Piglet Lungs Research Articles

Effects of Surfactant Lavage Combined With Intratracheal Budesonide Instillation on Meconium-Injured Piglet Lungs.

To evaluate the combined effects of surfactant lavage and intratracheally instillation of budesonide on meconium-injured piglet lungs. A prospective, randomized, animal model study. An experimental laboratory. Twenty-four anesthetized and mechanically ventilated newborn piglets. Human meconium slurry was intratracheally instilled into piglet lungs to induce lung injury. The injured piglets were randomly assigned to either the sham treatment group (control) or one of the three therapeutic groups: the intratracheally instilled budesonide (Bud) group, the bronchoalveolar lavage with diluted surfactant (dsBAL) group, and the combination therapy of Bud and dsBAL (dsBAL + Bud) group. Cardiopulmonary profiles were measured hourly. Proinflammatory cytokine (interleukin-1β, interleukin-6, and interleukin-8) levels in bronchoalveolar lavage fluid were measured. Finally, the pulmonary histology of the experimental subjects was examined at the end of experiments. Both of the lavaged groups (dsBAL and dsBAL + Bud) showed significantly better oxygenation than those that had not undergone lavage (control and Bud) (p < 0.05). The dsBAL + Bud group showed a significantly higher lung compliance and required a significantly lower peak inspiratory pressure during the experimental periods than the other three groups (p < 0.05). All treatment groups had significantly lower concentrations of interleukin-1β concentration in the bronchoalveolar lavage fluid than the control group (p < 0.05). The dsBAL + Bud group also had a significantly lower interleukin-6 concentration in the bronchoalveolar lavage fluid (p< 0.05), as well as a significantly lower lung injury score based on pulmonary histology than the control group (p < 0.05). Therapeutic bronchoalveolar lavage with diluted surfactant followed by intratracheal instillation of budesonide has a synergistic and beneficial effect when treating severe meconium-injured newborn piglet lungs.

The Chinese highly pathogenic porcine reproductive and respiratory syndrome virus infection suppresses Th17 cells response in vivo

Porcine reproductive and respiratory syndrome virus (PRRSV) has been shown to immunomodulate innate and adaptive immunity of pigs. The Chinese highly pathogenic PRRSV (HP-PRRSV) infection causes severe bacterial secondary infection in pigs. However, the mechanism in relation to the bacterial secondary infection induced by HP-PRRSV remains unknown. In the present study, Th17 cells response in peripheral blood, lungs, spleens and lymph nodes of piglets were analyzed, and bacterial loads in lungs of piglets were examined upon HP-PRRSV infection. Meanwhile the changes of CD4+ and CD8+ T cells in peripheral blood of the inoculated piglets were analyzed. The results showed that HP-PRRSV-inoculated piglets exhibited a suppressed Th17 cells response in peripheral blood and a reduced number of Th17 cells in lungs, and higher bacterial loads in lungs, compared with low pathogenic PRRSV. Moreover, HP-PRRSV obviously resulted in severe depletion of porcine T cells in peripheral blood at the early stage of infection. These findings indicate that HP-PRRSV infection suppresses the response of Th17 cells that play an important role in combating bacterial infections, suggesting a possible correlation between the suppression of Th17 cells response in vivo and bacterial secondary infection induced by HP-PRRSV. Our present study adds a novel insight into better understanding of the pathogenesis of the Chinese HP-PRRSV.

Chest compression during sustained inflation: hypoxic and oxidative stress

Current recommendation for chest compressions in neonatal resuscitation is to use a coordinated 3:1 ratio of chest compressions to ventilations (C:V), interrupting every third compression to deliver an assisted ventilation. Despite this recommendation, the evidence is still unclear on the optimal C:V ratio for use in neonates. Our team has previously reported a novel technique of sustained inflations with chest compressions (SI+CC) reduces time to return of spontaneous circulation and improves hemodynamic recovery. The objective of this study was to determine differences in hypoxic injury and oxidative stress markers of heart and lung in piglets resuscitated with SI+CC compared to a coordinated 3:1 C:V. We found that the SI+CC technique reduces oxidative stress in lung tissues and cumulative oxygen exposure with no differences in hypoxic injury. Our findings lend further support to transitioning this technique to neonatal resuscitation practice.

