Reactions of the retinal and cerebral microcirculation to ischaemia and hypoxia.
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Biomedical subjects
Publications and source records attributed to R W Russell.
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Blood viscosity, cerebral blood flow (CBF) and cerebral oxygen carriage (CBF X arterial oxygen content) were measured in 12 patients with polycythaemia secondary to hypoxic lung disease. CBF and cerebral oxygen carriage were both significantly higher than in a comparative group of 20 patients with raised packed cell volumes and normal lung function. The patients with secondary polycythaemia then underwent venesection and their mean packed cell volume fell from 0.613 to 0.495. This led to a consistent reduction in blood viscosity, which fell by 44% at a low shear rate (0.67/s) and 33% at a high shear rate (0.91/s). CBF rose by 21% (p less than 0.01), but cerebral oxygen carriage did not significantly increase in the group as a whole. Four of the patients with secondary polycythaemia had complained of episodes of confusion before venesection, which improved considerably once the packed cell volume had been lowered. Headache was relieved in a further two patients and none of the subjects was adversely affected by venesection. It was not possible, however, to show a correlation between symptomatic improvement and an increase in cerebral oxygen carriage.
In a study to assess the natural history of giant-cell arteritis, 90 patients with proved disease were followed up from the time of diagnosis. Early mortality was low and most commonly due to vertebral arteritis, but cerebral infarction did not appear to be a late complication. High maintenance dose steroids and visual loss were associated significantly with a shortened life span (p=0.0003 and p=0.0024). One-third of the patients developed chronic relapsing disease, but serious late complications were not encountered. After the initial attack has been controlled steroid dosage should be reduced to the minimum needed to alleviate symptoms.
Suppression of behavior accompanying increased ACh synthesis in the brain might account, at least in part, for the preferred use of lithium in antimanic therapy. Three experiments using rats as subjects were designed to test hypotheses about relationships among lithium, ACh synthesis and behavior. Experiment 1 established that hyporeactivity and greater exploratory behavior occurred in animals under LiCl treatment conditions shown to stimulate cholinergic activity in brain. Experiment 2 provided evidence of significant differences between controls and animals on the LiCl diet. Groups tested after 1 or 2 days of LiCl showed the decrease in reactivity to successive presentations of a loud auditory stimulus which characterizes the normal process of habituation. Groups tested after 5 or 10 days of liCl showed no evidence of habituation, their reactivity throughout the period of stimulation being at a level attained by the other groups when habituation reached its final asymptote. Experiment 3 established that effects of LiCl treatment were not manifested in all aspects of behavior: there was no evidence of impairment of motor activity or coordination; no analgesia; no impairment in sensory input nor in acquisition of new behaviors. The effect of the LiCl treatment was not complete inhibition but instead suppression of reactivity to environmental stimulation under conditions shown previously to increase cholinergic activity in brain.
Temperature and water uptake were reduced to a greater degree in ovariectomized female and normal male rats than in sham-operated female rats following an acute administration of 1 mg/kg of the anticholinesterase diisopropyl fluorophosphate (DFP). Ovariectomy also led to a significant reduction in the level of serum cholinesterase activity. These findings add further support for the hypothesis that the sex-dependent effects of DFP are due, at least in part, to sex differences in serum cholinesterase activity.
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The present experiments were designed to study behavioral effects of two chemicals, which have opposite influences on the cholinergic neurotransmitter system, and of their interaction. It has been proposed that deanol is a direct precursor of acetylcholine (ACh) in brain and may enhance cholinergic transmission, while hemicholinium-3 (HC-3) acts to decrease ACh synthesis. Rats served as subjects. Doses of the drugs were based on results of earlier experiments; all were injected cerebroventricularly. The six treatment groups were: saline only; HC-3 (10 micrograms); HC-3 (10 micrograms) + deanol (1 microgram); HC-3 (10 micrograms) + deanol (10 micrograms); deanol (1 microgram); and deanol (10 micrograms). Behaviors measured were: reactivity to visual and tactile stimuli; resistance to capture and handling, vocalization, muscular tension; reactivity to non-contingent aversive stimulation; and, shock-induced defence reaction. With the exception of the defence reaction, all behaviors showed significant effects between the various drug treatments: deanol had no significant effect on the behaviors; animals receiving HC-3 only clearly showed responses which were enhanced above the levels of any of the other treatment groups; deanol had a dose-dependent effect of suppressing HC-3 enhanced behavior. The present results are consistent with the generalization that decreased cholinergic activity is associated with hyper-reactivity, and increased cholinergic activity with hyporeactivity. They indicate that the behavioral effects of deanol are dependent upon the state of the cholinergic system, interacting in combination with HC-3 but not alone.
