Biomedical subjects

D Y Yu

Publications and source records attributed to D Y Yu.

At least 37 records · Page 2Linked to original sources

PubMed1994

Significance of Bruch's membrane in the creation of iatrogenic chorioretinal venous anastomosis.

Iatrogenic retinal to choroidal vein anastomoses, as a method of bypassing retinal venous occlusions has been reported in dogs in which Bruch's membrane is poorly formed. In order to determine whether chorioretinal venous anastomoses can be induced in an animal with a Bruch's membrane that is well developed as in humans, pigmented rats were chosen. A high intensity, small spot size argon green laser beam of 514 nm was used to induce the anastomosis. Three out of 5 rat eyes developed a retinal vein to choroidal vein anastomosis. The success rate of iatrogenic retinal to choroidal vein anastomoses in the rat was comparable to that obtained in the dog. This study suggests that Bruch's membrane was not significant in the creation of an iatrogenic chorioretinal venous anastomosis.

Anastomosis, Surgical↗

PubMed1994

Vasoactivity of intraluminal and extraluminal agonists in perfused retinal arteries.

PURPOSE: To evaluate the vasoactive response of isolated perfused arteries of the pig to K+ and adrenergic agonists and to compare the effects of intraluminal (IL) and extraluminal (EL) drug delivery. METHODS: A new microperfusion system was developed, in which short lengths of porcine retinal arteries (outer diameter 90.4 +/- 2.7 microns) were cannulated at both ends and perfused at a controlled rate (5 microliters/min) with outflow through a single side branch. The diameter of the vessel and the intraluminal pressure were monitored, and the effect of intraluminally and extraluminally applied agonists was determined. Endothelial cell function and the integrity of the blood retinal barrier was verified. RESULTS: Consistent vasoactive responses were obtained from most vessels. The resting diameter of the vessel was not greatly influenced by changes in flow rate or intraluminal pressure over the physiological range. Adrenaline and noradrenaline caused dose-dependent contractions, which were larger when applied intraluminally than they were when applied extraluminally. The largest contraction for adrenaline was 19.0% +/- 2.1% (n = 13) IL and 8.4% +/- 1.5% (n = 13) EL, and for noradrenaline, 17.8% +/- 1.9% (n = 13) IL and 6.8% +/- 1.1% (n = 13) EL. The IL contraction to 124-mM K+, 19.0% +/- 1.6% (n = 21), was also greater than that for EL application, 5.0% +/- 1.0% (n = 13). We found that the existence of myogenic contractions was restricted to the special case in which vessels with no branches were pressurized under zero flow conditions. CONCLUSIONS: Pig retinal arteries exhibited asymmetry in their responses to adrenergic agonists and K+, with contractions significantly larger when the drug was applied to the intraluminal surface rather than the extraluminal surface. This asymmetry may reflect an important property of retinal vessels. Microperfusion systems of this type may prove valuable in developing a better understanding of control mechanisms in retinal circulations.

Adrenergic alpha-Agonists↗

PubMed1994

Effects of extracellular pH on agonist-induced vascular tone of the cat ophthalmociliary artery.

