scholarly journals Prompt Graft Cooling Enhances Cardioprotection during Heart Transplantation Procedures through the Regulation of Mitophagy

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2912
Author(s):  
Zhichao Wu ◽  
Jialiang Liang ◽  
Wei Huang ◽  
Lin Jiang ◽  
Christian Paul ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Heart Transplantation ◽  
Heart Function ◽  
Graft Function ◽  
Protective Mechanism ◽  
Ischemic Time ◽  
Cold Preservation ◽  
Warm Ischemic Time ◽  
Group I ◽  
Group Ii

A complete and prompt cardiac arrest using a cold cardioplegic solution is routinely used in heart transplantation to protect the graft function. However, warm ischemic time is still inevitable during the procedure to isolate donor hearts in the clinical setting. Our knowledge of the mechanism changes prevented by cold storage, and how warm ischemia damages donor hearts, is extremely poor. The potential consequences of this inevitable warm ischemic time to grafts, and the underlying potential protective mechanism of prompt graft cooling, have been studied in order to explore an advanced graft protection strategy. To this end, a surgical procedure, including 10–15 min warm ischemic time during procurement, was performed in mouse models to mimic the clinical situation (Group I), and compared to a group of mice that had the procurement performed with prompt cooling procedures (Group II). The myocardial morphologic changes (including ultrastructure) were then assessed by electron and optical microscopy after 6 h of cold preservation. Furthermore, syngeneic heart transplantation was performed after 6 h of cold preservation to measure the graft heart function. An electron microscopy showed extensive damage, including hypercontracted myofibers with contraction bands, and damaged mitochondria that released mitochondrial contents in Group I mice, while similar patterns of damage were not observed in the mice from Group II. The results from both the electron microscopy and immunoblotting verified that cardiac mitophagy (protective mitochondrial autophagy) was present in the mice from Group II, but was absent in the mice from Group I. Moreover, the mice from Group II demonstrated faster rebeating times and higher beating scores, as compared to the mice from Group I. The pressure catheter system results indicated that the graft heart function was significantly more improved in the mice from Group II than in those from Group I, as demonstrated by the left ventricle systolic pressure (31.96 ± 6.54 vs. 26.12 ± 8.87 mmHg), the +dp/dt (815.6 ± 215.4 vs. 693.9 ± 153.8 mmHg/s), and the -dp/dt: (492.4 ± 92.98 vs. 418.5 ± 118.9 mmHg/s). In conclusion, the warm ischemic time during the procedure impaired the graft function and destroyed the activation of mitophagy. Thus, appropriate mitophagy activation has emerged as a promising therapeutic target that may be essential for graft protection and functional improvement during heart transplantation.

scholarly journals Ultrastructural evaluation of urine alkalinization versus hydration on colistin-induced nephrotoxicity

2019 ◽  
Vol 38 (12) ◽  
pp. 1366-1377
Author(s):  
B Korucu ◽  
I Unal ◽  
M Pekcan ◽  
AC Inkaya ◽  
H Yeter ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Drinking Water ◽  
Weak Acid ◽  
Group Iv ◽  
Ultrastructural Changes ◽  
Sprague Dawley ◽  
Group Iii ◽  
Group I ◽  
Urine Alkalinization ◽  
Group Ii

Objectives: Colistin is a vital antibiotic used in multidrug-resistant infections. Its most important side effect is nephrotoxicity. Colistin is a weak acid. This study aims to evaluate whether urine alkalinization is protective in the nephrotoxicity of colistin. Methods: Twenty-eight male Sprague-Dawley rats were divided into groups. Group I ( n = 4) was injected with intramuscular distilled water twice a day for 7 days. Group II ( n = 8) was injected with 750,000 IU/kg/day colistin for 7 days. Group III ( n = 8) was injected with the same dose of colistin after their urinary pH was ≥7 through the addition of bicarbonate in their drinking water. Group IV ( n = 8) was injected with the same dose of colistin after their urine density fell below 1010 through the addition of NaCl molds in their food and 12.6 mg/L NaCl in their drinking water. Results: According to tubular degenerations (scored 0–5), group I scored 0, group II scored 4.25, group III scored 2, and group IV scored 1.5. In groups III and IV, protection was achieved ( p = 0.001). The bicarbonate group was not superior to the NaCl group ( p = 0.789). In transmission electron microscopy, group III had more microvilli integrity and autophagic vacuoles compared to group IV. Group IV had mitochondrial swelling and cristae lysis. A lower urine density was related to lower tubular scores ( p = 0.001). Conclusions: Colistin was highly nephrotoxic without protection. Light microscopy findings revealed that urinary alkalinization and NaCl hydration were similarly protective. Urine alkalinization further prevents ultrastructural changes as revealed by electron microscopy.

