scholarly journals Phosphodiesterase-4 inhibition reduces ECLS-induced vascular permeability and improves microcirculation in a rodent model of extracorporeal resuscitation

2019 ◽  
Vol 316 (3) ◽  
pp. H751-H761 ◽  
Author(s):  
Jakob Wollborn ◽  
Svenja Siemering ◽  
Christoph Steiger ◽  
Hartmut Buerkle ◽  
Ulrich Goebel ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Extracorporeal Circulation ◽  
Sham Group ◽  
Life Support ◽  
Microvascular Complications ◽  
Rodent Model ◽  
Capillary Leak ◽  
Phosphodiesterase 4 ◽  
Extracorporeal Resuscitation ◽  
Camp Levels

Extracorporeal circulation can be accompanied by increased vascular permeability leading to pathological fluid balance and organ dysfunction. The second messenger cAMP is involved in capillary permeability and maintains endothelial integrity. The aim of the present study was to evaluate the effect of phosphodiesterase-4 (PDE4) inhibition with rolipram on extracorporeal circulation-induced capillary leakage, microcirculatory dysfunction, and organ injury in rodents. Rats were randomly allocated to the following groups: sham ( n = 5), venoarterial extracorporeal circulation [extracorporeal life support (ECLS), n = 7], ECLS + rolipram ( n = 7), extracorporeal resuscitation (ECPR; n = 7), and ECPR + rolipram ( n = 7). In the groups that underwent ECPR, ECLS-based cardiopulmonary resuscitation (ECPR) was performed after the induction of hypoxic cardiac arrest. Upon return of spontaneous circulation, rolipram was administered intravenously. The mesenteric microcirculation was studied using intravital microscopy, and organ specimens were harvested upon completion of the study. ECLS and ECPR induced a proinflammatory response (cytokines IL-1β, IL-6, and TNF-α). Although PDE4 expression was upregulated in vascular tissue, PDE4 inhibition abrogated impaired microcirculation and capillary leak (albumin extravasation of the sham group: 1 ± 0.03-fold, ECLS group: 1.2 ± 0.05-fold, ECLS + rolipram group: 0.99 ± 0.04-fold, ECPR group: 1.6 ± 0.04-fold, and ECPR + rolipram group: 1.06 ± 0.02-fold from the sham group, P < 0.05). PDE4 inhibition led to stabilization of vascular cAMP levels but did not affect cytokine levels. Capillary leak was reduced, as demonstrated by the decrease of the systemic biomarkers soluble vascular-endothelial cadherin and activated complement 3. Histological analysis revealed reduced injury to the lungs and kidneys after PDE4 inhibition, with a significant decrease in systemic renal damage markers. Our findings demonstrate that extracorporeal circulation causes an inflammatory reaction associated with decreased vascular cAMP levels, increased vascular permeability, and impaired microcirculation. PDE4 inhibition proved to be capable of reducing these side effects in ECLS and ECPR, leading to reduced microcirculatory, renal, and pulmonary injury. NEW & NOTEWORTHY Various complications are common after extracorporeal circulation. Among these, endothelial injury may cause impaired microcirculation and capillary leak. Here, we report that phosphodiesterase-4 inhibition targeting endothelial cAMP is capable of reducing microvascular complications in a rodent model of extracorporeal resuscitation. Microcirculation and vascular permeability are influenced without targeting extracorporeal circulation-induced inflammation. Thus, pulmonary and renal organ protection may be conferred.