Origin, evolution, and virulence of porcine deltacoronaviruses in the United States.

ABSTRACTA novel porcine deltacoronavirus (PdCV) was first discovered in Ohio and Indiana in February 2014, rapidly spread to other states in the United States and Canada, and caused significant economic loss in the swine industry. The origin and virulence of this novel porcine coronavirus are not known. Here, we characterized U.S. PdCV isolates and determined their virulence in gnotobiotic and conventional piglets. Genome analyses revealed that U.S. PdCV isolates possess unique genetic characteristics and share a close relationship with Hong Kong and South Korean PdCV strains and coronaviruses (CoVs) of Asian leopard cats and Chinese ferret-badgers. The PdCV-positive intestinal content (Ohio CVM1) and the cell culture-adapted PdCV Michigan (MI) strain were orally inoculated into gnotobiotic and/or conventional piglets. Within 1 to 3 days postinfection, profuse watery diarrhea, vomiting, and dehydration were observed. Clinical signs were associated with epithelial necrosis in the gastric pits and small intestine, the latter resulting in severe villous atrophy. Mild interstitial pneumonia was identified in the lungs of PdCV-infected piglets. High levels of viral RNA (8 to 11 log RNA copies/g) were detected in intestinal tissues/luminal contents and feces of infected piglets, whereas moderate RNA levels (2 to 5 log RNA copies/g) were detected in blood, lung, liver, and kidney, indicating multisystemic dissemination of the virus. Polyclonal immune serum against PdCV but not immune serum against porcine epidemic diarrhea virus (PEDV) reacted with PdCV-infected small-intestinal epithelial cells, indicating that PdCV is antigenically distinct from PEDV. Collectively, we demonstrate for the first time that PdCV caused severe gastrointestinal diseases in swine.

Pulmonary microRNA expression profiling in an immature piglet model of cardiopulmonary bypass-induced acute lung injury.

After surgery performed under cardiopulmonary bypass (CPB), severe lung injury often occurs in infants. MicroRNAs (miRNAs) are potentially involved in diverse pathophysiological processes via regulation of gene expression. The objective of this study was to investigate differentially expressed miRNAs and their potential target genes in immature piglet lungs in response to CPB. Fourteen piglets aged 18.6 ± 0.5 days were equally divided into two groups that underwent sham sternotomy or CPB. The duration of aortic cross-clamping was 2 h, followed by 2 h reperfusion. Lung injury was evaluated by lung function indices, levels of cytokines, and histological changes. We applied miRNA microarray and quantitative real-time polymerase chain reaction (qRT-PCR) analysis to determine miRNA expression. Meanwhile, qRT-PCR and enzyme-linked immunosorbent assay were used for validation of predicted mRNA targets. The deterioration of lung function and histopathological changes revealed the piglets' lungs were greatly impaired due to CPB. The levels of tumor necrosis factor alpha, interleukin 6, and interleukin 10 increased in the lung tissue after CPB. Using miRNA microarray, statistically significant differences were found in the levels of 16 miRNAs in the CPB group. Up-regulation of miR-21 was verified by PCR. We also observed down-regulation in the levels of miR-127, miR-145, and miR-204, which were correlated with increases in the expression of the products of their potential target genes PIK3CG, PTGS2, ACE, and IL6R in the CPB group, suggesting a potential role for miRNA in the regulation of inflammatory response. Our results show that CPB induces severe lung injury and dynamic changes in miRNA expression in piglet lungs. Moreover, the changes in miRNA levels and target gene expression may provide a basis for understanding the pathogenesis of CPB-induced injury to immature lungs.

New insights into the organ-specific adverse effects of fumonisin B1: comparison between lung and liver.

