Attila Rutai - Academia.edu (original) (raw)

Papers by Attila Rutai

Research paper thumbnail of A Porcine Sepsis Model With Numerical Scoring for Early Prediction of Severity

Frontiers in Medicine

IntroductionSepsis can lead to organ dysfunctions with disturbed oxygen dynamics and life-threate... more IntroductionSepsis can lead to organ dysfunctions with disturbed oxygen dynamics and life-threatening consequences. Since the results of organ-protective treatments cannot always be transferred from laboratory models into human therapies, increasing the translational potential of preclinical settings is an important goal. Our aim was to develop a standardized research protocol, where the progression of sepsis-related events can be characterized reproducibly in model experiments within clinically-relevant time frames.MethodsPeritonitis was induced in anesthetized minipigs injected intraperitoneally with autofeces inoculum (n = 27) or with saline (sham operation; n = 9). The microbial colony-forming units (CFUs) in the inoculum were retrospectively determined. After awakening, clinically relevant supportive therapies were conducted. Nineteen inoculated animals developed sepsis without a fulminant reaction. Sixteen hours later, these animals were re-anesthetized for invasive monitoring...

Research paper thumbnail of Microcirculatory-mitochondrial resuscitation with new anti-inflammatory therapies in experimental sepsis

Sepsis is a potentially life-threatening condition caused by a dysregulated host response to infe... more Sepsis is a potentially life-threatening condition caused by a dysregulated host response to infection. Along with its progression, regulatory failure is frequently associated with a mismatch between oxygen delivery (DO2), oxygen consumption (VO2) and a deficit in oxygen extraction (ExO2) at the cellular level. The poorly functioning microvasculature reduces delivery of oxygen to the tissue, while the mitochondrial electron transport system (ETS) is deficient, being unable to use oxygen efficiently. These processes are closely linked and ultimately lead to microcirculatory and mitochondrial distress syndrome (MMDS), which is thought to mediate end organ damage. Given this background, the major goal of this thesis was to find a novel, clinically applicable maneuver for microcirculatory recruitment and mitochondrial resuscitation to minimize the energy deficit of the organs in experimental sepsis. In our studies Sprague Dawley rats were subjected to fecal peritonitis or a sham operati...

Research paper thumbnail of Veno-Venous Extracorporeal Membrane Oxygenation in Minipigs as a Robust Tool to Model Acute Kidney Injury: Technical Notes and Characteristics

Frontiers in Medicine

ObjectiveVeno-venous extracorporeal membrane oxygenation (vv-ECMO) can save lives in severe respi... more ObjectiveVeno-venous extracorporeal membrane oxygenation (vv-ECMO) can save lives in severe respiratory distress, but this innovative approach has serious side-effects and is accompanied by higher rates of iatrogenic morbidity. Our aims were, first, to establish a large animal model of vv-ECMO to study the pathomechanism of complications within a clinically relevant time frame and, second, to investigate renal reactions to increase the likelihood of identifying novel targets and to improve clinical outcomes of vv-ECMO-induced acute kidney injury (AKI).MethodsAnesthetized Vietnamese miniature pigs were used. After cannulation of the right jugular and femoral veins, vv-ECMO was started and maintained for 24 hrs. In Group 1 (n = 6) ECMO was followed by a further 6-hr post-ECMO period, while (n = 6) cannulation was performed without ECMO in the control group, with observation maintained for 30 h. Systemic hemodynamics, blood gas values and hour diuresis were monitored. Renal artery flow...

Research paper thumbnail of The microbial composition of the initial insult can predict the prognosis of experimental sepsis

Scientific Reports

We hypothesized that the composition of sepsis-inducing bacterial flora influences the course of ... more We hypothesized that the composition of sepsis-inducing bacterial flora influences the course of fecal peritonitis in rodents. Saline or fecal suspensions with a standardized dose range of bacterial colony-forming units (CFUs) were injected intraperitoneally into Sprague–Dawley rats. The qualitative composition of the initial inoculum and the ascites was analyzed separately by MALDI-TOF mass spectrometry. Invasive monitoring was conducted in separate anesthetized groups (n = 12–13/group) after 12, 24, 48 and 72 h to determine rat-specific organ failure assessment (ROFA) scores. Death and ROFA scores peaked at 24 h. At this time, 20% mortality occurred in animals receiving a monomicrobial E. coli suspension, and ROFA scores were significantly higher in the monomicrobial subgroup than in the polymicrobial one (median 6.5; 5.0–7.0 and 5.0; 4.75–5.0, respectively). ROFA scores dropped after 48 h, accompanied by a steady decrease in ascites CFUs and a shift towards intra-abdominal monomi...

