Cold activated thrombogenesis in elderly mice

Prosjektansvarlig
James Mercer
Avd. F. Medisinsk fysiologi, IMB, UiTø, 9037 Tromsø.
Telefon: 776 44869.
E-post: james.mercer@fagmed.uit.no

Finansiering:
Bevilgning fra SAT.

Bakgrunn/ Problemstillinger:
To find evidence to support that mild exposure to cold may be an adequate stimulus for promoting a state of hypercoagulability, especially in elderly mice. Studying elderly mice is of particular interest since it is becoming increasingly clear that P-selectin is essential for the progression of atherosclerosis. Through these experiments it is expected to find further evidence to support our hypothesis that mild exposure to cold may be an important factor in the aetiology surrounding increased cardiovascular mortality during the winter months in the elderly.

Prosjektets hovedmål:
To compare the effect of short term and long-term exposure to 2 different levels of cooling (10°C and 20°C) on blood levels of the adhesion molecule P-Selectin, plasma fibrinogen, interleukin-8 and the fibrinolytic substance PAI-1 in young and elderly mice.

Materiale og metode:
Exposure of mice at different ages and different ambient temperature (Ta) and for different lengths of time. Analysis of blood for plasma levels of the adhesion molecule. P-Selectin. 4 different protocols - two different levels of exposure (up to 1 week at Ta10°C and up to 3 weeks at 20°C) in both young adult males (8 weeks) and in elderly males (40 weeks). In all protocols the animals will first be subjected to a familiarisation period of 1 week in the climatic chambers at thermoneutral ambient (28 ºC) conditions.
Protocol 1 (8 week old animals): During the cold exposure experiments the ‘cold’ climatic chamber will be maintained at 10ºC. Animals will be sacrificed for blood sampling at the end of the 1 week ‘warm’ adaptation period (control animals, 28°C) as well as at the end of set periods of cold exposure (experimental group) (12 animals at each time period).
Protocol 2 (40 week old animals): Following the 1 week familiarization period in the ‘warm’ (28ºC) climatic chamber the animals will be transferred to the ‘cold’ chamber (10ºC) and maintained at that temperature for a period of 1 -7 days. Animals will be sacrificed for blood sampling after being exposed to this air temperature for respectively 1, 3, 5 and 7 days).
Protocol 3 (8 week old animals): Similar to protocols 1 and 2 except that the level of cold exposure will be milder (20°C) and the exposure period longer (3 weeks). Animals will be sacrificed for blood sampling after being exposed to this Ta for respectively 1, 3, 7, 14 and 21 days.
Protocol 4 (40 week old animals): Similar to protocol 3.

Foreløpige resultater:
Vi har kommet sent i gang med prosjektet på grunn av tekniske problemer med vårt klimakammer for mus som er et sentralt redskap i dette prosjektet. Det mekanisk verkstedet på Det medisinske fakultet ved UiTø har flere ganger prøvd å reparere klimakammeret uten hell. Dette har medført at vi i 2004 har gjennomført kun cirka en fjerdedel av de planlagte eksperimentene. Det mekanisk verkstedet måtte til slutt gi opp og har nå designet et nytt klimakammer. Materiell er kjøpt inn og bygningsarbeid er påbegynt. På grunn av underbemanning ved verkstedet har hele prosessen tatt lengre tid enn forventet. Inntil det nye kammeret er ferdig har vi ikke kunnet bestille mus. Vi har nå fått beskjed om at kammeret skal stå ferdig i mars 2005.

Samarbeidspartnere:
Pål Vegar Storeheier, Senter for aldersforskning i Tromsø