Role of extracorporeal life support in thoracic surgery

2020 ◽  
Vol 99 (10) ◽  
Keyword(s):  
Thoracic Surgery ◽  
Extracorporeal Circulation ◽  
Life Support ◽  
Close Contact ◽  
Extracorporeal Life Support ◽  
Tumour Resection ◽  
R0 Resection ◽  
Malignant Tumours ◽  
En Bloc ◽  
Frequent Use

Besides the conventional extracorporeal circulation, commonly used in cardiac surgery, the methods of extracorporeal life support (ECLS) have been applied ever more frequently in thoracic surgery in recent years. The most commonly used modalities of such supports include extracorporeal membrane oxygenation (ECMO) and the Novalung interventional lung assist device (iLA). Successful application of ECLS has led to its more frequent use in general thoracic surgery, especially as a tool to treat hypercapnia and to ensure oxygenation and haemodynamic support. However, these methods are essential in lung transplant programmes; without their help, in most cases, it would not be possible to perform the transplantatioz or prevent the severe complications associated with critical primary graft dysfunction. Additionally, the extracorporeal circulation also facilitates the performing of specific surgical procedures that would not be feasible under standard conditions or would be associated with an inadequate risk. The application of extracorporeal life supports can fundamentally increase the level of resection when treating advanced intrathoracic malignancies that are in close contact with the heart and large vessels or even directly extend into them. Without the possibility of resecting such structures en bloc, together with the tumour, and, thus, achieving an R0 resection, these malignant tumours are often directly contraindicated for surgery or are operated non-radically, i.e. unsuccessfully. Complete tumour resection is the most important prognostic factor in the surgery.

scholarly journals Organization and Application of ECLS Therapy—A Nationwide Survey in German Cardiosurgical Departments

2018 ◽  
Vol 67 (03) ◽  
pp. 164-169
Author(s):  
Alexander Assmann ◽  
Udo Boeken ◽  
Stefan Klotz ◽  
Wolfgang Harringer ◽  
Andreas Beckmann
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Extracorporeal Circulation ◽  
Life Support ◽  
Extracorporeal Life Support ◽  
Nationwide Survey ◽  
Left Ventricular ◽  
Local Application ◽  
Circulatory Support ◽  
Anticoagulation Management ◽  
The Status

Background In context of the multidisciplinary German scientific guideline “Use of extracorporeal circulation (extracorporeal life support [ECLS]/extracorporeal membrane oxygenation) for cardiac and circulatory failure,” a nationwide survey should depict the status of organization and application of ECLS therapy in Germany. Methods Between June and October 2017, a standardized questionnaire consisting of 30 items related to ECLS therapy was sent to all German cardiosurgical departments, and all returned results were analyzed and evaluated. Results The return rate amounted to 92.9% (78 out of 84 departments). In the participating departments, ECLS therapy is subject to different responsibilities, and exhibits divergent processes and various ways for specialization of the involved personnel. This also concerns local application standards, such as cannulation strategies, anticoagulation management, left ventricular unloading, antiwatershed treatment, and weaning from circulatory support. Conclusion This nationwide survey underlines the necessity of a multidisciplinary guideline concerning ECLS therapy.

scholarly journals Extracorporeal resuscitation with carbon monoxide improves renal function by targeting inflammatory pathways in cardiac arrest in pigs

2019 ◽  
Vol 317 (6) ◽  
pp. F1572-F1581 ◽  
Author(s):  
Jakob Wollborn ◽  
Bjoern Schlueter ◽  
Christoph Steiger ◽  
Cornelius Hermann ◽  
Christian Wunder ◽  
...  
Keyword(s):  
Carbon Monoxide ◽  
Renal Function ◽  
Cardiac Arrest ◽  
Renal Injury ◽  
Porcine Model ◽  
Life Support ◽  
Apoptotic Cell ◽  
Extracorporeal Life Support ◽  
Successful Resuscitation ◽  
Extracorporeal Resuscitation

