The use of ex vivo perfused models can mimic the physiological conditions of the liver for short periods, but to maintain normal homeostasis for an extended perfusion period is challenging. We have added the kidney to our previous ex vivo perfused liver experiment model to reproduce a more accurate physiological state for prolonged experiments without using live animals. Five intact livers and kidneys were retrieved post-mortem from sacrificed pigs on different days and perfused for a minimum of 6 hr. Hourly arterial blood gases were obtained to analyze pH, lactate, glucose and renal parameters. The primary endpoint was to investigate the effect of adding one kidney to the model on the acid base balance, glucose, and electrolyte levels. The result of this liver-kidney experiment was compared to the results of five previous liver only perfusion models. In summary, with the addition of one kidney to the ex vivo liver circuit, hyperglycemia and metabolic acidosis were improved. In addition this model reproduces the physiological and metabolic responses of the liver sufficiently accurately to obviate the need for the use of live animals. The ex vivo liver-kidney perfusion model can be used as an alternative method in organ specific studies. It provides a disconnection from numerous systemic influences and allows specific and accurate adjustments of arterial and venous pressures and flow.
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http://dx.doi.org/10.3791/50567 | DOI Listing |
Clin Exp Nephrol
January 2025
Renal Medicine Division, Department of Medicine, Emory University School of Medicine, 101 Woodruff Circle, Woodruff Memorial Research Building, Office 338A, Atlanta, GA, 30322, USA.
Background: Renal autoregulatory mechanisms modulate renal blood flow. Connecting tubule glomerular feedback (CNTGF) is a vasodilator mechanism in the connecting tubule (CNT), triggered paracrinally when high sodium levels are detected via the epithelial sodium channel (ENaC). The primary activation factor of CNTGF-whether NaCl concentration, independent luminal flow, or the combined total sodium delivery-is still unclear.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, 30625 Hannover, Germany.
Ischemic heart disease is the leading cause of death worldwide. Reduced oxygen supply and myocardial hypoxia lead to tissue damage and impairment of the heart function. To the best of our knowledge, the primary functional effects of hypoxia in the multicellular model of living myocardial slices (LMSs) have not been investigated so far.
View Article and Find Full Text PDFFood Chem Toxicol
January 2025
INSERM, Univ Rennes, INRAE, Institut NUMECAN (Nutrition, Métabolismes et Cancer) UMR_A 1341, UMR_S 1317, F-35000, Rennes, France; Laboratoire de toxicologie biologique et Médico-légale, CHU Rennes, Rennes, France.
Objective: Recently, the pig liver model perfused ex vivo using a normothermic machine perfusion (NMP) has been proposed as a suitable model to study xenobiotic metabolism and biliary excretion. The aim of our study is to describe the metabolism of NPS such as cathinones (with a focus on 4-Cl-PVP and eutylone) in blood and bile, using a normothermic perfused pig liver model.
Methods: Livers (n = 4) from male large white pigs, 3-4 months of age and weighing approximately 75-80 kg, were harvested and reperfused onto an NMP (LiverAssist®, XVIVO) using autologous whole blood at 38 °C.
Ann Thorac Surg
January 2025
Division of Cardiac Surgery, Massachusetts General Hospital, 55 Fruit Street, Cox 630, Boston, MA 02114.
Liver Transpl
January 2025
Abdominal Center Department, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione (IRCCS ISMETT), University of Pittsburgh Medical Center Italy (UPMCI), Palermo, Italy.
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