Safety of hyperbaric oxygen therapy in patients with heart failure: A retrospective cohort study.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) has several hemodynamic effects including increases in afterload (due to vasoconstriction) and decreases in cardiac output. This, along with rare reports of pulmonary edema during emergency treatment, has led providers to consider HBOT relatively contraindicated in patients with reduced left ventricular ejection fraction (LVEF). However, there is limited evidence regarding the safety of elective HBOT in patients with heart failure (HF), and no existing reports of complications among patients with HF and preserved LVEF. We aimed to retrospectively review patients with preexisting diagnoses of HF who underwent elective HBOT, to analyze HBOT-related acute HF complications. METHODS: Research Ethics Board approvals were received to retrospectively review patient charts. Patients with a history of HF with either preserved ejection fraction (HFpEF), mid-range ejection fraction (HFmEF), or reduced ejection fraction (HFrEF) who underwent elective HBOT at two Hyperbaric Centers (Toronto General Hospital, Rouge Valley Hyperbaric Medical Centre) between June 2018 and December 2020 were reviewed. RESULTS: Twenty-three patients with a history of HF underwent HBOT, completing an average of 39 (range 6-62) consecutive sessions at 2.0 atmospheres absolute (ATA) (n = 11) or at 2.4 ATA (n = 12); only two patients received fewer than 10 sessions. Thirteen patients had HFpEF (mean LVEF 55 ± 7%), and seven patients had HFrEF (mean LVEF 35 ± 8%) as well as concomitantly decreased right ventricle function (n = 5), moderate/severe tricuspid regurgitation (n = 3), or pulmonary hypertension (n = 5). The remaining three patients had HFmEF (mean LVEF 44 ± 4%). All but one patient was receiving fluid balance therapy either with loop diuretics or dialysis. Twenty-one patients completed HBOT without complications. We observed symptoms consistent with HBOT-related HF exacerbation in two patients. One patient with HFrEF (LVEF 24%) developed dyspnea attributed to pulmonary edema after the fourth treatment, and later admitted to voluntarily holding his diuretics before the session. He was managed with increased oral diuretics as an outpatient, and ultimately completed a course of 33 HBOT sessions uneventfully. Another patient with HFpEF (LVEF 64%) developed dyspnea and desaturation after six sessions, requiring hospital admission. Acute coronary ischemia and pulmonary embolism were ruled out, and an elevated BNP and normal LVEF on echocardiogram confirmed a diagnosis of pulmonary edema in the context of HFpEF. Symptoms subsided after diuretic treatment and the patient was discharged home in stable condition, but elected not to resume HBOT. CONCLUSIONS: Patients with HF, including HFpEF, may develop HF symptoms during HBOT and warrant ongoing surveillance. However, these patients can receive HBOT safely after optimization of HF therapy and fluid restriction.

The effects of Crocus sativus extract on inhaled paraquat-induced lung inflammation, oxidative stress, pathological changes and tracheal responsiveness in rats.

Paraquat is a green liquid toxin that is used in agriculture and can induce multi-organ including lung injury. Various pharmacological effects of Crocus sativus (C. sativus) were indicated in previous studies. In this research, the effects of C. sativus extract and pioglitazone on inhaled paraquat-induced lung inflammation, oxidative stress, pathological changes, and tracheal responsiveness were studied in rats. Eight groups of rats (n = 7 in each) including control (Ctrl), untreated paraquat aerosol exposed group (54 mg/m3, 8 times in alternate days), paraquat treated groups with dexamethasone (0.03 mg/kg/day, Dexa) as positive control, two doses of C. sativus extract (20 and 80 mg/kg/day, CS-20 and CS-80), pioglitazone (5 and 10 mg/kg/day, Pio-5 and Pio-10), and the combination of CS-20 + Pio-5 were studied. Total and differential WBC, levels of oxidant and antioxidant biomarkers in the BALF, lung tissue cytokine levels, tracheal responsiveness (TR), and pathological changes were measured. The levels of IFN-γ, IL-10, SOD, CAT, thiol, and EC50 were reduced, but MDA level, total and differential WBC count in the BALF and lung pathological changes were increased in the paraquat group (all, p < 0.001). The levels of IFN-γ, IL-10, SOD, CAT, thiol and EC50 were increased but BALF MDA level, lung pathological changes, total and differential WBC counts were reduced in all treated groups. The effects of C. sativus high dose and combination groups on measured parameters were equal or even higher than dexamethasone (p < 0.05 to p < 0.001). The effects of the combination of CS-20 + Pio-5 on most variables were significantly higher than CS-20 and Pio-5 alone (p < 0.05 to p < 0.001). C. sativus treatment improved inhaled paraquat-induced lung injury similar to dexamethasone and showed a synergistic effect with pioglitazone, suggesting possible PPAR-γ receptor-mediated effects of the plant.