Deleterious consequences like acute kidney injury frequently occur upon successful resuscitation from cardiac arrest. Extracorporeal life support is increasingly used to overcome high cardiac arrest mortality. Carbon monoxide (CO) is an endogenous gasotransmitter, capable of reducing renal injury. In our study, we hypothesized that addition of CO to extracorporeal resuscitation hampers severity of renal injury in a porcine model of cardiac arrest. Hypoxic cardiac arrest was induced in pigs. Animals were resuscitated using a conventional [cardiopulmonary resuscitation (CPR)], an extracorporeal (E-CPR), or a CO-assisted extracorporeal (CO-E-CPR) protocol. CO was applied using a membrane-controlled releasing system. Markers of renal injury were measured, and histopathological analyses were carried out. We investigated renal pathways involving inflammation as well as apoptotic cell death. No differences in serum neutrophil gelatinase-associated lipocalin (NGAL) were detected after CO treatment compared with Sham animals (Sham 71 ± 7 and CO-E-CPR 95 ± 6 ng/mL), while NGAL was increased in CPR and E-CPR groups (CPR 135 ± 11 and E-CPR 124 ± 5 ng/mL; P < 0.05). Evidence for histopathological damage was abrogated after CO application. CO increased renal heat shock protein 70 expression and reduced inducible cyclooxygenase 2 (CPR: 60 ± 8; E-CPR 56 ± 8; CO-E-CPR 31 ± 3 µg/mL; P < 0.05). Caspase 3 activity was decreased (CPR 1,469 ± 276; E-CPR 1,670 ± 225; CO-E-CPR 755 ± 83 pg/mL; P < 0.05). Furthermore, we found a reduction in renal inflammatory signaling upon CO treatment. Our data demonstrate improved renal function by extracorporeal CO treatment in a porcine model of cardiac arrest. CO reduced proinflammatory and proapoptotic signaling, characterizing beneficial aspects of a novel treatment option to overcome high mortality.

Antinociceptive and anti-inflammatory effects of electroacupuncture on experimental arthritis of the rat temporomandibular joint

2012 ◽  
Vol 90 (4) ◽  
pp. 395-405 ◽  
Author(s):  
Delane Viana Gondim ◽  
Jéssyca Lima Costa ◽  
Suellen Sousa Rocha ◽  
Gerly Anne de Castro Brito ◽  
Ronaldo de Albuquerque Ribeiro ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Temporomandibular Joint ◽  
Sham Group ◽  
Neutrophil Migration ◽  
Low Frequency ◽  
Control Group ◽  
Histopathological Analysis ◽  
Myeloperoxidase Activity ◽  
Inflammatory Parameters ◽  
Anti Inflammatory

This study investigated the antinociceptive and anti-inflammatory effects of electroacupuncture (EA) on zymosan-induced acute arthritis of the rat temporomandibular joint (TMJ). Male Wistar rats were injected with saline or zymosan (control group; 2 mg) into the left TMJ. Low frequency EA (10 Hz, 30 min) was performed at acupoints (LI4, LI11, ST36, ST44) or sham points 2 h after or 1 h before zymosan administration. Mechanical hypernociception was accessed by the electronic Von Frey method after zymosan administration. Rats were sacrificed 6 h after zymosan administration and the joint was removed for histopathological analysis, myeloperoxidase activity assessment, vascular permeability observations, and immunohistochemical verification of inflammatory mediators. The results showed that EA inhibited zymosan-induced hypernociception, compared with the control group and with the sham group (p < 0.05). The results showed that EA inhibited inflammatory parameters such as neutrophil migration, vascular permeability, and tumour necrosis factor α (TNF-α), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) expression in the TMJ compared with the sham group (p < 0.05). Histopathological analysis showed that EA significantly inhibited edema and periarticular infiltration (p < 0.05) compared with the control and sham groups. EA at acupoints produced antinociceptive and anti-inflammatory effects on zymosan-induced arthritis in the rat TMJ.

scholarly journals Change of Hemoglobin Levels in the Early Post-cardiac Arrest Phase Is Associated With Outcome