Fumonisin B1 (FB1) is a well-known inhibitor of de novo sphingolipid biosynthesis, due to its ability to inhibit ceramide synthases (CerS) activity. In mammals, this toxin triggers broad clinical symptoms with multi-organ dysfunction such as hepatotoxicity or pulmonary edema. The molecular mechanism of CerS inhibition by FB1 remains unknown. Due to the existence of six mammalian CerS isoforms with a tissue-specific expression pattern, we postulated that the organ-specific adverse effects of FB1 might be due to different CerS isoforms. The sphingolipid contents of lung and liver were compared in normal and FB1-exposed piglets (gavage with 1.5mg FB1/kg body weight daily for 9days). The effect of the toxin on each CerS was deduced from the analysis of its effects on individual ceramide (Cer) and sphingomyelin (SM) species. As expected, the total Cer content decreased by half in the lungs of FB1-exposed piglets, while in contrast, total Cer increased 3.5-fold in the livers of FB1-exposed animals. Our data also indicated that FB1 is more prone to bind to CerS4 and CerS2 to deplete lung and to enrich liver in d18:1/C20:0 and d18:1/C22:0 ceramides. It alsointeract with CerS1 to enrich liver in d18:1/C18:0 ceramides. Cer levels were counterbalanced by those of SM. In conclusion, these results demonstrate that the specificity of the effects of FB1 on tissues and organs is due to the effects of the toxin on CerS4, CerS2, and CerS1.

Tylvalosin exhibits anti-inflammatory property and attenuates acute lung injury in different models possibly through suppression of NF-κB activation

Tylvalosin, a new broad-spectrum, third-generation macrolides, may exert a variety of pharmacological activities. Here, we report on its anti-oxidative and anti-inflammatory activity in RAW 264.7 macrophages and mouse treated with lipopolysaccharide (LPS) as well as piglet challenged with porcine reproductive and respiratory syndrome virus (PRRSV). Tylvalosin treatment markedly decreased IL-8, IL-6, IL-1β, PGE2, TNF-α and NO levels in vitro and in vivo. LPS and PRRSV-induced reactive oxygen species (ROS) production, and the lipid peroxidation in mice lung tissues reduced after tylvalosin treatments. In mouse acute lung injury model induced by LPS, tylvalosin administration significantly attenuated tissues injury, and reduced the inflammatory cells recruitment and activation. The evaluated phospholipase A2 (PLA2) activity and the increased expressions of cPLA2-IVA, p-cPLA2-IVA and sPLA2-IVE were lowered by tylvalosin. Consistent with the mouse results, tylvalosin pretreatment attenuated piglet lung scores with improved growth performance and normal rectal temperature in piglet model induced by PRRSV. Furthermore, tylvalosin attenuated the IκBα phosphorylation and degradation, and blocked the NF-κB p65 translocation. These results indicate that in addition to its direct antimicrobial effect, tylvalosin exhibits anti-inflammatory property and attenuates acute lung injury through suppression of NF-κB activation.

Comparative analysis of apoptotic changes in peripheral immune organs and lungs following experimental infection of piglets with highly pathogenic and classical porcine reproductive and respiratory syndrome virus

BackgroundOur previous studies have demonstrated that piglets infected with highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) may develop significant thymus atrophy, which related to thymocytes apoptosis. However, apart from that detected in the thymus, there are no reports describing cell apoptosis induced by HP-PRRSV infection. In this study, we analyzed comparatively the pathological changes, cell apoptosis and viral load in peripheral immune organs including tonsil, inguinal lymph nodes (ILNs) and spleen and lungs following experimental infection of piglets with HP-PRRSV HuN4 and classical PRRSV CH-1a.FindingsHP-PRRSV HuN4 exhibited much stronger cell tropism than CH-1a in immune organs and lungs of piglets. HuN4 infection led to the serious injuries in tonsils, ILNs, spleens and lungs, especially apoptosis in these organs was significant.ConclusionsHuN4 infection induced severe lesions (gross pathology, histopathology and cell apoptosis) in the peripheral immune organs and lungs of infected piglets. Large numbers of apoptotic cells in immune organs and lung induced by HuN4 may play a role in the pathogenesis of the HP-PRRS and the distinct injuries caused by HuN4 infection may be associated with the high mortality rate of HP-PRRS in pigs.