PURPOSE: To test whether changes in extracellular pH (pHe) in an in vitro preparation of the cat ophthalmociliary artery affect passive tone and agonist responses and whether the endothelial cells are mediators of any pH-induced effect. This will determine the ability of the ophthalmociliary artery to influence retinal and choroidal blood flow in response to metabolic stimuli. METHODS: The isometric tension generated by isolated ring segments preactivated by prostaglandin F2 alpha (PGF2 alpha), noradrenaline (NA), or 40 mM K+ was measured as the pHe of the bathing solution was changed stepwise from 6.0 to 8.0 by adjusting the bathing bicarbonate concentration in preparations with and without functioning endothelial cells. RESULTS: PGF2 alpha produces a concentration-dependent contraction that is insensitive to an alkaline shift from control pHe (7.4) in the bathing medium. For acidic shifts to pHe 7.0, there is no significant change in the magnitude of the PGF2 alpha contraction, whereas at pHe 6.0, the PGF2 alpha contraction is reduced to 23 +/- 4% (n = 23) of its value at pHe 7.4. Threshold response concentration remains unaffected. Deliberate damage to the endothelial cells does not significantly affect the magnitude of the 10(-5) M PGF2 alpha response at pHe 7.4 nor the effect of acidic pH on this response. The 10(-5) M NA response is reduced in a graded fashion to acidic shifts to pH 7.0 and 6.0 (40 +/- 4% [n = 23]) and also to alkaline shift to pH 8.0 (22 +/- 5% [n = 23]) when compared to the induced tension at pHe 7.4. For the acidic shift only, endothelial cell damage causes a further significant reduction in the NA response to 20 +/- 3% (n = 5). For vessels contracted with K(+)-Krebs solution, there is a small but significant reduction in response at pHe 6.0 to 84 +/- 6% (n = 25), whereas for pHe 8.0 there is a much larger reduction to 45 +/- 5% (n = 24). All pHe-induced relaxations of K+ are endothelium independent. Passive tension is unaffected by all pHe manipulations. CONCLUSIONS: Vessel responses to vasoactive agents are selectively mediated by pHe changes. Major acidic shifts cause reduced responses (relaxation) to NA, PGF2 alpha, or K+, whereas only vessels preactivated with NA and K+ relax to alkaline shifts. This implies that NA or K+ induced vascular responses are maximal close to neutral pHe with major shifts from neutrality in either the acidic or alkaline direction causing a reduced response. These results imply that the ophthalmociliary artery probably does not play a major role in controlling ocular blood flow in response to pHe changes within the normal metabolic range, but it may become important in ischemic conditions.

Animals↗

PubMed1993

Oxygen reactivity of the feline isolated ophthalmociliary artery.

PURPOSE: The goal of this study was to investigate the modulating role of oxygen tension on noradrenaline (NA) and KCl responses in the ophthalmociliary artery and to ascertain whether these effects are mediated by the endothelial cells. METHODS: The isometric tension generated by myograph ring segments activated by NA or KCl was measured as the PO2 of the bathing solution was decreased in discrete steps from 506.1 +/- 16.0 mmHg to 29.4 +/- 1.4 mmHg in preparations with and without endothelial cells. RESULTS: Vessels pre-activated with K+ Krebs solution were insensitive to oxygen tensions between 506.1 +/- 16.0 mmHg and 124.6 +/- 4.2 mmHg. Lower PO2s caused a graded and increasing contraction that reached 176 +/- 12% of the contraction at the highest PO2. Vessels pre-activated with NA had a dichotomous response to reductions in oxygen tension: 44% of vessels showed a graded contraction, whereas a graded relaxation was observed for the remaining 56% of vessels as bath PO2 was reduced. In all cases, a functional endothelium was demonstrated. However, deliberate disruption of the endothelium caused all vessels pre-activated with NA to exhibit a consistent graded contraction for PO2s below 124.6 +/- 4.2 mmHg, similar to that observed for endothelial intact vessels pre-activated with K+ Krebs. The acetylcholine dose-response curve and passive tension were not affected by changes in oxygen tension. CONCLUSIONS: Endothelial cells modify the intrinsic smooth muscle response to a gradual reduction in PO2 by releasing relaxing and contracting factors, causing the observed dichotomous response in NA-activated vessels. However, the KCl-induced response is modulated only by low oxygen tensions.

Animals↗

PubMed1993

Retinal blood flow by hydrogen clearance polarography in the streptozotocin-induced diabetic rat.

