scholarly journals Blood Cardioplegia Induction, Perfusion Storage and Graft Dysfunction in Cardiac Xenotransplantation

2021 ◽  
Vol 12 ◽  
Author(s):  
Corbin E. Goerlich ◽  
Bartley Griffith ◽  
Avneesh K. Singh ◽  
Mohamed Abdullah ◽  
Shreya Singireddy ◽  
...  
Keyword(s):  
Graft Function ◽  
Serum Lactate ◽  
Genetically Engineered ◽  
Inotropic Support ◽  
Graft Dysfunction ◽  
Perfusion System ◽  
Blood Cardioplegia ◽  
Genetic Modifications ◽  
And Storage ◽  
Continuous Perfusion

BackgroundPerioperative cardiac xenograft dysfunction (PCXD) describes a rapidly developing loss of cardiac function after xenotransplantation. PCXD occurs despite genetic modifications to increase compatibility of the heart. We report on the incidence of PCXD using static preservation in ice slush following crystalloid or blood-based cardioplegia versus continuous cold perfusion with XVIVO© heart solution (XHS) based cardioplegia.MethodsBaboons were weight matched to genetically engineered swine heart donors. Cardioplegia volume was 30 cc/kg by donor weight, with del Nido cardioplegia and the addition of 25% by volume of donor whole blood. Continuous perfusion was performed using an XVIVO © Perfusion system with XHS to which baboon RBCs were added.ResultsPCXD was observed in 5/8 that were preserved with crystalloid cardioplegia followed by traditional cold, static storage on ice. By comparison, when blood cardioplegia was used followed by cold, static storage, PCXD occurred in 1/3 hearts and only in 1/5 hearts that were induced with XHS blood cardioplegia followed by continuous perfusion. Survival averaged 17 hours in those with traditional preservation and storage, followed by 11.47 days and 15.03 days using blood cardioplegia and XHS+continuous preservation, respectively. Traditional preservation resulted in more inotropic support and higher average peak serum lactate 14.3±1.7 mmol/L compared to blood cardioplegia 3.6±3.0 mmol/L and continuous perfusion 3.5±1.5 mmol/L.ConclusionBlood cardioplegia induction, alone or followed by XHS perfusion storage, reduced the incidence of PCXD and improved graft function and survival, relative to traditional crystalloid cardioplegia-slush storage alone.

Continuous perfusion of donor hearts with oxygenated blood cardioplegia improves graft function

2010 ◽  
Vol 23 (11) ◽  
pp. 1164-1170 ◽  
Author(s):  
Fan Zhang ◽  
Ansheng Mo ◽  
Zhaoke Wen ◽  
Yifan Zhou ◽  
Shengjing Liang ◽  
...  
Keyword(s):  
Graft Function ◽  
Blood Cardioplegia ◽  
Continuous Perfusion

Abstract 18139: Myocardial Fibrosis Quantified by Cardiovascular Magnetic Resonance is Associated with Histology and Graft Function After Pediatric Heart Transplantation

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Brian Feingold ◽  
Cláudia M Salgado ◽  
Miguel Reyes-Múgica ◽  
Stacey Drant ◽  
Susan A Miller ◽  
...  
Keyword(s):  
Cardiovascular Magnetic Resonance ◽  
Magnetic Resonance ◽  
Heart Transplantation ◽  
Myocardial Fibrosis ◽  
Graft Failure ◽  
Extracellular Volume ◽  
Graft Function ◽  
Automated Image Analysis ◽  
Graft Dysfunction ◽  
Pediatric Heart Transplantation