2021 ◽  
Vol 8 ◽  
Author(s):  
Christoph Schriefl ◽  
Christian Schoergenhofer ◽  
Florian Ettl ◽  
Michael Poppe ◽  
Christian Clodi ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Vascular Permeability ◽  
Fluid Balance ◽  
Life Support ◽  
Extracorporeal Life Support ◽  
Multivariable Analysis ◽  
Cerebral Performance Category ◽  
Endothelial Activation ◽  
Temperature Management ◽  
Neurologic Function

Background: The post-cardiac arrest (CA) phase is characterized by high fluid requirements, endothelial activation and increased vascular permeability. Erythrocytes are large cells and may not leave circulation despite massive capillary leak. We hypothesized that dynamic changes in hemoglobin concentrations may reflect the degree of vascular permeability and may be associated with neurologic function after CA.Methods: We included patients ≥18 years, who suffered a non-traumatic CA between 2013 and 2018 from the prospective Vienna Clinical Cardiac Arrest Registry. Patients without return of spontaneous circulation (ROSC), with extracorporeal life support, with any form of bleeding, undergoing surgery, receiving transfusions, without targeted temperature management or with incomplete datasets for multivariable analysis were excluded. The primary outcome was neurologic function at day 30 assessed by the Cerebral Performance Category scale. Differences of hemoglobin concentrations at admission and 12 h after ROSC were calculated and associations with neurologic function were investigated by uni- and multivariable logistic regression.Results: Two hundred and seventy-five patients were eligible for analysis of which 143 (52%) had poor neurologic function. For every g/dl increase in hemoglobin from admission to 12 h the odds of poor neurologic function increased by 26% (crude OR 1.26, 1.07–1.49, p = 0.006). The effect remained unchanged after adjustment for fluid balance and traditional prognostication markers (adjusted OR 1.27, 1.05–1.54, p = 0.014).Conclusion: Increasing hemoglobin levels in spite of a positive fluid balance may serve as a surrogate parameter of vascular permeability and are associated with poor neurologic function in the early post-cardiac arrest period.

A new rotary blood pump for versatile extracorporeal circulation: the DeltaStream™

Perfusion ◽  
2002 ◽  
Vol 17 (5) ◽  
pp. 373-382 ◽  
Author(s):  
C Göbel ◽  
A Arvand ◽  
G Rau ◽  
H Reul ◽  
B Meyns ◽  
...  
Keyword(s):  
Extracorporeal Circulation ◽  
Life Support ◽  
Extracorporeal Life Support ◽  
Pulse Generation ◽  
Ventricular Assist Devices ◽  
Blood Pump ◽  
Rotary Blood Pump ◽  
Rotary Pumps

Today, rotary pumps are routinely used for extracorporeal circulation in different clinical settings and applications. A review of these applications and specific limitations in extracorporeal perfusion was performed and served as a basis for the development of the DeltaStream®. The Delta- Stream® is a miniaturized rotary blood pump of a new and unique design with an integrated drive unit. Despite its small design, the pump maintains a sufficient hydraulic capacity, which makes the DeltaStream® very flexible for intra- and perioperative applications. It also opens the field for short-term ventricular assist devices (VAD) applications or use as a component in extracorporeal life support systems (ECLS). The DeltaStream® and, specifically, its impeller design have been optimized with respect to haemolysis and nonthrombogenicity. Also, the pump facilitates an effective pulse generation in VAD applications and simulates heart action in a more physiological way than other rotary pumps or roller pumps. Hydraulic and haematological properties have been tested in vitro and in vivo. In a series of seven animal experiments in two different setups, the pump demonstrated its biocompatibility and applicability. Basic aspects of the DeltaStream® pump concept as well as important console features are presented. A summary of the final investigation of this pump is given with focus on hydraulic capabilities and results from animal studies.

