BACKGROUND A major cause of mortality in the coronavirus disease 2019(COVID-19)pandemic was acute respiratory distress syndrome(ARDS).Currently,moderate to severe ARDS induced by COVID-19(COVID ARDS)and other viral an...BACKGROUND A major cause of mortality in the coronavirus disease 2019(COVID-19)pandemic was acute respiratory distress syndrome(ARDS).Currently,moderate to severe ARDS induced by COVID-19(COVID ARDS)and other viral and non-viral etiologies are treated by traditional ARDS protocols that recommend 12-16 hours of prone position ventilation(PPV)with neuromuscular blocking agents(NMBA)and a trial of inhaled vasodilators(IVd)if oxygenation does not improve.However,debate on the efficacy of adjuncts to PPV and low tidal volume ventilation persists and evidence about the benefits of IVd/NMBA in COVID ARDS is sparse.In our multi-center retrospective review,we evaluated the impact of PPV,IVd,and NMBA on outcomes and lung mechanics in COVID ARDS patients with moderate to severe ARDS.AIM To evaluate the impact of PPV used alone or in combination with pulmonary IVd and/or NMBA in mechanically ventilated patients with moderate to severe ARDS during the COVID-19 pandemic.METHODS A retrospective study at two tertiary academic medical centers compared outcomes between COVID ARDS patients receiving PPV and patients in the supine position.PPV patients were divided based on concurrent use of ARDS adjunct therapies resulting in four subgroups:(1)PPV alone;(2)PPV and IVd;(3)PPV and NMBA;and(4)PPV,IVd,and NMBA.Primary outcomes were hospital and intensive care unit(ICU)length of stay(LOS),mortality,and venovenous extracorporeal membrane oxygenation(VV-ECMO)status.Secondary outcomes included changes in lung mechanics at 24-hour intervals for 7 days.RESULTS Total 114 patients were included in this study.Baseline respiratory parameters and Sequential Organ Failure Assessment scores were significantly worse in the PPV group.ICU LOS and LOS were significantly longer for patients who were proned,but no mortality benefit or difference in VV-ECMO status was found.Among the subgroups,no difference in primary outcomes were found.In the secondary analysis,PPV was associated with a significant improvement in arterial oxygen partial pressure(PaO_(2))/fractional inspired oxygen(FiO_(2))(P/F)ratio from day 1 to day 4(P<0.05)and higher driving pressures day 5 to day 7(P<0.05).The combination of PPV and IVd together resulted in improvements in P/F ratio from day 1 to day 7 and plateau pressure on day 4 and day 6(P<0.05).PPV with NMBA was not associated with improvements in any of the secondary outcomes.The use of all three rescue therapies together resulted in improvements in lung compliance on day 2(P<0.05)but no other improvements.CONCLUSION In mechanically ventilated patients diagnosed with moderate to severe COVID ARDS,PPV and PPV with the addition of IVd produced a significant and sustained increase in P/F ratio.The combination of PPV,IVd and NMBA improved compliance however this did not reach significance.Mortality and LOS did not improve with adjunct therapies.Further research is warranted to determine the efficacy of these therapies alone and in combination in the treatment of COVID ARDS.展开更多
A series of new 2 (alkylthio) 5,7 dimethyl 1,2,4 triazolopyrimidines and 3 (alkylthio) 5,7 dimethyl 1,2,4 triazolopyrimidines have been synthesized. These derivatives were evaluated for inhibitory effects on...A series of new 2 (alkylthio) 5,7 dimethyl 1,2,4 triazolopyrimidines and 3 (alkylthio) 5,7 dimethyl 1,2,4 triazolopyrimidines have been synthesized. These derivatives were evaluated for inhibitory effects on 85 7 mmol·L 1 K + and 10 4 mmol·L -1 NE (nor epinephrine) induced contraction of rat aorta strips.展开更多
Vasodilator therapy is common in acute heart failure (AHF) patients, although evidence for morbidity and mortality benefits is limited for many of these drugs. AHF is frequently accompanied by renal dysfunction, which...Vasodilator therapy is common in acute heart failure (AHF) patients, although evidence for morbidity and mortality benefits is limited for many of these drugs. AHF is frequently accompanied by renal dysfunction, which is a strong, independent predictor for poor prognosis. Several hemodynamic and neurohormonal effects of vasodilators—including preload and afterload reduction, activation or inhibition of neurohormonal and inflammatory cascades—have the potential to modulate cardiorenal interaction and impact renal function. However, the effect of vasodilators on renal function in acute heart failure is often poorly described. In this review, we provide an overview of the known cardiorenal effects of traditional and novel vasodilators in patients with acute heart failure.展开更多
Objective: The internal thoracic artery (ITA) is the conduit of choice for coronary artery bypass grafting (CABG). To avoid spasm of the ITA various topical vasodilators have been suggested either intraluminally or by...Objective: The internal thoracic artery (ITA) is the conduit of choice for coronary artery bypass grafting (CABG). To avoid spasm of the ITA various topical vasodilators have been suggested either intraluminally or by topical application. In order to describe the best vasodilating agent for preparation of the ITA, a randomized double-blind placebo controlled clinical work was performed in a group of CABG patients. Methods: Three hundred consecutive patients submitted for elective first time coronary artery bypass grafting were randomly subdivided into five groups. The first measurement was performed shortly after the internal thoracic artery was dissected from the chest wall and the second just prior to performing distal anastomosis to the left anterior descending coronary artery. During the time interval between the two measurements topical vasodilator has been injected into the endothoracic fascia of the ITA using the following drugs: papaverine 2 mg/ml, nitrogly-cerin 1 mg/ml, nitroprusside 0.5 mg/ml, mixed solution include sodium nitroprusside (1 mg/ml) and diltiazem (0.5 mg/ml) and normal saline 0.9%. Results: No statistically significant differences were found between the groups in respect to age, body surface area, cardiopulmonary bypass time, cross clamping time, and time interval between the two flow measurements. Mean arterial pressure at the time of the first and second internal thoracic artery flow measurements did not show statistically significant differences either within or between the groups. In all five groups, the free flow of the internal thoracic artery increased significantly with time. However, no statistically significant differences were shown between the five groups with respect to second flow. Conclusions: We suggest that preparation of the ITA by topical vasodilators injection into the endothoracic fascia does not result in a significantly superior free flow than placebo.展开更多
