Project G: Suspended Animation with H2S: in vitro observations

Department of Transplantation Medicine
Coordinators: H Leuvenink, H van Goor

Research type:
This basic research project will be performed with cell systems. Measurements will be performed in real time (membrane potential) and after collection of cells and cell culture medium. Biochemical techniques will be used.

Discipline:
Transplantation Medicine, translational medicine,

Background:
During an organ transplantation process several periods of ischemia occur. In the donor hypoperfusion of the organ is common especially in the Non-Heart-Beating donor. During the explantation phase and the cold preservation phase extended ischemia exists. In the implantation phase the last period of ischemia is followed by the reperfusion phase in which the accumulated injury during the preceding periods becomes obvious.

In order to reduce ischemic injury the metabolism of the organ can be reduced by reducing the temperature. This so called cold preservation has however limitations in terms of applicability and efficacy but more importantly inflicts additional injury to the graft to be.

With the use of a mitochondrial inhibitor the metabolism can be slowed down as well. Recently H2S was discovered as a natural inhibitor of a hibernative state in mice. This led us to the assumption that H2S could be useful in organ transplantation.

Pilot experiments in renal tubular cells showed protective effects of H2S against warm ischemic injury. In this project the effect of H2S under semi-warm conditions will be studied.

Research Question:
Can H2S protect cells against ischemia reperfusion injury?

Work plan:
In this project cell culture systems will be used.The impact of temperature, ischemia and duration of reperfusion will be studied on selected human cell types. The cells will be incubated with different dosages of H2S to protect against ischemia.