Temporary mechanical circulatory support (tMCS) devices such as intra-aorticballoon pumps, veno-arterial extracorporeal membrane oxygenation, and percutaneousventricular assist devices, play a major role in supporting...Temporary mechanical circulatory support (tMCS) devices such as intra-aorticballoon pumps, veno-arterial extracorporeal membrane oxygenation, and percutaneousventricular assist devices, play a major role in supporting patients withend-stage heart failure and bridging them to transplant. In 2018, the United Networkfor Organ Sharing heart allocation criteria was modified by increasing thenumber of statuses in the heart transplant waitlist to differentiate and favor thesickest patients awaiting transplantation. Within this new system, patients withtMCS devices receive the highest priority statuses. While the 2018 allocationsystem has reduced waitlist times and mortality for the highest-priority patients,some studies have shown a concomitant rise in the utilization of tMCS devices asbridge to transplant after its enaction. In this narrative review, we describe thesechanges in tMCS utilization and provide insights on how the upcoming creationof a continuous distribution allocation system may further impact these trends.展开更多
BACKGROUND Splenic artery aneurysm(SAA)rupture is a rare,life-threatening condition characterized by acute intra-abdominal hemorrhage and hemodynamic instability.Ruptured SAAs may exhibit a biphasic and relatively slo...BACKGROUND Splenic artery aneurysm(SAA)rupture is a rare,life-threatening condition characterized by acute intra-abdominal hemorrhage and hemodynamic instability.Ruptured SAAs may exhibit a biphasic and relatively slow clinical progression,commonly referred to as the“double-rupture phenomenon”.The reported incidence of the double-rupture phenomenon ranges 12%-21%in patients with ruptured SAAs,potentially due to variations in intra-abdominal pressure.Following anesthesia induction,muscle relaxation can decrease intra-abdominal pressure,potentially triggering the double-rupture phenomenon and leading to circulatory collapse.CASE SUMMARY A 61-year-old female presented to the Department of Emergency with upper abdominal pain,abdominal distension,dizziness,and vomiting.Her vital signs were initially stable.Physical examination revealed abdominal tenderness and positive-shifting dullness.Abdominal contrast-enhanced computed tomography revealed cirrhosis,severe portal hypertension,and splenomegaly.Acute rupture was suggested by a hematoma on the upper left side outside the SAA.Surgeons deemed intravascular intervention challenging and open splenectomy inevitable.Circulatory collapse occurred after anesthesia induction,likely due to a double rupture of the SAA.This double-rupture phenomenon may have resulted from an initial rupture of the SAA into the omental bursa,forming a hematoma that exerted a tamponade effect.A second rupture into the peritoneal cavity may have been triggered by decreased intra-abdominal pressure following anesthesia induction.The patient’s life was saved through early,coordinated,multidisciplinary significant postoperative bleeding or hypoxic encephalopathy.CONCLUSION Anesthesia-induced pressure reduction may trigger a second SAA rupture,causing collapse.Early diagnosis and multidisciplinary teamwork improve outcomes.This is a rare and life-threatening case of SAA rupture,which is of great significance to the medical community for understanding and handling such emergencies.展开更多
BACKGROUND Liver cirrhosis is a progressive disease with high morbidity and mortality requiring effective management strategies to improve patient outcomes.Various therapies including albumin infusion,volume expanders...BACKGROUND Liver cirrhosis is a progressive disease with high morbidity and mortality requiring effective management strategies to improve patient outcomes.Various therapies including albumin infusion,volume expanders(VEs),and vasoactive agents are used to manage patients with cirrhosis.Despite numerous clinical trials,a comprehensive meta-analysis comparing the effectiveness of albumin infusion against alternative treatments is limited.This study provides the current and comprehensive synthesis of evidence,offering key insights for optimizing therapeutic strategies in patients with liver cirrhosis.AIM To systematically update available data on therapies of liver cirrhosis,we performed a meta-analysis to evaluate and compare the clinical efficacy of albumin infusion