Avtor/Urednik		Podobnik, Blaž; Miklavčič, Damijan
Naslov		Influence of hydralazine on interstitial fluid pressure in experimental tumors - a preliminary study
Prevedeni naslov		Vpliv hydralazina na tlak medcelične tekočine v poskusnih tumorjih
Tip		članek
Vir		Radiol Oncol
Vol. in št.		Letnik 34, št. 1
Leto izdaje		2000
Obseg		str. 59-65
Jezik		eng
Abstrakt		Background. Interstitial fluid pressure (IFP) has been recognised as the most important obstacle in macromolecular drug delivery to solid tumors. Our interest was to reduce differentialy tumor IFP with respect to IFP in surrounding and normal tissues in order to increase drug delivery to tumors as well to increase tumor blood flow and potentialy tumor tissue oxygenation. In this preliminary study we used hydralazine, a longacting arterial vasodilator. Materials and methods. Measurements of interstitial fluid pressure were performed in vivo on CBA mice bearing SAF tumors using wick-in-needle technigue. Altogether eleven measurements were obtained on different animals with tumors of different size. Results. IFP in tumors after hydralazine administration was significantly lower than initial values in corresponding tumors. On average tumor IFP decreased for 33 % from initial value. On the contrary, no change in IFP in normal tissue was observed after hydralazine administration. Also, after injection of physiological saline instead of hydralazine there was no change in IFP neither in tumors nor in muscle. The results of our preliminary study on the effect of hydralazine on IFP in SAF tumor model is in accordance to previously reported studies. The decrease in tumor IFP was only observed in tumors, but not in muscle and surrounding subcutis. Conclusion. Hydralazine is a vasodilator which is capable of decreasing tumor IFP, reproducibly and with favorably long lasting dynamics.
Izvleček		Izhodišča. Tlak medcelične tekočine (TMT) predstavlja glavno oviro pri vnosu makromolekul v čvrste tumorje. Naš namen je, znižati diferencialno tumorski TMT glede na TMT v okoliškem tkivu, da bi povečali vnos makromolekul, tumorski krvni pretok in s tem eventuelno izboljšati tudi oskrbo tumorskega tkiva s kisikom. V tej uvodni študiji je bil kot vazoaktivator uporabljen hidralazin (vazodilator z dolgotrajnim učinkom). Materiali in metode. Meritve tlaka medcelične tekočine smo opravili s pomočjo igle s stenjem (angl. Wick-in-Needle - WIN technique) na miših tipa CBA s podkožno nasajenimi tumorji SAF. Skupno smo opravili enajst meritev na različnih živalih in v tumorjih različne velikosti. Rezultati. TMT v tumorjih po vbrizgu hidralazina je bil značilno nižji, od začetne vrednosti TMT v teh istih tumorjih. V povprečju je padla vrednost TMT za 33% glede na začetno vrednost, medtem, ko v normalnem-zdravem tkivu po vbrizgu hidralazina ni bilo zaznati sprememb tlaka. Pri kontrolni skupini miši, kjer smo namesto hidralazina vbrizgali fizioloko raztopino sprememb TMT v tumorju in mišici nismo zaznali. Rezultati naše uvodne študije vpliva hidralizina na TMT v SAF tumorskih modelih so ponovljivi in se ujemajo z rezultati predhodnih študij. Znižanje TMT je opazno le v tumorjih medtem, ko v mišici in okoliškem tkivu teh sprememb ni bilo. Zaključek. Rezultati potrjujejo, da je hidralazin vazodilator, ki značilno in za ustrezen čas zniža tlak medcelične tekočine v tumorjih.
Deskriptorji		SARCOMA, EXPERIMENTAL HYDRALAZINE EXTRACELLULAR SPACE MICE, INBRED CBA MANOMETRY