Background: Late survival after pediatric heart transplantation (HTx) remains poor. Many late deaths are due to “graft failure,” typically in the presence of vasculopathy and diffuse myocardial fibrosis (DMF) - a process associated with ventricular remodeling and heart failure (HF). Cardiovascular magnetic resonance (CMR)-derived extracellular volume (ECV) is a validated measure of DMF in the absence of edema or infiltrative disease, and predicts outcomes of HF and mortality in adults. We hypothesize that ECV is a meaningful biomarker of graft dysfunction following pediatric HTx. Objective: To test the association of ECV with histologic myocardial fibrosis after pediatric HTx. We also explored associations of ECV with hemodynamic, echocardiographic, and serum measures of graft function. Methods: We prospectively enrolled consecutive HTx recipients who were ≥13 years old and ≥9 months post HTx for ECV quantification at the time of surveillance endomyocardial biopsy (EMB). Fibrosis was quantified on EMB by automated image analysis after picrosirius staining and digital scanning. CMR measures of blood and myocardial T1 from basal and mid short axis slices, along with contemporaneous hematocrit, quantified ECV. Results: Nineteen pts (12 male) underwent CMR at a mean age of 18.4 ± 2.8 yrs (range 14.9 - 24.4 yrs) and a mean time after HTx of 10.4 ± 6.6 yrs (1.0 - 20.7 yrs). Four pts were excluded from analysis due to acute rejection (ISHLT grade ≥2R) on concurrent EMB (n=2) or poor quality imaging (n=2). Mean ECV was 27.1 ± 3.8 (20.9 - 32.1). Late gadolinium enhancement was observed in 1 pt. ECV showed moderate correlations with histologic myocardial fibrosis (r=0.61; p=0.02) and serum b-type natriuretic peptide (r=0.66; p=0.008). There was a trend to correlation with pulmonary capillary wedge pressure (r=0.51; p=0.06). We found no associations of ECV with systolic or diastolic function, time after HTx, or graft age. Conclusions: We demonstrate a novel association of ECV with histologic myocardial fibrosis and serum and hemodynamic markers of HF after pediatric HTx. Given prior observations of myocardial fibrosis in chronic graft failure, these findings suggest that ECV may be a relevant, noninvasive marker of graft dysfunction and a potential therapeutic target.

Association of Factor V Leiden Mutation with Delayed Graft Function, Acute Rejection Episodes and Long-term Graft Dysfunction in Kidney Transplant Recipients

2002 ◽  
Vol 87 (02) ◽  
pp. 194-198 ◽  
Author(s):  
Torsten Slowinski ◽  
Ingeborg Hauser ◽  
Birgit Vetter ◽  
Lutz Fritsche ◽  
Daniela Bachert ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Kidney Transplant ◽  
Graft Function ◽  
Factor V Leiden ◽  
Factor V ◽  
Transplant Recipients ◽  
Graft Dysfunction ◽  
Kidney Transplant Recipients ◽  
Factor V Leiden Mutation

SummaryWe analysed whether the factor V Leiden mutation – the most common hereditary predisposing factor for venous thrombosis – is associated with early and long-term graft dysfunction after kidney transplantation in 394 Caucasian kidney transplant recipients. The presence of factor V Leiden mutation was identified by allele specific PCR. The prevalence of the factor V Leiden mutation was compared to 32216 unselected neonates. The prevalence of the factor V Leiden mutation (GA genotype) was similar in 394 kidney transplant recipients and 32216 neonates. The frequency of known factors predicting long-term graft function were similar in patients with the GA genotype and with the normal factor V gene (GG genotype). The GA genotype was associated with the occurrence of no primary graft function (risk: 2.87; 95% confidence interval: 1.01-8.26; p < 0.05), the number of dialysis after transplantation in patients with no primary graft function until graft function (7.5 ± 2.06 dialysis in GA patients; 4.2 ± 0.36 dialyses in GG patients; p < 0.05), and the risk for at least one acute rejection episode (risk: 3.83; 95% confidence interval: 1.38-10.59; p < 0.02). The slope of 1/creatinine per year was significantly lower in patients with the GA genotype (GA patients: – 0.0204 ± 0.008 dl/mg per year; GG patients: 0.0104 ± 0.004 dl/mg per year; p < 0.02). The annual enhancement of the daily protein excretion rate was elevated in patients with the GA genotype (GA patients: 38.5 ± 16.6 mg/24 h per year; GG patients: 4.9 ± 4.4 mg/24 h per year; p < 0.02). Our study showed that the factor V Leiden mutation is associated with the occurrence of delayed graft function, acute rejection episodes and chronic graft dysfunction after kidney transplantation.

scholarly journals Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

2020 ◽  
Vol 21 (15) ◽  
pp. 5404 ◽  
Author(s):  
Marco Quaglia ◽  
Guido Merlotti ◽  
Gabriele Guglielmetti ◽  
Giuseppe Castellano ◽  
Vincenzo Cantaluppi
Keyword(s):  
Graft Survival ◽  
Biological Fluids ◽  
Imaging Techniques ◽  
Graft Function ◽  
Kidney Graft ◽  
Graft Dysfunction ◽  
Prognostic Information ◽  
Management Of Complications ◽  
Wide Range ◽  
New Biomarkers