Value of Thoracic Echocardiography in the Diagnosis of Acute Heart Failure: Systematic Review and Meta-analysis.

Context: For patients with acute heart failure (AHF), the methods of clinical diagnosis of pulmonary edema mainly include clinical symptoms, laboratory results, and an imaging examination. The common diagnostic methods, such as chest X-rays and computerized tomography (CT) scanning, haven't been completely satisfactory. Objective: The study intended to systematically, quantitatively, and comprehensively evaluate the value of a lung (pulmonary) ultrasound, performed at a patient's bedside, in the diagnosis of acute heart failure (AHF), to provide an objective basis for its clinical application and further research. Design: The research team searched PubMed, Excerpta Medica Database (EMBASE), ScienceDirect, Cochrane Library, China Journal Full-text Database (CNKI), VIP Full-text Database, Wanfang Database, and China Biomedical Literature Database (CBM) for relevant literature, from January 2010 to the present, about the use of a lung ultrasound for diagnosis of AHF patients. The team used keywords to search literature: ultrasound, AHF diagnosis, cardiogenic pulmonary edema, ultrasonic examination, AHF diagnosis, and cardiogenic pulmonary edema. The research team then conducted a meta-analysis of the collected data according to the Cochrane Handbook 5.3 with RevMan 5.3 statistical software. Setting: The study took place at Jinan. Outcome Measures: The research team: (1) evaluated the quality of the included studies; (2) examined the accuracy of a lung ultrasound in the diagnosis of AHF compared to computerized tomography (CT) as well as to the conventional ultrasonic cardiogram (echocardiogram) that a cardiologist performs; (3) determined the sensitivity, specificity, and predictive value of lung ultrasound using data from two of the included studies; (4) evaluated the data by drawing funnel charts; and (5) examined the publication bias of the included studies. Results: The research team selected six controlled clinical studies, with 345 data samples, for the meta-analysis. The team performed heterogeneity tests for the included research data. For the first test, the team compared the accuracy of lung ultrasound and CT in diagnosing AHF and found obvious heterogeneity, with χ2 = 11.40, df = 3, P = .010, and I2 = 74%. Based on an analysis using a random effects model, the team found no significant differences between the two methods in the diagnosis of AHF (P = .35). For the second test, the team compared the accuracy of lung ultrasound and an ultrasonic cardiogram in diagnosing AHF and found that the data didn't differ significantly, with χ2 = 0.08, df = 1, P = .78, I2 = 0%. Based on an analysis using a fixed effects model, the team found that the accuracy of the lung ultrasound in diagnosing AHF was significantly higher than that of ultrasonic cardiogram (P = .01). In the two studies, the sensitivity and specificity were high. The majority of the funnel charts were symmetrical, but a few were asymmetrical, suggesting a publication bias, which the heterogeneity in the studies and the limited number of examined examples may explain. Conclusions: Lung ultrasound is of great value in the diagnosis of AHF. It's highly efficient, has prospects for broad clinical application, and is worth popularizing, benefiting patients. Scholars need to verify the current study's findings in follow-up studies and in more high-quality case-control trials.

Yinma Jiedu Granule attenuates LPS-induced acute lung injury in rats via suppressing inflammation level.

ETHNOPHARMACOLOGICAL RELEVANCE: Yinma Jiedu Granule (YMJD) is a traditional Chinese patent medicine (CPM), which has been proved to have anti-inflammatory effects and therapeutical effects on obstructive pulmonary disease. AIM OF STUDY: The purpose of the current investigation is to find out if YMJD can alleviate acute lung injury (ALI) induced by lipopolysaccharide (LPS) in rats and its underlying mechanisms. MATERIALS AND METHODS: Rats were treated with either vehicle or YMJD for 14 consecutive days, and 2 h after the last administration, the rat model of ALI was induced by the intratracheal instillation of LPS. High performance liquid chromatography (HPLC) was applied for the fingerprint analysis of YMJD. The efficacy and molecular mechanisms were investigated. RESULTS: The results showed that treatment with YMJD improved the general state of rats, reduced weight loss and serum lactate (LA) levels, attenuated pulmonary edema and pathological damage of the lung tissue. Moreover, we found that YMJD effectively decreased the infiltration of white blood cells (WBC), lymphocytes (LYM), mononuclear cells (MON) and neutrophils (NEUT) in bronchoalveolar lavage fluid (BALF), reduced the concentration of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) and inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in the lung tissue. Additionally, we found that YMJD could significantly increase the activity of superoxide dismutase (SOD) and reduce the malondialdehyde (MDA) level in the lung tissue. By employing RNA-sequencing, we have identified that JAK2/STAT1 is an important pathway that is involved in the lung protection of YMJD, and further Western blot assay verified that YMJD could effectively inhibit the activation of the JAK2/STAT1 pathway. CONCLUSIONS: YMJD could attenuate LPS-induced ALI through suppressing inflammation and oxidative stress in the lung tissue of rats, associating with the inhibition of JAK2/STAT1 activation. These findings provide evidence for the clinical use of YMJD for treatment of inflammatory pulmonary diseases like ALI.