scholarly journals Hubungan antara Total Waktu Iskemik pada Transplan Ginjal dengan Lama Perawatan di Rumah Sakit: A Single Center Report

2020 ◽  
Vol 7 (1) ◽  
pp. 41-45
Author(s):  
Eriawan Agung Nugroho ◽  
Muhamad Azwin Kamar ◽  
Ardy Santosa ◽  
Nanda Daniswara ◽  
Sofyan Rais Addin
Keyword(s):  
Kidney Transplantation ◽  
Graft Function ◽  
Delay Graft Function ◽  
Therapeutic Modality ◽  
Ischemic Time ◽  
Warm Ischemic Time ◽  
Cold Ischemic Time ◽  
Hospitalization Time ◽  
End Stage ◽  
Spearman Test

Latar Belakang : Transplantasi ginjal diakui sebagai kemajuan utama pengobatan modern yang memberikan kehidupan berkualitas tinggi kepada pasien penyakit ginjal stadium akhir (End Stage Renal Disease). Waktu iskemik dingin /Cold Ischemic Time (CIT) telah ditemukan sebagai faktor risiko independen yang penting untuk delay graft function (DGF) pada transplantasi ginjal. Terdapat informasi terbaru bahwa waktu iskemik hangat /Warm Ischemic Time (WIT) yang lama dapat mengurangi kelangsungan hidup graft dalam donor hidup transplantasi ginjal. Tujuan dari penelitian ini adalah untuk mengevaluasi hubungan total ischemik time selama operasi penerima dengan lama rawat inap. Metode : Penelitian ini merupkaan studi observational-cross sectional. Data didapatkan dari catatan medis pasien yang telah menjalani transplantasi ginjal dari Januari 2014 – Desember 2018 du RS Umum dr. Kariadi semarang. Terdapat 28 pasien, 18 diantaranya adalah laki-laki dan 10 adalah wanita. Data total waktu iskemik dibandingkan dengan lamanya rawat inap. Data dianalisa dengan tes Spearman menggunakan software SPSS versi 23. Hasil : Pada studi ini menunjukkan adanya korelasi yang signifikan antara total waktu iskemik dengan lama perawatan di rumah sakit (p<0.001). Akan tetapi, umur donor tidak mempengaruhi total waktu iskemik (p=0.673), tidak signifikan (signifikan jika p<0.005). Simpulan : Adanya hubungan yang signifikan antara total waktu iskemik dengan lama perawatan rumah sakit. Namun, tidak ditemukannya hubungan yang signifikan pada usia donor dan total waktu iskemik. Kata kunci: total waktu iskemik, lama perawatan, transplantasi ginjal   Background: Kidney transplantation is recognized as an advanced modern therapeutic modality, providing a better life for patients with end stage renal failure globally. Cold Ischemic Time (CIT) has been found as an important independent risk factor for delay graft function (DGF) in kidney transplantation. DGF also associated with patient’s survival post-operatively. Recent studies suggested that prolonged Warm Ischemic Time (WIT) may decrease graft’s survival in living kidney transplantation donor. This study aimed to evaluate the total ischemic time during recipient surgery and accessed its contribution for hospitalization time in kidney transplantation patients. Methods: This is a descriptive retrospective study. This study was started in 2014 until December 2018, including data from patients’ medical record whom underwent kidney transplantation in Kariadi General Hospital Semarang. Data was collected from 28 patients, including 18 male patients and 10 female patients. The author found a significant correlation between patient’s age and total ischemic time. Total ischemic time also compared with hospitalization time. Data was processed using Spearman test in SPSS software. Results: Based on Spearman test, Total ischemic time was significantly correlated with hospitalization time (p < 0.001). However, donor’s age did not affect prolonged total ischemic time with p = 0.673, which is not significant (significant if p value < 0.05). Conclusion: Total ischemic time has a significant correlation with hospitalization time. In contrary, no significant correlation between donor’s age and prolonged total ischemic time. Key Words: Total ischemic time, hospitalization time, kidney transplantation