First complete genomic characterization of a porcine parvovirus 5 isolate from China

To investigate porcine parvovirus 5 (PPV5) infections in swine herds in China, clinical specimens of piglet lungs were examined for the presence of PPV5 using a polymerase chain reaction method. A strain of PPV5 was detected, and its genome was sequenced and analyzed. In the sequence alignment and phylogenetic analysis, the Chinese PPV5 strain clustered into a distinct clade with the reference PPV5 strains. These results provide direct evidence that PPV5 is present in pigs in China. Extensive epidemiological studies are warranted to determine the geographic distribution of PPV5 in China.

Experimental Model of Atelectasis in Newborn Piglets

There are few studies using animal models in chest physical therapy. However, there are no models to assess these effects in newborns. This study aimed to develop a model of obstructive atelectasis induced by artificial mucus injection in the lungs of newborn piglets, for the study of neonatal physiotherapy. Thirteen newborn piglets received artificial mucus injection via the endotracheal tube. X-rays and blood gas analysis confirmed the atelectasis. The model showed consistent results between oxygenation parameters and radiological findings. Ten (76.9%) of the 13 piglets responded to the intervention. This did not significantly differ from the expected percentage of 50% by the binomial test (95% CI 46.2-95%, P = .09). Our model of atelectasis in newborn piglets is both feasible and appropriate to evaluate the impact of physical therapies on atelectasis in newborns.

The role of CFTR in transepithelial liquid transport in pig alveolar epithelia

The role of CFTR in transepithelial liquid transport in pig alveolar epithelia

Prolonged hypoxia augments l-citrulline transport by System A in the newborn piglet pulmonary circulation

Pulmonary arterial endothelial cells (PAECs) express the enzymes needed for generation of l-arginine from intracellular l-citrulline but do not express the enzymes needed for de novo l-citrulline synthesis. Hence, l-citrulline levels in PAECs are dependent on l-citrulline transport. Once generated, l-arginine can be converted to l-citrulline and nitric oxide (NO) by the enzyme NO synthase. We sought to determine whether hypoxia, a condition aetiologically linked to pulmonary hypertension, alters the transport of l-citrulline and the expression of the sodium-coupled neutral amino acid transporters (SNATs) in PAECs from newborn piglets. PAECs isolated from newborn piglets were cultured under normoxic and hypoxic conditions and used to measure SNAT1, 2, 3, and 5 protein expression and (14)C-l-citrulline uptake. SNAT1 protein expression was increased, while SNAT2, SNAT3, and SNAT5 expression was unaltered in hypoxic PAECs. (14)C-l-citrulline uptake was increased in hypoxic PAECs. Studies with inhibitors of System A (SNAT1/2) and System N (SNAT3/5) revealed that the increased (14)C-l-citrulline uptake was largely due to System A-mediated transport. Additional studies were performed to evaluate SNAT protein expression and l-citrulline levels in lungs of piglets with chronic hypoxia-induced pulmonary hypertension and comparable age controls. Lungs from piglets raised in chronic hypoxia exhibited greater SNAT1 expression and higher l-citrulline levels than lungs from controls. Increased SNAT1 expression and the concomitant enhanced ability to transport l-citrulline in PAECs could represent an important regulatory mechanism to counteract NO signalling impairments known to occur during the development of chronic hypoxia-induced pulmonary hypertension in newborns.