Initiating Continuous Renal Replacement Therapy in Patients With Transurethral Resection of Prostate Syndrome: A Case Report.

With advances and developments in hysteroscopy, cystoscopy, transurethral resection of bladder tumor, and arthroscopy, transurethral resection of prostate (TURP) syndrome has been increasingly reported. TURP syndrome is often accompanied by severe hyponatremia, fluid overload, and a plasma hypotonic state, resulting in heart failure and pulmonary and cerebral edema. Conventional treatment methods, such as intravenous infusion of hyperosmotic saline, can rapidly reverse the downward trend of serum sodium levels in efforts to prevent and treat cerebral edema. However, this may not be suitable for patients with cardiac and renal insufficiency and may induce central pontine myelinolysis due to the possibility of worsening volume load and difficulty in controlling the correction rate of serum sodium. The patient described in this report presented with severe hyponatremia (sodium<100 mmol/L) combined with intraoperative pulmonary edema; his cardiac function and oxygenation status deteriorated after an intravenous infusion of 3% hypertonic saline. He underwent continuous renal replacement therapy (CRRT) to prevent the progression of multiple-organ edema and cardiac insufficiency. CRRT has demonstrated efficacy in the treatment of chronic hyponatremia in patients with renal failure, and can slowly and continuously correct water-electrolyte imbalance, acid-base imbalance, and volume overload. TURP syndrome with severe hyponatremia and pulmonary edema was diagnosed; accordingly, the patient was treated with 3% hypertonic saline, furosemide, and CRRT, without the development of overt neurological sequelae.

23-O-acetylshengmanol-3-O-α-L-arabinoside alleviates lipopolysaccharide-induced acute lung injury through inhibiting IκB/NF-κB and MAPK/AP-1 signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Cimicifuga foetida L. is a well-established traditional Chinese medicine with heat-clearing and detoxifying effects and has good therapeutic effect on oral mucosal ulcer and pharyngitis. The rhizome of this herb is rich in triterpenoid glycosides, including 23-O-acetylshengmanol-3-o-α-L-arabinoside (DA). AIM OF THE STUDY: Whether and how DA attenuates acute lung injury (ALI) are unclear. Accordingly, we focused on its anti-inflammatory effects and underlying molecular mechanisms in lipopolysaccharide (LPS)-stimulated ALI mice and RAW264.7 cells. MATERIALS AND METHODS: The model of ALI mice was established by exposed intratracheal instillation of LPS. Lung pathological changes were evaluated by hematoxylin and eosin staining. Pulmonary function was assessed by whole-body plethysmography. Total protein content in bronchoalveolar lavage fluid (BALF) was detected by bicinchoninic acid method. Wet/dry lung ratio was used to evaluate the degree of pulmonary edema in mice. The levels of pro-inflammatory mediators were measured using enzyme-linked immunosorbent assay. The relative expression of pro-inflammatory gene mRNA was examined by RT-qPCR. The expression of inflammatory-related proteins was detected by Western blot. RAW264.7 cells were used to test the anti-inflammatory effects of DA in vitro. Cytotoxicity was assessed using a MTT assay. Nitric oxide production was measured by Griess assay. The production and expression of inflammatory mediators and the protein levels of inflammatory signaling molecules in the NF-κB and MAPK pathways were measured. Furthermore, immunofluorescence staining was used to analyze the expression of p-IκBα, p-ERK, and p-p38 in lung macrophages and the nuclear translocation of NF-κB p65 and AP-1 in cells. RESULTS: DA evidently alleviated histopathological changes and ameliorated pulmonary edema. Moreover, DA could reduce excessive inflammatory reaction in lung tissue as manifested by the reduction of proinflammatory mediators (IL-1ß, IL-6, TNF-α, MCP-1, iNOS, and COX-2) in BALF, serum, and lung tissues. Further, DA inhibited the activation of the NLRP3/caspase-1 pathway in the lung. DA reduced the production and expression of the proinflammatory mediators above in RAW264.7 cells. Mechanistically, DA remarkably blocked the nuclear translocation of NF-κB p65, suppressed IκBα phosphorylation, and markedly reduced the nuclear translocation of AP-1 and the phosphorylation of ERK and p38. CONCLUSIONS: The findings demonstrated that DA exerts anti-inflammatory effects in LPS-stimulated ALI mice and macrophages by downregulating the NLRP3/caspase-1 signaling pathway in lung tissue and the IκB/NF-κB and MAPKs/AP-1 pathways in macrophages, suggesting that DA may be promising in ALI treatment.

