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Biomedical subjects

N M Branston

Publications and source records attributed to N M Branston.

At least 37 records · Page 2Linked to original sources
PubMed1985

CBF and time thresholds for the formation of ischemic cerebral edema, and effect of reperfusion in baboons.

Ischemic cerebral edema has been studied in 41 baboons, with regional cerebral blood flow (CBF) determined by hydrogen clearance, and edema measured by microgravimetry. A threshold of ischemia has been identified for baboon cortex and subcortical white matter, which has to be crossed before edema formation begins. This threshold is 40.5% of normal CBF in cortex, and 34.4% of normal flow in subcortical white matter. A time threshold has also been determined, and the baboon brain can withstand 30 minutes of ischemia of the middle cerebral artery without significant edema formation. Reperfusion of ischemic brain has no effect on tissue water if the ischemic flow and time thresholds have not been crossed. Reperfusion of cortex, where water has begun to accumulate, exacerbates the water accumulation in proportion to the extent of the reperfusion. If these results are applicable to man, restoration of flow should not be attempted after an ischemic insult that reduces flow to less than 40% of normal unless it can be accomplished within 30 minutes of the insult. Provided CBF can be restored to above the 40% threshold within 30 minutes, reversal of the neurological deficit and prevention of ischemic edema can be expected.

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PubMed1984

Comparison of the effects of ischaemia on early components of the somatosensory evoked potential in brainstem, thalamus, and cerebral cortex.

In 14 ventilated, normocapnic baboons anaesthetised with alpha-chloralose, local CBF (hydrogen clearance) and the amplitude and latency of local components of the somatosensory evoked potential (SEP, median nerve stimulation) were measured bilaterally in ventrobasal thalamus (VPL), medial lemniscus (ML), and cerebral cortex before and during progressive ischaemia, produced by occlusion of the right middle cerebral artery and subsequent controlled reductions in mean systemic blood pressure (MSBP). The first significant reduction from control of the left cortical SEP amplitude occurred in the range of 30-40 mm Hg MSBP, but those of the VPL and ML responses only below 30 mm Hg; in the range of 20-30 mm Hg, the average SEP amplitudes in cortex, VPL, and ML were 8.6, 72.6, and 90.7% of control, respectively. In terms of local CBF, the cortical SEP threshold was in the range of 15-20 ml/100 g/min (as in previous work), that of VPL in the range of 10-15 ml/100 g/min, but the ML response was only markedly reduced below 10 ml/100 g/min. Thus, the differential ischaemic sensitivity of the SEP between the three regions was clearly demonstrated. These results indicate that as one descends the neuraxis, there is an increasing resistance of electrophysiological function to systemic hypotension, together with a decreasing threshold for local ischaemia.

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PubMed1984

An experimental study of acute subarachnoid haemorrhage in baboons: changes in cerebral blood volume, blood flow, electrical activity and water content.

Subarachnoid haemorrhage following transection of the posterior artery was produced in 10 baboons. Cerebral blood volume (CBV) decreased transiently after subarachnoid haemorrhage. Two basic patterns of intracranial pressure (ICP) were observed; in one ICP returned to normal but in the other it remained elevated. In this latter group four out of five animals showed an increase in CBV above the original level. There were delays in sensory conduction (measured using somatosensory evoked potentials) bilaterally; those on the contralateral side to the bleed were correlated with ICP whereas other factors are implicated on the ipsilateral side. Initial flow reduction and restoration of cerebral blood flow were both correlated with water content.

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PubMed1982

Calcium ions and calcium antagonists in 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 autoregulation to reduced blood pressure were severely impaired. 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.

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PubMed1982

Kinetics of resolution of transient increases in extracellular potassium activity: relationships to regional blood flow in primate cerebral cortex.

Previous studies have established that in cerebral cortex subjected to progressive reduction in blood flow, two distinct thresholds of flow may be identified below which cellular function is impaired: the cortical evoked response loses amplitude when local flow falls below 18ml/100gm/min, and below 11ml/100gm/min a major increase in extracellular K+ activity (Ke) occurs. However, further evidence suggests that even at higher flows the capacity of the tissue to handle induced ionic changes may be impaired. To investigate this point, we studied the kinetics of resolution of Ke following a transient increase produced by local electrical stimulation, in relation to the local pre-stimulus flow (reduced by acute middle cerebral artery occlusion) in baboons. Flow was measured by the hydrogen clearance method and Ke by ion-exchanger micro-electrodes, in the same cortical regions. In primary induced transients (those increases in Ke elicited by cortical stimulation, and reported previously,) Ke attained a maximum value of 8-10 mM and then decayed towards the 4-mM baseline. The half-time of this decay was significantly increased from normal in the flow range 20-40 ml/100 gm/min, and increased further at lower flows until, below 11ml/100gm/min, Ke clearance was undetectable. Thus, cortical ion homeostasis appeared impaired at flows substantially closer to normal than those thresholds mentioned above, a result discussed in terms of impairment of active Ke clearance mechanisms. Secondary induced transients arose during a primary induced transient, reaching considerably higher peak values (8-30 mM) of Ke (indicating temporary clearance loss) and with slower decay rate than the primary. Spontaneous transients, not associated with any stimulus, were also observed; like secondary transients, they occurred only at flows below 20ml/100gm/min and showed a reduction in clearance rate with progressive ischemia. They resemble spreading depression and their generation is discussed in terms of the ionic and metabolic conditions at their time of origin.