PURPOSE: The authors compared retinal blood flow in rats after 5 weeks of streptozotocin (STZ)-induced diabetes with that in age-matched control animals. METHODS: The flow measurements were based on the hydrogen clearance technique and the intraocular placement microelectrodes at the surface of the retina. The hydrogen was delivered by bolus injection (100 microliters) of hydrogen-saturated saline into the ipsilateral carotid artery using a cannula through the lingual artery. The rats were anesthetized and artificially ventilated. Care was taken to match the systemic blood pressure and blood gases in the two groups. RESULTS: The mean retinal blood flow in the STZ group after 5-6 weeks duration of hyperglycemia was 487 +/- 59 ml/min/100g (standard error) compared with 330 +/- 16 ml/min/100 g in the age-matched controls. The variation in retinal blood flow was far more pronounced in the STZ group, even in different locations in the same eye. Changes in fundus appearance were also noted, with second-order arterioles being more apparent and the retina more "pinkish" in appearance in the STZ animals. CONCLUSIONS: The mean retinal blood flow in the region of retina studied in the two groups was significantly higher in the STZ animals than in age-matched controls. The increased heterogeneity of retinal blood flow may reflect a disruption to the normal blood flow control mechanisms in the retina after only 5 weeks of STZ-induced diabetes.

Animals↗

PubMed1992

Intravitreal and intraretinal oxygen tension in the rat eye.

We have successfully measured the intravitreal and intraretinal oxygen distribution in normal rats, during both normoxia and hyperoxia. The feasibility of such measurements in the very small rat eye has opened up the opportunity for the use of the many rat models of vascular disease in physiological experiments of retinal oxygen supply and consumption.

Animals↗

PubMed1992

Oxygen tension and blood flow in the retina of normal and diabetic rats.

The use of microelectrode techniques for studying oxygen distribution and blood flow in the eye of a physiologically well maintained rat provides a very convenient model in which to study oxygen supply to the retina. The availability of rat models of vascular disease such as diabetes and hypertension, and the existence of several models of retinal degeneration, make studies of oxygen supply in the rat eye of particular relevance. The experiments reported in this paper demonstrate changes in oxygen distribution and blood flow very early in STZ induced diabetes. Thus, we have established a preparation in which the role of changes in oxygen supply can be correlated with the pathological events that are apparent later in the disease.

Animals↗

PubMed1992

Pharmacological and mechanical heterogeneity of cat isolated ophthalmociliary artery.

The mechanical, histological and pharmacological properties of the isolated cat ophthalmociliary artery are reported and compared for passively stretched ring segments from three locations on the artery. Ring segments were mounted in a modified myograph system after the method of Hogestatt, Andersson and Edvinsson (1983, Acta Physiol Scand. 117, 49-61) and comparative length tension curves were measured. The most distal segment (DOA), nearest the eye, developed by far the smallest maximal tension compared to the middle segment (MOA) and the most proximal segment (POA), despite the fact that lumen diameters were similar. All segments displayed a phasic and tonic component in response to passive stretching and during activation with K(+)-Krebs. Cumulative contractile dose-response curves were measured for nine agonists: histamine (HIS), 5-hydroxytryptamine (5-HT), dopamine (DOPA), adrenaline (A), noradrenaline (NA), tyramine (TYR), phenylephrine (PHE), isoproterenol (ISOP) and xylazine (XYL) and the maximum active tension developed at a concentration of 10(-3) M was compared with that for 0.124 M K(+)-Krebs. The order of contraction magnitude in the three segments was: POA, HIS much greater than Kmax much greater than NA greater than A greater than DOPA greater than PH = TYR greater than 5-HT = ISOP greater than XYL; MOA, Kmax much greater than NA much greater than A = HIS much greater than DOPA greater than ISOP = PHE greater than TYR = 5-HT greater than XYL; DOA, Kmax much greater than NA greater than A greater than HIS = DOPA greater than ISOP greater than PHE = 5-HT greater than XYL = TYR. Pre-activation did not produce relaxation in response to histamine and isoproterenol. Testing with specific alpha 1 and beta antagonists supported the presence of alpha 1 receptors but not beta receptors. It is concluded that functional HIS, alpha 1 and 5-HT receptors are present and that the ophthalmociliary artery is heterogeneous in its response to HIS, with the POA segment producing the largest responses. The magnitude of the contractile responses to A and NA grew with increasing passive tension, whereas the response to histamine was independent of passive tension.