Objective To explore the feasibility of a coronary angiography-based method developed with artificial intelligence which was able to automatically and quickly calculate coronary volumetric blood flow and coronary flow...Objective To explore the feasibility of a coronary angiography-based method developed with artificial intelligence which was able to automatically and quickly calculate coronary volumetric blood flow and coronary flow reserve (CFR),and explore the differences in CFR after injection of different vasodilators.展开更多
Minoxidil is a potent vasodilator primarily used for the treatment of severe hypertension,and androgenic alopecia.Although known adverse effects include fluid retention,tachycardia and hypertrichosis,its potential to ...Minoxidil is a potent vasodilator primarily used for the treatment of severe hypertension,and androgenic alopecia.Although known adverse effects include fluid retention,tachycardia and hypertrichosis,its potential to induce coronary vasospasm remains largely underreported.[1]Minoxidil is currently reserved for treating alopecia for various causes.展开更多
Identifying a potential dietary non-pharmacological treatment to prevent cerebrovascular damage in Alzheimer's disease is crucial for alleviating cognitive decline in older adults and enhancing quality of life.Thi...Identifying a potential dietary non-pharmacological treatment to prevent cerebrovascular damage in Alzheimer's disease is crucial for alleviating cognitive decline in older adults and enhancing quality of life.This study featured the combined supplementation of soy lecithin(SL)and soy isoflavones(SIF),using in vivo animal models,in vitro vascular ring preparation,and cell studies to investigate the potential advantages and mechanisms of SL combined with SIF on cognitive function and cerebrovascular health from multiple perspectives.The results show that Aβcan significantly induce learning and memory impairment in rats,as well as pathological changes in brain blood vessels,exacerbating damage to cerebral vasodilation function and subsequently reducing cerebral blood flow in the brain.The above-mentioned phenomena induced by Aβcan be significantly improved by the combined intervention of SL and SIF.Further research has revealed that the combined intervention of SL and SIF can reverse the downregulation of the PI3K/PIP3/PDK-1/Akt/eNOS signaling pathway and phosphorylated protein expression induced by Aβin rat brain vascular tissues and bEND.3 cells.Silencing PDK-1 expression in bEND.3 cells showed that the upregulation effect of SL and SIF on Akt and eNOS disappeared.Here we find that prophylactically supplementation with SL in conjunction with SIF appears to effectively activate the PI3K/PIP3/PDK-1/Akt/e NOS pathway within cerebral vascular.This activation improves cerebrovascular vasodilation,offering potential protective effects for both cerebral vascular health and cognitive function.展开更多
Objective To decompose and reformulate Banxia Baizhu Tianma Decoction（BBT） in order to optimize its ratio for vasodilatory effect.The fingerprints of these six component herbs were also studied via Tri-step FTIR ana...Objective To decompose and reformulate Banxia Baizhu Tianma Decoction（BBT） in order to optimize its ratio for vasodilatory effect.The fingerprints of these six component herbs were also studied via Tri-step FTIR analysis.Methods The herbal components of BBT were extracted separately with different solvents,such as 95%ethanol,50%ethanol,and distilled water.The vasodilatory effect of the extracts was studied using the in vitro pre-contracted aortic ring model.Among these extracts,the water extracts of Pinellia ternata[PT（W）]and Citri reticulatae[CR（W）],50%ethanol extracts of Castrodia elata[GE（50）]and Clycyrrhiza uralensis[GU（50）],and 95%ethanol extracts of Atractylodes macrocephala[AM（E）],and Poria cocos[PC（E）]were selected for the orthogonal stimulus-response compatibility group study due to their high effectiveness in vasodilation.Results The best combination ratio（G2） was GE（50）,GU（50）,AM（E）,PC（E）,CR（W）,and PT（W） at EC0,EC5,EC5,EC5,EC5,and EC5,with EC50 of（0.06 ± 0.01） mg/mL.Comparison between the vasodilatory effects of extracts derived from G2 and BBT were also studied.From the results,the 50%ethanol extract following G2 ratio was found to be most potent extract with the highest vasodilatory effect compared with other extracts derived from G2 or BBT,with EC50 of（0.05 ±0.005） mg/mL.Conclusion The optimum ratio and appropriate extraction method for the new BBT formulae are obtained.G2 is determined as the best formulae with the highest potency in producing the vasodilatory effect on isolated rat aortic rings.The results obtained suggest that 50%ethanol is found to be the best solvent to extract the vasoactive compounds of G2 in order to exhibit the highest efficacy of vasodilatory effect.展开更多
Objective: To study the effect of Xiongshao Capsule (芎芍胶囊, XSC), a TCM herb that can promote blood circulation to remove blood stasis, on the endothelial dependent relaxation function, serum nitric oxide (NO), and...Objective: To study the effect of Xiongshao Capsule (芎芍胶囊, XSC), a TCM herb that can promote blood circulation to remove blood stasis, on the endothelial dependent relaxation function, serum nitric oxide (NO), and plasma endothelin-KET-1) of the patients with cervical atherosclerosis. Methods: Forty patients were randomly divided into two groups; XSC group and Probucol group (western medicine control). In addition, 20 healthy people were set as a normal control group. Plasma ET-1, serum NO, the internal diameter of basal brachial artery, endothelial dependent flow mediated dilation (FMD) and non-endothelial dependent nitroglycerin induced dilation (NID) to the trial group before and after therapy and to the healthy control group were determined respectively. Results; Compared to the healthy control group, FMD of patients with atherosclerosis was damaged obviously, the serum NO level decreased, plasma ET-1 increased (P< 0. 01), NID also decreased (P<0. 05), the internal diameter of basal brachial artery has no obvious difference (P>0. 05). After the patients with atherosclerosis were treated with Xiongshao Capsule for 12 weeks, FMD increased evidently, plasma ET-1 decreased, serum NO and the ratio of NO/ET-1 increased, compared with the level before therapy and Probucol group, the difference was significant (P<0.05, P<0.01), NID didn't change obviously (P>0.05). Conclusion: XSC could regulate vascular activity factor and improve the function of endothelial dependent vascular dilation of patients with atherosclerosis.展开更多