scholarly journals Drungno kraujo kardioplegijos įvertinimas atliekant trijų vožtuvų korekcijos operacijas

2007 ◽  
Vol 5 (3) ◽  
pp. 0-0
Author(s):  
Gintaras Turkevičius ◽  
Stanislovas Stankevič ◽  
Arimantas Grebelis ◽  
Rasa Čypienė ◽  
Palmyra Semėnienė
Keyword(s):  
Cardiac Surgery ◽  
Heart Function ◽  
Severe Heart Failure ◽  
Valve Surgery ◽  
University Hospital ◽  
Blood Cardioplegia ◽  
Group I ◽  
Group Ii ◽  
Vilnius University ◽  
Triple Valve

Gintaras Turkevičius1, Stanislovas Stankevič2, Arimantas Grebelis3, Rasa Čypienė3, Palmyra Semėnienė31 Vilniaus universiteto ligoninės Santariškių klinikų Širdies chirurgijos centras,Santariškių g. 2, LT-08661 Vilnius2 Vilniaus universiteto ligoninės Santariškių klinikų Anesteziologijos,intensyvios terapijos ir skausmo gydymo centras, Santariškių g. 2, LT-08661 Vilnius3 Vilniaus universiteto Širdies chirurgijos centras, Santariškių g. 2, LT-08661 VilniusEl paštas: [email protected] Ligoniai ir metodai 58 ligoniai (amžiaus vidurkis 66 metai), NYHA III–IV funkcinės klasės, suskirstyti į dvi grupes. Pirmoje grupėje (19 ligonių) taikyta pastovi retrogradinė drungno kraujo kardioplegija, antroje (39 ligoniai) – antegradinė frakcinė drungno kraujo kardioplegija. Aortos perspaudimo laikas 93 ± 5 min. Abiejų grupių ligoniams buvo vertinamas savaiminis širdies veiklos atsikūrimas po aortos atleidimo, EKG normalizavimosi laikas, trukmė nuo aortos atleidimo iki dirbtinės kraujo apytakos sustabdymo, adrenomimetikų poreikis pirmą pooperacinę parą, echoskopinis kairiojo skilvelio funkcijos įvertinimas prieš operaciją ir po jos. Rezultatai Išgyveno 54 ligoniai, mirė 4 (po 2 iš abiejų grupių). Vienas ligonis mirė nuo smegenų pažeidimo, du nuo dauginio organų nepakankamumo ir vienas nuo širdies silpnumo. Buvo geresni visų vertinamų tyrimų antros ligonių grupės rezultatai (1 lentelė). Išvados Trijų širdies vožtuvų korekcijos operacijose miokardo apsaugai tinkama naudoti tiek pastovi retrogradinė drungno kraujo kardioplegija, tiek frakcinė antegradinė drungno kraujo kardioplegija. Kiek geresni buvo antros ligonių grupės rezultatai. Pagrindiniai žodžiai: kardioplegija, vožtuvų korekcija Evaluation of tepid blood cardioplegia in three heart valve surgical correction Gintaras Turkevičius1, Stanislovas Stankevič2, Arimantas Grebelis3, Rasa Čypienė3, Palmyra Semėnienė31 Vilnius University Hospital „Santariškių klinikos“, Cardiac Surgery Centre, Santariškių str. 2, LT-08661 Vilnius2 Vilnius University Hospital „Santariškių klinikos“, Anesteziology,Intensive Care and Pain Management Center, Santariškių str. 2, LT-08661 Vilnius3 Vilnius University, Cardiac Surgery Centre, Santariškių str. 2, LT-08661 VilniusE-mail: [email protected] Objective Analysis of myocardial protection technique for triple valve surgery was performed. Patients and methods Fifty-eight NYHA III–IV F.cl patients, mean age 66 years, were the investigated. All the patients were divided into two groups. Continuous retrograde tepid blood cardioplegia was used in group I patients (19) and antegrade intermittent tepid blood cardioplegia in 39 patients (group II). Aorta cross-clamp time was 93 ± 5 min. After declamping the aorta, the following criteria were analysed: heart rhythm self-restoration, time to ECG normalization and time from declamping the aorta till weaning from CPB (reperfusion), epinephrine doses after surgery, left ventricle ejection fraction before and after procedure. Results Fifty-four patients survived and 4 patients died after surgery. The causes of death were: 1 – postoperative brain damage, 2 – multiorgan failure, 1 – severe heart failure. Postoperative heart function was better preserved in group II of the patients. Conclusions Both type of cardioplegia are suitable for triple valve surgery. A slight improvement of hemodynamic data was noted when intermittent tepid blood cardioplegia was used. Key words: cardioplegia, valve correction