Adrenergic Agonists↗

PubMed1992

Relaxation effects of diltiazem, verapamil, and tolazoline on isolated cat ophthalmociliary artery.

This study investigates the ability of an alpha 1-adrenergic blocker, tolazoline, two Ca2+ entry channel blockers, verapamil and diltiazem, acetylcholine and Ca(2+)-free solutions to relax alpha 1-adrenergically activated cat ophthalmociliary artery ring segments. The form of a contraction elicited with adrenaline, noradrenaline or phenylephrine was shown to depend on the passive tension set. As passive tension was increased, which is equivalent to increasing blood pressure in vivo, the alpha 1-adrenergic elicited contraction became more sustained. Incubation with the Ca2+ channel blockers diltiazem and verapamil was ineffective in reducing the phasic response to the alpha 1-adrenergic agonists whereas addition of these blockers in increasing concentrations during a sustained adrenergic contraction caused a graded and significant relaxation. This implies that therapeutic use of Ca2+ channel blockers may act directly on the ophthalmociliary artery to inhibit the autonomic control of sustained tone in this vessel. Removal of exogenous Ca2+ from the bathing medium initially reduced the phasic component and eliminated the tonic component of the alpha 1-adrenergic contraction. Repeated exposure of the ring segment to Ca(2+)-free medium further reduced the phasic component elicited with alpha 1-adrenergic contraction. Pre-incubation with the alpha 1-adrenergic blocker Tolazoline reduced the alpha 1-adrenergic antagonist phasic response only at high concentrations (10(-4) M), whereas Tolazoline applied during the tonic phase was an effective relaxant at lower concentrations. Acetylcholine added to the bath during an alpha 1-adrenergic contraction induced relaxation at low concentrations and contraction for higher concentrations. The relaxation was eliminated by removal of the endothelial cell layer. These data support the notion that the phasic component of an alpha 1-adrenergic contraction is mainly dependent on intracellular Ca2+ stores whereas the tonic component relies almost exclusively on extracellular Ca2+. It is suggested that Ca2+ channel blockers and alpha 1-adrenergic antagonists may potentially play a role in relaxing the ophthalmociliary artery to improve the ocular circulation in vascular diseases in which there is considerable vascular tone present.

Animals↗

PubMed1992

Induced chorioretinal venous anastomosis in experimental retinal branch vein occlusion.

Iatrogenic retinal vein to choroidal vein anastomoses were created using laser photocoagulation in six of seven dog eyes in which a partial branch retinal vein occlusion had previously been created photochemically. A similar attempt to create an anastomosis was made in six control eyes in which no branch vein occlusion was present. In the eyes in which a branch retinal vein had been created, a venous chorioretinal anastomosis appeared to be present by 3 to 6 weeks. In three control eyes similar venous anastomosis was created; however this took 6 to 8 weeks to develop and was of much smaller calibre than the one that developed in the presence of a partial branch retinal vein occlusion. No adverse complications were noted in the period of the study (3 months). This study demonstrates that chorioretinal venous anastomoses can be created and may be of use in the treatment of partial retinal vein occlusions that show signs of progression.

Anastomosis, Surgical↗

PubMed1992

Comparison of hematologic parameters in normal and streptozotocin-induced diabetic rats.

Hematologic values are compared for normal and streptozotocin-induced diabetic rats after 6 weeks of induced diabetes. Most hematologic parameters were the same in the two groups except for blood glucose, glycated hemoglobin, and 2,3 diphosphoglycerate, all of which were elevated in the streptozotocin group. However the P50 (the PO2 at which the oxygen-carrying capacity of blood is 50% of maximal) remained normal. We hypothesize that a left shift in the oxyhemoglobin dissociation curve caused by the glycation of a small percentage of the hemoglobin is compensated by elevation in the 2,3-diphosphoglycerate which returns the P50 to normal values. This compensatory mechanism also occurs in some stages of human diabetes.