In order to inquire into the therapeutic effects of Xin Mai Tong Capsule (心脉通胶囊) on coronary heart disease with myocardial ischemia, 40 patients were randomly divided into two groups (Xin Mai Tong group and the c...In order to inquire into the therapeutic effects of Xin Mai Tong Capsule (心脉通胶囊) on coronary heart disease with myocardial ischemia, 40 patients were randomly divided into two groups (Xin Mai Tong group and the control group). The plasma endothelin (ET) levels in the two groups of patients were markedly higher than that of the healthy people (P<0.001), and the calcitonin gene related peptide (CGRP) was similar to that of the healthy people (P>0.05). After treatment, ET and symptomatic scores in the two groups decreased markedly (P<0.01), and their S-T segments were elevated obviously (P<0.01). But the decrease of ET and symptomatic scores and elevation of S-T segment in Xin Mai Tong group were superior to those of the control group (P<0.05～0.01). The CGRP level in the control group did not vary obviously post-treatment, but it increased markedly (P<0.01) with the addition of Xin Mai Tong Capsule in Xin Mai Tong group.展开更多
Recent reports from pulmonary arterial hypertension （PAH） registries suggest that the mean age at diagnosis is increasing in a growing proportion of elderly patients. The combination of several reasons such as aging...Recent reports from pulmonary arterial hypertension （PAH） registries suggest that the mean age at diagnosis is increasing in a growing proportion of elderly patients. The combination of several reasons such as aging popula- tion, increase in life expectancy, growing PAH awareness of physicians and patients, and availability of more treatment options could explain the changing picture of PAH. PAH should be considered as an emerging entity in the elderly.展开更多
It has become increasingly apparent that the looming epidemic of heart failure calls for systematic treatment approaches tailored to the needs of individual patient phenotypes. Although chronic heart failure (CHF) the...It has become increasingly apparent that the looming epidemic of heart failure calls for systematic treatment approaches tailored to the needs of individual patient phenotypes. Although chronic heart failure (CHF) therapies are continuously evolving based on the increasing understanding of the involved etiology, acute heart failure (AHF) therapies are still based on hemodynamic improvements and symptom alleviation. Guidelines on AHF management have highlighted that the currently administered AHF therapies lack evidence and have raised concerns on the safety and efficacy of some of the hitherto accepted treatment modalities. Additionally, the high mortality and morbidity rates associated with the current AHF therapies also add to the imperative need to revisit AHF management. The last decade has witnessed a paradigm shift in the way we define and diagnose AHF. Apart from it being recognized as a distinct clinical entity, research has also led to new data on the pathophysiological changes associated with AHF. These developments along with the limited short- and long-term effects of currently used therapies may herald a paradigm shift in the way we plan and deliver management strategies to treat the pathological progression of heart failure.展开更多
In an attempt to demonstrate the biological activities of a short peptide.Arg-Gly-Asp- Ser (RGDS) was synthesized and used for bioassay,The data obtained here proved that RGDS ob- viously inhibited PAF- and/or ADP-ind...In an attempt to demonstrate the biological activities of a short peptide.Arg-Gly-Asp- Ser (RGDS) was synthesized and used for bioassay,The data obtained here proved that RGDS ob- viously inhibited PAF- and/or ADP-induced platelet aggregation.The present paper revealed that RG- DS had vasodilative action and the cGMP accumulation may be one of the mechanisms of RGDS exer- ting bioactivities.展开更多
Objective: To discover the mechanism behind ameliorative effects of Michelia champaca(M. champaca) in gastrointestinal, respiratory and cardiovascular disorders. Methods: Antispasmodic potential was evaluated by tryin...Objective: To discover the mechanism behind ameliorative effects of Michelia champaca(M. champaca) in gastrointestinal, respiratory and cardiovascular disorders. Methods: Antispasmodic potential was evaluated by trying the M. champaca extract(aqueous:ethanolic) on rabbit aorta, trachea and jejunum in vitro. Isotonic and isometric transducers coupled with Power Lab data acquisition system was used to record the responses of isolated tissues. Results: M. champaca extract relaxed the spontaneous and high K^+(80 mmol/L)-induced contractions of isolated jejunum preparation of rabbit showing a Ca^(2+) channel blocking mechanism. Moreover, extract shifted calcium concentration response curves towards right like standard calcium channel blocker verapamil. In rabbit tracheal preparation, M. champaca relaxed both carbachol(1 μmol/L) and high K^+-induced contractions, likewise verapamil. In rabbit aorta preparation, M. champaca relaxed phenylephrine(1 μmol/L) and high K^+-induced contractions similar to verapamil. Conclusion: M. champaca possesses spasmolytic, airways relaxant and vasodilator actions mediated perhaps due to blocking of Ca^(2+) channels, hence validating its therapeutic usage in diarrhea, asthma and hypertension.展开更多
We present the case of a 65-year-old male with vasospastic angina(VSA)whose condition worsened during the perioperative period.He had been diagnosed with VSA 10 years prior.He was treated with two types of vasodilator...We present the case of a 65-year-old male with vasospastic angina(VSA)whose condition worsened during the perioperative period.He had been diagnosed with VSA 10 years prior.He was treated with two types of vasodilators and had not experienced any chest symptoms for 5 years.At this juncture,he underwent surgery for relapsed maxillary sublingual carcinoma.He had taken two vasodilators one day prior to surgery.Intravenous infusion of nitroglycerin(NTG)was initiated immediately before the surgery and continued the following day.Instead of stopping NTG,a dermal isosorbide dinitrate tape was applied on post-operative day 1.Two days later,a complete atrioventricular block with pulseless electrical activity appeared.After cardiopulmonary resuscitation,emergent coronary angiography showed severe coronary spasm in both the left and right coronary arteries.Intracoronary infusion of nitroglycerin and epinephrine with percutaneous cardiopulmonary support relieved the coronary spasm.During the perioperative period,several factors can trigger coronary vasospasm,including the discontinuation of vasodilators.Thus,surgeons,anesthetists,and cardiologists should watch for coronary vasospasm during this period and for worsening coronary spasm when discontinuing vasodilators in patients at risk for VSA.展开更多