Unexpected systolic anterior motion of the mitral valve-related hypoxemia during transurethral resection of the prostate under spinal anesthesia: a case report.

BACKGROUND: Dynamic obstruction of the left ventricular outflow tract resulting from systolic anterior motion of the mitral valve can be an unexpected cause of acute and severe perioperative hypotension in noncardiac surgery. We report a patient undergoing spinal anesthesia for transurethral resection of the prostate who experienced sudden hypoxemia caused by systolic anterior motion-induced mitral regurgitation but with a clinically picture simulating fluid overload. CASE PRESENTATION: An 83-year-old man with a history of hypertension was scheduled for transurethral resection of the prostate. One hour after spinal anesthesia, he developed acute restlessness and dyspnea, with pink frothy sputum and progressive hypoxemia. Slight hypertension was noted, and an electrocardiogram showed atrial fibrillation with a rapid ventricular response. Furosemide and nitroglycerin were thus administered for suspected fluid overload or transurethral resection of the prostate syndrome; however, he then became severely hypotensive. After tracheal intubation, intraoperative transesophageal echocardiography was promptly performed, which revealed an empty hypercontractile left ventricle, significant mitral regurgitation and mosaic flow signal in the left ventricular outflow tract. Following aggressive fluid therapy, his hemodynamic changes stabilized. Repeat echocardiography in intensive care unit confirmed the presence of systolic anterior motion of the anterior mitral leaflet obstructing the left ventricular outflow tract. We speculate that pulmonary edema was induced by systolic anterior motion-associated mitral regurgitation and rapid atrial fibrillation, and the initial management had worsened his hypovolemia and provoked left ventricular outflow tract obstruction and hemodynamic instability. CONCLUSIONS: Pulmonary edema caused by systolic anterior motion of the mitral valve can be difficult to clinically differentiate from that induced by fluid overload. Therefore, bedside echocardiography is paramount for timely diagnosis and prompt initiation of appropriate therapy in the perioperative care setting.

Polystichum braunii ameliorates airway inflammation by attenuation of inflammatory and oxidative stress biomarkers, and pulmonary edema by elevation of aquaporins in ovalbumin-induced allergic asthmatic mice.

Asthma is a chronic inflammation of pulmonary airways associated with bronchial hyper-responsiveness. The study was aimed to validate the folkloric use of Polystichum braunii (PB) against ovalbumin (OVA)-induced asthmatic and chemical characterization OF both extracts. Allergic asthma was developed by intraperitoneal sensitization with an OVA on days 1 and 14 followed by intranasal challenge. Mice were treated with PB methanolic (PBME) and aqueous extract (PBAE) orally at 600, 300, and 150 mg/kg and using dexamethasone (2 mg/kg) as standard from day 15 to 26. High performance liquid chromatography-diode array detector analysis revealed the presence of various bioactive compounds such as catechin, vanillic acid, and quercetin. The PBME and PBAE profoundly (p < 0.0001-0.05) declined immunoglobulin E level, lungs wet/dry weight ratio, and total and differential leukocyte count in blood and bronchial alveolar lavage fluid of treated mice in contrast to disease control. Histopathological examination showed profoundly decreased inflammatory cell infiltration and goblet cell hyperplasia in treated groups. Both extracts caused significant (p < 0.0001-0.05) diminution of IL-4, IL-5, IL-13, IL-6, IL-1ß, TNF-α, and NF-κB and upregulation of aquaporins (1 and 5), which have led to the amelioration of pulmonary inflammation and attenuation of lung edema in treated mice. Both extracts profoundly (p < 0.0001-0.05) restored the activities of SOD, CAT, GSH and reduced the level of MDA dose dependently. Both extracts possessed significant anti-asthmatic action mainly PBME 600 mg/kg might be due to phenols and flavonoids and could be used as a potential therapeutic option in the management of allergic asthma.