Phosphodiesterase 4 Inhibition Dose Dependently Stabilizes Microvascular Barrier Functions and Microcirculation in a Rodent Model of Polymicrobial Sepsis

Shock ◽  
2014 ◽  
Vol 41 (6) ◽  
pp. 537-545 ◽  
Author(s):  
Sven Flemming ◽  
Nicolas Schlegel ◽  
Christian Wunder ◽  
Michael Meir ◽  
Wolfgang Baar ◽  
...  
Keyword(s):  
Rodent Model ◽  
Polymicrobial Sepsis ◽  
Barrier Functions ◽  
Phosphodiesterase 4

scholarly journals Hemodynamic and Pulmonary Permeability Characterization of Hantavirus Cardiopulmonary Syndrome by Transpulmonary Thermodilution

2019 ◽  
Author(s):  
René López ◽  
Rodrigo Pérez ◽  
Álvaro Salazar ◽  
Ana L Ulloa ◽  
Cecilia Vial ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Transpulmonary Thermodilution ◽  
Myocardial Dysfunction ◽  
Systolic Dysfunction ◽  
Capillary Leak ◽  
Lung Water ◽  
Pulmonary Vascular Permeability ◽  
End Diastolic Volume ◽  
Hemodynamic Pattern ◽  
Hemodynamic Impairment

Hantavirus cardiopulmonary syndrome (HCPS) is characterized by capillary leak, pulmonary edema (PE) and shock that leads to death in up to 40% of patients. Treatment is supportive, including mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO). Hemodynamic monitoring is critical to titrate therapy and to decide ECMO support. Transpulmonary thermodilution (TPTD) provides hemodynamic and PE data that has not been systematically used to understand HCPS pathophysiology. We identified 11 HCPS patients monitored with TPTD; 5 on MV, 3 on ECMO. We analyzed 133 measurements to describe the hemodynamic pattern and its association to PE. The main findings were reduced stroke volume, global ejection fraction (GEF) and preload parameters associated to increased extravascular lung water and pulmonary vascular permeability compatible with hypovolemia, myocardial dysfunction and increased permeability PE. Lung water correlated positively with heart rate (HR, r=0.20) and negatively with mean arterial pressure (r=-0.27) and GEF (r=-0.36), suggesting that PE is linked to hemodynamic impairment. Pulmonary vascular permeability correlated positively with HR (r=0.31) and negatively with cardiac index (r=-0.49), end-diastolic volume (r=-0.48) and GEF (r=-0.40), suggesting that capillary leak contributes to hypovolemia and systolic dysfunction. In conclusion, TPTD data suggests that in HCPS patients, increased permeability leads to PE, hypovolemia and circulatory impairment.

scholarly journals A European pharmacotherapeutic agent Roflumilast exploring integrated preclinical and clinical evidences for SARS CoV-2 mediated inflammation to organ damage

2021 ◽  
Author(s):  
yogendra Singh ◽  
Neeraj Fuloria ◽  
Shivkanya Fuloria ◽  
Vetriselvan Subramaniyan ◽  
Waleed Almalki ◽  
...  
Keyword(s):  
Immune Cell ◽  
Organ Damage ◽  
Pde4 Inhibitor ◽  
The European Union ◽  
Phosphodiesterase 4 ◽  
Organ Systems ◽  
Major Organ ◽  
Organ Tissue ◽  
Camp Levels ◽  
Inflammatory Burden

COVID-19 has spread globally, affecting almost 160 million individuals. Elderly and pre-existing patients (such as diabetes, heart disease and asthma), seems more susceptible to serious illness with COVID-19. Roflumilast was licensed for usage in the European Union in July 2010 as a phosphodiesterase-4 (PDE4) inhibitor. Roflumilast has been shown to decrease bleomycin-induced lung fibrosis, lung hydroxyproline, right heart thickning in animal prophylactic. The current study reviewed existing data that the PDE-4 inhibitor protects not just renal tissues but also other major organ systems after COVID-19 infection by decreasing immune cell infiltration. These immune-balancing effects of roflumilast were related with a decrease in oxidative and inflammatory burden, caspase-3 suppression, and increased PKA/cAMP levels in renal and other organ tissue.

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