Dataset Information

A cardiopulmonary bypass with deep hypothermic circulatory arrest rat model for the investigation of the systemic inflammation response and induced organ damage.

ABSTRACT:

Background

Cardiopulmonary bypass (CPB) is a commonly used technique in cardiac surgery. CPB is however associated with a strong induction of systemic inflammatory response syndrome (SIRS) which in conjunction with ischemia and reperfusion may lead to multiple organ failure. The aim of the study was to establish and characterize a CPB rat model incorporating deep hypothermic circulatory arrest with a specific focus on the extent of the inflammatory reactions and organ damage as a groundwork for novel therapeutics against SIRS and I/R induced organ injury.

Materials and methods

Male Wistar rats (n?=?6) were cannulated for CPB, connected to a heart-lung-machine (HLM) and cooled to a temperature of 16°C before they underwent 45 minutes of deep hypothermic circulatory arrest with global ischaemia. Arrest was followed by rewarming and 60 minutes of reperfusion. Haemodynamic and vital parameters were recorded throughout the CPB procedure. Only animals displaying sinus rhythm throughout reperfusion were utilized for analysis. Rats were euthanized and tissue samples were harvested. Blood gas analysis was performed and blood samples were taken. Induction of organ damage was examined by analysis of protein levels and phosphorylation status of kinases and stress proteins. Results were compared to animals (n?=?6) which did not undergo CPB.

Results

CPB induced leucocytosis and an increase of interleukin-6 and TNF-? plasma values indicating an inflammatory response. Markers of tissue damage and dysfunction, such as troponin T, creatinine and AST were elevated. Phosphorylation of STAT3 was induced in all examined organs. Activation of MAPK and induction of heat shock proteins occurred in an organ-specific manner with most pronounced effects in heart, lungs and kidneys.

Conclusions

The presented CPB rat model shows the induction of SIRS and activation of specific signalling cascades. SIRS seems not to be provoked during DHCA and is elicited mainly during reperfusion. This model might be suitable to test the efficacy of therapeutics applied in major heart surgery with and without DHCA.

SUBMITTER: Engels M

PROVIDER: S-EPMC4231204 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

A cardiopulmonary bypass with deep hypothermic circulatory arrest rat model for the investigation of the systemic inflammation response and induced organ damage.

Engels Melanie M Bilgic Esra E Pinto Antonio A Vasquez Edwin E Wollschläger Lena L Steinbrenner Holger H Kellermann Kristine K Akhyari Payam P Lichtenberg Artur A Boeken Udo U

Journal of inflammation (London, England) 20140812

<h4>Background</h4>Cardiopulmonary bypass (CPB) is a commonly used technique in cardiac surgery. CPB is however associated with a strong induction of systemic inflammatory response syndrome (SIRS) which in conjunction with ischemia and reperfusion may lead to multiple organ failure. The aim of the study was to establish and characterize a CPB rat model incorporating deep hypothermic circulatory arrest with a specific focus on the extent of the inflammatory reactions and organ damage as a groundw ...[more]

PMID: 25400510

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Project description:Cardiac surgery, especially when employing cardiopulmonary bypass and deep hypothermic circulatory arrest, is associated with systemic inflammatory responses that significantly affect morbidity and mortality. Intestinal perfusion abnormalities have been implicated in such responses, but the mechanisms linking local injury and systemic inflammation remain unclear. Intestinal mast cells are specialized immune cells that secrete various preformed effectors in response to cellular stress. We hypothesized that mast cells are activated in a microenvironment shaped by intestinal ischemia/reperfusion, and investigated local and systemic consequences.Rat model of deep hypothermic circulatory arrest.University research laboratory.Twelve- to 14-week-old male Sprague-Dawley rats.Rats were anesthetized and cooled to 16°C to 18°C on cardiopulmonary bypass before instituting deep hypothermic circulatory arrest for 45 minutes. Specimens were harvested following rewarming and 2 hours of recovery.Significant intestinal barrier disruption was found, together with macro- and microscopic evidence of ischemia/reperfusion injury in ileum and colon, but not in the lungs or kidneys. Immunofluorescence and toluidine blue staining revealed increased numbers of mast cells and their activation in the gut. In animals pretreated with the mast cell stabilizer, cromolyn sodium, mast cell degranulation was blocked, and intestinal morphology and barrier function were preserved following deep hypothermic circulatory arrest. Furthermore, cromolyn sodium treatment was associated with reduced intestinal neutrophil influx and blunted systemic release of proinflammatory cytokines.Our data provide primary evidence that intestinal ischemia/reperfusion is a leading pathophysiologic process in a rat model of deep hypothermic circulatory arrest, and that intestinal injury, and local and systemic inflammatory responses are critically dependent on mast cell activation. This identifies intestinal mast cells as central players in deep hypothermic circulatory arrest-associated responses, and opens novel therapeutic possibilities for patients undergoing this procedure.

