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Biomedical subjects

A Bill

Publications and source records attributed to A Bill.

At least 19 recordsLinked to original sources
PubMed1997

Glucose metabolism in pig outer retina in light and darkness.

Glucose metabolism in the outer retina of pigs was studied in the light and in the dark in pentobarbital anaesthetized pigs. Blood was collected from a vortex vein and an artery, and the arteriovenous concentration differences of lactate, glucose and oxygen were determined in light-adapted eyes. Local blood flows were simultaneously determined using the microsphere method. In a second group of experiments, the flow from a vortex vein and arteriovenous concentration differences were measured in both darkness and light. In light, the mean net lactate formation and oxygen and glucose consumption in the outer retina were about 0.137, 0.150 and0.115 mumol min-1, respectively. In eyes previously dark-adapted, constant light caused a 63% reduction in lactate formation, whilst oxygen and glucose consumptions were reduced by 40 and 44%, respectively. The results indicate that in both darkness and constant light, most of the glucose consumed by the outer retina is used in lactate formation, and that less than 20% is oxidized. Energy production through glycolysis and glucose oxidation is approx. 42% lower in constant light than in darkness.

Adaptation, Ocular↗
PubMed1997

Glucose metabolism of the inner retina in pigs in darkness and light.

In the pig eye, oxygen and glucose consumption in the outer retina are reduced in light compared to the consumption in the dark and most of the glucose consumed is metabolized to lactate both in light and in the dark. In the present study, in order to characterize the metabolism of glucose in the inner retina. Blood was collected from an artery and from a plexus on the optic nerve draining blood from the retina. Arteriovenous concentration differences for glucose, lactate and oxygen were determined. Observations were made in dark-adapted eyes and then after light adaptation. The consumption of oxygen and glucose and the lactate formation in the inner retina were calculated on the basis of these observations and recent data for retinal blood flow. In dark-adapted eyes, approx. 69% of the glucose was oxidized and approx. 20% was used in lactate formation. After 5-10 min of exposure to constant light, the levels of oxygen consumption and lactate formation were no different from those in darkness. The results indicate that lactate formation is a normal property of the pig inner retina, but that it is much less pronounced than in the outer part. The metabolism of the inner retina in constant light is similar to that in darkness. A comparison with data for the outer retina indicates that oxygen consumption in the inner retina in constant light is approx. 47% of that in the whole retina, while for glucose consumption and lactate production, the corresponding figures are approx. 12 and 8%, respectively.

Animals↗
PubMed1997

Effects of constant and flickering light on retinal metabolism in rabbits.

PURPOSE: To characterize the glucose metabolism in the rabbit retina. METHODS: An artery and a vortex vein were cannulated. Arteriovenous differences in oxygen, lactate and glucose concentrations, and blood flow were determined during either 1) darkness and light, or 2) light and 4 Hz flickering light. RESULTS: In darkness, oxygen consumption, glucose consumption, and lactate formation were 0.122 +/- 0.014, 0.204 +/- 0.015 and 0.160 +/- 0.023 micromol/min (mean +/- SE), respectively. Constant light reduced oxygen consumption insignificantly, and had no effect on glucose consumption. Hyperoxia did not affect the lactate formation. Flickering light increased the glucose consumption and lactate formation by 15-20%. CONCLUSIONS: In rabbits, 10% of the glucose consumed is oxidized, 40-50% is metabolized to lactate and the rest is used for other purposes. The glycolysis is primarily aerobic. Flickering light increases the glucose metabolism, constant light having little effect.

Adaptation, Ocular↗
PubMed1997

The role of nitric oxide in hyperaemic response to flicker in the retina and optic nerve in cats.

PURPOSE: To elucidate the role of nitric oxide (NO) in the eye and the flicker-induced vascular response. METHODS: The blood flow in the retina and different parts of the optic nerve was compared in cats treated with the NO-synthase blocker, N(G)-nitro-L-arginine methyl ester and in control animals. In both groups, one of the eyes was dark-adapted, the other was subjected to 8 Hz flickering light. The regional blood flow was measured with the microsphere method. RESULTS: In control animals, flickering light increased blood flow in the retina and optic nerve head by 39% and 256%, respectively. Pretreatment with N(G)-nitro-L-arginine methyl ester prevented this increase in retinal blood flow and markedly reduced the blood flow in the optic nerve heads. CONCLUSION: NO release may mediate much of the vasodilating effect of flicker in cats, and play a role in maintaining normal vascular tone in the optic nerve head.