Research paper thumbnail of Divergent Effects of the N-Methyl-D-Aspartate Receptor Antagonist Kynurenic Acid and the Synthetic Analog SZR-72 on Microcirculatory and Mitochondrial Dysfunction in Experimental Sepsis

Frontiers in Medicine

Introduction: Sepsis is a dysregulated host response to infection with macro- and microhemodynami... more Introduction: Sepsis is a dysregulated host response to infection with macro- and microhemodynamic deterioration. Kynurenic acid (KYNA) is a metabolite of the kynurenine pathway of tryptophan catabolism with pleiotropic cell-protective effects under pro-inflammatory conditions. Our aim was to investigate whether exogenously administered KYNA or the synthetic analog SZR-72 affects the microcirculation and mitochondrial function in a clinically relevant rodent model of intraabdominal sepsis.Methods: Male Sprague–Dawley rats (n = 8/group) were subjected to fecal peritonitis (0.6 g kg−1 feces ip) or a sham operation. Septic animals were treated with sterile saline or received ip KYNA or SZR-72 (160 μmol kg−1 each) 16 and 22 h after induction. Invasive monitoring was performed on anesthetized animals to evaluate respiratory, cardiovascular, renal, hepatic and metabolic dysfunctions (PaO2/FiO2 ratio, mean arterial pressure, urea, AST/ALT ratio and lactate levels, respectively) based on th...

Research paper thumbnail of Kynurenic Acid and Its Synthetic Derivatives Protect Against Sepsis-Associated Neutrophil Activation and Brain Mitochondrial Dysfunction in Rats

Frontiers in Immunology

Background and AimsThe systemic host response in sepsis is frequently accompanied by central nerv... more Background and AimsThe systemic host response in sepsis is frequently accompanied by central nervous system (CNS) dysfunction. Evidence suggests that excessive formation of neutrophil extracellular traps (NETs) can increase the permeability of the blood–brain barrier (BBB) and that the evolving mitochondrial damage may contribute to the pathogenesis of sepsis-associated encephalopathy. Kynurenic acid (KYNA), a metabolite of tryptophan catabolism, exerts pleiotropic cell-protective effects under pro-inflammatory conditions. Our aim was to investigate whether exogenous KYNA or its synthetic analogues SZR-72 and SZR-104 affect BBB permeability secondary to NET formation and influence cerebral mitochondrial disturbances in a clinically relevant rodent model of intraabdominal sepsis.MethodsSprague–Dawley rats were subjected to fecal peritonitis (0.6 g kg-1 ip) or a sham operation. Septic animals were treated with saline or KYNA, SZR-72 or SZR-104 (160 µmol kg-1 each ip) 16h and 22h after...

Research paper thumbnail of Methane Exhalation Can Monitor the Microcirculatory Changes of the Intestinal Mucosa in a Large Animal Model of Hemorrhage and Fluid Resuscitation

Research paper thumbnail of Endothelin A and B Receptors

Research paper thumbnail of Kynurenic Acid and Its Synthetic Derivatives Protect Against Sepsis-Associated Neutrophil Activation and Brain Mitochondrial Dysfunction in Rats

Frontiers in Immunology

Background and AimsThe systemic host response in sepsis is frequently accompanied by central nerv... more Background and AimsThe systemic host response in sepsis is frequently accompanied by central nervous system (CNS) dysfunction. Evidence suggests that excessive formation of neutrophil extracellular traps (NETs) can increase the permeability of the blood–brain barrier (BBB) and that the evolving mitochondrial damage may contribute to the pathogenesis of sepsis-associated encephalopathy. Kynurenic acid (KYNA), a metabolite of tryptophan catabolism, exerts pleiotropic cell-protective effects under pro-inflammatory conditions. Our aim was to investigate whether exogenous KYNA or its synthetic analogues SZR-72 and SZR-104 affect BBB permeability secondary to NET formation and influence cerebral mitochondrial disturbances in a clinically relevant rodent model of intraabdominal sepsis.MethodsSprague–Dawley rats were subjected to fecal peritonitis (0.6 g kg-1 ip) or a sham operation. Septic animals were treated with saline or KYNA, SZR-72 or SZR-104 (160 µmol kg-1 each ip) 16h and 22h after...