vs other VEs and vasoactive agents in patients with liver cirrhosis.METHODS A literature search from the PubMed and Embase databases(inception till June 2024)focused on hyponatremia(primary outcome)and various outcomes such as gastrointestinal bleeding,hepatic encephalopathy,severe infection,post-paracentesis-induced circulatory dysfunction(PICD),ascites reappearance,spontaneous bacterial peritonitis,hepatorenal syndrome,renal impairment,hospital stay,mortality,and safety was performed.The primary analysis pooled studies that compared albumin infusion with control.In the subgroup analysis,comparisons were made within the stratified treatment categories included in the control group.RESULTS Of the 2957 studies retrieved,31 studies(27 randomized controlled trials and 4 observational studies)comprising 6255 patients were included.Albumin use was significant in reducing odds of hyponatremia[odds ratio(OR)=0.67;95%confidence interval(95%CI)=0.53-0.85]and PICD(OR=0.38;95%CI=0.20-0.71),whereas the reduction in severe infection(OR=0.55;95%CI=0.28-1.07)did not reach statistical significance.In the subgroup analysis,albumin demonstrated a favorable improvement in lowering the incidence of hyponatremia vs inactive/standard medical therapy(OR=0.54;95%CI=0.27-1.09).For PICD,albumin use was significant compared with other VEs(OR=0.31;95%CI=0.11-0.85)but not with vasoconstrictors(OR=0.63;95%CI=0.21-1.91).In the overall subgroup analysis,a significant reduction was observed in hyponatremia(OR=0.67;95%CI=0.53-0.85)and PICD(OR=0.38;95%CI=0.20-0.71).CONCLUSION Human albumin has been shown to significantly reduce the incidence of hyponatremia and PICD in patients with liver cirrhosis,whereas its effect on severe infection remains suggestive but not statistically significant.展开更多
BACKGROUND Marginal donation after circulatory death(DCD)liver grafts are carefully used to combat the constant shortage of donors.Clinically,the worst outcomes are mainly related to severe ischemia-reperfusion-injury...BACKGROUND Marginal donation after circulatory death(DCD)liver grafts are carefully used to combat the constant shortage of donors.Clinically,the worst outcomes are mainly related to severe ischemia-reperfusion-injury and the dangerous effect of various inflammatory cytokines(CK).The machine perfusion(MP)is a promising device to rescue these grafts.AIM To analyze the role of MP connected to a sorbent cartridge(PerSorb®)and used for very damaged DCD pig livers.METHODS Seven grafts were procured from pigs from a slaughterhouse.Grafts were made very marginal with at least 60 minutes of donor warm ischemia time and 24 hours of static-cold ischemia time:(1)3 grafts were perfused in hypothermic MP with PerSorb(Sorb);(2)2 other grafts in hypothermic MP(HMP)without the cartridge(NoSorb);and(3)The other 2 livers stored in the ice box(NoTreat).The CK were measured at HMP start(T0)and at the end(Tend).Biopsies were taken at T0 and Tend.RESULTS All 5 grafts treated with HMP had a negative lactate trend after 3 hours of treatment(8.83 at T0 vs 6.4 at Tend of Sorb;15 at T0 vs 5.45 at Tend for NoSorb,P value>0.05).At Tend,both Sorb and NoSorb groups had better hemodynamic parameters,comparable between the two groups.Enzyme-linked immunosorbent assay analysis showed a reduction of monocyte chemotactic protein-1,tumor necrosis factor-alpha and interleukin-1βfor NoSorb group at Tend and a complete downregulation to physiological levels of the same CK in Sorb livers after 3 hours of treatment.Biopsies showed a reduction of the perisinusoidal edema for the Sorb grafts compared with the NoSorb livers.CONCLUSION These data suggest a potential protective role of treatment of grafts with MP and sorbent cartridge in reducing the inflammatory response after a severe ischemic injury.展开更多
BACKGROUND The normothermic machine perfusion pump(NMPP)could shape the future of transplantation.Providing ex-vivo optimization,NMPP attenuates ischemic insult while replenishing energy.An understanding of machine pe...BACKGROUND The normothermic machine perfusion pump(NMPP)could shape the future of transplantation.Providing ex-vivo optimization,NMPP attenuates ischemic insult while replenishing energy.An understanding of machine perfusion time(MPT)impact and potential clinical benefits is paramount and necessitates exploration.AIM To investigate the relationship between MPT and post-transplant graft function.METHODS Retrospective review of the first 50 donation after circulatory death(DCD)grafts