Probable positive effects of the photobiomodulation as an adjunctive treatment in COVID-19: A systematic review.

BACKGROUND: COVID-19, as a newly-emerged viral infection has now spread all over the world after originating in Wuhan, China. Pneumonia is the hallmark of the disease, with dyspnea in half of the patients and acute respiratory distress syndrome (ARDS) in up to one -third of the cases. Pulmonary edema, neutrophilic infiltration, and inflammatory cytokine release are the pathologic signs of this disease. The anti-inflammatory effect of the photobiomodulation (PBM) has been confirmed in many previous studies. Therefore, this review study was conducted to evaluate the direct effect of PBM on the acute lung inflammation or ARDS and also accelerating the regeneration of the damaged tissues. The indirect effects of PBM on modulation of the immune system, increasing the blood flow and oxygenation in other tissues were also considered. METHODOLOGY: The databases of PubMed, Cochrane library, and Google Scholar were searched to find the relevant studies. Keywords included the PBM and related terms, lung inflammation, and COVID-19 -related signs. Studies were categorized with respect to the target tissue, laser parameters, and their results. RESULTS: Seventeen related papers were included in this review. All of them were in animal models. They showed that the PBM could significantly decrease the pulmonary edema, neutrophil influx, and generation of pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), intracellular adhesion molecule (ICAM), reactive oxygen species (ROS), isoform of nitric oxide synthase (iNOS), and macrophage inflammatory protein 2 (MIP-2)). CONCLUSION: Our findings revealed that the PBM could be helpful in reducing the lung inflammation and promoting the regeneration of the damaged tissue. PBM can increase the oxygenation indirectly in order to rehabilitate the affected organs. Thus, the infra-red lasers or light-emitting diodes (LEDs) are recommended in this regard.

Arenaria kansuensis attenuates pulmonary fibrosis in mice via the activation of Nrf2 pathway and the inhibition of NF-kB/TGF-beta1/Smad2/3 pathway.

Pulmonary fibrosis is a key feature of COVID-19, Chinese herbal medicine Arenaria kansuensis has been used for curing pulmonary disease and antivirus for a long time and it has the potential against COVID-19. In this work, protective effect of A. kansuensis ethanol extract (AE) on pulmonary fibrosis was evaluated through paraquat (PQ)-induced pulmonary fibrosis animal model. Results showed that AE could significantly improve the survival rate, increase the body weight and reduce the lung index of mice at the raw drug doses of 700 and 350 mg/kg. Histopathological observation results showed that the destruction degree of lung tissue structure in mice was significantly improved with the increase of AE dosage. Collagen deposition in lung interstitium was significantly reduced. The marker protein alpha-SMA involved in PF were significantly inhibited through repressing TGF-beta1/Smads pathway. The degree of inflammatory infiltration was significantly reduced and inflammatory cytokines were significantly inhibited in mice through inhibiting the NF-kB-p65. Besides, oxidant stress level including upregulated ROS and down-regulated SOD and GSH was efficiently improved by AE through upregulation of Nrf2 and downregulation of NOX4. In summary, this study firstly showed that the protective effect of AE on pulmonary fibrosis was partly due to activation of Nrf2 pathway and the inhibition of NF-kB/TGF-beta1/Smad2/3 pathway.

Nicardipine: When high dose nitrates fail in treating heart failure.

Sympathetic Crashing Acute Pulmonary Edema (SCAPE) describes patients who present with acute hypertensive cardiogenic pulmonary edema. These patients present in respiratory distress, and requiring immediate medical and airway management. The treatment of SCAPE includes non-invasive positive pressure ventilation (NIPPV) to maintain oxygenation, and high dose nitrates to lower blood pressure and reduce afterload. We present a case report of a patient with refractory hypertension to high dose nitrates likely due to nitroglycerin resistance or an attenuated response. The addition of nicardipine led to marked clinical improvement, normalized blood pressure and spared the patient from endotracheal intubation and admission to the intensive care unit.

Amelioration of airway inflammation and pulmonary edema by Teucrium stocksianum via attenuation of pro-inflammatory cytokines and up-regulation of AQP1 and AQP5.

