Protective effects of CDP-choline on blood pressure and tissue injury in septic shock model


Thesis Type: Postgraduate

Institution Of The Thesis: Bursa Uludağ University, SAĞLIK BİLİMLERİ ENSTİTÜSÜ, Turkey

Approval Date: 2014

Thesis Language: Turkish

Student: Çiğdem Sevim

Abstract:

CDP-Cholin is a medication in nucleotide structure used in head traumas. It is a compound produced in the body endogenously. It has been demonstrated that it cures the hemodynamic parameters in different shock models and prevents tissue damage in rats. Mostly, the activation of the cholinergic system acts as intermediary in these effects of the CDP-Cholin. In our study we examined the effects of the CDP-Cholin on hypotension and inflammation which develops as based on shock in septic shock models which was not previously examined in any other study. The protective effects of the CDP-Cholin has also been examined. Sprague-Dawley male rats were used in the experiments. The artery (a. Carotis) and vein (v. Jugularis) cannulations were performed under Sevoflurane anesthesia (% 2,5-4). The septic shock table was formed with the cecal ligation-incision method. For this purpose, the cecums of the animals were taken out and cut as 0.75 mm in size with the help of a bistoury. Only cecal ligation was performed in the Sham group. After the operation, we waited for 10 minutes for stabilization, and then started the experimental monitorization. CDP-Cholin (100 mg/kg) or saline (1ml/kg) injection was performed intravenously in the 180th minute of the experiment. The animals were observed for 210 minutes after the injections, and then blood samples were taken (200 ul) for cytokine measurements. These were perfused under sevoflurane anesthesia, and the livers, kidneys and spleens were taken out for immune-histo-chemical examinations. The Cecal ligation-incision process decreased the blood pressure and increased the heart beat rate. The CDP-Cholin injected in the 180th minute (100 mg/kg; i.v.) quickly recovered the hypotension, and increased the blood pressure up to control levels in the first 60 minutes. The effect lasted for 3 hours. The medication did not affect the heart beat rate. The CDP-Cholin decreased the TNFα, IL-1b and IL-6 levels which had occurred before due to the septic shock, and prevented the damage in the lungs, liver and kidneys. The CDP-Cholin did not have a meaningful effect on the damage on the spleen tissue. The findings show that the CDP-Cholin applied intravenously to the septic shock models in rats regulates the blood pressure, decreases inflammation and prevents tissue damage. Key Words: CDP-Cholin, inflammation, septic shock, cytokine, multiple organ failure.