scholarly journals Laparoscopic Live Donor Nephrectomy: Comparison of Left-sided and Right-sided Approach in Our First 50 Cases

2015 ◽  
Vol 22 (1) ◽  
Author(s):  
Albertus Marcelino ◽  
Chaidir Arif Mochtar ◽  
Irfan Wahyudi ◽  
Bagus Baskoro ◽  
Arry Rodjani ◽  
...  
Keyword(s):  
Left Kidney ◽  
Graft Function ◽  
Donor Nephrectomy ◽  
Live Donor ◽  
Ischemic Time ◽  
Operative Results ◽  
Warm Ischemic Time ◽  
Live Donor Nephrectomy ◽  
The Right ◽  
Laparoscopic Live Donor Nephrectomy

Objectives: To compare the operative results and outcomes between right and left laparoscopic live donor nephrectomy (LLDN). Methods: We retrospectively analyzed the first 50 consecutive LLDN in Indonesia performed between November 2011 and February 2013. Of these patients, 6 underwent right LLDNs and 44 left LLDNs. All patients underwent LLDNs in Cipto Mangunkusumo Hospital. All LLDNs were done by the same surgical teams. Intraoperative, post-operative donor and recipient data results were compared.Results: There were no significant differences of intraoperative, post-operative and recipient data results in both groups.  The first warm ischemic time (mean±SD, 6min 55sec±145sec vs 7min 37sec±177 sec, p>0.05), the second warm ischemic time (41min 35sec ± 7min 45sec vs 48min 36sec ± 8min 41sec, p>0.05), and the operative time (4hour 41min ± 31min vs 4hour 32min ± 49 min, p>0.05) showed similar results in the right and left LLDN, respectively. Active mobilization on 72-hour post-operation was found in 83,3% in the right LLDN compared to 95,5% (p>0.05). There were no delayed graft function and post-operative hemodialysis within one week in the recipients of right LLDN group. Conclusion: Right LLDN has equal operative results and outcomes compared to left LLDN. Right-sided LLDN may be a judicious approach for donors with unfavorable characteristics of the left kidney.

scholarly journals Warm Ischemic Time in Orthotopic Heart Transplantation: Is Faster Really Better?

2021 ◽  
Vol 40 (4) ◽  
pp. S263
Author(s):  
D. Megna ◽  
D. Emerson ◽  
T. Singer-Englar ◽  
A. Roach ◽  
A. Trento ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Orthotopic Heart Transplantation ◽  
Ischemic Time ◽  
Warm Ischemic Time

scholarly journals Novel Injectable Bioartificial Tissue Facilitates Targeted, Less Invasive, Large-Scale Tissue Restoration on the Beating Heart After Myocardial Injury