Furegrelate, a Thromboxane Synthase Inhibitor, Blunts the Development of Pulmonary Arterial Hypertension in Neonatal Piglets

The development of pulmonary arterial hypertension (PAH) in pediatric patients has been linked to the production of the arachidonic acid metabolite, thromboxane A2 (TxA2). The present study evaluated the therapeutic effect of furegrelate sodium, a thromboxane synthase inhibitor, on the development of PAH in a neonatal piglet model. Three-day-old piglets were exposed to 21 days of normoxia (N; 21% FIO2) or chronic hypoxia (CH; 10% FIO2). A third group of piglets received the oral TxA2 synthase inhibitor, furegrelate (3 mg/kg, 2 or 3 times daily) at the induction of CH. In vivo hemodynamics confirmed a 2.55-fold increase of the pulmonary vascular resistance index (PVRI) in CH piglets (104±7 WU) compared to N piglets (40±2 WU). The CH piglets treated twice daily with furegrelate failed to show improved PVRI, but furegrelate three times daily lowered the elevated PVRI in CH piglets by 34% to 69±5 WU and ameliorated the development of right ventricular hypertrophy. Microfocal X-ray computed tomography (CT) scanning was used to estimate the diameter-independent distensibility term, α (% change in diameter per Torr). Pulmonary arterial distensibility in isolated lungs of CH piglets (α=1.0±0.1% per Torr) was lower than that of N piglets (α=1.5±0.1% per Torr) indicative of vascular remodeling. Arterial distensibility was partially restored in furegrelate-treated CH piglets (α =1.2±0.1% per Torr) and microscopic evidence showing muscularization of small pulmonary arteries also was less prominent in these animals. Finally, isolated lungs of furegrelate-treated piglets showed lower basal and vasodilator-induced transpulmonary pressures compared to CH animals. These findings suggest that pharmacological inhibition of TxA2 synthase activity by furegrelate blunts the development of hypoxia-induced PAH in an established neonatal piglet model primarily by preserving the structural integrity of the pulmonary vasculature.

Pathogenicity characterization of a bovine triple reassortant rotavirus in calves and piglets

Rotaviruses are important human and animal pathogens with high impact on public health and livestock industry. There is little evidence about the cross-species pathogenicity and extra-intestinal infections of animal and human reassortant rotaviruses, particularly based on all 11 genotyping data. In this study, the bovine triple reassortant KJ56-1 strain harboring two bovine-like genome segments, eight porcine-like genome segments, and one human-like genome segment was used to evaluate the cross-species pathogenicity in its parent species, calves and piglets, and to determine its abilities of causing viremia and extra-intestinal tropisms in piglets. The KJ56-1 strain isolated from a calf diarrhea fecal sample replicated without causing diarrhea and severe intestinal pathology in calves. However, piglets inoculated with this strain showed persistent severe diarrhea and marked intestinal pathology. By SYBR Green real-time RT-PCR, viral RNA was detected in the sera, mesenteric lymph node, lung, liver, choroid plexus, and cerebrospinal fluid in the experimental piglets. An immunofluorescence assay confirmed viral replication in these extra-intestinal organs and tissues. These results indicated that the bovine triple reassortant KJ56-1 strain was virulent to piglets but not to calves. Our data also demonstrated that the reassortant rotaviruses had the ability to spread to the bloodstream from the gut, enter and amplify in the mesenteric lymph node, and disseminate to the extra-intestinal organs and tissues.

Angiotensin II type 1 receptor blockade partially attenuates hypoxia-induced pulmonary hypertension in newborn piglets: relationship with the nitrergic system