New biomarkers of early and late graft dysfunction are needed in renal transplant to improve management of complications and prolong graft survival. A wide range of potential diagnostic and prognostic biomarkers, measured in different biological fluids (serum, plasma, urine) and in renal tissues, have been proposed for post-transplant delayed graft function (DGF), acute rejection (AR), and chronic allograft dysfunction (CAD). This review investigates old and new potential biomarkers for each of these clinical domains, seeking to underline their limits and strengths. OMICs technology has allowed identifying many candidate biomarkers, providing diagnostic and prognostic information at very early stages of pathological processes, such as AR. Donor-derived cell-free DNA (ddcfDNA) and extracellular vesicles (EVs) are further promising tools. Although most of these biomarkers still need to be validated in multiple independent cohorts and standardized, they are paving the way for substantial advances, such as the possibility of accurately predicting risk of DGF before graft is implanted, of making a “molecular” diagnosis of subclinical rejection even before histological lesions develop, or of dissecting etiology of CAD. Identification of “immunoquiescent” or even tolerant patients to guide minimization of immunosuppressive therapy is another area of active research. The parallel progress in imaging techniques, bioinformatics, and artificial intelligence (AI) is helping to fully exploit the wealth of information provided by biomarkers, leading to improved disease nosology of old entities such as transplant glomerulopathy. Prospective studies are needed to assess whether introduction of these new sets of biomarkers into clinical practice could actually reduce the need for renal biopsy, integrate traditional tools, and ultimately improve graft survival compared to current management.

scholarly journals Cerebral Effects of Circulatory Arrest at 20° C in the Infant Pig

1974 ◽  
Vol 2 (1) ◽  
pp. 33-42 ◽  
Author(s):  
G. C. Fisk ◽  
J. S. Wright ◽  
B. B. Turner ◽  
W. de C. Baker ◽  
R. G. Hicks ◽  
...  
Keyword(s):  
Brain Damage ◽  
Heart Surgery ◽  
Circulatory Arrest ◽  
Open Heart Surgery ◽  
Open Heart ◽  
Membrane Oxygenator ◽  
Perfusion System ◽  
Experimental Procedure ◽  
Hypothermic Arrest ◽  
Continuous Perfusion

Circulatory arrest at 20° C is used during open heart surgery in infants. It has been stated that significant brain damage does not occur. Piglets between two and six weeks of age were cooled to 20° C using extracorporeal circulation and a membrane oxygenator. After one hour of circulatory arrest the perfusion system was used to rewarm the animals and restore normal circulation. Electroencephalogram was monitored throughout perfusion and surgery, and repeated on surviving animals on the third, fifth, seventh and tenth postoperative days. On the tenth day the animals were killed by injection of pentobarbitone. Other groups were subjected to Continuous perfusion at 20° C, Continuous perfusion at 37° C, Thoracotomy and cannulation, Ischaemia, and Hypoxia. The return of E.E.G. activity was delayed after circulatory arrest compared with those continuously perfused. Lesions were found in the cerebral cortex in all the animals which had circulatory arrest and those subjected to ischaemia and hypoxia. The brains of animals of the other groups were indistinguishable from those killed without any experimental procedure. Despite apparent recovery, brain damage following hypothermic arrest during open heart surgery remains possible.

scholarly journals Mathematical Model of Mouse Embryonic Cardiomyocyte Excitation–Contraction Coupling

2008 ◽  
Vol 132 (4) ◽  
pp. 407-419 ◽  
Author(s):  
Topi Korhonen ◽  
Risto Rapila ◽  
Pasi Tavi
Keyword(s):  
Mathematical Model ◽  
Genetically Engineered ◽  
Ion Currents ◽  
Electrical Excitation ◽  
Contraction Coupling ◽  
Genetic Modifications ◽  
Genetically Engineered Mice ◽  
Embryonic Cardiomyocytes ◽  
Hyperpolarization Activated Current ◽  
Functional Alteration