Current study investigates the immunomodulatory effects of T. stocksianum using mouse model of ovalbumin (OVA)-induced allergic asthma. The mice were treated with methanolic extract, n-hexane, and ethyl acetate fractions for consecutive 7 days along with intranasal challenge. The mRNA expression levels of interleukin-4 (IL-4), IL-5, Aquaporin-1 (AQP1) and Aquaporin-5 (AQP5) were evaluated using reverse transcription polymerase chain reaction. The data showed that T. stocksianum significantly reduced airway inflammation as indicated by reduced inflammatory cell infiltration in lungs, and attenuated total and differential leukocyte counts both in blood and BALF. Expression levels of pro-inflammatory IL-4 and IL-5 in lungs were also found significantly reduced. T. stocksianum significantly reduced pulmonary edema as indicated by reduced lung wet/dry ratio and goblet cell hyperplasia. AQP1 and AQP5 expression levels were also found elevated in treatment groups. In conclusion, T. stocksianum possesses anti-asthmatic activity which may be attributed to reduction in IL-4 and IL-5 expression levels, and elevation in AQP1 and AQP5 expression levels.

An aqueous pomegranate peel extract (Punica granatum) protect against Elastase-induced pulmonary emphysema in Sprague Dawley rats model

We investigated the effect of Punica granatum peel aqueous extract (PGE), on pulmonary inflammation and alveolar degradation induced by intratracheal administration of Elastase in Sprague Dawley rats. Lung inflammation was induced in rats by intratracheal instillation of Elastase. On day 1 and 2, animals received an intraperitoneal injection of PGE (200 mg/mL), three hours later, they were intratracheally instilled with 25U/kg pancreatic porcine Elastase. Animals were sacrificed 7 days later. Bronchoalveolar lavage (BAL) were collected and cellularity, histology and mRNA expression of Monocyte chemotactic protein 1(MCP-1), Tumor Necrosis Factor-Alpha (TNF-α), Interleukin 6 (IL-6), and Matrix Metalloproteinase-2 (MMP-2) were studied. In addition, activity of TNF- α, IL-6 and MCP-1 on BAL were also analyzed by ELISA Kit. Elastase administration increased: BAL cellularity, neutrophils recruitment and BAL MCP1, IL-6 expressions. It also increased lung TNF-α, MCP-1, MMP-2 expressions, platelets recruitment, histological parameters at 7th day of elastase treatment. Intraperitoneal injection of 200 mg/kg of PGE reduced, significantly, BAL cellularity, and neutrophils recruitment. However, in animal treated with PGE, MCP-1, MMP-2 and IL-6 on day 7, were similar to the Sham group. Treatment with PGE (200 mg/ kg) also significantly reduced lung TNF-α, and MCP-1 expression. This study reveals that PGE Punica granatum protects against elastase lung inflammation and alveolar degradation induced in rats

Chinese medicinal plants for the potential management of high-altitude pulmonary oedema and pulmonary hypertension.

CONTEXT: Despite the abundance of knowledge regarding high-altitude pulmonary edoema (HAPE) and high-altitude pulmonary hypertension (HAPH), their prevalence continues to be on the rise. Thus, there is an urgent need for newer safe, effective, and relatively economic drug candidates. China is particularly known for the use of medicinal plants. OBJECTIVE: This review summarizes the medicinal plants used for HAPE and HAPH in the past 30 years, as well as some potential plants. METHODS: Publications on HAPE and HAPH from 1990 to 2020 were identified using Web of Science, PubMed, SCOPUS, Springer Link, Google Scholar databases, Chinese Clinical Trial Registry and CNKI with the following keywords: 'medicinal plants,' 'hypoxia,' 'high altitude pulmonary edema,' 'high altitude pulmonary hypertension,' 'pathophysiology,' 'mechanisms,' 'prevention,' 'treatment,' 'human,' 'clinical,' 'safety,' and 'pharmacokinetics.' RESULTS: We found 26 species (from 20 families) out of 5000 plants which are used for HAPE and HAPH prevention or treatment. Rhodiola rosea Linn. (Crassulaceae) is the most widely utilized. The most involved family is Lamiaceae, which contains 5 species. DISCUSSION AND CONCLUSIONS: We mainly reviewed the medicinal plants and mechanisms for the treatment of HAPE and HAPH, and we also assessed related toxicology experiments, pharmacokinetics and bioavailability. Potential medicinal plants were also identified. Further research is needed to determine the pharmacological effects and active ingredients of these potential medicinal plants.

Mangaba (Hancornia speciosa Gomes) fruit juice decreases acute pulmonary edema induced by Tityus serrulatus venom: Potential application for auxiliary treatment of scorpion stings.