The objective of this study was to observe possible interactions between the renin-angiotensin and nitrergic systems in chronic hypoxia-induced pulmonary hypertension in newborn piglets. Thirteen chronically instrumented newborn piglets (6.3 ± 0.9 days; 2369 ± 491 g) were randomly assigned to receive saline (placebo, P) or the AT1 receptor (AT1-R) blocker L-158,809 (L) during 6 days of hypoxia (FiO2 = 0.12). During hypoxia, pulmonary arterial pressure (Ppa; P < 0.0001), pulmonary vascular resistance (PVR; P < 0.02) and the pulmonary to systemic vascular resistance ratio (PVR/SVR; P < 0.05) were significantly attenuated in the L (N = 7) group compared to the P group (N = 6). Western blot analysis of lung proteins showed a significant decrease of endothelial NOS (eNOS) in both P and L animals, and of AT1-R in P animals during hypoxia compared to normoxic animals (C group, N = 5; P < 0.01 for all groups). AT1-R tended to decrease in L animals. Inducible NOS (iNOS) did not differ among P, L, and C animals and iNOS immunohistochemical staining in macrophages was significantly more intense in L than in P animals (P < 0.01). The vascular endothelium showed moderate or strong eNOS and AT1-R staining. Macrophages and pneumocytes showed moderate or strong iNOS and AT1-R staining, but C animals showed weak iNOS and AT1-R staining. Macrophages of L and P animals showed moderate and weak AT2-R staining, respectively, but the endothelium of all groups only showed weak staining. In conclusion, pulmonary hypertension induced by chronic hypoxia in newborn piglets is partially attenuated by AT1-R blockade. We suggest that AT1-R blockade might act through AT2-R and/or Mas receptors and the nitrergic system in the lungs of hypoxemic newborn piglets.

Adrenomedullin is inactivated in the lungs of neonatal piglets.

Adrenomedullin, a novel 52 amino acid peptide normally present in adult human plasma, has been shown to induce systemic hypotension in the adult rat, pig and cat, and in the new-born piglet. Little is known about the site (s) of adrenomedullin inactivation in adults or neonates. Groups of five 0-2-day old and 2-week old anaesthetized piglets were prepared to enable continuous monitoring of cardiac output, mean systemic arterial pressure, mean pulmonary artery pressure, mean systemic vascular resistance and mean pulmonary vascular resistance. In both age groups, injections of human adrenomedullin1-52 into the left atrium produced significant (P < 0.05) reductions in mean systemic arterial pressure and mean pulmonary artery pressure. Although injections of similar doses of human adrenomedullin1-52 into the right atrium produced significant (P < 0.05) decreases in mean pulmonary artery pressure, there were no appreciable alterations in mean systemic arterial pressure in either age group. These results suggest that the systemic vasodilator properties of human adrenomedullin1-52 are reduced upon first pass through the pulmonary circulation in 2-week old piglets, a phenomenon that is present at birth.

Cystic Fibrosis Pigs Develop Lung Disease and Exhibit Defective Bacterial Eradication at Birth

Lung disease causes most of the morbidity and mortality in cystic fibrosis (CF). Understanding the pathogenesis of this disease has been hindered, however, by the lack of an animal model with characteristic features of CF. To overcome this problem, we recently generated pigs with mutated CFTR genes. We now report that, within months of birth, CF pigs spontaneously developed hallmark features of CF lung disease, including airway inflammation, remodeling, mucus accumulation, and infection. Their lungs contained multiple bacterial species, suggesting that the lungs of CF pigs have a host defense defect against a wide spectrum of bacteria. In humans, the temporal and causal relations between inflammation and infection have remained uncertain. To investigate these processes, we studied newborn pigs. Their lungs showed no inflammation but were less often sterile than controls. Moreover, after introduction of bacteria into their lungs, pigs with CF failed to eradicate bacteria as effectively as wild-type pigs. These results suggest that impaired bacterial elimination is the pathogenic event that initiates a cascade of inflammation and pathology in CF lungs. Our finding that pigs with CF have a host defense defect against bacteria within hours of birth provides an opportunity to further investigate CF pathogenesis and to test therapeutic and preventive strategies that could be deployed before secondary consequences develop.