preserved using NMPP in a tertiary institution was performed.Essential preser-vation time points,graft parameters,recipient information,and postoperative outcomes were prospectively recorded.Early allograft dysfunction(EAD),L-Graft7 score and 90-day outcomes were collected for all grafts.The first 20 re-cipients were allocated into the early group,considered the learning curve population for the center.The subsequent 30 were allocated into the late group.Recipients were also stratified into cohorts depending on MPT,i.e.,short(<8 hours),medium(8-16 hours)and long(>16 hours).RESULTS NMPP operational parameters were not predictive of EAD,L-GrAFT7 or 90-day outcomes.The early group had significantly less MPT and cold ischemia time than the late group(553 minutes vs 850 minutes,P<0.001)and(127.5 minutes vs 154 minutes,P=0.025),respectively.MPT had no impact in either group.CONCLUSION Increased MPT of DCD liver grafts had no adverse recipient results for the times utilized in this population,indicating its upper limits,likely beyond 24 hours,are not demonstrated within this study.Future studies are necessary to determine whether longer MPT is beneficial or detrimental to graft function and,if the latter,what is the maximum safe duration.Further studies of the effect of normothermic machine perfusion pump duration on long-term outcomes are also needed.展开更多
Portal hypertension is a clinical syndrome which leads to several clinical complications, such as the formation and rupture of esophageal and/or gastric varices, ascites, hepatic encephalopathy and hepato-renal syndro...Portal hypertension is a clinical syndrome which leads to several clinical complications, such as the formation and rupture of esophageal and/or gastric varices, ascites, hepatic encephalopathy and hepato-renal syndrome. In cirrhosis, the primary cause of the increase in portal pressure is the enhanced resistance to portal outflow. However, also an increase in splanchnic blood flow worsens and maintains portal hypertension. The vasodilatation of arterial splanchnic vessels and the opening of collateral circulation are the determinants of the increased splanchnic blood flow. Several vasoactive systems/substances, such as nitric oxide, cyclooxygenase-derivatives, carbon monoxide and endogenous cannabinoids are activated in portal hypertension and are responsible for the marked splanchnic vasodilatation. Moreover, an impaired reactivity to vasoconstrictor systems, such as the sympathetic nervous system, vasopressin, angiotensin II and endothelin-1, plays a role in this process. The opening of collateral circulation occurs through the reperfusion and dilatation of preexisting vessels, but also through the generation of new vessels. Splanchnic vasodilatation leads to the onset of the hyperdynamic circulatory syndrome, a syndrome which occurs in patients with portal hypertension and is characterized by increased cardiac output and heart rate, and decreased systemic vascular resistance with low arterial blood pressure. Understanding the pathophysiology of splanchnic vasodilatation and hyperdynamic circulatory syndrome is mandatory for the prevention and treatment of portal hypertension and its severe complications.展开更多
Using deep hypothermic circulatory arrest, thoracic aorta diseases and complex heart diseases can be subjected to corrective procedures. However, mechanisms underlying brain protection during deep hypothermic circulat...Using deep hypothermic circulatory arrest, thoracic aorta diseases and complex heart diseases can be subjected to corrective procedures. However, mechanisms underlying brain protection during deep hypothermic circulatory arrest are unclear. After piglet models underwent 60 minutes of deep hypothermic circulatory arrest at 14°C, expression of microRNAs(miRNAs) was analyzed in the hippocampus by microarray. Subsequently, TargetScan 6.2, RNA22 v2.0, miRWalk 2.0, and miRanda were used to predict potential targets, and gene ontology enrichment analysis was carried out to identify functional pathways involved. Quantitative reverse transcription-polymerase chain reaction was conducted to verify miRNA changes. Deep hypothermic circulatory arrest altered the expression of 35 miRNAs. Twenty-two miRNAs were significantly downregulated and thirteen miRNAs were significantly upregulated in the hippocampus after deep hypothermic circulatory arrest. Six out of eight targets among the differentially expressed miRNAs were enriched for neuronal