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PubMed1981

Changes in extracellular calcium activity in cerebral ischaemia.

Changes in extracellular ion activities were measured during partial ischaemia of the cerebral cortex of primates anaesthetized with alpha-chloralose. Triple-barrelled, double-ion-sensitive microelectrodes were used to measure the extracellular potassium (Kc) and calcium (Cac) activity at the same point simultaneously. The ion changes were related to local cerebral blood flow, and it was shown that at a blood flow of approximately 10 ml 100 g-1 min-1, there is a threshold below which ion homeostasis is disturbed. This is associated with a dramatic rise in Ke and fall in Cae. Cae falls from a normal value of 1.31 +/- 0.1 mM to approximately 0.28 mM in densely ischaemic tissue. In ischaemia, Ke reaches 13.4 +/- 3.8 mM before Cae begins to fall. The fall in Cae, although related to reduced blood flow, is closely associated with and follows the rise in Ke. The change in Cae is probably due to an increase in membrane permeability, as a result of either depolarisation or a critical lowering of cellular energy reserves.

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PubMed1978

Reversibility of ischaemically induced changes in extracellular potassium in primate cortex.

Following the massive increase in extracellular potassium activity that occurs in cerebral cortex when local blood flow falls below 8--11 ml/100 g/min, recovery of potassium toward normal levels might be expected when flow is restored. This study assessed the reversibility of such potassium increases, produced by middle cerebral artery occlusion in 13 baboons anaesthetised with alpha-chloralose, in relation to a wide range of ischaemic duration and density and post-occlusion flow. Potassium was measured with ion-exchanger microelectrodes and flow by hydrogen clearance. The artery was occluded for 136 +/- 63 min (mean +/- SD) and measurements were continued thereafter for 93 +/- 57 min without systemic hypertension. Upon reperfusion, partial or complete recovery (i.e., to within control confidence limits) of potassium was seen in all animals, but the rate of recovery varied widely and potassium clearance showed bi-compartmental characteristics in 7 animals. The fast component (or initial slope) rate constant was significantly correlated with post-occlusion flow and (inversely) with the duration of occlusion for which flow fell below the arbitrary threshold of 10 ml/100 g/min (the flow deficit). The slow component was unrelated to these quantities. Complete recovery was associated with a significantly higher post-occlusion flow, and smaller flow deficit, than was partial recovery. Secondary increases in potassium, associated with relatively high flow deficits and post-occlusion flows, were seen in 5 animals. These results are discussed in terms of factors that may determine potassium clearance and the possibility that elevated levels of potassium (demonstrated here to be prolonged well into the post-occlusion phase) might influence the evolution of a cortical infarct.

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PubMed1977

Extracellular potassium activity, evoked potential and tissue blood flow. Relationships during progressive ischaemia in baboon cerebral cortex.

Extracellular K+ activity (Ke), local tissue blood flow and the cortical evoked potential (EP) were measured concurrently in the cerebral cortex of baboons anaesthetised with a-chloralose. Flows were progressively reduced from normal by occlusion of the middle cerebral artery and controlled steps of exsanguination. Our data suggest that 3 stages may be identified in the disturbance of K+ homeostasis produced by progressive ischaemia. In the first stage, at flow levels similar to those sufficient to abolish the EP (12-16 ml/100 g/min), small, self-limiting increases in Ke occur, probably reflecting K+ efflux into the extracellular space (ECS) with partial impairment of K+ clearance from the ECS. The second stage occurs at distinctly lower (P less than 0.01) levels of flow (8-11 ml/100 g/min), and is characterized by a massive (30-80 mM) increase in Ke, which we attribute to an increase in ionic permeability of cell membranes with further impairment or overloading of K+ clearance mechanisms. In the third stage, at flows below about 6-8 ml/100 g/min, the data indicate an inverse relationship between flow and Ke with persisting high Ke levels, suggesting complete loss of K+ clearance. Transient increases of Ke also occur in the flow range 4-13 ml/100 g/min, the rate of recovery of Ke in their decay phase being positively corelated with flow (P less than 0.005).

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