Animals↗
PubMed1997

Glucose metabolism in cat outer retina. Effects of light and hyperoxia.

PURPOSE: To determine the roles of oxidation and glycolysis with aerobic and anaerobic lactate formation in the glucose metabolism of the cat outer retina in light and darkness. METHODS: Blood was collected from a choroidal vein and from an artery, and veno-arterial differences in lactate concentration (Lac(v-a) were determined at increasing light intensities. Blood also was sampled under conditions of darkness, light, and hyperoxia and were analyzed for oxygen, glucose, and lactate concentrations with or without blood flow determinations. RESULTS: When the dark-adapted eye was subjected to increasing light intensities, there was a reduction in the Lac(v-a), indicating reduced glycolysis in the outer part of the retina as the rods saturated. In darkness, the mean lactate formation per retina was 0.409 mumol/minute, oxygen consumption was 0.198 mumol/minute, and glucose consumption 0.236 mumol/minute. In light, the corresponding figures were 0.253, 0.166, and 0.123 mumol/minute. Hyperoxia reduced lactate formation and increased oxygen consumption in light and in darkness. CONCLUSIONS: Approximately 80% of the glucose consumed by the outer retina is used primarily in aerobic lactate formation. Because it is more efficient, oxidation of glucose still accounts for most of the energy production in light and in darkness. Light reduces oxidation as well as aerobic and anaerobic lactate formation.

Adaptation, Ocular↗
PubMed1996

An experimental model of cerebral microischemia in rabbits.

Multiinfarct dementia is the second most common form of dementia in the elderly. An animal model of microischemia may provide information about the pathophysiology relevant when searching for prevention or treatment of microinfarctions in humans. The purpose of the present study was to develop an experimental model useful for studying discrete microischemic foci. In order to achieve single cerebral microischemic foci plastic beads with diameters of about 100 microns were injected into the left heart ventricle of anesthetized rabbits. 2-Deoxy-[14C]glucose (2-DG) and autoradiography were used to detect regions with disturbed metabolism. The tissue sections were inspected for impacted beads. Foci with markedly increased 2-DG accumulation and with diameters of about 1 mm were detected in all parts of the brain, indicating hypoxic regions with enhanced glycolysis. In some foci, located mainly in the basal ganglia, a central dip in the 2-DG profile was seen, suggesting poor glucose supply to the central ischemic region. The ratio foci/beads was about 1 in the brain stem (diencephalon included) and about 0.5 in the cortex. Twenty-four hours after embolization, infarctions, mainly in the deeper brain regions, were seen. There were still foci with increased 2-DG uptake, which were mainly located in the cortex. The results suggest that microemboli reaching the deeper brain regions give rise to metabolic disturbances more often than emboli reaching the cortex and that the ischemic foci in deeper brain regions are more prone to develop further into infarctions.

Animals↗
PubMed1994

Platelet aggregation on the endothelium of Schlemm's canal.

By using monkey eyes and light microscopy, transmission electron microscopy and scanning electron microscopy we have studied the role of platelets in Schlemm's canal. In eyes connected to a reservoir and subjected to an elevated intraocular pressure, there was break-down of the cell membranes facing the invaginations into the endothelial cells, resulting in local protrusions from the invaginations and ruptures. Other unphysiological openings in the inner wall were due to separation of the intercellular junctions. Aggregates of platelets were observed at both these types of openings. Small aggregates were observed also in massaged eyes and in eyes which had not been touched before fixation. It seems likely that the intercellular junctions are fragile, tending to disrupt even under normal conditions and that platelets play a role in their repair. It is also suggested that platelets tend to restrict the size of the physiological pores.

Animals↗
PubMed1994

Effects of high intraocular pressure on the glucose metabolism in the retina and optic nerve in old atherosclerotic monkeys.