Background and Aim of Study: The phosphodiesterase inhibitors (Sildenafil and Milrinone), Nitric Oxide donor Sodium Nitroprusside (SNP) and prostacyclin analogs are commonly used pulmonary vasodilators to treat pulmon...Background and Aim of Study: The phosphodiesterase inhibitors (Sildenafil and Milrinone), Nitric Oxide donor Sodium Nitroprusside (SNP) and prostacyclin analogs are commonly used pulmonary vasodilators to treat pulmonary hypertension. In the past few years, we have used human pulmonary artery rings in vitro to evaluate pulmonary vascular resistance. The main objective of the current study is to document the pharmacological impact of clinically used prostacyclin analogs on the human pulmonary system in parallel with phosphodiesterase inhibitors and SNP. Methods: The study used human pulmonary artery rings of internal diameter of 2 - 4 mm and length of 2 mm. These were extracted from patients with lung resections. These rings were then mounted on a multiwire myograph, and changes in isometric tension were noted. Then, concentration response curves were constructed to Sildenafil (Sd), Milrinone (Mil), Sodium Nitroprusside (SNP), Epoprostenol (Ep), Iloprost (Ip) and Treprostinil (Tp). Results: 52 pulmonary artery rings were used in these experiments. Sildenafil, Milrinone, SNP, Epoprostenol, Iloprost and Treprostinil caused a concentration-dependent vasodilation in small human pulmonary arteries (pEC50: 5.97 ± 0.22, 5.99 ± 0.12, 7.64 ± 0.08, 7.53 ± 0.14, 8.84 ± 0.15 and 9.48 ± 0.13 respectively, n = 8 to 12). The efficacy for the same was in the order: Tp = Ip > Ep > Mil > SNP > Sd. The potency varied in the order: Tp > Ip > SNP > Ep > Mil > Sd. Conclusion: This research showed the efficacy as well as the potency of SNP and phosphodiesterase inhibitors and prostacyclin analogs on the human pulmonary vasculature. Treprostinil and Iloprost exhibited maximum relaxation. However, Sildenafil and SNP showed lesser impact. These effects need to be considered for clinical studies for enhanced patient outcomes.展开更多
Aim: To report a case of longer-lived patent ductus arteriosus with features of pulmonary arterial hypertension up to the age of 65 years in an elderly woman. Introduction: The clinical recognition of patent ductus ar...Aim: To report a case of longer-lived patent ductus arteriosus with features of pulmonary arterial hypertension up to the age of 65 years in an elderly woman. Introduction: The clinical recognition of patent ductus arteriosus with severe pulmonary hypertension is difficult. Only 60% of adults presented with a continuous murmur in a recent series. Asymptomatic patent ductus arteriosus tolerated for many years and may not require closure. Case Report: A 65 years old female presented with dyspnea had signs of pulmonary arterial hypertension with enlarged pulmonary artery and its branches, atrial fibrillation along with a continuous murmur in the left second intercostal space. Echocardiography revealed a 13 mm size patent ductus arteriosus and a bidirectional with predominant left-to-right shunt. Patient was managed conservatively and symptoms got improved with medical therapy. Conclusion: Treatment of patent ductus arteriosus in the setting of pulmonary hypertension is challenging. Early repair can mitigate the development of pulmonary hypertension and reverse vasculopathy in more advanced disease. Maternal aspirin ingestion should be avoided in pregnancy since it causes constriction of fetal ductus.展开更多
Buyang Huanwu Decoction （BYHWD） is a well-known traditional Chinese medicine prescription which is used to treat ischaemic stroke and stroke-induced disabilities. However, the exact mechanism underlying BYHWD＇s ame...Buyang Huanwu Decoction （BYHWD） is a well-known traditional Chinese medicine prescription which is used to treat ischaemic stroke and stroke-induced disabilities. However, the exact mechanism underlying BYHWD＇s amelioration of ischaemic stroke and its effective constituents remain unclear. The present study aimed to identify the effective constituents of BYHWD and to further explore its action mechanisms in the amelioration of ischaemic stroke by testing the activities of 15 absorbable chemical constituents of BYHWD with the same methods under the same conditions. The following actions of these 15 compounds were revealed： 1） Ferulic acid, calycosin, formononetin, astrapterocarpan-3-O-β-D-glucoside, paeonol, calycosin-7-O-β-D-glucoside, astraisofla- van-7-O-β-D-glucoside, ligustrazine, and propyl gallate significantly suppressed concanavalin A （Con A）-induced T lymphocyte proliferation; 2） Propyl gallate, calycosin-7-O-β-D-glucoside, paeonol, and ferulic acid markedly inhibited LPS-induced apoptosis in RAW264.7 cells; 3） Propyl gallate and formononetin significantly inhibited LPS-induced NO release; 4） Hydroxysaffior yellow A and inosine protected PC12 cells against the injuries caused by glutamate; and 5） Formononetin, astragaloside IV, astraisofiavan-7-O-β-D- glucoside, inosine, paeoniflorin, ononin, paeonol, propyl gallate, ligustrazine, and ferulic acid significantly suppressed the constriction of the thoracic aorta induced by KCI in rats. In conclusion, the results from the present study suggest that BYHWD exerts its ischaemic stroke ameliorating activities by modulating multiple targets with multiple components.展开更多