Circulation ◽  
2005 ◽  
Vol 112 (9_supplement) ◽  
Author(s):  
Theo Kofidis ◽  
Darren R. Lebl ◽  
Eliana C. Martinez ◽  
Grant Hoyt ◽  
Masashi Tanaka ◽  
...  
Keyword(s):  
Stem Cells ◽  
Large Scale ◽  
Heart Function ◽  
Left Ventricular ◽  
Group Iv ◽  
Group Iii ◽  
Left Anterior Descending Artery ◽  
Group I ◽  
Bonferroni Test ◽  
Group Ii

Background— Implantation of bioartificial patches distorts myocardial geometry, and functional improvement of the recipient heart is usually attributed to reactive angiogenesis around the graft. With the liquid bioartificial tissue compound used in this study, we achieved targeted large-scale support of the infarcted left ventricular wall and improvement of heart function. Methods and Results— A liquid compound consisting of growth factor-free Matrigel and 10 6 green fluorescent protein (GFP)-positive mouse (129sv) embryonic stem cells (ESCs) was generated and injected into the area of ischemia after ligation of the left anterior descending artery in BALB/c mice (group I). Left anterior descending artery-ligated mice (group II) and mice with Matrigel (group III) or ESC treatment alone (group IV) were used as the control groups (n=5 in all groups). The hearts were harvested for histology 2 weeks later after echocardiographic assessment with a 15-MHz probe. The liquid injectable tissue solidified at body temperature and retained the geometry of the infarcted lateral wall. Immunofluorescence stains revealed voluminous GFP grafts. The quality of restoration (graft/infarct area ratio) was 45.5±10.8% in group I and 29.1±6.7% in group IV ( P =0.034). ESCs expressed connexin 43 at intercellular contact sites. The mice treated with the compound had a superior heart function compared with the controls ( P <0.0001 by ANOVA/Bonferroni test; group I: 27.1±5.4, group II:11.9±2.4, group III:16.2±2.8, group IV: 19.1±2.7). Conclusions— Injectable bioartificial tissue restores the heart’s geometry and function in a targeted and nondistorting fashion. This new method paves the way for novel interventional approaches to myocardial repair, using both stem cells and matrices.

Delayed graft function and perfusion parameters of kidneys from uncontrolled donors after circulatory death

Perfusion ◽  
2020 ◽  
pp. 026765912093892
Author(s):  
Adriano Peris ◽  
Giorgio Enzo Fulceri ◽  
Chiara Lazzeri ◽  
Manuela Bonizzoli ◽  
Vincenzo Li Marzi ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Delayed Graft Function ◽  
Machine Perfusion ◽  
Hemodynamic Parameters ◽  
Ischemic Time ◽  
Warm Ischemic Time ◽  
Hypothermic Machine Perfusion ◽  
Circulatory Death

Better preservation and evaluation of kidneys from donors after circulatory death serve to increase the number of kidneys available for transplantation and hypothermic machine perfusion has been shown to decrease ischemia reperfusion injury and delayed graft function. Data on relation between hemodynamic parameters during hypothermic machine perfusion and delayed graft function in kidneys from donors after circulatory death are so far scarce and not univocal. We aimed at assessing whether hemodynamic parameters measured during hypothermic machine perfusion (flow, mean perfusion pressure, and renal resistance) are associated with delayed graft function in 26 kidneys retrieved from uncontrolled donors after circulatory death. In our series, the incidence of delayed graft function was 57.7% (15/26). Recipients who developed delayed graft function had a longer warm ischemic time (p = 0.04). All hemodynamic parameters measured during hypothermic machine perfusion were comparable between recipients with delayed graft function and those without. According to our data, in kidneys from uncontrolled donors after circulatory death, a longer warm ischemic time (that is the overall time of no flow, as the sum of the no-flow and the no-touch period) is associated with delayed graft function. This finding underscores the pivotal role of ischemic injury in terms of absence of flow in affecting graft function. No association was detectable between hemodynamic parameters during hypothermic machine perfusion and the development of delayed graft function in our series.

scholarly journals Ultrastructural observation of the airways of recovered and susceptible pigs after inoculation with Mycoplasma hyopneumoniae