BACKGROUND: There are reasons to suspect that in patients with high intraocular pressure and glaucoma, there is underperfusion of the intraocular tissues and optic nerve head, leading to tissue hypoxia and neuronal damage. Studies in young, healthy monkeys have demonstrated that there is efficient autoregulation of the blood flow, and essentially normal glucose consumption, even at very high intraocular pressures that reduce the perfusion pressure to levels around 30 mm Hg. It seemed likely that the conditions might be different in old monkeys that had been on atherogenic diet for long periods of time and that such monkeys were a better model for glaucomatous patients. METHODS: The perfusion pressure in one eye was reduced to 30-35 mmHg in four old rhesus monkeys that had been on atherogenic diet for 12.5 years, and the glucose consumption in the eyes and optic nerves was studied with the 14C-2-deoxyglucose (2DG) method of Sokoloff et al. RESULTS: There was enhanced uptake of 2DG in the inner as well as outer parts of the retina and in the optic nerve head in all four monkeys studied, indicating compromised supply of oxygen resulting in anaerobic glycolysis. CONCLUSION: Old monkeys that have been on atherogenic diet seem more susceptible to elevation of the intraocular pressure than young, healthy monkeys, thereby suggesting defective autoregulation in them. Such differences in susceptibility may play a role also in the development of ischemic disorders of the optic nerve head and glaucomatous optic neuropathy.

Animals↗
PubMed1993

C-terminal calcitonin gene-related peptide fragments and vasopressin but not somatostatin-28 induce miosis in monkeys.

The miotic effects of C-terminal calcitonin gene-related peptide (CGRP) fragments, somatostatin-28 and vasopressin have been evaluated with special attention being paid to possible interactions with cholecystokinin (CCK)A receptors. The peptides were injected intracamerally to anesthetized monkeys pretreated with indomethacin and atropine. CGRP-(32-37) induced a miosis with a potency 1000 times lower than that previously found with sulphated CCK-8. Two other fragments, CGRP-(30-37) and CGRP-(31-37), also had miotic properties. The CGRP-(32-37)-induced miosis was antagonized by the CCKA receptor antagonist loxiglumide. No contractile effect was elicited by 67 pmol-7.4 nmol somatostatin-28. Vasopressin (360 pmol) caused a small reduction in pupil size. Loxiglumide pretreatment did not affect the reduction in pupil size but a vasopressin receptor antagonist partly inhibited the response. The results indicate that CGRP-(32-37) is a miotic with low potency but high efficacy in the monkey eye, probably interacting with CCKA receptors, and that vasopressin is a mitotic with low potency and efficacy, probably acting via vasopressin receptors.

Analysis of Variance↗
PubMed1993

Some aspects of aqueous humour drainage.

It is now 50 years since the discovery of the aqueous veins by Karl Ascher. His finding had a great impact on ophthalmology since it showed that the aqueous humour is not a stagnant fluid; there had to be a continuous formation of aqueous humour by the ciliary processes, flow from the posterior chamber into the anterior chamber and outflow in the chamber angle. Since that time it has become clear that there is also some drainage of aqueous humour via uveoscleral routes. Furthermore the flow through the inner wall of Schlemm's canal has been shown to take place through about 20,000 pores each with diameter of around 0.1-3 microns. Recent measurements of the pressures in the outflow routes indicate that in normal monkey eyes the main outflow resistance is located close to the inner wall of the canal. Most of the aqueous humour leaving Schlemm's canal via the collector channels mixes with blood within the sclera. This is a consequence of the embryology of Schlemm's canal; it develops by the merging of blind extensions from intrascleral veins. Despite its specialisation the endothelium of Schlemm's canal retains the properties of a blood vessel. Platelets are likely to play in role in the integrity of Schlemm's canal as they do in blood vessels and may in fact control the size of the pores by occluding pores larger than 3 microns. It seems likely that in vitro perfusion of glaucomatous eyes with enzymes may be useful in the search for new methods of treatment for glaucoma.

Aged↗
PubMed1993

Effects of NG-nitro-L-arginine methyl ester on the cardiovascular system of the anaesthetized rabbit and on the cardiovascular response to thyrotropin-releasing hormone.