In liver cirrhosis, the circulatory hemodynamic alterations of portal hypertension signifi cantly contribute to many of the clinical manifestations of the disease. In the physiopathology of this vascular alteration, m...In liver cirrhosis, the circulatory hemodynamic alterations of portal hypertension signifi cantly contribute to many of the clinical manifestations of the disease. In the physiopathology of this vascular alteration, mesen- teric splanchnic vasodilation plays an essential role by initiating the hemodynamic process. Numerous studies performed in cirrhotic patients and animal models have shown that this splanchnic vasodilation is the result of an important increase in local and systemic vasodilators and the presence of a splanchnic vascular hyporesponsiveness to vasoconstrictors. Among the molecules and factors known to be potentially involved in this arterial vasodilation, nitric oxide seems to have a crucial role in the physiopathology of this vascular alteration. However, none of the wide variety of mediators can be described as solely responsible, since this phenomenon is multifactorial in origin. Moreover, angiogenesis and vascular remodeling processes alsoseem to play a role. Finally, the sympathetic nervous system is thought to be involved in the pathogenesis of the hyperdynamic circulation associated with portal hypertension, although the nature and extent of its role is not completely understood. In this review, we discuss the different mechanisms known to contribute to this complex phenomenon.展开更多
Intracerebral hemorrhage(ICH) remains the second-most common form of stroke with high morbidity and mortality.ICH can be divided into two pathophysiological stages:an acute primary phase,including hematoma volume expa...Intracerebral hemorrhage(ICH) remains the second-most common form of stroke with high morbidity and mortality.ICH can be divided into two pathophysiological stages:an acute primary phase,including hematoma volume expansion,and a subacute secondary phase consisting of blood-brain barrier disruption and perihematomal edema expansion.To date,all major trials for ICH have targeted the primary phase with therapies designed to reduce hematoma expansion through blood pressure control,surgical evacuation,and hemostasis.However,none of these trials has resulted in improved clinical outcomes.Magnesium is a ubiquitous element that also plays roles in vasodilation,hemostasis,and blood-brain barrier preservation.Animal models have highlighted potential therapeutic roles for magnesium in neurological diseases specifically targeting these pathophysiological mechanisms.Retrospective studies have also demonstrated inverse associations between admission magnesium levels and hematoma volume,hematoma expansion,and clinical outcome in patients with ICH.These associations,coupled with the multifactorial role of magnesium that targets both primary and secondary phases of ICH,suggest that magnesium may be a viable target of study in future ICH studies.展开更多
文摘BACKGROUND A major cause of mortality in the coronavirus disease 2019(COVID-19)pandemic was acute respiratory distress syndrome(ARDS).Currently,moderate to severe ARDS induced by COVID-19(COVID ARDS)and other viral and non-viral etiologies are treated by traditional ARDS protocols that recommend 12-16 hours of prone position ventilation(PPV)with neuromuscular blocking agents(NMBA)and a trial of inhaled vasodilators(IVd)if oxygenation does not improve.However,debate on the efficacy of adjuncts to PPV and low tidal volume ventilation persists and evidence about the benefits of IVd/NMBA in COVID ARDS is sparse.In our multi-center retrospective review,we evaluated the impact of PPV,IVd,and NMBA on outcomes and lung mechanics in COVID ARDS patients with moderate to severe ARDS.AIM To evaluate the impact of PPV used alone or in combination with pulmonary IVd and/or NMBA in mechanically ventilated patients with moderate to severe ARDS during the COVID-19 pandemic.METHODS A retrospective study at two tertiary academic medical centers compared outcomes between COVID ARDS patients receiving PPV and patients in the supine position.PPV patients were divided based on concurrent use of ARDS adjunct therapies resulting in four subgroups:(1)PPV alone;(2)PPV and IVd;(3)PPV and NMBA;and(4)PPV,IVd,and NMBA.Primary outcomes were hospital and intensive care unit(ICU)length of stay(LOS),mortality,and venovenous extracorporeal membrane oxygenation(VV-ECMO)status.Secondary outcomes included changes in lung mechanics at 24-hour intervals for 7 days.RESULTS Total 114 patients were included in this study.Baseline respiratory parameters and Sequential Organ Failure Assessment scores were significantly worse in the PPV group.ICU LOS and LOS were significantly longer for patients who were proned,but no mortality benefit or difference in VV-ECMO status was found.Among the subgroups,no difference in primary outcomes were found.In the secondary analysis,PPV was associated with a significant improvement in arterial oxygen partial pressure(PaO_(2))/fractional inspired oxygen(FiO_(2))(P/F)ratio from day 1 to day 4(P<0.05)and higher driving pressures day 5 to day 7(P<0.05).The combination of PPV and IVd together resulted in improvements in P/F ratio from day 1 to day 7 and plateau pressure on day 4 and day 6(P<0.05).PPV with NMBA was not associated with improvements in any of the secondary outcomes.The use of all three rescue therapies together resulted in improvements in lung compliance on day 2(P<0.05)but no other improvements.CONCLUSION In mechanically ventilated patients diagnosed with moderate to severe COVID ARDS,PPV and PPV with the addition of IVd produced a significant and sustained increase in P/F ratio.The combination of PPV,IVd and NMBA improved compliance however this did not reach significance.Mortality and LOS did not improve with adjunct therapies.Further research is warranted to determine the efficacy of these therapies alone and in combination in the treatment of COVID ARDS.
文摘A series of new 2 (alkylthio) 5,7 dimethyl 1,2,4 triazolopyrimidines and 3 (alkylthio) 5,7 dimethyl 1,2,4 triazolopyrimidines have been synthesized. These derivatives were evaluated for inhibitory effects on 85 7 mmol·L 1 K + and 10 4 mmol·L -1 NE (nor epinephrine) induced contraction of rat aorta strips.
文摘Vasodilator therapy is common in acute heart failure (AHF) patients, although evidence for morbidity and mortality benefits is limited for many of these drugs. AHF is frequently accompanied by renal dysfunction, which is a strong, independent predictor for poor prognosis. Several hemodynamic and neurohormonal effects of vasodilators—including preload and afterload reduction, activation or inhibition of neurohormonal and inflammatory cascades—have the potential to modulate cardiorenal interaction and impact renal function. However, the effect of vasodilators on renal function in acute heart failure is often poorly described. In this review, we provide an overview of the known cardiorenal effects of traditional and novel vasodilators in patients with acute heart failure.