projection(cyclin dependent kinase, CDK16 and SLC1 A2), central nervous system development(FOXO3, TYRO3, and SLC1 A2), ion transmembrane transporter activity(ATP2 B2 and SLC1 A2), and interleukin-6 receptor binding(IL6 R)– these are the key functional pathways involved in cerebral protection during deep hypothermic circulatory arrest. Quantitative reverse transcription-polymerase chain reaction confirmed the results of microarray analysis. Our experimental results illustrate a new role for transcriptional regulation in deep hypothermic circulatory arrest, and provide significant insight for the development of miRNAs to treat brain injuries. All procedures were approved by the Animal Care Committee of Xuanwu Hospital, Capital Medical University, China on March 1, 2017(approval No. XW-INI-AD2017-0112).展开更多
AIM: To investigate the effects of 1400W-a selective inducible nitric oxide synthase(iN OS) inhibitor in a model of donation after circulatory death(DCD) kidneys. METHODS: Porcine kidneys were retrieved after 25 min w...AIM: To investigate the effects of 1400W-a selective inducible nitric oxide synthase(iN OS) inhibitor in a model of donation after circulatory death(DCD) kidneys. METHODS: Porcine kidneys were retrieved after 25 min warm ischemia. They were then stored on ice for 18 h before being reperfused ex vivo with oxygenated autologous blood on an isolated organ perfusion system. The selective i NOS inhibitor 1400W(10 mg/kg) was administered before reperfusion(n = 6) vs control group(n = 7). Creatinine(1000 μmol/L) was added to the system, renal and tubular cell function and the level of ischemia reperfusion injury were assessed over 3 h of reperfusion using plasma, urine and tissue samples. RESULTS: Kidneys treated with 1400 W had a higher level of creatinine clearance(CrC l) [area under the curve(AUC) CrC l: 2.37 ± 0.97 mL /min per 100 g vs 0.96 ± 0.32 mL /min per 100 g, P = 0.004] and urine output [Total: 320 ± 96 mL vs 156 ± 82 mL, P = 0.008]. There was no significant difference in levels of fractional excretion of sodium(AUC, Fr ex Na+: Control, 186.3% ± 81.7%.h vs 1400 W, 153.4% ± 12.1%.h, P = 0.429). Levels of total protein creatinine ratio were significantly lower in the 1400 W group after 1 h of reperfusion(1h Pr/Cr: 1400 W 9068 ± 6910 mg/L/mmol/L vs Control 21586 ± 5464 mg/L/mmol/L, P = 0.026). Levels of 8-isoprostane were significantly lower in the 1400 W group [8-iso/creatinine ratio: Control 239 ± 136 pg/L/mmol/L vs 1400 W 139 ± 47 pg/L/mmol/L, P = 0.041].CONCLUSION: This study demonstrated that 1400 W reduced ischaemia reperfusion injury in this porcine kidney model of DCD donor. Kidneys had improved renal function and reduced oxidative stress.展开更多
AIM: To investigate the role of prostacyclin (PGI2) and nitric oxide (NO) in the development and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats. METHODS: Ninety male Sprague-Dawley r...AIM: To investigate the role of prostacyclin (PGI2) and nitric oxide (NO) in the development and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats. METHODS: Ninety male Sprague-Dawley rats were divided into three groups: intrahepatic portal hypertension (IHPH) group by injection of CCI4, prehepatic portal hypertension (PHPH) group by partial stenosis of the portal vein and sham-operation control (SO) group. One week after the models were made, animals in each group were subdivided into 4 groups: saline controlled group (n = 23), Nω-nitro-L-arginine (L-NNA)group (n = 21) group, indomethacin (INDO) group (n = 22) and high-dose heparin group (n = 24). The rats were administrated 1mL of saline, L-NNA (3.3 mg/kg-d) and INDO (5 mg/kg·d) respectively through gastric tubes for one week/then heparin (200 IU/Kg/min) was given to rats by intravenous injection for an hour. Splanchnic and systemic hemodynamics were measured using radioactive microsphere techniques. The serum nitrate/nitrite(NO2-/NO3-) levels as a marker of production of NO were assessed by a colorimetric method, and concentration of 6-keto-PGF1α, a stable hydrolytic product of PGI2, was determined by radioimmunoassay. RESULTS: The concentrations of plasma 6-keto-PGFla (pg/mL) and serum NO2-/NO3- (μmol/L) in IHPH rats (1123.85±153.64, 73.34±4.31) and PHPH rats (891.88±83.11, 75.21±6.89) were significantly higher than those in SO rats (725.53±105.54, 58.79±8.47) (P<0.05). Compared with SO rats, total peripheral vascular resistance (TPR) and spanchnic vascular resistance (SVR) decreased but cardiac index (CI) and portal venous inflow (PVI) increased obviously in IHPH and PHPH rats (P<0.05). L-NNA and indomethacin could decrease the concentrations of plasma 6-keto-PGFla and serum NO2/7NO3-in IHPH and PHPH rats (P<0.05) .Meanwhile, CI, FPP and PVI lowered but MAP, TPR and SVR increased(P<0.05). After deduction of the action of NO, there was no significant correlation between plasma PGI2 level and hemodynamic parameters such as CI, TPR, PVI and SVR. However, after deduction of the action of PGI2, NO still correlated highly with the hemodynamic parameters, indicating that there was a close correlation between NO and the hemodynamic parameters. After administration of high-dose heparin, plasma 6-keto- concentrations in IHPH, PHPH and SO rats were significantly higher than those in rats administrated vehicle (P<0.05). On the contrary, levels of serum NO2-/NO3- in IHPH, PHPH and SO rats were significantly lower than those in rats administrated Vehicle (P<0.05). Compared with those rats administrated vehicle, the hemodynamic parameters of portal hypertensive rats, such as CI and PVI, declined significantly after administration of high-dose heparin (P<0.05), while TPR and SVR increased significantly (P<0.05). CONCLUSION: It is NO rather than PGI2 that is a mediator in the formation and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats.展开更多
文摘Temporary mechanical circulatory support (tMCS) devices such as intra-aorticballoon pumps, veno-arterial extracorporeal membrane oxygenation, and percutaneousventricular assist devices, play a major role in supporting patients withend-stage heart failure and bridging them to transplant. In 2018, the United Networkfor Organ Sharing heart allocation criteria was modified by increasing thenumber of statuses in the heart transplant waitlist to differentiate and favor thesickest patients awaiting transplantation. Within this new system, patients withtMCS devices receive the highest priority statuses. While the 2018 allocationsystem has reduced waitlist times and mortality for the highest-priority patients,some studies have shown a concomitant rise in the utilization of tMCS devices asbridge to transplant after its enaction. In this narrative review, we describe thesechanges in tMCS utilization and provide insights on how the upcoming creationof a continuous distribution allocation system may further impact these trends.
基金Supported by National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-119.
文摘BACKGROUND Splenic artery aneurysm(SAA)rupture is a rare,life-threatening condition characterized by acute intra-abdominal hemorrhage and hemodynamic instability.Ruptured SAAs may exhibit a biphasic and relatively slow clinical progression,commonly referred to as the“double-rupture phenomenon”.The reported incidence of the double-rupture phenomenon ranges 12%-21%in patients with ruptured SAAs,potentially due to variations in intra-abdominal pressure.Following anesthesia induction,muscle relaxation can decrease intra-abdominal pressure,potentially triggering the double-rupture phenomenon and leading to circulatory collapse.CASE SUMMARY A 61-year-old female presented to the Department of Emergency with upper abdominal pain,abdominal distension,dizziness,and vomiting.Her vital signs were initially stable.Physical examination revealed abdominal tenderness and positive-shifting dullness.Abdominal contrast-enhanced computed tomography revealed cirrhosis,severe portal hypertension,and splenomegaly.Acute rupture was suggested by a hematoma on the upper left side outside the SAA.Surgeons deemed intravascular intervention challenging and open splenectomy inevitable.Circulatory collapse occurred after anesthesia induction,likely due to a double rupture of the SAA.This double-rupture phenomenon may have resulted from an initial rupture of the SAA into the omental bursa,forming a hematoma that exerted a tamponade effect.A second rupture into the peritoneal cavity may have been triggered by decreased intra-abdominal pressure following anesthesia induction.The patient’s life was saved through early,coordinated,multidisciplinary significant postoperative bleeding or hypoxic encephalopathy.CONCLUSION Anesthesia-induced pressure reduction may trigger a second SAA rupture,causing collapse.Early diagnosis and multidisciplinary teamwork improve outcomes.This is a rare and life-threatening case of SAA rupture,which is of great significance to the medical community for understanding and handling such emergencies.
