cardiopulmonary-bypass-in-a-mouse-model-a-novel-approach

Cardiopulmonary Bypass in a Mouse Model: A Novel Approach

As prolonged cardiopulmonary bypass becomes more essential during cardiac interventions, an increasing clinical demand arises for procedure optimization ...

veno-venous-extracorporeal-membrane-oxygenation-in-a-mouse

Veno-Venous Extracorporeal Membrane Oxygenation in a Mouse

The use of extracorporeal membrane oxygenation (ECMO) has increased substantially in recent years. ECMO has become a reliable and effective therapy for ...

Hannover medical school

Based on the 3-dimensional visualization of vascular supply and drainage, a vessel-oriented resection technique was optimized. The new surgical technique was used to determine the maximal reduction in liver mass enabling a 50% 1-week survival rate.

Marginal hepatectomy in the rat: from anatomy to surgery.

Live liver donation requires extended liver resection in the donor with transection of the middle hepatic vein. This leads to focal outflow obstruction in the remnant liver or the partial graft. This study was designed to characterize the pathophysiological correlate of focal outflow obstruction in a small-for-size liver and its course of recovery in a rat model.

Recovery of liver perfusion after focal outflow obstruction and liver resection.

The incidence of the small-for-size syndrome (SFSS) is inversely correlated to the size of the remnant liver or the partial graft. The relevance of factors besides the absolute liver mass is discussed controversially. It is the aim of this study to test the effect of two different mass ligation techniques in comparison with our newly developed parenchyma-preserving vessel-oriented liver resection technique on the induction of a SFSS after extended 90% liver resection in the rat.

Small-for-size syndrome in the rat: does size or technique matter?

Extended liver resection is applied in the treatment of liver tumors and during living-related liver transplantation. This procedure can lead to transient, in some patients even lethal liver failure. Administration of G-CSF is associated with an increased survival after toxic liver damage. It is the aim of this study to test the effect of G-CSF administration in the rat 90% extended liver resection model.

G-CSF administration in a small-for-size liver model.

Outcomes following lung transplantation are limited by bronchiolitis obliterans syndrome (BOS). As the number of circulating regulatory T cells (Treg) is lower in lung recipients with BOS than in stable lung recipients, we hypothesized that Treg is also correlated with lung function in the early post-transplantation period.

Lung function early after lung transplantation is correlated with the frequency of regulatory T cells.

Different types of endothelial cells (EC) fulfill distinct tasks depending on their microenvironment. ECs are therefore difficult to genetically manipulate ex vivo for functional studies or gene therapy. We assessed lentiviral vectors (LVs) targeted to the EC surface marker CD105 for in vivo gene delivery. The mouse CD105-specific vector, mCD105-LV, transduced only CD105-positive cells in primary liver cell cultures. Upon systemic injection, strong reporter gene expression was detected in liver where mCD105-LV specifically transduced liver sinusoidal ECs (LSECs) but not Kupffer cells, which were mainly transduced by nontargeted LVs. Tumor ECs were specifically targeted upon intratumoral vector injection. Delivery of the erythropoietin gene with mCD105-LV resulted in substantially increased erythropoietin and hematocrit levels. The human CD105-specific vector (huCD105-LV) transduced exclusively human LSECs in mice transplanted with human liver ECs. Interestingly, when applied at higher dose and in absence of target cells in the liver, huCD105-LV transduced ECs of a human artery transplanted into the descending mouse aorta. The data demonstrate for the first time targeted gene delivery to specialized ECs upon systemic vector administration. This strategy offers novel options to better understand the physiological functions of ECs and to treat genetic diseases such as those affecting blood factors.

Specific gene delivery to liver sinusoidal and artery endothelial cells.

Bronchiolitis obliterans syndrome is caused by a fibroproliferative process in lung allografts resulting in irreversible damage. In this study, we induced obliterative bronchiolitis and studied the contribution of regulatory T cells to its development in immune-deficient mice receiving heterotopic porcine bronchus transplants, and major histocompatibility complex-mismatched porcine peripheral blood mononuclear cell. Furthermore, we aimed to corroborate our findings in a humanized mouse model.

Allogeneic CD4+CD25high T cells regulate obliterative bronchiolitis of heterotopic bronchus allografts in both porcinized and humanized mouse models.

Cardiopulmonary bypass (CPB) is an essential component of many cardiac interventions, and therefore, there is an increasing critical demand to minimize organ damage resulting from prolonged extracorporeal circulation. Our goal was to develop the first clinically relevant mouse model of CPB and to examine the course of extracorporeal circulation by closely monitoring haemodynamic and oxygenation parameters.

Novel mouse model of cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) with moderate hypothermic cardiac arrest (MHCA) is essential for prolonged complex procedures in cardiac surgery and is associated with postoperative complications. Although cytokine release provoked through MHCA under CPB plays a pivotal role in postoperative organ damage, the pathomechanisms are unclear. Here, we investigated the cytokine release pattern and histological organ damage after MHCA using a recently described mouse CPB model. Eight BALB/c mice underwent 60 minutes of circulatory arrest under CPB, were successively rewarmed and reperfused. Blood cytokine concentrations and liver and kidney function parameters were measured and histological changes to these organs were compared to control animals. Our results showed a marked increase in proinflammatory cytokines and histological changes in the kidney, lung, and liver after CPB. Furthermore, clinical chemistry showed signs of hemolysis and acute kidney injury. These results suggest early onset of solid organ injury which correlates with increased leukocyte infiltration. A better understanding of the interplay between pro-inflammatory cytokine activation and solid organ injury in this model of CBP with MHCA will inform strategies to reduce organ damage during cardiac surgeries in the clinic.

Blood cytokine expression correlates with early multi-organ damage in a mouse model of moderate hypothermia with circulatory arrest using cardiopulmonary bypass.

ArticleTotal : 2	Year
Publication title Cited by 9	2017
Publication title Cited by 10	2018

Article	Year
Marginal hepatectomy in the rat: from anatomy to surgery. Annals of surgery\| PubMed ID: 16794393	2006
Recovery of liver perfusion after focal outflow obstruction and liver resection. Transplantation\| PubMed ID: 18337670	2008
Small-for-size syndrome in the rat: does size or technique matter? The Journal of surgical research\| PubMed ID: 18394648	2008
G-CSF administration in a small-for-size liver model. Journal of investigative surgery : the official journal of the Academy of Surgical Research\| PubMed ID: 19466653	2009
Lung function early after lung transplantation is correlated with the frequency of regulatory T cells. Surgery today\| PubMed ID: 22173646	2012
Specific gene delivery to liver sinusoidal and artery endothelial cells. Blood\| PubMed ID: 23884859	2013
Allogeneic CD4+CD25high T cells regulate obliterative bronchiolitis of heterotopic bronchus allografts in both porcinized and humanized mouse models. Transplantation\| PubMed ID: 25695787	2015
Novel mouse model of cardiopulmonary bypass. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery\| PubMed ID: 28977367	2018
Blood cytokine expression correlates with early multi-organ damage in a mouse model of moderate hypothermia with circulatory arrest using cardiopulmonary bypass. PloS one\| PubMed ID: 30308065	2018

Nodir Madrahimov

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