1. The effects of 300 mg kg-1 of the nitric oxide (NO) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on the regional blood flow, on the flow response to 1 mg kg-1 of thyrotropin-releasing hormone (TRH) and on cerebral blood flow autoregulation were studied in urethane anesthetized rabbits subjected to unilateral sectioning of the cervical sympathetic claim. The blood flow measurements were performed by the tracer microspheres method. 2. The cerebral arteriovenous difference in oxygen saturation (CAVOD) was measured before and after the administration of L-NAME and TRH in order to ascertain whether the effects on cerebral blood flow that were observed were secondary to changes in cerebral metabolism. 3. L-NAME caused a significant decrease in blood flow in several cerebral regions; CBFtot decreased to 72 +/- 4% of control (P < 0.001). An increase in blood pressure and a concurrent decrease in heart rate and cardiac output were noted. 4. In the eye, L-NAME caused a reduction in uveal blood flow which was more pronounced on the sympathetically intact side; in the retina the blood flow decreased to 50% of control on both sides. 5. The administration of TRH in animals pretreated with L-NAME caused a significant increase in blood pressure and cerebral blood flow. 6. In L-NAME-treated animals the CBF was not affected when the mean arterial blood pressure was increased by ligation of the abdominal aorta. 7. The CAVOD increased from 56.0 +/- 5.2 to 73.6 +/- 3.5%, 20 min after the administration of L-NAME. In animals given 1 mg kg-1 TRH after L-NAME the CAVOD decreased to 54.6 +/- 4.6%, 5 min after the injection of TRH.8. The results of the present study indicate that endogenous NO is involved in the regulation of regional blood flow and blood pressure in the anaesthetized rabbit. The reduction in cerebral blood flow that was caused by L-NAME was not due to a reduction in cerebral metabolism. An interaction between the NO synthesis/release/effect and the sympathetic nervous system was found in the uvea. There was no evidence for a major involvement of NO in the cardiovascular responses to TRH and autoregulation of cerebral blood flow was not abolished by L-NAME.

Anesthesia↗
PubMed1993

Vascular effects of endothelin-1 in the cat; modification by indomethacin and L-NAME.

Intravenous infusion of endothelin-1 (ET-1) in the cat, 60 pmol x kg body wt-1 x min-1 for 5 min, induced an increase in mean arterial blood pressure (MAP) of 41.3 +/- 4.8 mmHg (n = 6; P < 0.001). Blood flow, as determined with radioactive microspheres, was reduced in many tissues. Reductions by 70-80% were observed in the choroid plexus, pineal and pituitary glands. Total cerebral blood flow was reduced by 18-23%. Pre-treatment with indomethacin or a combination of indomethacin and L-NAME caused vasoconstriction in many tissues and modified the responses to ET-1 in a variable way, suggesting that normally, ET-1 tends to release arachidonic acid metabolites and nitric oxide with great variations between different tissues. Intracerebroventricular infusion (i.c.v.) of ET-1, 10 pmol x kg body wt-1 x min-1, caused an increase in MAP of 79 +/- 11 mmHg (n = 6; P < 0.001). Regional blood flow in the medulla oblongata, medulla spinalis, choroid plexus, pineal and pituitary glands was reduced by 60-80%. Heart rate, cardiac output and coronary blood flow were significantly increased after 30 min i.c.v. infusion, indicating an activation of the heart, most probably as part of a central ischaemic response. Our results indicate that in many tissues the vasoconstrictive effect of ET-1 is influenced by indomethacin- and L-NAME-sensitive vasodilator mechanisms that are activated by the peptide. In the CNS, there may be marked effects on regional blood flow after i.c.v. infusion.

Animals↗
PubMed1992

Cholecystokinin contracts isolated human and monkey iris sphincters; a study with CCK receptor antagonists.

The contractile effects of cholecystokinin (CCK) on iris sphincter and ciliary muscles from monkey and human eyes were studied using an isolated smooth muscle bath. The ability of the CCKA receptor antagonists, lorglumide and loxiglumide, to inhibit CCK-8s-induced contraction was also examined. Various neuropeptides reported to be present in capsaicin-sensitive sensory neurons were also screened for contractile effect. CCK contracted isolated human and monkey iris sphincters at nM concentrations. Both antagonists caused a rightward shift of the dose-response curve for CCK-8s on the monkey iris sphincter. The ciliary muscle from both species failed to contract in response to CCK-8s. Of the eight other neuropeptides screened on the monkey iris sphincter, only [Arg8]vasopressin elicited a weak contraction when used in microM concentrations. These results indicate that the primate iridial sphincter muscle exhibits a high sensitivity to CCK, and that CCKA receptor antagonists effectively block the CCK-induced contraction.

Aged↗
PubMed1992

Aspects of the development of Schlemm's canal.