Project description:BackgroundGuidelines recommend evaluation for electrographic seizures in neonates and children at risk, including after cardiopulmonary bypass (CPB). Although initial research using screening electroencephalograms (EEGs) in infants after CPB found a 21% seizure incidence, more recent work reports seizure incidences ranging 3-12%. Deep hypothermic cardiac arrest was associated with increased seizure risk in prior reports but is uncommon at our institution and less widely used in contemporary practice. This study seeks to establish the incidence of seizures among infants following CPB in the absence of deep hypothermic cardiac arrest and to identify additional risk factors for seizures via a prediction model.MethodsA retrospective chart review was completed of all consecutive infants ≤ 3 months who received screening EEG following CPB at a single center within a 2-year period during 2017-2019. Clinical and laboratory data were collected from the perioperative period. A prediction model for seizure risk was fit using a random forest algorithm, and receiver operator characteristics were assessed to classify predictions. Fisher's exact test and the logrank test were used to evaluate associations between clinical outcomes and EEG seizures.ResultsA total of 112 infants were included. Seizure incidence was 10.7%. Median time to first seizure was 28.1 h (interquartile range 18.9-32.2 h). The most important factors in predicting seizure risk from the random forest analysis included postoperative neuromuscular blockade, prematurity, delayed sternal closure, bypass time, and critical illness preoperatively. When variables captured during the EEG recording were included, abnormal postoperative neuroimaging and peak lactate were also highly predictive. Overall model accuracy was 90.2%; accounting for class imbalance, the model had excellent sensitivity and specificity (1.00 and 0.89, respectively).ConclusionsSeizure incidence was similar to recent estimates even in the absence of deep hypothermic cardiac arrest. By employing random forest analysis, we were able to identify novel risk factors for postoperative seizure in this population and generate a robust model of seizure risk. Further work to validate our model in an external population is needed.

Project description:BackgroundThis study aimed to evaluate whether the use of mild hypothermic circulatory arrest (HCA) with selective cerebral perfusion (SCP) in open arch procedure provides comparable perioperative results to moderate HCA for patients with dissected or degenerative arch pathologies.MethodsBetween January 2017 and September 2020, a total of 88 consecutive patients (mean age 47±11 years, 71 males) underwent open arch repair under a single surgeon at our institution with mild or moderate systemic hypothermia assisted by unilateral or bilateral SCP. Patients were divided into groups according to the nasopharyngeal temperature at the beginning of HCA: a moderate HCA group (n=47, 53.4%) and a mild HCA group (n=41, 46.6%). The postoperative mortality, morbidity, and visceral organ functions between these groups were analyzed retrospectively.ResultsCompared to the moderate HCA group, the mild HCA group had a significantly higher core temperature (nasopharynx: 24.4±0.8 vs. 28.5±2, P<0.001; bladder 25.9±0.9 vs. 30±1.2, P<0.001), and the incidence of major adverse events (MAE) in this group was markedly lower (21.3% vs. 4.9%, P=0.031). No differences were identified between the two groups refer to in-hospital mortality, permanent neurological deficit (PND), temporary neurological deficit (TND), and paraplegia (8.5% vs. 2.4%, P=0.366; 8.5% vs. 0, P=0.120; 6.4% vs. 7.3%, P=1.0; 4.3% vs. 2.4%, P=1.0, respectively). In the moderate HCA group, 6 patients (12.8%) developed acute renal failure needing replacement therapy, which did not occur in the mild HCA group (P=0.028). The duration of ventilator support and intensive care unit stay was shorter in the mild HCA group, as well as a decreased volume of drainage during the first 24 h and reduced platelet transfusion.ConclusionsThe preliminary results of the mild HCA group with SCP applied in open arch repair, mainly in total arch replacement (TAR) and stented elephant trunk (SET) implantation for aortic dissection, were satisfactory. Furthermore, comparable inferior outcomes were obtained with mild HCA compared with that of the conventional moderate HCA strategy. These encouraging surgical and postoperative results favor this more aggressive hypothermia strategy in open arch repair.

Dataset Information

A cardiopulmonary bypass with deep hypothermic circulatory arrest rat model for the investigation of the systemic inflammation response and induced organ damage.

Background

Materials and methods

Results

Conclusions

Publications

A cardiopulmonary bypass with deep hypothermic circulatory arrest rat model for the investigation of the systemic inflammation response and induced organ damage.

Similar Datasets

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