基金Supported by National Natural Science Foundation of China,No.82070604 and No.82270618the Shanghai Municipal Key Clinical Specialty,China,No.shslczdzk01103。
文摘BACKGROUND Liver cirrhosis is a progressive disease with high morbidity and mortality requiring effective management strategies to improve patient outcomes.Various therapies including albumin infusion,volume expanders(VEs),and vasoactive agents are used to manage patients with cirrhosis.Despite numerous clinical trials,a comprehensive meta-analysis comparing the effectiveness of albumin infusion against alternative treatments is limited.This study provides the current and comprehensive synthesis of evidence,offering key insights for optimizing therapeutic strategies in patients with liver cirrhosis.AIM To systematically update available data on therapies of liver cirrhosis,we performed a meta-analysis to evaluate and compare the clinical efficacy of albumin infusion vs other VEs and vasoactive agents in patients with liver cirrhosis.METHODS A literature search from the PubMed and Embase databases(inception till June 2024)focused on hyponatremia(primary outcome)and various outcomes such as gastrointestinal bleeding,hepatic encephalopathy,severe infection,post-paracentesis-induced circulatory dysfunction(PICD),ascites reappearance,spontaneous bacterial peritonitis,hepatorenal syndrome,renal impairment,hospital stay,mortality,and safety was performed.The primary analysis pooled studies that compared albumin infusion with control.In the subgroup analysis,comparisons were made within the stratified treatment categories included in the control group.RESULTS Of the 2957 studies retrieved,31 studies(27 randomized controlled trials and 4 observational studies)comprising 6255 patients were included.Albumin use was significant in reducing odds of hyponatremia[odds ratio(OR)=0.67;95%confidence interval(95%CI)=0.53-0.85]and PICD(OR=0.38;95%CI=0.20-0.71),whereas the reduction in severe infection(OR=0.55;95%CI=0.28-1.07)did not reach statistical significance.In the subgroup analysis,albumin demonstrated a favorable improvement in lowering the incidence of hyponatremia vs inactive/standard medical therapy(OR=0.54;95%CI=0.27-1.09).For PICD,albumin use was significant compared with other VEs(OR=0.31;95%CI=0.11-0.85)but not with vasoconstrictors(OR=0.63;95%CI=0.21-1.91).In the overall subgroup analysis,a significant reduction was observed in hyponatremia(OR=0.67;95%CI=0.53-0.85)and PICD(OR=0.38;95%CI=0.20-0.71).CONCLUSION Human albumin has been shown to significantly reduce the incidence of hyponatremia and PICD in patients with liver cirrhosis,whereas its effect on severe infection remains suggestive but not statistically significant.
文摘BACKGROUND Marginal donation after circulatory death(DCD)liver grafts are carefully used to combat the constant shortage of donors.Clinically,the worst outcomes are mainly related to severe ischemia-reperfusion-injury and the dangerous effect of various inflammatory cytokines(CK).The machine perfusion(MP)is a promising device to rescue these grafts.AIM To analyze the role of MP connected to a sorbent cartridge(PerSorb®)and used for very damaged DCD pig livers.METHODS Seven grafts were procured from pigs from a slaughterhouse.Grafts were made very marginal with at least 60 minutes of donor warm ischemia time and 24 hours of static-cold ischemia time:(1)3 grafts were perfused in hypothermic MP with PerSorb(Sorb);(2)2 other grafts in hypothermic MP(HMP)without the cartridge(NoSorb);and(3)The other 2 livers stored in the ice box(NoTreat).The CK were measured at HMP start(T0)and at the end(Tend).Biopsies were taken at T0 and Tend.RESULTS All 5 grafts treated with HMP had a negative lactate trend after 3 hours of treatment(8.83 at T0 vs 6.4 at Tend of Sorb;15 at T0 vs 5.45 at Tend for NoSorb,P value>0.05).At Tend,both Sorb and NoSorb groups had better hemodynamic parameters,comparable between the two groups.Enzyme-linked immunosorbent assay analysis showed a reduction of monocyte chemotactic protein-1,tumor necrosis factor-alpha and interleukin-1βfor NoSorb group at Tend and a complete downregulation to physiological levels of the same CK in Sorb livers after 3 hours of treatment.Biopsies showed a reduction of the perisinusoidal edema for the Sorb grafts compared with the NoSorb livers.CONCLUSION These data suggest a potential protective role of treatment of grafts with MP and sorbent cartridge in reducing the inflammatory response after a severe ischemic injury.
文摘BACKGROUND The normothermic machine perfusion pump(NMPP)could shape the future of transplantation.Providing ex-vivo optimization,NMPP attenuates ischemic insult while replenishing energy.An understanding of machine perfusion time(MPT)impact and potential clinical benefits is paramount and necessitates exploration.AIM To investigate the relationship between MPT and post-transplant graft function.METHODS Retrospective review of the first 50 donation after circulatory death(DCD)grafts preserved using NMPP in a tertiary institution was performed.Essential preser-vation time points,graft parameters,recipient information,and postoperative outcomes were prospectively recorded.Early allograft dysfunction(EAD),L-Graft7 score and 90-day outcomes were collected for all grafts.The first 20 re-cipients were allocated into the early group,considered the learning curve population for the center.The subsequent 30 were allocated into the late group.Recipients were also stratified into cohorts depending on MPT,i.e.,short(<8 hours),medium(8-16 hours)and long(>16 hours).RESULTS NMPP operational parameters were not predictive of EAD,L-GrAFT7 or 90-day outcomes.The early group had significantly less MPT and cold ischemia time than the late group(553 minutes vs 850 minutes,P<0.001)and(127.5 minutes vs 154 minutes,P=0.025),respectively.MPT had no impact in either group.CONCLUSION Increased MPT of DCD liver grafts had no adverse recipient results for the times utilized in this population,indicating its upper limits,likely beyond 24 hours,are not demonstrated within this study.Future studies are necessary to determine whether longer MPT is beneficial or detrimental to graft function and,if the latter,what is the maximum safe duration.Further studies of the effect of normothermic machine perfusion pump duration on long-term outcomes are also needed.