Research paper thumbnail of A Porcine Sepsis Model With Numerical Scoring for Early Prediction of Severity

Frontiers in Medicine

IntroductionSepsis can lead to organ dysfunctions with disturbed oxygen dynamics and life-threate... more IntroductionSepsis can lead to organ dysfunctions with disturbed oxygen dynamics and life-threatening consequences. Since the results of organ-protective treatments cannot always be transferred from laboratory models into human therapies, increasing the translational potential of preclinical settings is an important goal. Our aim was to develop a standardized research protocol, where the progression of sepsis-related events can be characterized reproducibly in model experiments within clinically-relevant time frames.MethodsPeritonitis was induced in anesthetized minipigs injected intraperitoneally with autofeces inoculum (n = 27) or with saline (sham operation; n = 9). The microbial colony-forming units (CFUs) in the inoculum were retrospectively determined. After awakening, clinically relevant supportive therapies were conducted. Nineteen inoculated animals developed sepsis without a fulminant reaction. Sixteen hours later, these animals were re-anesthetized for invasive monitoring...

Research paper thumbnail of Microcirculatory-mitochondrial resuscitation with new anti-inflammatory therapies in experimental sepsis

Sepsis is a potentially life-threatening condition caused by a dysregulated host response to infe... more Sepsis is a potentially life-threatening condition caused by a dysregulated host response to infection. Along with its progression, regulatory failure is frequently associated with a mismatch between oxygen delivery (DO2), oxygen consumption (VO2) and a deficit in oxygen extraction (ExO2) at the cellular level. The poorly functioning microvasculature reduces delivery of oxygen to the tissue, while the mitochondrial electron transport system (ETS) is deficient, being unable to use oxygen efficiently. These processes are closely linked and ultimately lead to microcirculatory and mitochondrial distress syndrome (MMDS), which is thought to mediate end organ damage. Given this background, the major goal of this thesis was to find a novel, clinically applicable maneuver for microcirculatory recruitment and mitochondrial resuscitation to minimize the energy deficit of the organs in experimental sepsis. In our studies Sprague Dawley rats were subjected to fecal peritonitis or a sham operati...

Research paper thumbnail of Veno-Venous Extracorporeal Membrane Oxygenation in Minipigs as a Robust Tool to Model Acute Kidney Injury: Technical Notes and Characteristics

Frontiers in Medicine

ObjectiveVeno-venous extracorporeal membrane oxygenation (vv-ECMO) can save lives in severe respi... more ObjectiveVeno-venous extracorporeal membrane oxygenation (vv-ECMO) can save lives in severe respiratory distress, but this innovative approach has serious side-effects and is accompanied by higher rates of iatrogenic morbidity. Our aims were, first, to establish a large animal model of vv-ECMO to study the pathomechanism of complications within a clinically relevant time frame and, second, to investigate renal reactions to increase the likelihood of identifying novel targets and to improve clinical outcomes of vv-ECMO-induced acute kidney injury (AKI).MethodsAnesthetized Vietnamese miniature pigs were used. After cannulation of the right jugular and femoral veins, vv-ECMO was started and maintained for 24 hrs. In Group 1 (n = 6) ECMO was followed by a further 6-hr post-ECMO period, while (n = 6) cannulation was performed without ECMO in the control group, with observation maintained for 30 h. Systemic hemodynamics, blood gas values and hour diuresis were monitored. Renal artery flow...

Research paper thumbnail of The microbial composition of the initial insult can predict the prognosis of experimental sepsis

Scientific Reports

We hypothesized that the composition of sepsis-inducing bacterial flora influences the course of ... more We hypothesized that the composition of sepsis-inducing bacterial flora influences the course of fecal peritonitis in rodents. Saline or fecal suspensions with a standardized dose range of bacterial colony-forming units (CFUs) were injected intraperitoneally into Sprague–Dawley rats. The qualitative composition of the initial inoculum and the ascites was analyzed separately by MALDI-TOF mass spectrometry. Invasive monitoring was conducted in separate anesthetized groups (n = 12–13/group) after 12, 24, 48 and 72 h to determine rat-specific organ failure assessment (ROFA) scores. Death and ROFA scores peaked at 24 h. At this time, 20% mortality occurred in animals receiving a monomicrobial E. coli suspension, and ROFA scores were significantly higher in the monomicrobial subgroup than in the polymicrobial one (median 6.5; 5.0–7.0 and 5.0; 4.75–5.0, respectively). ROFA scores dropped after 48 h, accompanied by a steady decrease in ascites CFUs and a shift towards intra-abdominal monomi...