文摘Objective: The internal thoracic artery (ITA) is the conduit of choice for coronary artery bypass grafting (CABG). To avoid spasm of the ITA various topical vasodilators have been suggested either intraluminally or by topical application. In order to describe the best vasodilating agent for preparation of the ITA, a randomized double-blind placebo controlled clinical work was performed in a group of CABG patients. Methods: Three hundred consecutive patients submitted for elective first time coronary artery bypass grafting were randomly subdivided into five groups. The first measurement was performed shortly after the internal thoracic artery was dissected from the chest wall and the second just prior to performing distal anastomosis to the left anterior descending coronary artery. During the time interval between the two measurements topical vasodilator has been injected into the endothoracic fascia of the ITA using the following drugs: papaverine 2 mg/ml, nitrogly-cerin 1 mg/ml, nitroprusside 0.5 mg/ml, mixed solution include sodium nitroprusside (1 mg/ml) and diltiazem (0.5 mg/ml) and normal saline 0.9%. Results: No statistically significant differences were found between the groups in respect to age, body surface area, cardiopulmonary bypass time, cross clamping time, and time interval between the two flow measurements. Mean arterial pressure at the time of the first and second internal thoracic artery flow measurements did not show statistically significant differences either within or between the groups. In all five groups, the free flow of the internal thoracic artery increased significantly with time. However, no statistically significant differences were shown between the five groups with respect to second flow. Conclusions: We suggest that preparation of the ITA by topical vasodilators injection into the endothoracic fascia does not result in a significantly superior free flow than placebo.
文摘Objective To explore the feasibility of a coronary angiography-based method developed with artificial intelligence which was able to automatically and quickly calculate coronary volumetric blood flow and coronary flow reserve (CFR),and explore the differences in CFR after injection of different vasodilators.
文摘Minoxidil is a potent vasodilator primarily used for the treatment of severe hypertension,and androgenic alopecia.Although known adverse effects include fluid retention,tachycardia and hypertrichosis,its potential to induce coronary vasospasm remains largely underreported.[1]Minoxidil is currently reserved for treating alopecia for various causes.
基金supported by the National Natural Science Foundation of China(82273620,81302427)。
文摘Identifying a potential dietary non-pharmacological treatment to prevent cerebrovascular damage in Alzheimer's disease is crucial for alleviating cognitive decline in older adults and enhancing quality of life.This study featured the combined supplementation of soy lecithin(SL)and soy isoflavones(SIF),using in vivo animal models,in vitro vascular ring preparation,and cell studies to investigate the potential advantages and mechanisms of SL combined with SIF on cognitive function and cerebrovascular health from multiple perspectives.The results show that Aβcan significantly induce learning and memory impairment in rats,as well as pathological changes in brain blood vessels,exacerbating damage to cerebral vasodilation function and subsequently reducing cerebral blood flow in the brain.The above-mentioned phenomena induced by Aβcan be significantly improved by the combined intervention of SL and SIF.Further research has revealed that the combined intervention of SL and SIF can reverse the downregulation of the PI3K/PIP3/PDK-1/Akt/eNOS signaling pathway and phosphorylated protein expression induced by Aβin rat brain vascular tissues and bEND.3 cells.Silencing PDK-1 expression in bEND.3 cells showed that the upregulation effect of SL and SIF on Akt and eNOS disappeared.Here we find that prophylactically supplementation with SL in conjunction with SIF appears to effectively activate the PI3K/PIP3/PDK-1/Akt/e NOS pathway within cerebral vascular.This activation improves cerebrovascular vasodilation,offering potential protective effects for both cerebral vascular health and cognitive function.
基金Exploratory Research Grant Scheme(ERGS)(203/PFARMASI/6730122)Universiti Sains Malaysia-Research University Grants(1001/PFARMASI/812195)
文摘Objective To decompose and reformulate Banxia Baizhu Tianma Decoction（BBT） in order to optimize its ratio for vasodilatory effect.The fingerprints of these six component herbs were also studied via Tri-step FTIR analysis.Methods The herbal components of BBT were extracted separately with different solvents,such as 95%ethanol,50%ethanol,and distilled water.The vasodilatory effect of the extracts was studied using the in vitro pre-contracted aortic ring model.Among these extracts,the water extracts of Pinellia ternata[PT（W）]and Citri reticulatae[CR（W）],50%ethanol extracts of Castrodia elata[GE（50）]and Clycyrrhiza uralensis[GU（50）],and 95%ethanol extracts of Atractylodes macrocephala[AM（E）],and Poria cocos[PC（E）]were selected for the orthogonal stimulus-response compatibility group study due to their high effectiveness in vasodilation.Results The best combination ratio（G2） was GE（50）,GU（50）,AM（E）,PC（E）,CR（W）,and PT（W） at EC0,EC5,EC5,EC5,EC5,and EC5,with EC50 of（0.06 ± 0.01） mg/mL.Comparison between the vasodilatory effects of extracts derived from G2 and BBT were also studied.From the results,the 50%ethanol extract following G2 ratio was found to be most potent extract with the highest vasodilatory effect compared with other extracts derived from G2 or BBT,with EC50 of（0.05 ±0.005） mg/mL.Conclusion The optimum ratio and appropriate extraction method for the new BBT formulae are obtained.G2 is determined as the best formulae with the highest potency in producing the vasodilatory effect on isolated rat aortic rings.The results obtained suggest that 50%ethanol is found to be the best solvent to extract the vasoactive compounds of G2 in order to exhibit the highest efficacy of vasodilatory effect.
文摘Objective: To study the effect of Xiongshao Capsule (芎芍胶囊, XSC), a TCM herb that can promote blood circulation to remove blood stasis, on the endothelial dependent relaxation function, serum nitric oxide (NO), and plasma endothelin-KET-1) of the patients with cervical atherosclerosis. Methods: Forty patients were randomly divided into two groups; XSC group and Probucol group (western medicine control). In addition, 20 healthy people were set as a normal control group. Plasma ET-1, serum NO, the internal diameter of basal brachial artery, endothelial dependent flow mediated dilation (FMD) and non-endothelial dependent nitroglycerin induced dilation (NID) to the trial group before and after therapy and to the healthy control group were determined respectively. Results; Compared to the healthy control group, FMD of patients with atherosclerosis was damaged obviously, the serum NO level decreased, plasma ET-1 increased (P< 0. 01), NID also decreased (P<0. 05), the internal diameter of basal brachial artery has no obvious difference (P>0. 05). After the patients with atherosclerosis were treated with Xiongshao Capsule for 12 weeks, FMD increased evidently, plasma ET-1 decreased, serum NO and the ratio of NO/ET-1 increased, compared with the level before therapy and Probucol group, the difference was significant (P<0.05, P<0.01), NID didn't change obviously (P>0.05). Conclusion: XSC could regulate vascular activity factor and improve the function of endothelial dependent vascular dilation of patients with atherosclerosis.
