Effects of dexmedetomidine on lung apoptosis in increased intra-abdominal pressure rats

VIII. SUMMARYEffects of Dexmedetomidine on Lung Apoptosis inIncreased Intra-abdominal Pressure RatsAn increase in intra-abdominal pressure in patients staying in intensivecare units is a common problem. A steady increase in the intra-abdominalpressure can lead to clinical tablo characterized with multiple organdysfunctions mainly in cardiovascular, respiratory and renal systems.Deksmedetomidine is a good alternative in intensive care since it doesn?tlead to respiratory depression and due to its sedative, anxiolitic and analgesiceffects. It has the minimal affect on the respiratory system, which makes itadvantageous to other analgesics which cause respiratory depression.In this study, it was aimed to investigate the effects of deksmedetomidineon pulmonary defects developing from the increase in the intra-abdominalpressure.With this goal in mind, after 32 adult Wistar Albino male rats wereanaesthetized by administering rata ?ksalazin/ketamin? combination with IMinjection, a 12-15 mmHg increase in intra-abdominal pressure wasaccomplished by using pressure cuff. Rats were left to spontaneous respirationfor two hours. After the two hours, rats were randomly divided into four groups.The first group underwent no process and used as control group. One cc 0.9 %NaCl bolus was intravenously administered to the second group and used asSF group. To the third group 0.2 μg/kg dexmedetomidine and the fourth group0.7 μg/kg dexmedetomidine were intravenously administered. After theintravenous injections, in order to observe the effects of the medicines, wewaited 30 minutes. After the organs to be worked on were removed from therats which were under deep anesthesia, the rats were sacrificed throughcervical dislocation.Lung tissues were fixed in 10 % formalin and they were underwentroutine paraffin protocols. Five micron sections were taken and they were usedfor both histochemical and immunohistochemical studies.For histochemical studies, sections were stained with direct hematoxylin-eosin in order to study the morphology of the tissues. Other cross sections were48stained with TUNEL method in order to determine apoptotic cells. Forimmunohistochemical studies, rests of the sections were stained with anti-caspase-3, anti-caspase-8, anti-caspase-9 and anti-Fas/FAsL antibodies usingindirect immunohistochemical techniques.As result of the comparison of the lung tissues of the groups stained withhematoxylin-eosin, it was seen that histological changes were less in the 0.2μg/kg dexmedetomidine group than in the other groups and that there were noatalectatic changes in the same group. PNL infiltration was higher in the 0.7μg/kg dexmedetomidine group than in the other groups, and interalveolarthickness was relatively higher too.In indirect immunohistochemical studies, in the 0.2 μg/kgdexmedetomidine group, especially immunoreactivity of caspase-8 andcaspase-3 were increased, however, caspase-3 immunoreactivity was less thancaspase-8 immunoreactivity. These result supported that when 0.2 μg/kgdexmedetomidine was administered; apoptosis, though delayed, started andextrinsic pathways was used through apoptotic pathways. After it wasdetermined that caspase 3 immunoreactivity is higher in the 0.7 μg/kgdexmedetomidine group than in the 0.2 μg/kg dexmedetomidine group, it wasconcluded that lower-dose-dexmedetomidine therapy delayed apoptosis in thelungs.49