Research paper thumbnail of Divergent Effects of the N-Methyl-D-Aspartate Receptor Antagonist Kynurenic Acid and the Synthetic Analog SZR-72 on Microcirculatory and Mitochondrial Dysfunction in Experimental Sepsis

Frontiers in Medicine

Introduction: Sepsis is a dysregulated host response to infection with macro- and microhemodynami... more Introduction: Sepsis is a dysregulated host response to infection with macro- and microhemodynamic deterioration. Kynurenic acid (KYNA) is a metabolite of the kynurenine pathway of tryptophan catabolism with pleiotropic cell-protective effects under pro-inflammatory conditions. Our aim was to investigate whether exogenously administered KYNA or the synthetic analog SZR-72 affects the microcirculation and mitochondrial function in a clinically relevant rodent model of intraabdominal sepsis.Methods: Male Sprague–Dawley rats (n = 8/group) were subjected to fecal peritonitis (0.6 g kg−1 feces ip) or a sham operation. Septic animals were treated with sterile saline or received ip KYNA or SZR-72 (160 μmol kg−1 each) 16 and 22 h after induction. Invasive monitoring was performed on anesthetized animals to evaluate respiratory, cardiovascular, renal, hepatic and metabolic dysfunctions (PaO2/FiO2 ratio, mean arterial pressure, urea, AST/ALT ratio and lactate levels, respectively) based on th...

Research paper thumbnail of Kynurenic Acid and Its Synthetic Derivatives Protect Against Sepsis-Associated Neutrophil Activation and Brain Mitochondrial Dysfunction in Rats

Frontiers in Immunology

Background and AimsThe systemic host response in sepsis is frequently accompanied by central nerv... more Background and AimsThe systemic host response in sepsis is frequently accompanied by central nervous system (CNS) dysfunction. Evidence suggests that excessive formation of neutrophil extracellular traps (NETs) can increase the permeability of the blood–brain barrier (BBB) and that the evolving mitochondrial damage may contribute to the pathogenesis of sepsis-associated encephalopathy. Kynurenic acid (KYNA), a metabolite of tryptophan catabolism, exerts pleiotropic cell-protective effects under pro-inflammatory conditions. Our aim was to investigate whether exogenous KYNA or its synthetic analogues SZR-72 and SZR-104 affect BBB permeability secondary to NET formation and influence cerebral mitochondrial disturbances in a clinically relevant rodent model of intraabdominal sepsis.MethodsSprague–Dawley rats were subjected to fecal peritonitis (0.6 g kg-1 ip) or a sham operation. Septic animals were treated with saline or KYNA, SZR-72 or SZR-104 (160 µmol kg-1 each ip) 16h and 22h after...

Research paper thumbnail of Methane Exhalation Can Monitor the Microcirculatory Changes of the Intestinal Mucosa in a Large Animal Model of Hemorrhage and Fluid Resuscitation

Research paper thumbnail of Endothelin A and B Receptors

Research paper thumbnail of Kynurenic Acid and Its Synthetic Derivatives Protect Against Sepsis-Associated Neutrophil Activation and Brain Mitochondrial Dysfunction in Rats

Frontiers in Immunology

Background and AimsThe systemic host response in sepsis is frequently accompanied by central nerv... more Background and AimsThe systemic host response in sepsis is frequently accompanied by central nervous system (CNS) dysfunction. Evidence suggests that excessive formation of neutrophil extracellular traps (NETs) can increase the permeability of the blood–brain barrier (BBB) and that the evolving mitochondrial damage may contribute to the pathogenesis of sepsis-associated encephalopathy. Kynurenic acid (KYNA), a metabolite of tryptophan catabolism, exerts pleiotropic cell-protective effects under pro-inflammatory conditions. Our aim was to investigate whether exogenous KYNA or its synthetic analogues SZR-72 and SZR-104 affect BBB permeability secondary to NET formation and influence cerebral mitochondrial disturbances in a clinically relevant rodent model of intraabdominal sepsis.MethodsSprague–Dawley rats were subjected to fecal peritonitis (0.6 g kg-1 ip) or a sham operation. Septic animals were treated with saline or KYNA, SZR-72 or SZR-104 (160 µmol kg-1 each ip) 16h and 22h after...