文摘In order to inquire into the therapeutic effects of Xin Mai Tong Capsule (心脉通胶囊) on coronary heart disease with myocardial ischemia, 40 patients were randomly divided into two groups (Xin Mai Tong group and the control group). The plasma endothelin (ET) levels in the two groups of patients were markedly higher than that of the healthy people (P<0.001), and the calcitonin gene related peptide (CGRP) was similar to that of the healthy people (P>0.05). After treatment, ET and symptomatic scores in the two groups decreased markedly (P<0.01), and their S-T segments were elevated obviously (P<0.01). But the decrease of ET and symptomatic scores and elevation of S-T segment in Xin Mai Tong group were superior to those of the control group (P<0.05～0.01). The CGRP level in the control group did not vary obviously post-treatment, but it increased markedly (P<0.01) with the addition of Xin Mai Tong Capsule in Xin Mai Tong group.
文摘Recent reports from pulmonary arterial hypertension （PAH） registries suggest that the mean age at diagnosis is increasing in a growing proportion of elderly patients. The combination of several reasons such as aging popula- tion, increase in life expectancy, growing PAH awareness of physicians and patients, and availability of more treatment options could explain the changing picture of PAH. PAH should be considered as an emerging entity in the elderly.
文摘It has become increasingly apparent that the looming epidemic of heart failure calls for systematic treatment approaches tailored to the needs of individual patient phenotypes. Although chronic heart failure (CHF) therapies are continuously evolving based on the increasing understanding of the involved etiology, acute heart failure (AHF) therapies are still based on hemodynamic improvements and symptom alleviation. Guidelines on AHF management have highlighted that the currently administered AHF therapies lack evidence and have raised concerns on the safety and efficacy of some of the hitherto accepted treatment modalities. Additionally, the high mortality and morbidity rates associated with the current AHF therapies also add to the imperative need to revisit AHF management. The last decade has witnessed a paradigm shift in the way we define and diagnose AHF. Apart from it being recognized as a distinct clinical entity, research has also led to new data on the pathophysiological changes associated with AHF. These developments along with the limited short- and long-term effects of currently used therapies may herald a paradigm shift in the way we plan and deliver management strategies to treat the pathological progression of heart failure.
基金This project was supported by the National Natural Science Foundation
文摘In an attempt to demonstrate the biological activities of a short peptide.Arg-Gly-Asp- Ser (RGDS) was synthesized and used for bioassay,The data obtained here proved that RGDS ob- viously inhibited PAF- and/or ADP-induced platelet aggregation.The present paper revealed that RG- DS had vasodilative action and the cGMP accumulation may be one of the mechanisms of RGDS exer- ting bioactivities.
文摘Objective: To discover the mechanism behind ameliorative effects of Michelia champaca(M. champaca) in gastrointestinal, respiratory and cardiovascular disorders. Methods: Antispasmodic potential was evaluated by trying the M. champaca extract(aqueous:ethanolic) on rabbit aorta, trachea and jejunum in vitro. Isotonic and isometric transducers coupled with Power Lab data acquisition system was used to record the responses of isolated tissues. Results: M. champaca extract relaxed the spontaneous and high K^+(80 mmol/L)-induced contractions of isolated jejunum preparation of rabbit showing a Ca^(2+) channel blocking mechanism. Moreover, extract shifted calcium concentration response curves towards right like standard calcium channel blocker verapamil. In rabbit tracheal preparation, M. champaca relaxed both carbachol(1 μmol/L) and high K^+-induced contractions, likewise verapamil. In rabbit aorta preparation, M. champaca relaxed phenylephrine(1 μmol/L) and high K^+-induced contractions similar to verapamil. Conclusion: M. champaca possesses spasmolytic, airways relaxant and vasodilator actions mediated perhaps due to blocking of Ca^(2+) channels, hence validating its therapeutic usage in diarrhea, asthma and hypertension.
文摘We present the case of a 65-year-old male with vasospastic angina(VSA)whose condition worsened during the perioperative period.He had been diagnosed with VSA 10 years prior.He was treated with two types of vasodilators and had not experienced any chest symptoms for 5 years.At this juncture,he underwent surgery for relapsed maxillary sublingual carcinoma.He had taken two vasodilators one day prior to surgery.Intravenous infusion of nitroglycerin(NTG)was initiated immediately before the surgery and continued the following day.Instead of stopping NTG,a dermal isosorbide dinitrate tape was applied on post-operative day 1.Two days later,a complete atrioventricular block with pulseless electrical activity appeared.After cardiopulmonary resuscitation,emergent coronary angiography showed severe coronary spasm in both the left and right coronary arteries.Intracoronary infusion of nitroglycerin and epinephrine with percutaneous cardiopulmonary support relieved the coronary spasm.During the perioperative period,several factors can trigger coronary vasospasm,including the discontinuation of vasodilators.Thus,surgeons,anesthetists,and cardiologists should watch for coronary vasospasm during this period and for worsening coronary spasm when discontinuing vasodilators in patients at risk for VSA.
