Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2007, vol. 16, nr 5, September-October, p. 609–618

Publication type: original article

Language: English

The Role of Calcium Channel−Blocking Drugs in Preserving Rat Liver for Transplantation

Wpływ leków blokujących kanały wapniowe na wątrobę przechowywaną do transplantacji

Małgorzata Trocha1,, Adam Szeląg1,

1 Department of Pharmacology, Silesian Piasts University of Medicine in Wrocław, Poland

Abstract

Background. Liver transplantation has become a widely accepted therapy for patients with end−stage liver diseases. The efficacy of this method depends on many different factors. Calcium plays a crucial role in physiological processes in liver cells; however, in high concentrations its ions can be pathogenic and lead to cell death. Because calcium ions enter the cell mostly through calcium channels, it has been suggested that calcium channel inhibitors (CCIs) could protect hepatocytes from the action of toxic substances.
Objectives. Using an extracorporeal liver perfusion model, the protective actions of nitrendipine and nifedipine during ischemia and reperfusion on the structure and function of rat liver preserved for transplantation were evaluated.
Material and Methods. The study was carried out on livers isolated from adult male Wistar rats. The rat livers were preserved for 24 hours in HTK solution (4ºC) with or without nifedipine or nitrendipine. After preservation, the livers were flushed with Ringer’s solution and perfused for two hours with a perfusion fluid. Glucose concentration and ALT, AST, and LDH activities were measured during perfusion. After perfusion all the produced bile was collected and the livers were histologically examined.
Results. Astatistically significant influence of nitrendipine on the activities of the liver enzymes was found. Livers which were both perfused and rinsed with addition of this drug showed the lowest levels of enzyme activity and histological damage among all the examined groups. No statistically significant differences between the groups in glucose concentration and total amount of bile were observed.
Conclusion. Nitrendipine demonstrated a protective influence on the function and structure of rat liver preserved for transplantation and maintained its action throughout perfusion, especially when added not only to the perfusion fluid, but also to the Ringer’s solution used for rinsing.

Streszczenie

Wprowadzenie. Obecnie przeszczepianie wątroby jest popularną i akceptowaną metodą leczenia pacjentów w ostatnim stadium niewydolności wątroby. Skuteczność tej metody zależy od wielu czynników. Jednym z nich jest prawidłowe stężenie jonów wapnia w tym narządzie. Jeśli nasilenie uszkodzeń w wątrobie podczas jej przechowywania do przeszczepienia zależy od wzrostu stężenia wapnia w komórce, to leki, które hamują jego napływ do komórki, powinny działać cytoprotekcyjnie.
Cel pracy. Ocena cytoprotekcyjnego działania nitrendypiny i nifedypiny na strukturę i czynność wątroby szczurzej przechowywanej do przeszczepienia.
Materiał i metody. Czynność wątroby badano podczas dwugodzinnej perfuzji pozaustrojowej. W grupie zerowej wątroby perfundowano bezpośrednio po izolacji narządu z organizmu, w pozostałych grupach – po 24−godzinnym okresie przechowywania w temperaturze 4ºC w roztworze HTK. W grupach badanych do płynu HTK dodano nitrendypinę lub nifedypinę w stężeniu 20 μmol/l. Dodatkowo, w ostatniej grupie badanej, nitrendypinę w tym samym stężeniu dodano także do roztworu Ringera służącego do przepłukania i ogrzania wątroby. Podczas perfuzji oznaczano aktywność enzymów wątrobowych (ALT, AST i LDH) oraz stężenie glukozy. Pod koniec perfuzji oznaczano całkowitą ilość wydzielonej żółci. W mikroskopie świetlnym oceniano zmiany strukturalne. Liczbę uszkodzonych komórek niemiąższowych oceniano, licząc jądra tych komórek wybarwione błękitem trypanu.
Wyniki. W badaniu wykazano statystycznie istotny wpływ nitrendypiny na aktywność enzymów wątrobowych. W grupie, w której dodano nitrendypinę zarówno do płynu HTK, jak i roztworu Ringera aktywność enzymów była najmniejsza, a zmiany histopatalogiczne najsłabiej wyrażone. Nie wykazano żadnych istotnych różnic w stężeniu glukozy i całkowitej ilości żółci między grupami.
Wnioski. Nitrendypina wykazuje ochronne działanie na czynność i strukturę wątroby szczurzej przechowywanej do przeszczepienia. Działanie to utrzymuje się przez cały okres perfuzji, szczególnie wtedy, gdy została podana zarówno do płynu HTK, jak i roztworu Ringera.

Key words

calcium channel blockers, liver, preservation−reperfusion injury, extracorporeal perfusion

Słowa kluczowe

leki blokujące kanały wapniowe, wątroba, uszkodzenia niedokrwienno−reperfuzyjne, perfuzja pozaustrojowa

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