Scorpionism represents a serious public health problem due to its increasing incidence. In Brazil, Tityus serrulatus is a species of major medical importance, especially in children and the elderly, as envenomation may induce serious acute pulmonary edema. "Mangaba" (Hancornia speciosa Gomes) fruit juice is popularly used in the treatment of several inflammatory disorders. The objective of this study was to analyze the chemical composition of fruit juice of H. speciosa by HPLC-DAD-MS/MS, as well as to evaluate its anti-inflammatory potential and antioxidant activity, and analyze the biochemical and hematological parameters in acute pulmonary edema induced by T. serrulatus venom (TsV) in mice. Mice were challenged with TsV (30 µg/kg, subcutaneously) and were treated with dexamethasone (2 mg/kg, intraperitoneally) or fruit juice (pre- or post-treatment protocols, by intra-gastric route at 100 and 200 mg/kg), and 2 h later were anesthetized for blood, lung, and kidney collection, for several biochemical analyses. Results showed that the juice decreased edema, myeloperoxidase levels, vascular permeability, and production of cytokines (IL-1ß, IL-6, and TNF-α) in lung tissue. Also, the juice reduced the concentration of nitrite and malondialdehyde oxidative stress markers in renal tissue. Amylase, lactate dehydrogenase, aspartate aminotransferase, and creatine kinase seric levels were reduced when the animals were treated with the juice. HPLC-DAD-MS/MS analysis identified 13 phenolic derivatives. The results suggest that the juice was able to decrease the inflammatory effects induced by T. serrulatus, demonstrating that the use of juice can be relevant for the treatment of scorpion stings.

Systems pharmacology reveals the mechanism of activity of Ge-Gen-Qin-Lian decoction against LPS-induced acute lung injury: A novel strategy for exploring active components and effective mechanism of TCM formulae.

Acute lung injury (ALI), a severe and life-threatening inflammation of the lung, with high morbidity and mortality, underscoring the urgent need for novel treatments. Ge-Gen-Qin-Lian decoction (GQD), a classic Chinese herbal formula, has been widely used to treat intestine-related diseases in the clinic for centuries. In recent years, a growing number of studies have found that GQD has a favorable anti-inflammatory effect. With the further study on the viscera microbiota, the link between the lungs and the gut-the gut-lung axis has been established. Based on the theory of the gut-lung axis, we used systems pharmacology to explore the effects and mechanisms of GQD treatment in ALI. Hypothesizing that GQD inhibits ALI progression, we used the experimental model of lipopolysaccharide (LPS)-induced ALI in Balb/c mice to evaluate the therapeutic potential of GQD. Our results showed that GQD exerted protective effects against LPS-induced ALI by reducing pulmonary edema and microvascular permeability. Meanwhile, GQD can downregulate the expression of LPS-induced TNF-α, IL-1ß, and IL-6 in lung tissue, bronchoalveolar lavage fluid (BLAF), and serum. To further understand the molecular mechanism of GQD in the treatment of ALI, we used the network pharmacology to predict the disease targets of the active components of GQD. Lung tissue and serum samples of the mice were separately analyzed by transcriptomics and metabolomics. KEGG pathway analysis of network pharmacology and transcriptomics indicated that PI3K/Akt signaling pathway was significantly enriched, suggesting that it may be the main regulatory pathway for GQD treatment of ALI. By immunohistochemical analysis and apoptosis detection, it was verified that GQD can inhibit ALI apoptosis through PI3K/Akt signaling pathway. Then, we used the PI3K inhibitor LY294002 to block the PI3K/Akt signaling pathway, and reversely verified that the PI3K/Akt signaling pathway is the main pathway of GQD anti-ALI. In addition, differential metabolites in mice serum samples indicate that GQD can inhibit the inflammatory process of ALI by reversing the imbalance of energy metabolism. Our study showed that, GQD did have a better therapeutic effect on ALI, and initially elucidated its molecular mechanism. Thus, GQD could be exploited to develop novel therapeutics for ALI. Moreover, our study also provides a novel strategy to explore active components and effective mechanism of TCM formula combined with TCM theory to treat ALI.

The unknown known: non-cardiogenic pulmonary edema in amlodipine poisoning, a cohort study.