Global transcriptional response of pig brain and lung to natural infection by Pseudorabies virus

BackgroundPseudorabies virus (PRV) is an alphaherpesviruses whose native host is pig. PRV infection mainly causes signs of central nervous system disorder in young pigs, and respiratory system diseases in the adult.ResultsIn this report, we have analyzed native host (piglets) gene expression changes in response to acute pseudorabies virus infection of the brain and lung using a printed human oligonucleotide gene set from Illumina. A total of 210 and 1130 out of 23,000 transcript probes displayed differential expression respectively in the brain and lung in piglets after PRV infection (p-value < 0.01), with most genes displaying up-regulation. Biological process and pathways analysis showed that most of the up-regulated genes are involved in cell differentiation, neurodegenerative disorders, the nervous system and immune responses in the infected brain whereas apoptosis, cell cycle control, and the mTOR signaling pathway genes were prevalent in the infected lung. Additionally, a number of differentially expressed genes were found to map in or close to quantitative trait loci for resistance/susceptibility to pseudorabies virus in piglets.ConclusionThis is the first comprehensive analysis of the global transcriptional response of the native host to acute alphaherpesvirus infection. The differentially regulated genes reported here are likely to be of interest for the further study and understanding of host viral gene interactions.

Effect of recruitment maneuver on pulmonary surfactant in young piglets with acute lung injury

Objective To investigate the effect of recruitment maneuver(RM) on surfactant proteins in young piglets with acute lung injury and the possible mechanisms of lung recruitment after RM.Methods The piglet model of ALI was established by lipopolysaccharide intravenous injection,12 male piglets were randomly divided into two groups:conventional ventilation group(control group) and RM with low tidal volume group(RM group).After 8 hours of ventilation,mRNA expression of surfactant protein-A(SP-A),SP-B,SP-C,SP-D in the piglet lungs were determined by real time PCR and SP-A protein distribution was assessed by immunohistochemistry.Biochemical analyses of TP,total phospholipids(TPL),DSPC were conducted as well.SP-A levels in bronchoalveolar lavage fluid(BALF) and plasma were measured by enzymelinked immunosorbent assay(ELISA).Results As compared with control group,RM group had higher expression of SP-A,SP-B,SP-C and SP-D.SP-A average gray values of control group and RM group were 97.8±6.4 and 106.3±8.5,and there was significant difference(P＜0.01).RM group showed significant increase of TPL,DSPC and DSPC/TP.The concentration of SP-A in BALF was higher in RM group than that of the control group,however,SP-A plasma level was lower in RM group than that of the control group.Conclusion RM can increase suffactant protein expression in ALI animals,alleviate surfactant protein dysfunction and regulate the concentration of SP-A,which may improve alveolar recruitment following the RM and alleviate ventilator-induced lung injury. Key words: Acute lung injury; Recruitment maneuver; Pulmonary suffactant

Thromboxane Synthase Inhibition Blunts the Development of Pulmonary Hypertension and Vascular Remodeling in Hypoxic Neonatal Piglets

The development of chronic hypoxia (CH)‐induced neonatal pulmonary hypertension (PH) is associated with increased production of thromboxane (TxA2) and an upregulation of L‐type calcium (CaL) channels. Thus, we hypothesized that TxA2 synthase inhibition may blunt the development of PH by mitigating the upregulation of CaL channels. Newborn piglets were exposed to 21 days of normoxia (N), CH or CH plus the TxA2 synthase inhibitor, furegrelate (oral 3 mg/kg, 3x daily). In vivo pulmonary vascular resistance index (PVRI) was 3.15 ‐fold higher in CH (104±1 WU) compared to N (33±1 WU) piglets. Furegrelate partially blunted the elevated PVRI in CH piglets (64±0.5 WU). Furegrelate also reversed the elevated transpulmonary pressure in isolated lungs of CH piglets by 66%, and blunted the overexpression of CaL channels and anomalous Ca2+‐dependent tone. Pulmonary arterial distensibility was decreased in lungs of CH compared to N piglets, indicative of vascular remodeling. Furegrelate partially restored distensibility to normal levels. Our findings suggest that pharmacological inhibition of TxA2 synthase blunts the development of hypoxia‐induced neonatal PH by preserving vascular function and structural integrity. Funded by NIH R01 HL83013