N. W. C. Dorsch

The Hydrogen Clearance Method in Assessment of Blood Flow in Cortex, White Matter and Deep Nuclei of Baboons

The technique of hydrogen clearance by an inhalation method is discussed. The electronic instrumentation necessary to secure stability and reproducibility from the recordings is described. Clearance rates in gray matter of about 80 ml/100 gm per minute in the cortex and putamen have been obtained, and of about 20 ml/100 gm per minute in white matter. Clearance curves have invariably been monoexponential in character in white matter, and in over half the cases in the putamen. In the remainder of the putamen curves and in 60% of the cortical clearance curves, the curves could be resolved into only two exponentials. Using bicompartmental analysis, the fast-clearing components of biexponential curves in both cortex and deep nuclei gave the same figures as clearance curves of an entirely monoexponential character from these two tissues. The importance of recirculation time, concentration of hydrogen inhalation, and verification of the tissue placement by subsequent dissection are discussed. The capacity of the method to detect sudden changes in flow during clearance is described.

A Study of Regional Autoregulation in the Cerebral Circulation to Increased Perfusion Pressure in Normocapnia and Hypercapnia

Catheterization of Labbés vein and of a pial branch of the middle cerebral artery has been performed on anesthetized baboons. Closure of the skull has enabled the reaction of the venous outflow from Labbés vein to be monitored in response to pressure step increases in the pial arterial pressure induced by gas compression of a perfusion mixture connected to the arterial line. Rapid changes in cerebrovascular resistance with swift emergence of regulatory constancy have been shown, and the time characteristics of the resistance changes strongly suggest that they are primarily myogenic in origin. Induction of hypercapnia did not interfere with this autoregulatory mechanism to increased perfusion pressure, which indeed appeared to be more effective at raised arterial PCO2, but the mechanism was abolished by the induction of ischemia from middle cerebral occlusion.

Local Cerebral Blood Flow and Vascular Reactivity in a Chronic Stable Stroke in Baboons

Blood flow in the hemispheres of baboons three years after middle cerebral artery occlusion has been assessed by the hydrogen clearance technique. Blood flow in the infarct itself varied from very low (8 ml/100 gm per minute) to very high (89 ml/100 gm per minute) values and, averaging the values for the infarct as a whole, it was impossible to distinguish average flows in the infarct from those of the normal hemisphere. Flow values in surrounding zones of the infarct remained significantly lower than those of comparable normal hemispheres, and, excluding the infarct, the mean average hemispheral blood flow was 35.2 ml/100 gm per minute. This indicates a significant reduction in flow in the cortex, subsequently shown histologically to be normal, compared with normal blood flow values for the baboon hemisphere. Autoregulation was lost in the infarct and impaired in surrounding tissue. CO2 reactivity was grossly reduced in the hemisphere as a whole but was present in all areas, even occasionally in electrode placements within the infarct itself. After perfusion fixation of the head, pathological study of the area of infarction showed a fairly consistent distribution, the infarct itself consisting of many dilated blood vessels of non-capillary nature scattered among fibrous tissue in what was virtually a glial scar.

Physiological Responses of Local Areas of the Cerebral Circulation in Experimental Primates Determined by the Method of Hydrogen Clearance

The reactivity of cortex, putamen and white matter to changes in arterial CO2 tension has been assessed. There was no significant difference between the CO2 reactivity obtained for the three tissues which were in the region of 2% to 3.5% increase over basal blood flow per mm Hg PCO2 increase. The data suggested a somewhat greater reactivity for white matter than for gray matter, though differences were not significant. Excellent autoregulation to altered perfusion pressure, induced either by hemorrhage or by raising the intracranial pressure with cisternal infusion, was found in gray matter of cortex and putamen and in white matter. With reduction of perfusion pressure by both techniques, it appeared that zero blood flow could be more readily induced in white matter than in gray matter. Autoregulatory curves to change in perfusion pressure obtained by either method seemed identical, suggesting that the mechanisms involved in the maintenance of cerebral blood flow in the face of reduced arterial pressure or rising intracranial pressure are the same. Hyperemia was observed in all three areas of the cerebral circulation examined following the restoration of perfusion pressure after a period of reduction. No significant differences in the degree of hyperemia induced by similar stimuli were observed in these three sites.

PRESSURE WAVES IN SO-CALLED LOW-PRESSURE HYDROCEPHALUS

Abstract Episodes of raised intracranial pressure were discovered in patients who were thought to have low-pressure hydrocephalus. Possibly these episodes identify patients in whom continuing deterioration may be expected, and the long-term measurement of intracranial pressure in such patients may be valuable in deciding which of them should have a ventriculo-atrial shunt operation.

The Production and Clinical Features of a Chronic Stroke Model in Experimental Primates

The characteristics of stroke in baboons produced by transcranial occlusion of the middle cerebral artery were studied by clinical examination and serial cinematographic studies, the animals being maintained for three years following the stroke. The characteristic deficit in all animals was an initial, fairly dense faciobrachial weakness with, in a few instances, some accompanying leg weakness for a few days, rapidly improving over the first few months. Some animals retained very evident arm weakness; most animals retained weakness of the face; the majority showed recovery of reaching and placing reactions and some movement in all joints ofthe upper limb, although fine movements of the fingers remained invariably impaired. Homonymous hemianopia, at least to attention, also appeared to be characteristic, but all of the animals recovered a normal gait and leaping was regained. The close correlation between this and human stroke appears to confirm that middle cerebral artery occlusion in the baboon is a reliable, repeatable and acceptable stroke model.

The Validity of Extradural Measurement of the Intracranial Pressure

The use of extradural methods of monitoring intracranial pressure (ICP) is based on the “coplanar principle” discussed by McKAY (1). Pressure within a hollow organ can be measured from outside its enclosing membrane provided the latter is not indented by the pressure sensor, i.e. the sensor is coplanar within the outer surface of the membrane. This eliminates the effect of changes in the tension of the membrane that accompany changes in intra-cavitary pressure. Forces due to such tension must act in the plane of the membrane (i.e. at any one point, at a tangent to it), while the force due to pressure inside the cavity can be taken to act along a radius from the centre of the cavity. These two forces are at right angles, and it is a well known law of physics that a vector quantity such as a force has zero component at a right angle to its line of action. In other words, the force due to membrane tension has no component along the line of action of intra-cavitary pressure, which should be the line of maximum sensitivity of the extradural transducer.

Lactic acid efflux from ischaemic brain: An experimental study

Abstract The lactate acid content of venous blood draining via Labbes vein from the lateral aspect of the two hemispheres of baboons has been compared. One hemisphere was rendered partially ischaemic by temporary occlusion of the middle cerebral artery and a significant increase in lactic acid content in the draining venous blood was found within 1 min of the occlusion. There was an accompanying significant fall in venous pH. The systemic arterial pH, pO 2 and lactate showed no significant change. It appears that the known prompt increase in cerebral lactic acid content following the establishment of ischaemia is reflected promptly in the lactate content in the draining veins of the infarct.