wedge pressure offers an alternative but has not been validated in this patient population. Methods: We prospectively studied 18 children with shunt-dependent pulmonary blood flow. Pulmonary venous wedge pressure and directly measured pulmonary arterial pressures were independently assessed by two blinded cardiologists. Results: Directly measured mean pulmonary arterial pressure and pulmonary venous wedge pressure are closely correlated (R2 = 0.80, P < 0.01). Agreement between the two measures is improved at lower mean pressures with greater differences at higher pressures. For 20 of 24 ipsilateral measurements, pulmonary venous wedge pressure was , directly measured pulmonary arterial pressure. Pulmonary venous wedge pressure never underestimated pulmonary arterial pressure by more than 3 mm Hg. Conclusions: Pulmonary venous wedge pressure provides a safe and accurate means of estimating pulmonary arterial pressure in children with shunt-dependent pulmonary blood flow. The slightly lower pressures seen on direct measurement compared with the reverse pulmonary vein may reflect impairment of flow across the shunt by the catheter. © 2009 Wiley-Liss, Inc. 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