1998 ◽  
Vol 18 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Luiz Francisco Irigoyen ◽  
William Van Alstine ◽  
John Turek ◽  
L. Kirk Clark
Keyword(s):  
Electron Microscopy ◽  
Morphological Changes ◽  
Light And Electron Microscopy ◽  
Mycoplasma Hyopneumoniae ◽  
Group Iv ◽  
Control Group ◽  
Ultrastructural Observation ◽  
Group Iii ◽  
Group I ◽  
Group Ii

To determine the morphological differences in the epithelium of the airways of recovered and susceptible pigs after Mycoplasma hyopneumoniae challenge, twenty-four 4-week-old M. hyopneumoniae-free pigs were intratracheally inoculated with 107ccu/ml of a pure low-passaged culture of the P5722-3 strain of M. hyopneumoniae challenge material. Eight pigs (group I) were challenged at the beginning of the experiment and rechallenged 3 months later. Group II pigs were also challenged at the beginning of the experiment and necropsied 3 months later. Group III pigs were challenged at the same time as the rechallenge of group I pigs. Eight nonchallenged pigs served as controls (group IV). Three days after the second challenge of group I and the first challenge of group III, and every 3 and 4 days thereafter, two pigs from each group were euthanatized by electrocution and necropsied. Samples of bronchi and lung tissue were examined using light and electron microscopy (SEM and TEM). Macroscopic lesions were observed in the lungs of all group III pigs (average = 4.74%) and were characterized by purple-red areas of discoloration and increased firmness affecting the cranioventral aspect of the lungs. Macroscopic lesions of pneumonia in groups I and II were minimal (less than 1%). There were no gross lesions of pneumonia in control (group IV) pigs. Microscopic lesions were characterized by hyperplasia of the peribronchial lymphoid tissue and mild neutrophilic infiltrates in alveoli. Electron microscopy showed patchy areas with loss of cilia and presence of leukocytes and mycoplasmas in bronchi of susceptible pigs (group III). The bronchial epithelium of rechallenged (group I), recovered (group II), and control (group IV) pigs was ultrastructurally similar indicating recovery of the former two groups. Although mycoplasmas were seen among cilia, a second challenge on pigs of group I did not produce another episode of the disease nor did it enhance morphological changes, suggesting that those pigs could become carriers of M. hyopneumoniae.

scholarly journals Short- and Long-Time Improvement of Graft Function Using Iron-Chelator Supplemented Bretschneider Solution in a Canine Model of Orthotopic Heart Transplantation

2021 ◽  
Author(s):  
Gabor Szabo ◽  
Sivakkanan LOGANATHAN ◽  
Sevil KORKMAZ-ICÖZ ◽  
Ágnes BALOGH ◽  
Zoltan PAPP ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Vascular Function ◽  
Graft Function ◽  
Iron Chelator ◽  
Canine Model ◽  
High Energy ◽  
Left Ventricular ◽  
Lv Function ◽  
Ischemic Time

Abstract An increasing organ demand is facing a constant number of donors. Nevertheless, not all organs are utilized due to a limited time window for heart transplantation (HTX). Therefore, we aimed to evaluate, if iron chelator supplemented Bretschneider solution can protect the graft in a clinically relevant canine model of HTX with prolonged ischemic storage.HTX was performed in foxhounds. The ischemic time was standardized to 4h, 8h, 12h or 16h depending on the experimental group. Left ventricular (LV) and vascular function were measured. Additionally, myocardial high energy phosphate and iron content and in-vitro myocyte force were evaluated.Iron chelator supplementation proved superior at a routine preservation time of 4h as well as for prolonged times of 8h and longer. The supplementation groups recovered quickly compared to their controls. The LV function was preserved and coronary blood flow increased. This was also confirmed by in vitro myocyte force and vasorelaxation experiments. Additionally, the biochemical results showed significantly higher adenosine-triphosphate content in supplementation groups. The iron chelator LK614 played an important role in this mechanism by reducing the chelatable iron content.This study shows that iron chelator supplemented Bretschneider solution effectively prevents myocardial/endothelial damage during short as well as long term conservation.

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