Forsøksdyr: Effects of newlt designed Albumin-derivfed perfluorodecalin-containing nanocapsules in the therapy of decompression induced gas embolisms in rats

Godkjenningsdato 20.03.2018

When exposed to a decrease in the surrounding pressure, gas in blood and tissue can come out of solution forming gas bubbles. These bubbles are known to increase the risk of decompression sickness (DCS). Since such bubbles can be detected and observed using ultrasound, it is consensus today that decompression induced vascular bubbles can be used as a measure of decompression stress and hence decompression safety. The more bubbles observed, the more stressful the pressure-exposure has been. We have previously documented adverse effects of these decompression induced bubbles on the vascular endothelium, the cerebral circulation and an overall better survival in animals with few or no bubbles compared with animals with many bubbles.

In the present experiment, we want to investigate the effect of using a newly designed Albumin-derived perfluorodecalin-containing nanocapsules (A-PFD-N) post-decompression on adverse effects of decompression. Perfluorcarbons (PFCs) have in general a high capacity for dissolving respiratory gases, and do also have the ability to dissolve nitrogen which makes it an obvious candidate for treatment of DCS.

We want to study the effect of A-PFD-N in both a hyper- and hypobaric setting, and hence we apply for a total of 85 rats that will be divided in six groups, where one of the groups will serve as control animals for both experimental settings to reduce the amount of animals. The animals will also dive two at a time, and with both small houses to play in and with wooden sticks to chew on while in the chamber. All to make the situation as little stressfull as possible for the animals.

Through a series of experiments, we will investigate the possible reduction of adverse effects of decompression by administrating perfluorcarbons following decompression in both a hyper- and hypobaric setting. In the present series of experiments, we will use rats in an established model of decompression research at our research group. The rats will undergo either a simulated dive where they will experience an increase in the surrounding pressure and a following decompression back to normal atmosphere. Or they will take part in a simulated flight, where the surrounding pressure will be reduced to simulate altitude, before they will be compressed back to normal atmospheric surroundings. It is in the decompression part of the experiment, that dissolved gas within the organism can come out of solution and form bubbles. These bubbles can be observed with the aid of ultrasound, and the amount of bubbles are linked to the risk of decompression sickness. The animals will be anaesthetised immediately following the simulated dive/flight, and we expect that if some of the rats do experience some discomfort due to the formation of vascular gas bubbles, the duration of discomfort will be very short.