Lindsay Symon

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.

The Distribution and Density of Reduced Cerebral Blood Flow Following Acute Middle Cerebral Artery Occlusion: An Experimental Study by the Technique of Hydrogen Clearance in Baboons

The effect of middle cerebral arterial occlusion on blood flow over the parietal aspect of the cortex and in the putamen of baboons has been assessed by the technique of hydrogen clearance. Reduction of blood flow was present over the entire lateral aspect of the cerebral hemisphere, maximal in the regions of frontal, parietal and temporal opercula where the blood flow was reduced to some 25% of control levels, and in the deep nuclei where the average flow in three animals was 20%. Reactivity to carbon dioxide was correspondingly reduced and, indeed, paradoxical reactivity or intracerebral steal was found in the most densely ischemic opercular zone. There was no evidence in the present studies of any area with increased tissue blood flow following middle cerebral occlusion. Under control conditions, some inhomogeneity of blood flow was evident in the cortical areas studied, the parietal association areas having a significantly lower blood flow than the more anterior regions of the hemisphere.

The effects of a calcium antagonist, nimodipine, upon physiological responses of the cerebral vasculature and its possible influence upon focal cerebral ischaemia.

The effects of a calcium antagonist, nimodipine, were tested on the response of the cerebral circulation to arterial pCO2 and blood pressure changes. The effects of reduced blood flow upon oedema formation and extracellular ion homeostasis under nimodipine preloading were studied. Both open and closed skull primate models were used, with alpha-chloralose anaesthesia. Nimodipine infusion increased basal blood flow in the open skull, but not the closed skull animals. Autoregulation to increased blood pressure was little affected. Responses to arterial pCO2 changes and autorerulation to reduced blood pressure were severely imparied. Residual blood flow after middle cerebral artery occlusion was significantly higher with nimodipine than in controls. The threshold levels of blood flow for the development of cortical oedema and for disturbance of ion homeostasis were, however, increased, suggesting that nimodipine interferes with cellular energy metabolism and increases the susceptibility of tissue to ischaemic damage.

Cerebral blood flow and edema following carotid occlusion in the gerbil.

A technique for measuring focal cerebral blood flow (CBF) and brain specific gravity (SG) in gerbils is described; CO2 reactivity and autoregulation were tested. The mean CBF was 29.5 ± 4.5 ml/100 gm/min and brain SG 1.0500 ±0.0004. Unilateral carotid occlusion resulted in a reduction of flow to 12.8 ± 5.8 ml/100 gm/min in the ipsilateral hemisphere with little change in the contralaterai hemisphere; there was also a decrease in brain SG. One hour after occlusion, brain edema, as judged by decreased SG, developed at CBF less than 20 ml/100 gm/min and reached maximal levels at 7 ± 2 ml/100 gm/min. The amount of edema appeared to be related chiefly to the residual post-occlusion flow. With bilateral occlusion, CBF was close to zero and there was no change in SG, indicating that in the “no flow” situation, there is no edema.

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.

Regional blood flow in the normal cerebral hemisphere.

Measurement of the rate of clearance of 133Xenon from the brain after injection of this radioisotope into the internal carotid artery has become an accepted method for estimating cerebral blood flow (H0edt-Rasmussen, 1965, 1967; Ingvar, Cronqvist, Ekberg, Risberg, and H0edt-Rasmussen, 1965). Resolution of the clearance curves into two components, fast and slow, may be carried out (H0edtRasmussen, 1965,1967; Ingvar etal., 1965; Wollman, Alexander, Cohen, Stephen, and Zeiger, 1965; Mallett and Veall, 1965). Many workers feel confident that in normal circumstances, at least, the fast component refers to the clearance of 133Xenon from the grey matter, and the slow component refers to its clearance from the white matter (Kety, 1965). If this hypothesis is correct, it means that from a single clearance curve obtained by a gamma-ray detector monitoring cerebral tissue one may ascertain: (1) the blood flow rate in the grey matter; (2) the blood flow rate in the white matter; (3) the relative weights of the perfused grey and white matter in the field of observation of the detector-for example, the cerebral tissue in a particular field of observation might consist of 56% grey matter and 44% white matter; (4) an average flow rate for the cerebral tissue in the field of observation, knowing the perfusion rates and the relative weights of the two component tissues; this is known as the weighted mean flow rate. Recently the gradient of the initial slope of the clearance curve when plotted logarithmically has been used as an index of flow (H0edt-Rasmussen, Skinkoj, Paulson, Ewald, Bjerrum, Fahrenkrug, and Lassen, 1967; Paulson, 1968) and its value as a rapid assessment of flow in the resting state, and during short-lived physiological test situations, has been stressed. In this report the clearance-of 133Xenon from the cerebral hemisphere after a single intracarotid injection has been observed by 16 regional detectors

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.

Surgical management of syringomyelia--current results

A retrospective study of the surgical results of 98 patients with syringomyelia was carried out. As primary surgical management, 38 cases were treated by craniovertebral decompression, 28 cases by craniovertebral decompression with syringotomy, and 22 cases in which Gardners operation was performed. Primary syringoperitoneal shunt was done on six patients and the other primary procedures were performed on four. As the secondary operation, syringostomy was performed on nine patients and syringoperitoneal shunt on seven. Better results were obtained in patients managed by craniovertebral decompression with syringotomy or Gardners operation. However, Gardners operation had a higher mortality rate and a higher incidence of complication. If a second operation was required, syringoperitoneal shunt had a higher rate of stabilization than syringostomy.

Are prostaglandins involved in experimental ischemic edema in gerbils

Sixty-five male gerbils, divided into 3 groups, were used in this study, in which focal brain specific gravity, taken as a measure of edema, was compared to the corresponding focal cerebral blood flow using the hydrogen washout technique. Extracranlal unilateral or bilateral carotid ligation was performed and one hour later toe animal was sacrificed. When focal blood flow was less than 20 ml/100 g/mln, edema developed and increased with progressive ischemia, reaching maximal values at 5-7 ml/100 g/mln. In the zero flow situation there was no edema. Pretreatment of the other 2 groups with indomethacin or dexamethasone, did not prevent edema formation at flows of 20-12 ml/100 g/min, but considerably reduced the edema previously noted at low flows (5-7 ml/100 g/min). The drugs did not affect the decreased flow in the iscbemic area. We conclude that prostaglandins, released by membrane disruption, are involved in the development of ischemic edema.