We have tried to answer the question of whether the endothelium of Schlemm's canal is derived from and retains properties of blood vessels by studying: (1) the development of Schlemm's canal in human fetal eyes; (2) the existence of Weibel-Palade bodies in human neonatal, adult human and adult monkey eyes; and (3) the presence of blood coagulation Factor VIII-related antigen in adult human and monkey eyes. (1) We observed that the intrascleral plexus of the limbal region extended deep into the sclera forming a deep scleral plexus by the 17th week of gestation. After 17 weeks gestation, extensions from the deep scleral plexus had reached the region of the future corneoscleral meshwork where the trabecular cells appeared oriented circumferentially. The blind endings of these extensions appeared to grow circumferentially in the supposed region of Schlemm's canal and at 27 weeks gestation they formed an incomplete Schlemm's canal. A complete Schlemm's canal was observed in some sections of the limbal region at 28 weeks gestation and at approximately 40 weeks gestation the canal was complete in most sections. (2) Weibel-Palade bodies were found in the endothelium of aqueous veins and in the inner and outer wall endothelium of Schlemm's canal. (3) Blood coagulation Factor VIII-related antigen was detected in the endothelium of the collector channels and Schlemm's canal, as well as in the blood vessels of the other parts of the eye. Our results indicate that the endothelium of Schlemm's canal is derived from a vascular origin and that even in the adult eye it retains some of the properties of a blood vessel.

Adult↗
PubMed1992

Pressures in the juxtacanalicular tissue and Schlemm's canal in monkeys.

A micropuncture technique involving the use of microcannulas with tip diameters less than 5 microns was used to measure the pressure in Schlemm's canal and in the meshwork at distances approximately 7 and 14 microns from the inner wall of Schlemm's canal. In one set of experiments where the spontaneous intraocular pressure (IOP) was 12.2 +/- 0.5 cmH2O and the Schlemm's canal pressure (PSc) was 7.6 +/- 0.7 cmH2O, the pressure at 7 microns from the inner wall of Schlemm's canal was found to be 8.9 +/- 0.7 cmH2O and at a distance of 14 microns, 11.0 +/- 0.5 cmH2O--that is, 1.3 +/- 0.2 and 3.4 +/- 0.3 cmH2O respectively, higher than the PSc. In another set of experiments, the spontaneous IOP and PSc were also measured and then the IOP was increased by means of an external reservoir and measured once again. Spontaneous IOP was 16.0 +/- 1.3 cmH2O and the PSc was 11.5 +/- 1.4 cmH2O before the IOP was increased. After the IOP was increased to 20.2 +/- 1.2 cmH2O, the PSc was 11.7 +/- 1.6 cmH2O. When the microcannula was introduced into the juxtacanalicular tissue to locations at about 7 and 14 microns from the inner wall of Schlemm's canal the pressure measured at 7 microns was 16.9 +/- 1.3 and at 14 microns it was 18.9 +/- 1.4 cmH2O--that is, 5.2 +/- 0.8 and 7.2 +/- 1.0 cmH2O respectively, higher than the PSc. The results indicate that at the spontaneous IOP about 75% of the resistance between the anterior chamber and Schlemm's canal is located within 14 microns from the canal with some 50% being located within the region 7 and 14 microns from the canal. After a small increase in IOP, the tissue causing most of the outflow resistance became relocated to a region within 7 microns from the canal.

Animals↗
PubMed1992

Ocular effects of endothelin-1 in the cat.

The effects of intravitreal and intracameral administration of endothelin-1 were studied in the anaesthetized cat. Intravitreal injection of 0.4 nmol endothelin-1 induced a 34 +/- 10% (n = 5; P less than 0.05) reduction in retinal blood flow in the experimental eye compared to the control eye 80 minutes after the injection. Blood flow in the ciliary body, iris and choroid remained unaffected by the injection of endothelin-1. Intracameral administration of endothelin-1 at pmol doses caused a reduction in pupil size, an increase in the aqueous humor protein concentration (indicating a break-down of the blood-aqueous barrier) and an increase in the concentration of prostaglandin E2 in the aqueous humor. The effect of endothelin-1 on pupil size was abolished by indomethacin pretreatment, indicating that this effect was mediated by arachidonic acid metabolites.

Animals↗
PubMed1992

[New aspects of surgical treatment of glaucoma. Comparison of viscoelastic substances in chamber angle surgery].

The development of new viscoelastic substances opens up new perspectives for chamber angle surgery under direct view. The success of "Cyclodialysis ab interno" treating children with glaucoma is often reduced by scar formation of the cleft. Therefore four different viscoelastic substances were instilled during an animal experimental study into the cleft and compared in their effect. We used hyaluronic acid with different molecular weight (Healon and Healon GV) and cross-linked forms of hyaluronan as a fluid and a gel (Hylan fluid and Hylan gel). A cyclodialysis ab interno was performed on 14 eyes of cynomolgus monkeys. The functional results (tonometry, outflow facility, autoradiography) and the morphological findings will be presented and their consequences for an extended indication of the cyclodialysis ab interno will be discussed.

Animals↗