文摘Portal hypertension is a clinical syndrome which leads to several clinical complications, such as the formation and rupture of esophageal and/or gastric varices, ascites, hepatic encephalopathy and hepato-renal syndrome. In cirrhosis, the primary cause of the increase in portal pressure is the enhanced resistance to portal outflow. However, also an increase in splanchnic blood flow worsens and maintains portal hypertension. The vasodilatation of arterial splanchnic vessels and the opening of collateral circulation are the determinants of the increased splanchnic blood flow. Several vasoactive systems/substances, such as nitric oxide, cyclooxygenase-derivatives, carbon monoxide and endogenous cannabinoids are activated in portal hypertension and are responsible for the marked splanchnic vasodilatation. Moreover, an impaired reactivity to vasoconstrictor systems, such as the sympathetic nervous system, vasopressin, angiotensin II and endothelin-1, plays a role in this process. The opening of collateral circulation occurs through the reperfusion and dilatation of preexisting vessels, but also through the generation of new vessels. Splanchnic vasodilatation leads to the onset of the hyperdynamic circulatory syndrome, a syndrome which occurs in patients with portal hypertension and is characterized by increased cardiac output and heart rate, and decreased systemic vascular resistance with low arterial blood pressure. Understanding the pathophysiology of splanchnic vasodilatation and hyperdynamic circulatory syndrome is mandatory for the prevention and treatment of portal hypertension and its severe complications.
基金supported by the National Natural Science Foundation of China,No.81401084(to XHW)the Beijing Municipal Administration of Hospital Ascent Plan in China,No.DFL20150802(to TLW)+2 种基金the Beijing 215 High Level Healthcare Talent Plan Academic Leader in China,No.008-0027(to TLW)the Beijing Municipal Commission of Health and Family Planning in China,No.PXM2017_026283_000002(to TLW)the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support in China,No.ZYLX201706(to TLW),303-01-005-0137-11(to TLW),65683.00(to TLW)
文摘Using deep hypothermic circulatory arrest, thoracic aorta diseases and complex heart diseases can be subjected to corrective procedures. However, mechanisms underlying brain protection during deep hypothermic circulatory arrest are unclear. After piglet models underwent 60 minutes of deep hypothermic circulatory arrest at 14°C, expression of microRNAs(miRNAs) was analyzed in the hippocampus by microarray. Subsequently, TargetScan 6.2, RNA22 v2.0, miRWalk 2.0, and miRanda were used to predict potential targets, and gene ontology enrichment analysis was carried out to identify functional pathways involved. Quantitative reverse transcription-polymerase chain reaction was conducted to verify miRNA changes. Deep hypothermic circulatory arrest altered the expression of 35 miRNAs. Twenty-two miRNAs were significantly downregulated and thirteen miRNAs were significantly upregulated in the hippocampus after deep hypothermic circulatory arrest. Six out of eight targets among the differentially expressed miRNAs were enriched for neuronal projection(cyclin dependent kinase, CDK16 and SLC1 A2), central nervous system development(FOXO3, TYRO3, and SLC1 A2), ion transmembrane transporter activity(ATP2 B2 and SLC1 A2), and interleukin-6 receptor binding(IL6 R)– these are the key functional pathways involved in cerebral protection during deep hypothermic circulatory arrest. Quantitative reverse transcription-polymerase chain reaction confirmed the results of microarray analysis. Our experimental results illustrate a new role for transcriptional regulation in deep hypothermic circulatory arrest, and provide significant insight for the development of miRNAs to treat brain injuries. All procedures were approved by the Animal Care Committee of Xuanwu Hospital, Capital Medical University, China on March 1, 2017(approval No. XW-INI-AD2017-0112).
