Enfoques teóricos de la transferencia monetaria condicionada

2.1 ISCHAEMIC MODEL

Introduction

The baboon model of focal ischaemia u sed in this study was adapted from that developed by Symon et al (1974; Symon, 1975). Models of focal ischaemia have certain advantages over other ischaemic models due to the large portion of the brain that is left intact. Having normal and ischaemic brain in the same animal eliminates the need for, and cost of, control studies and also reduces the effect of inter-animal variation. A further advantage of this model is the similarity of primate and human cerebral circulations, increasing the relevance of experimental results to the problems of the clinic. The large animal size provides other advantages including: ease and stability of anaesthesia over long periods, the availability of a large brain area for numerous electrode insertions, and the ability to draw a large number of blood samples without undue effect on blood v o l u m e .

Occlusion of the middle cerebral artery produces graded ischaemia across the cortex with the densest region in the sylvian opercula. Each animal responds d i f f erently to the MCAO due to variations in collateral circulation. In some animals, the cortical blood flow following MCAO may not fall to a level where major pathological events occur. Previous workers have aided the formation of dense ischaemia in such animals by a process of exsanguination. In this investigation however, such interference with the circu l a t i o n w ould have influenced the effects of haemodilution. To encourage a sufficiently dense area of ischaemia, additional o cclusion of the anterior cerebral artery was p e r f o r m e d in some of the animals. This was only necessary in smaller, younger animals which usually had better collateral circulation.

The animals used in the study were all male baboons (Papio anubis or Papio c y n o c e p h a l u s ).

Preparation

On the m o r ning of an experiment, fasted animals were sedated with an intramuscular dose of ketamine (7mg kg"\* Ketalar, Parke-Davis) and atropine sulphate (1.2pg k g ‘^; Antigen Pharmaceuticals). The head, chest, groin and calf were shaved and a V e n flon 2 catheter (Viggo) placed in the saphenous vein for administration of maintenance doses of sodium thiopentone

(5mg kg"^ IV; Intraval, May and Baker). Intubation and ventilation on pure oxygen using a Starling pump (20 strokes m i n “^; CF Palmer) was followed by a paral y s i n g dose of gallamine triethiodide (Img k g “^ hr"^ IV; Flaxedil, May and Baker) . The femoral arteries and veins of each leg were c a t h e t e r i s e d . One arterial catheter was connected to a blood sampling set, and the other to a pressure transducer (Bell and Howell) for continuous monitoring of blood pressure. The venous catheters were used for drug and drip infusion of saline (0.5ml min"\ Hartmanns, Baxter), and for later infusion of the h a e m o d i l u t e n t . The animals were permanently anaesthetised with an intravenous dose of a l p h a -chloralose (60mg kg"^; BDH Chemicals Ltd). External skin electrodes were arranged on the chest for EGG monitoring. Blood gases were m a intained in the normal range through repetitive arterial blood sampling, blood gas analysis (AVL Medical, Model 995) and subsequent adjustment of the ventilatory stroke volume. Body temperature was maintained using a electric heating blanket with feedback control from a rectal temperature probe. Blood glucose was monitored using glucosticks read by a glucometer (Ames).

The animals were positioned on their chests and the scalp and temporal muscle removed with monop o l a r diathermy. Four craniectomies of approximately 4cmf were made in the skull, three over the right hemisphere exposing the base of the operculum and sylvian fissure, the p o st-central region, and the parasaggital region. The other opening was over the left hemisphere. The dura was reflected and, following haemostasis, the brain was kept moist with patties and warmed

saline irrigation.

The recording electrodes for m o n i t o r i n g b l o o d flow, oxygen tension and direct cortical response were p l aced w i t h i n or on the cortex of the exposed brain (details in relevant electrode chapters). Positioning of up to ten elec t r o d e s in each area was achieved using an array of small electrode manipulators. After drawing a plan of the electrode positions, the electrodes were c emented in place u s i n g bone acrylic (Surgical Simplex, How M e d i c a ) .

When all the electrodes were in place, the animals were turned onto their backs and the contents of the right orbit were removed. Using a air drill and burr, the base of the orbit was drilled through and the d ura refle c t e d to expose the origin of the middle cerebral artery.

In a number of smaller animals, the p roximal anterior cerebral and common anterior cerebral arteries were also exposed. The vessels were dissected s u f f i ciently for later o c clusion with one or more Scoville Lewis clips (10x1mm, Downs Surgical).