Context: Amlodipine is the most common calcium channel blocker (CCB) on the Swedish market, and poison center (PC) consultations for amlodipine overdoses are increasing. The clinical picture is dominated by vasodilation with relative preservation of cardiac function. CCBs selectively dilate vessels on the afferent side of the capillary network which, in states of preserved or increased blood flow may lead to edema formation, including non-cardiogenic pulmonary edema (NCPE). This complication has been considered rare in CCB poisoning. In this cohort study of nineteen amlodipine poisonings with high amlodipine blood levels, the incidence and clinical significance of NCPE in severe amlodipine poisoning are explored.Methods: During 2017-2018 the Swedish PC prospectively encouraged the gathering of blood samples in amlodipine poisonings with symptoms requiring treatment with inotropes or vasopressors. Samples were sent by mail to the Forensic Toxicology Division at the Swedish National Board of Forensic Medicine for screening and quantification of relevant toxicants. Patients with blood amlodipine levels >0.25 µg/mL were included in a cohort whose case details were gathered from medical records and PC-case notes with a special focus on signs of NCPE.Results: Nineteen patients met the blood amlodipine inclusion criteria. Four (21%) died and one patient was treated with VA-ECMO. Nine patients developed NCPE defined as a need for positive pressure ventilation (PPV) while having an echocardiographically normal left ventricular function.Conclusion: In this prospective cohort study of consecutive and analytically confirmed significant amlodipine poisonings NCPE was a common finding occurring in 47% of the whole cohort and in 64% of patients who did not go on to develop complete hemodynamic collapse.

Innate inflammatory response to acute inhalation exposure of riot control agent oleoresin capsicum in female rats: An interplay between neutrophil mobilization and inflammatory markers.

Aim: The use of oleoresin capsicum (OC) sprays, due to their irreversible health effects has now grown into a matter of heated debate. In the present study, the early phase pulmonary events involving chemotactic and inflammatory mediators after short-exposure duration to OC have been presented.Materials and methods: Female Wistar rats used in the evaluation of respiratory parameters at 1 h, 3 h, and 24 h post-exposure, were sacrificed for the evaluation of blood cell counts, BALF cytokine estimation, lung capillary leakage, study of oxidative stress and histopathology of the lungs.Results: Results confirmed a dose-dependent effect of OC exposure on serum clinical chemistry and hematological parameters. Subsequent upregulation of IL-l and TNF-α indicated lung's responses to acute oxidant-induced injury and inflammation after OC exposure. Significant alterations in the pulmonary levels of reactive oxygen intermediates were seen following the inhalation of OC. Infiltration of polymorphonuclear leukocytes, mostly neutrophils, into the site of infection was evident in the cytocentrifuged samples of BALF. Histological samples of rat lung sections revealed the recruitment of inflammatory cells in the airways and around blood vessels in the subepithelium of conducting airways.Conclusion: Results of the present study demonstrated that, exposure to OC spray may mitigate inflammatory response and development of acute lung injury in rats. However, it can be concluded that although OC spray causes pulmonary hazards in the aforementioned concentrations, it can be used as a non-lethal riot control agent in minimal concentration. Understanding the in-depth mechanism of action in the molecular and receptor level will help in developing effective antagonist against OC.

Ganoderic Acid A Inhibits Bleomycin-Induced Lung Fibrosis in Mice.

BACKGROUND: To study the protective effects of ganoderic acid A (GAA) on bleomycin (BLM)-induced pulmonary fibrosis. METHODS: ICR mice were intratracheally instilled with BLM to induce pulmonary fibrosis on day 0. Then the mice were orally given GAA (25, 50 mg/kg) or dexamethasone (2 mg/kg). After treatment for 21 days, the mice were sacrificed. Wet dry weight (W/D) ratio of lung was used to detect pulmonary edema. Myeloperoxidase (MPO), interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), and superoxide dismutase (SOD) were detected by enzyme-linked immunosorbent assay. Hematoxylin and eosin staining was used to evaluate the pathological changes. The levels of transforming growth factor ß (TGF-ß), phosphorylated-smad3 (p-smad3), p-IκB, and p-nuclear factor-kappa B (NF-κB) in lung tissue were detected by western blot. RESULTS: GAA treatment significantly improved MPO activity, W/D ratio, and lung histopathology. The protective effect of GAA may be related to downregulation of TNF-α, IL-1ß, IL-6, MDA and upregulation of SOD. In addition, GAA significantly decreased the levels of TGF-ß, p-smad3, p-IκB, and p-NF-κB, compared with those in BLM group. CONCLUSION: GAA has protective effect on BLM-induced lung injury, and TGF-ß/Smad-3/NF-κB signaling pathway may play an important role in the pathogenesis of BLM-induced lung injury.