The technical difficulties of serial intravesical administration of drugs are a significant problem in preclinical studies of the effectiveness of local chemotherapy for superficial bladder cancer. The aim of the study was to develop and evaluate the effectiveness of the method of serial intravesical administration of drugs in the experiment. The study included 49 Wistar rats of both sexes. Five proposed methods of intravesical administration of drugs were investigated: retrograde catheterization of the urinary bladder under anesthesia, method of transcutaneous puncture of the urinary bladder in rats, intraoperative puncture of the bladder, method of subcutaneous fixation of the bladder for subsequent puncture in the experiment, method of serial intravesical administration of drugs in female rats using special catheter. The obtained data were processed using a package of statistical programs SPSS 20.0 for Windows. The disadvantage of the first technique is its trauma – each insertion of the catheter is accompanied by trauma of the urethral mucosa and associated pain. The manipulations were failed because of edema of the urethral mucosa. The manipulation should be performed under general anesthesia. The second technique also requires general anesthesia. The aggressive cytostatic action of Doxorubicin prevented the closure of the puncture hole and caused the development of complications. Sealing the bladder with a collagen plate when performing the third technique prevents the release of the drug into the abdominal cavity, however, the adhesion of the tissues of the surrounding organs to the plate promotes the formation of an adhesive conglomerate and makes further manipulations impossible. The withdrawal of the bladder from the abdominal cavity during the implementation of the fourth technique, theoretically, should have helped to avoid the complications observed during the third technique. However, insufficiently reliable fixation of the urinary and adhesions in the area of the implanted ring make this technique such that it does not correspond to the tasks set. The fifth method was the only one proposed that met all the assigned tasks. This technique made it possible to perform a series of 5 intravesical injections of Doxorubicin without general anesthesia and without the development of postoperative complications from the postoperative wound and abdominal cavity. The proposed method of serial intravesical administration of drugs in female rats using a special catheter makes it technically easy to perform serial intravesical administration of drugs without the use of general anesthesia and without the development of complications from the postoperative wound and abdominal cavity.

Along with a good antitumor effect, Doxorubicin has a systemic effect with damage to vital organs, in particular the heart. The lack of a unified approach to dosing and the frequency of administration of Doxorubicin in the experiment prompts the search for an optimal model of Doxorubicin cardiomyopathy. The aim of the study was to develop a method of serial administration of Doxorubicin in medium therapeutic doses in an experiment and to evaluate the cardiotoxic effect of the drug. 42 female Wistar rats were included in the study. The control group consisted of 7 intact rats. The experimental group consisted of 35 rats who received systemic chemotherapy with Doxorubicin at a dose of 5 mg/kg once a week for 5 weeks. On days 7th, 14th, 21st, 28th, 35th, the hearts of experimental animals were taken for morphological examination. Histomorphometrically determined: the diameter of cardiomyocytes (in the middle part) and the transverse diameter of their nucleus, the width of the interstitial space (endo- and perimysia). The data of histomorphological and histomorphometric examination of the myocardium testified that all animals of the experimental group had a circulatory disorder in the heart muscle at the level of hemomicrocirculation. Such changes led to cardiomyocyte hypotrophy, interstitial edema and fibrosis. During systemic chemotherapy, the animals showed marked changes in the myocardium, such as expansion of the endomysial zone, due to capillary congestion and edema, in comparison with animals of the intact group. At the end of the experiment, the animals of the experimental group retained the expansion of the endomysial zone, mainly due to interstitial fibrosis. Such changes indicate myocardial hypoxemia with damage and death of cardiomyocytes, activation of interstitial and replacement collagen formation. The obtained morphological data indicate the development of dilated cardiomyopathy in experimental animals. Serial intraperitoneal administration of Doxorubicin at a dose of 5 mg/kg once a week for 5 weeks causes morphological changes in the myocardium of experimental animals, similar to changes in the heart of people undergoing chemotherapy with this drug.

Along with a pronounced antitumor effect, Doxorubicin causes systemic effects with damage to vital organs, including the heart. It prompts the search for ways to prevent the cardiotoxic effect of the drug, one of which could be its intravesical administration. The aim of the study was to develop a method of serial intravesical administration of Doxorubicin in medium therapeutic doses in an experiment and to evaluate the cardiotoxic effect of the drug. 42 female Wistar rats were included in the study. The control group consisted of 7 intact rats. The experimental group consisted of 35 rats who received intravesical chemotherapy with Doxorubicin at a dose of 5 mg/kg once a week for 5 weeks. On days 7th, 14th, 21st, 28th, 35th the hearts of experimental animals were taken for morphological examination. Histomorphometrically determined: the diameter of cardiomyocytes (in the middle part) and the transverse diameter of their nucleus, the width of the interstitial space (endo- and perimysium). The data of histomorphological and histomorphometric examination of the myocardium testified that all animals of the experimental group had a circulatory disorder in the heart muscle at the level of hemomicrocirculation. Such changes led to cardiomyocyte hypotrophy, interstitial edema and fibrosis. During intravesical chemotherapy, the animals showed marked changes in the myocardium, such as expansion of the endomysial zone, due to capillary congestion and edema, in comparison with animals of the intact group. At the end of the experiment, the animals of the experimental group retained the expansion of the endomysial zone, mainly due to interstitial fibrosis. Such changes indicate myocardial hypoxemia with damage and death of cardiomyocytes, activation of interstitial and replacement collagen formation. The obtained morphological data partially indicate the development of dilated cardiomyopathy in experimental animals. However, these changes were less pronounced than the previously described changes that occur after systemic administration of the drug. Additional studies of the electrophysiological activity of the heart and biochemical markers will make it possible to fully assess the degree of cardiotoxicity of Doxorubicin after its intravesical administration. Thus, serial intravesical administration of Doxorubicin in moderate therapeutic doses according to the proposed method causes changes in the myocardium of experimental animals, which are partially similar to the changes in the heart of people receiving chemotherapy with this drug.

Кафедра променевої діагностики, променевої терапії та онкології (зав.-д.мед.н. О.Г. Костюк) Вінницького національного медичного університету імені М.І. Пирогова РЕГЕНЕРАЦІЯ УРОЕПІТЕЛІЯ СЕЧОВОГО МІХУРА ПІСЛЯ ВИДАЛЕННЯ СЛИЗОВОЇ ОБОЛОНКИ Резюме. У даній роботі наводяться дані особливості відновлення в динаміці уроепітелію слизової оболонки сечового міхура після її видалення. Показано, що регенерація уроепітелію починається з першої доби після видалення слизової оболонки. Більш виражене наповзання уроепітелія у вигляді клину відбувається на третю добу. На сьому добу спостерігали наявність повного покриття підслизової основи клітинами уроепітелію. Регенерація уроепітелію в подальшому протікає без ускладнень і негативних наслідків. Ключові слова: уроепітелій сечового міхура, регенерація.

Резюме. В роботі наводяться результати спостереження за 32 онкологічними хворими, у яких була клінічна необхідність проведення тривалої протипухлинної хіміотерапії. Показано, що за частого використання периферійних вен передпліччя відбуваються зміни в ендотелії, які призводять до зменшення діаметра їх просвіту, появи у місці пункції вен гематом з подальшим розвитком непрохідності. Постає необхідність створення альтернативного венозного доступу за потреби багаторазового внутрішньовенного введення хіміопрепаратів без значного пошкодження її стінки. Ключові слова: багаторазове внутрішньовенне введення хіміопрепаратів, наслідки.