文摘Background and Aim of Study: The phosphodiesterase inhibitors (Sildenafil and Milrinone), Nitric Oxide donor Sodium Nitroprusside (SNP) and prostacyclin analogs are commonly used pulmonary vasodilators to treat pulmonary hypertension. In the past few years, we have used human pulmonary artery rings in vitro to evaluate pulmonary vascular resistance. The main objective of the current study is to document the pharmacological impact of clinically used prostacyclin analogs on the human pulmonary system in parallel with phosphodiesterase inhibitors and SNP. Methods: The study used human pulmonary artery rings of internal diameter of 2 - 4 mm and length of 2 mm. These were extracted from patients with lung resections. These rings were then mounted on a multiwire myograph, and changes in isometric tension were noted. Then, concentration response curves were constructed to Sildenafil (Sd), Milrinone (Mil), Sodium Nitroprusside (SNP), Epoprostenol (Ep), Iloprost (Ip) and Treprostinil (Tp). Results: 52 pulmonary artery rings were used in these experiments. Sildenafil, Milrinone, SNP, Epoprostenol, Iloprost and Treprostinil caused a concentration-dependent vasodilation in small human pulmonary arteries (pEC50: 5.97 ± 0.22, 5.99 ± 0.12, 7.64 ± 0.08, 7.53 ± 0.14, 8.84 ± 0.15 and 9.48 ± 0.13 respectively, n = 8 to 12). The efficacy for the same was in the order: Tp = Ip > Ep > Mil > SNP > Sd. The potency varied in the order: Tp > Ip > SNP > Ep > Mil > Sd. Conclusion: This research showed the efficacy as well as the potency of SNP and phosphodiesterase inhibitors and prostacyclin analogs on the human pulmonary vasculature. Treprostinil and Iloprost exhibited maximum relaxation. However, Sildenafil and SNP showed lesser impact. These effects need to be considered for clinical studies for enhanced patient outcomes.
文摘Aim: To report a case of longer-lived patent ductus arteriosus with features of pulmonary arterial hypertension up to the age of 65 years in an elderly woman. Introduction: The clinical recognition of patent ductus arteriosus with severe pulmonary hypertension is difficult. Only 60% of adults presented with a continuous murmur in a recent series. Asymptomatic patent ductus arteriosus tolerated for many years and may not require closure. Case Report: A 65 years old female presented with dyspnea had signs of pulmonary arterial hypertension with enlarged pulmonary artery and its branches, atrial fibrillation along with a continuous murmur in the left second intercostal space. Echocardiography revealed a 13 mm size patent ductus arteriosus and a bidirectional with predominant left-to-right shunt. Patient was managed conservatively and symptoms got improved with medical therapy. Conclusion: Treatment of patent ductus arteriosus in the setting of pulmonary hypertension is challenging. Early repair can mitigate the development of pulmonary hypertension and reverse vasculopathy in more advanced disease. Maternal aspirin ingestion should be avoided in pregnancy since it causes constriction of fetal ductus.
基金supported by National Natural Science Foundation of China(No.81470050)Beijing Natural Science Foundation(No.7122097)
文摘Buyang Huanwu Decoction （BYHWD） is a well-known traditional Chinese medicine prescription which is used to treat ischaemic stroke and stroke-induced disabilities. However, the exact mechanism underlying BYHWD＇s amelioration of ischaemic stroke and its effective constituents remain unclear. The present study aimed to identify the effective constituents of BYHWD and to further explore its action mechanisms in the amelioration of ischaemic stroke by testing the activities of 15 absorbable chemical constituents of BYHWD with the same methods under the same conditions. The following actions of these 15 compounds were revealed： 1） Ferulic acid, calycosin, formononetin, astrapterocarpan-3-O-β-D-glucoside, paeonol, calycosin-7-O-β-D-glucoside, astraisofla- van-7-O-β-D-glucoside, ligustrazine, and propyl gallate significantly suppressed concanavalin A （Con A）-induced T lymphocyte proliferation; 2） Propyl gallate, calycosin-7-O-β-D-glucoside, paeonol, and ferulic acid markedly inhibited LPS-induced apoptosis in RAW264.7 cells; 3） Propyl gallate and formononetin significantly inhibited LPS-induced NO release; 4） Hydroxysaffior yellow A and inosine protected PC12 cells against the injuries caused by glutamate; and 5） Formononetin, astragaloside IV, astraisofiavan-7-O-β-D- glucoside, inosine, paeoniflorin, ononin, paeonol, propyl gallate, ligustrazine, and ferulic acid significantly suppressed the constriction of the thoracic aorta induced by KCI in rats. In conclusion, the results from the present study suggest that BYHWD exerts its ischaemic stroke ameliorating activities by modulating multiple targets with multiple components.
基金Supported by the Grants from the Ministerio de Educacióny Ciencia, No. SAF2006-0314the Ministerio de Cienciae Innovación, No. SAF2009-08354
文摘In liver cirrhosis, the circulatory hemodynamic alterations of portal hypertension signifi cantly contribute to many of the clinical manifestations of the disease. In the physiopathology of this vascular alteration, mesen- teric splanchnic vasodilation plays an essential role by initiating the hemodynamic process. Numerous studies performed in cirrhotic patients and animal models have shown that this splanchnic vasodilation is the result of an important increase in local and systemic vasodilators and the presence of a splanchnic vascular hyporesponsiveness to vasoconstrictors. Among the molecules and factors known to be potentially involved in this arterial vasodilation, nitric oxide seems to have a crucial role in the physiopathology of this vascular alteration. However, none of the wide variety of mediators can be described as solely responsible, since this phenomenon is multifactorial in origin. Moreover, angiogenesis and vascular remodeling processes alsoseem to play a role. Finally, the sympathetic nervous system is thought to be involved in the pathogenesis of the hyperdynamic circulation associated with portal hypertension, although the nature and extent of its role is not completely understood. In this review, we discuss the different mechanisms known to contribute to this complex phenomenon.
文摘Intracerebral hemorrhage(ICH) remains the second-most common form of stroke with high morbidity and mortality.ICH can be divided into two pathophysiological stages:an acute primary phase,including hematoma volume expansion,and a subacute secondary phase consisting of blood-brain barrier disruption and perihematomal edema expansion.To date,all major trials for ICH have targeted the primary phase with therapies designed to reduce hematoma expansion through blood pressure control,surgical evacuation,and hemostasis.However,none of these trials has resulted in improved clinical outcomes.Magnesium is a ubiquitous element that also plays roles in vasodilation,hemostasis,and blood-brain barrier preservation.Animal models have highlighted potential therapeutic roles for magnesium in neurological diseases specifically targeting these pathophysiological mechanisms.Retrospective studies have also demonstrated inverse associations between admission magnesium levels and hematoma volume,hematoma expansion,and clinical outcome in patients with ICH.These associations,coupled with the multifactorial role of magnesium that targets both primary and secondary phases of ICH,suggest that magnesium may be a viable target of study in future ICH studies.