文摘AIM: To investigate the effects of 1400W-a selective inducible nitric oxide synthase(iN OS) inhibitor in a model of donation after circulatory death(DCD) kidneys. METHODS: Porcine kidneys were retrieved after 25 min warm ischemia. They were then stored on ice for 18 h before being reperfused ex vivo with oxygenated autologous blood on an isolated organ perfusion system. The selective i NOS inhibitor 1400W(10 mg/kg) was administered before reperfusion(n = 6) vs control group(n = 7). Creatinine(1000 μmol/L) was added to the system, renal and tubular cell function and the level of ischemia reperfusion injury were assessed over 3 h of reperfusion using plasma, urine and tissue samples. RESULTS: Kidneys treated with 1400 W had a higher level of creatinine clearance(CrC l) [area under the curve(AUC) CrC l: 2.37 ± 0.97 mL /min per 100 g vs 0.96 ± 0.32 mL /min per 100 g, P = 0.004] and urine output [Total: 320 ± 96 mL vs 156 ± 82 mL, P = 0.008]. There was no significant difference in levels of fractional excretion of sodium(AUC, Fr ex Na+: Control, 186.3% ± 81.7%.h vs 1400 W, 153.4% ± 12.1%.h, P = 0.429). Levels of total protein creatinine ratio were significantly lower in the 1400 W group after 1 h of reperfusion(1h Pr/Cr: 1400 W 9068 ± 6910 mg/L/mmol/L vs Control 21586 ± 5464 mg/L/mmol/L, P = 0.026). Levels of 8-isoprostane were significantly lower in the 1400 W group [8-iso/creatinine ratio: Control 239 ± 136 pg/L/mmol/L vs 1400 W 139 ± 47 pg/L/mmol/L, P = 0.041].CONCLUSION: This study demonstrated that 1400 W reduced ischaemia reperfusion injury in this porcine kidney model of DCD donor. Kidneys had improved renal function and reduced oxidative stress.
文摘AIM: To investigate the role of prostacyclin (PGI2) and nitric oxide (NO) in the development and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats. METHODS: Ninety male Sprague-Dawley rats were divided into three groups: intrahepatic portal hypertension (IHPH) group by injection of CCI4, prehepatic portal hypertension (PHPH) group by partial stenosis of the portal vein and sham-operation control (SO) group. One week after the models were made, animals in each group were subdivided into 4 groups: saline controlled group (n = 23), Nω-nitro-L-arginine (L-NNA)group (n = 21) group, indomethacin (INDO) group (n = 22) and high-dose heparin group (n = 24). The rats were administrated 1mL of saline, L-NNA (3.3 mg/kg-d) and INDO (5 mg/kg·d) respectively through gastric tubes for one week/then heparin (200 IU/Kg/min) was given to rats by intravenous injection for an hour. Splanchnic and systemic hemodynamics were measured using radioactive microsphere techniques. The serum nitrate/nitrite(NO2-/NO3-) levels as a marker of production of NO were assessed by a colorimetric method, and concentration of 6-keto-PGF1α, a stable hydrolytic product of PGI2, was determined by radioimmunoassay. RESULTS: The concentrations of plasma 6-keto-PGFla (pg/mL) and serum NO2-/NO3- (μmol/L) in IHPH rats (1123.85±153.64, 73.34±4.31) and PHPH rats (891.88±83.11, 75.21±6.89) were significantly higher than those in SO rats (725.53±105.54, 58.79±8.47) (P<0.05). Compared with SO rats, total peripheral vascular resistance (TPR) and spanchnic vascular resistance (SVR) decreased but cardiac index (CI) and portal venous inflow (PVI) increased obviously in IHPH and PHPH rats (P<0.05). L-NNA and indomethacin could decrease the concentrations of plasma 6-keto-PGFla and serum NO2/7NO3-in IHPH and PHPH rats (P<0.05) .Meanwhile, CI, FPP and PVI lowered but MAP, TPR and SVR increased(P<0.05). After deduction of the action of NO, there was no significant correlation between plasma PGI2 level and hemodynamic parameters such as CI, TPR, PVI and SVR. However, after deduction of the action of PGI2, NO still correlated highly with the hemodynamic parameters, indicating that there was a close correlation between NO and the hemodynamic parameters. After administration of high-dose heparin, plasma 6-keto- concentrations in IHPH, PHPH and SO rats were significantly higher than those in rats administrated vehicle (P<0.05). On the contrary, levels of serum NO2-/NO3- in IHPH, PHPH and SO rats were significantly lower than those in rats administrated Vehicle (P<0.05). Compared with those rats administrated vehicle, the hemodynamic parameters of portal hypertensive rats, such as CI and PVI, declined significantly after administration of high-dose heparin (P<0.05), while TPR and SVR increased significantly (P<0.05). CONCLUSION: It is NO rather than PGI2 that is a mediator in the formation and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats.