Excitation–contraction (E–C) coupling is the mechanism that connects the electrical excitation with cardiomyocyte contraction. Embryonic cardiomyocytes are not only capable of generating action potential (AP)-induced Ca2+ signals and contractions (E–C coupling), but they also can induce spontaneous pacemaking activity. The spontaneous activity originates from spontaneous Ca2+ releases from the sarcoplasmic reticulum (SR), which trigger APs via the Na+/Ca2+ exchanger (NCX). In the AP-driven mode, an external stimulus triggers an AP and activates voltage-activated Ca2+ intrusion to the cell. These complex and unique features of the embryonic cardiomyocyte pacemaking and E–C coupling have never been assessed with mathematical modeling. Here, we suggest a novel mathematical model explaining how both of these mechanisms can coexist in the same embryonic cardiomyocytes. In addition to experimentally characterized ion currents, the model includes novel heterogeneous cytosolic Ca2+ dynamics and oscillatory SR Ca2+ handling. The model reproduces faithfully the experimentally observed fundamental features of both E–C coupling and pacemaking. We further validate our model by simulating the effect of genetic modifications on the hyperpolarization-activated current, NCX, and the SR Ca2+ buffer protein calreticulin. In these simulations, the model produces a similar functional alteration to that observed previously in the genetically engineered mice, and thus provides mechanistic explanations for the cardiac phenotypes of these animals. In general, this study presents the first model explaining the underlying cellular mechanism for the origin and the regulation of the heartbeat in early embryonic cardiomyocytes.

scholarly journals Improved Production of Tryptophan in Genetically EngineeredEscherichia coliwith TktA and PpsA Overexpression

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Tong Shen ◽  
Qing Liu ◽  
Xixian Xie ◽  
Qingyang Xu ◽  
Ning Chen
Keyword(s):  
Critical Factor ◽  
Batch Cultivation ◽  
Genetically Engineered ◽  
High Cell ◽  
Fed Batch ◽  
Acid Productivity ◽  
Genetic Modifications ◽  
Low Copy Number ◽  
Cell Densities ◽  
Fed Batch Cultivation

Intracellular precursor supply is a critical factor for amino acid productivity. In the present study,ppsAandtktAgenes were overexpressed in genetically engineeredEscherichia colito enhance the availability of two precursor substrates, phosphoenolpyruvate and erythrose-4-phosphate. The engineered strain, TRTH0709 carrying pSV709, produced 35.9 g/L tryptophan from glucose after 40 h in fed-batch cultivation. The two genes were inserted, independently or together, into a low-copy-number expression vector (pSTV28) and transferred to TRTH0709. Fed-batch fermentations at high cell densities of the recombination strains revealed that overexpression of theppsAgene alone does not significantly increase tryptophan yield. On the other hand, overexpression of thetktAgene, alone or with theppsAgene, could further improve tryptophan yield to a final tryptophan titer of 37.9 and 40.2 g/L, respectively. These results represent a 5.6% and 11.9% enhancement over the titer achieved by TRTH0709. No evident genetic modifications leading to growth impairment were observed.

scholarly journals Eculizumab for the Treatment of Severe Antibody-Mediated Rejection: A Case Report and Review of the Literature

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Duy Tran ◽  
Anne Boucher ◽  
Suzon Collette ◽  
Alexis Payette ◽  
Virginie Royal ◽  
...  
Keyword(s):  
Treatment Options ◽  
Graft Function ◽  
Deceased Donor ◽  
Immunosuppressive Regimen ◽  
Review Of The Literature ◽  
Graft Dysfunction ◽  
End Stage Kidney Disease ◽  
Antibody Mediated Rejection ◽  
End Stage ◽  
Acute Graft

In renal transplantation, treatment options for antibody-mediated rejection are limited. Here, we report a case of severe AMR treated with eculizumab. A 50-year-old woman known for end stage kidney disease secondary to IgA nephropathy received a kidney transplant from a 50-year-old deceased donor. At 5 months after transplantation, she presented with acute graft dysfunction and biopsy showed a severe antibody-mediated rejection associated with thrombotic microangiopathy. Despite an aggressive conventional immunosuppressive regimen, signs of rejection persisted and the patient was treated with 3 doses of eculizumab. Following the therapy, markers of TMA improved and graft function stabilized. However, ongoing signs of rejection remained in the repeated biopsy. In kidney transplantation, eculizumab is an expensive treatment and its role in the treatment of antibody-mediated rejection remains to be determined.

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