An easy, reliable, and specific ion-exchange method is presented for isolating glucose for specific radioactivity determinations from both blood plasma and buffered in vitro incubation media. The use of a glucose binding resin (borate-charged anion resin) combined speed of ion exchange with specificity of derivative formation. Glucose specific radioactivities, determined by ion exchange on protein-free filtrates of plasma containing [carbon-14] glucose, show excellent agreement with those from the popular glucose pentaacetate derivative method and are less variable. Carry-over of labeled acetate, propionate, lactate, glyoxylate, alanine, aspartate, or glutamate into the glucose fraction is less than .2%. Glycerol carryover is 1.2%. Glucose recovery is increased about three times that of the glucose pentaacetate derivative method and averaged 94% from plasma filtrates.
Patients with high-normal or above-normal haematocrit were found to have impaired alertness when compared with a control group matched for age and occupation. On retesting the controls had improved alertness scores attributable to a practice effect; but the patients, when retested after reduction of haematocrit by venesection, had improved significantly more than the controls. Improvement in alertness correlated very well with the increase in cerebral blood flow which followed venesection. Levels of venous haematocrit that are generally accepted as normal may not necessarily be optimum.
An inability to close the eyes voluntarily while at the same time retaining reflex blinking is described in three patients with Creutzfeldt-Jakob's disease. In one patient it is was an early symptom but in the others it formed part of a generalized spastic paralysis. By analogy with other reports it is deduced that in the case of a supranuclear palsy of this type the site of the lesion is probably in the cortical neurons rather than in the descending motor tracts.
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It has been suggested that blood viscosity is involved in the control of cerebral blood flow (CBF) (Thomas et al. 1977a, b, Humphrey et al. 1979). CBF, using the intravenous Xenon133 technique, blood viscosity and haematocrit were measured in 21 patients with elevated viscosity due to paraproteinaemia and found to be the same as in normal subjects. However, the paraproteinaemic patients were anaemic with a mean haematocrit of 0.342. This degree of anaemia would normally be associated with a high CBF. The paraproteinaemic patients were then compared with a group of 10 anaemic patients with matched haematocrits but without paraprotein bands. The whole blood and plasma viscosities were significantly higher in the paraproteinaemic patients and the CBF was significantly lower. The haematocrit, and therefore oxygen carriage, was similar in the two groups. It is likely that in the anaemia of paraproteinaemia the expected increase in CBF did not occur because of the limiting factor of increased viscosity. This suggests that in this instance viscosity rather than oxygen carriage is a major determinant in the control of CBF. This is further emphasized by the better correlation between CBF and blood viscosity than between CBF and haematocrit. It seems likely that viscosity and oxygen carriage are independent variables in the control of CBF.
The cerebral blood flow is low in primary polycythaemia, and it has been suggested that this is due to the increase in viscosity which accompanies the elevated haematocrit. In the present study cerebral blood flow has been measured by a non-invasive 133Xenon technique in six subjects with an elevated haematocrit secondary to a haemoglobin variant with increased oxygen affinity. Flow was significantly higher than normal and 81% higher than in 11 subjects of comparable age, matched for haematocrit and viscosity, but without the haemoglobin variant. In patients with this unusual type of polycythaemia, cerebral blood flow is high despite the elevated blood viscosity and the implications of these results are discussed.
