A porcine model for sequential assessments of cerebral haemodynamics and metabolism

Abstract

We present a physiologically stable porcine model designed for sequential assessments of pharmacological effects on mean hemispheric cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) at sustained normocapnia. The dynamic influence of continuously administered fentanyl (0.040 mg.kg-1.h-1 i.v.), nitrous oxide (70%) and pancuronium (0.30 mg.kg-1.h-1 i.v.) on these variables was studied in eight normoventilated pigs. CBF was reliably assessable at 10-min intervals by clearance of intra-arterially injected 133Xe, monitored by an extracranial scintillation detector. CMRO2 was calculated from CBF and the simultaneously measured cerebral arteriovenous difference in blood oxygen content. The intracerebral distribution of a contrast medium injected into the external and internal carotid arteries was studied by angiography, and the cerebral venous outflow was investigated by measurements of the distribution of an intra-arterially administered non-diffusible tracer, [99mTc]pertechnetate, to the internal and external jugular veins. After a 3-h equilibration period, CBF and CMRO2 were determined on six occasions over a study period lasting 1 h 40 min. The mean ranges of these variables were 56-60 and 1.9-2.0 ml.100 g-1.min-1, respectively. We conclude that the model enables repeated assessments of CBF and CMRO2 under stable physiological background conditions and thus valid cerebral pharmacodynamic investigations of drugs given for anaesthesia.

Racemic ketamine does not abolish cerebrovascular autoregulation in the pig

“…Our method of CBF determination following intraarterial injection of 133 Xe with extracranial scintillation detection has been validated earlier in this species and allows for frequently repeated measurements (8). By further reducing the amount of isotope injected on each measurement we were able to decrease the interval between measurements and thereby enhance the resolution in time for the pharmacodynamic response.…”

“…Surgical preparation has been reported in detail elsewhere (8). The right common carotid artery was cannulated with a 45-mm 20-G catheter for injection of the 133 Xe tracer substance (Mallinckrodt, UK).…”

Desflurane results in higher cerebral blood flow than sevoflurane or isoflurane at hypocapnia in pigs

“…Unless some artefact tainted the washout curve, only one injection of tracer was made at each measure point. The reliability of this model for repeated measurements of CBF with the xenon washout technique has previously been verified (5,6). Bipolar electroencephalographic (EEG) signals were recorded by two pairs of needle electrodes, inserted subcutaneously over frontal and occipital regions of the cerebral hemispheres, with a ground electrode inserted subcutaneously in the neck.…”

Statistical mapping of effects of middle cerebral artery occlusion (MCAO) on blood flow and oxygen consumption in porcine brain

“…However, the use of primate models for invasive research is now impossible in Denmark, and may be especially problematic in the field of stroke research: experimental animals could experience considerable neurological deficits, were they to survive the experimental procedure. The size of the young adult pig's body (40 kg) and brain (100 g), and the similarity of the pig's homeostatic mechanisms to those of humans, makes it a suitable experimental model for studies of human pathophysiology and cerebral hemodynamics (Akeson et al, 1992;Foreman et al, 1976). We have used living pigs for quantitative positron emission tomographic (PET) studies of CBF and CMRO 2 during acute ischemic stroke following MCAO Sakoh et al, 2000aSakoh et al, ,b, 2001.…”