243 measurements of cerebral blood flow by a noninvasive (133)Xe clearance technique have been made in 45 patients undergoing surgery for a recently ruptured cerebral aneurysm. Two groups of patients have been defined by the presence or absence of a postoperative rise in cerebral blood flow which showed a significant correlation with level of consciousness after operation.
Four Holstein steers fed 2.86 kg of corn and 3.50 kg of chopped alfalfa hay in 12 equal portions daily were used to determine effects of intravenously infused zeranol on glucose kinetics. In period I (1 wk), only carrier (9:1, propylene glycol:ethanol) was infused. Five [6-3H] glucose kinetic experiments were conducted on each of three steers, and three experiments were done on the fourth. In period II (2 wk), two steers were infused continuously with .9 mg zeranol daily via a vena cava catheter, and two were infused with 2.3 mg of zeranol. Six experiments were conducted per steer. In period III (2 wk), dosages were reversed for six more experiments. Period IV (2 wk) was a repeat of carrier infusion with three kinetic experiments per steer. Glucose kinetic averages for initial control, .9 mg zeranol, 2.3 mg zeranol, and final control were: irreversible loss (g/day), 1032, 1016, 992, and 1025; total entry rate (g/day), 2395, 2542, 2617, and 2438; recycling (g/day), 1362, 1558, 1625, and 1413; and pool size (g), 43.4, 45.4, 43.9, and 46.5. Combined control and treatment means were significantly different for total entry rate and recycling. Glucose irreversible loss is not affected by .9 or 2.3 mg of zeranol infused directly into the blood. Increases in total entry rate and recycling, however, suggest that zeranol may affect some aspects of glucose utilization and synthesis. Zeranol caused no changes in concentrations of blood glucose, growth hormone, insulin, or cortisol of plasma.
The role of pregastric esterase was investigated in four abomasally-cannulated calves during a sequence of ten 3-day periods beginning when calves were 2 to 5 days of age. Two calves were fed whole milk from nipple bottles to maximize exposure to pregastric esterases, and two other calves were given milk by infusion directly into the abomasum to minimize exposure. The initial system of feeding each calf was continued for eight periods after which treatments were reversed. Postfeeding lipolytic activity of samples of abomasal contents and of intragastric lipolysis of milk fat were markedly greater for orally-fed calves than for abomasally-fed. Systems of feeding effected no significant differences in a) digestibility of dry matter, fat, crude protein, and nitrogen-free extract, b) retention of nitrogen, and c) percentage weight gains. Digestibility of dry matter, crude protein, and nitrogen-free extract of milk and retention of nitrogen were greater in later periods than in initial. Although age of calves was a positive factor associated with utilization of milk, decreased exposure of milk to pregastric esterase and the resulting reduction of lipolysis in the abomasum did not effect a detectable lowering of milk utilization by calves in age groups studied.
This brief review of ocular pain arising from vascular structures attempts to summarize the principal clinical features under three main headings; migraine, arteritis, and aneurysm, with a short note of recent developments in each category.
Cerebral blood flow (CBF), red-cell mass, and plasma volume were measured in 39 patients with venous haematocrit values in the range 0.47--0.58. Patients with true polycythaemia were thus excluded. The 39 patients studied fell into two groups--those with a measured red-cell mass in the high-normal range and those with normal red-cell-mass values but reduced plasma-volume values (the relative-polycythaemia, low-plasma-volume group). The mean CBF was low in both the high-normal red-cell-mass (HNRCM) group (45.8 ml/100 g/min) and low-plasma-volume (LPV) group (48.8 ml/100 g/min). The haematocrit in the HNRCM group was 0.504 and in the LPV group 0.513. In a control group of subjects with a mean haematocrit of 0.421 CBF was 68.6 ml/100 g/min. Venesection was associated with a significant rise in CBF in both groups of patients--to 59.7 ml/100 g/min in the HNRCM group and 65.0 ml/100 g/min in the LPV group. Whole-blood viscosity fell significantly in both groups. Both groups demonstrated significant inverse relationships between CBF and haematocrit and between CBF and blood viscosity.