2,3-Diphosphoglycerate↗

PubMed1992

Agonist response of human isolated posterior ciliary artery.

The isometric responses of isolated human posterior ciliary artery to adrenergic agonists, histamine (HIS), and 5-hydroxytryptamine (5-HT) were studied in passively stretched ring segments mounted in a myograph bath. Cumulative dose response curves were measured for nine agonists: HIS, 5-HT, dopamine (DOPA), epinephrine (A), norepinephrine (NA), tyramine (TYR), phenylephrine (PHE), isoproterenol (ISOP), and xylazine (XYL), and the log(molar concentration) at which one half of the maximum active tension was developed (EC50) was estimated. The ring segments were unresponsive to DOPA and XYL; HIS and ISOP produced biphasic responses with a mild relaxation for low concentrations and small contractions for high concentrations of the agonist. The remaining agonists caused contractile responses of magnitude listed in the rank order following compared with the maximum active tension in response to 0.124 M K(+)-Krebs: Kmax much greater than A greater than 5-HT = PHE greater than NA greater than TYR It was concluded that functional HIS, alpha 1-adrenergic, and 5-HT receptors were present on human posterior ciliary artery but that there are no alpha 2-adrenergic receptors.

Adrenergic Agonists↗

PubMed1991

Intraretinal oxygen tension in the rat eye.

Oxygen-sensitive microelectrodes were used to measure the intraretinal oxygen distribution in the rat during both air and oxygen breathing. During air breathing the average PO2 profile obtained showed a value of 19 +/- 2.5 mmHg (n = 36) at the internal limiting membrane (ILM). As the penetration depth increased, a minimal PO2 of 8.2 +/- 2.4 mmHg was attained at 50% of the retinal depth, from which point the PO2 increased to a peak of 33 +/- 3.3 mmHg at 100% of the retinal depth at Bruch's membrane. During oxygen ventilation, all intraretinal oxygen tensions were increased and the profile became almost monotonic, increasing from 36.1 +/- 3.3 mmHg (n = 9) at the ILM to 134.3 +/- 6.7 mmHg at 100% of the retinal depth. These results are qualitatively similar to those found in the cat, and they demonstrate the importance of oxygen delivery by both the retinal and the choroidal circulation during normoxia, as well as the inability of vascular autoregulation to maintain a constant retinal PO2 during hyperoxic ventilation.

Animals↗

PubMed1991

Changes in vitreal oxygen tension distribution in the streptozotocin diabetic rat.

Measurements of vitreal oxygen tension have been made for the first time in the streptozotocin-induced diabetic rat eye. A total of 36 Sprague Dawley rats were divided into a control (n = 18) and streptozotocin injected group (n = 18), and after 5-6 weeks of established hyperglycaemia, an acute experiment was performed in which vitreal oxygen tension profiles were determined with oxygen sensitive microelectrodes. The control rats had significant oxygen tension gradients in the vitreous close to retinal arteries with relatively flat oxygen tension profiles close to retinal veins and intermediate regions. All control rats had a substantial arteriovenous oxygen tension difference when measurements were made on retinal arteries and veins. In contrast the oxygen tension profiles measured in the vitreous of streptozotocin rats showed markedly reduced oxygen gradients in the vicinity of retinal arteries and a smaller arteriovenous oxygen tension difference. In both groups of rats, for distances of 500 microns and greater from the retina (mid vitreous) a plateau oxygen tension value was observed. No significant difference was found in this mean mid vitreous value between the control rats and diabetic rats under the same systemic conditions. We conclude that there are significant changes in oxygen tension near retinal arteries in streptozotocin-induced diabetes before any histopathological changes are evident.

Animals↗

PubMed1991

Vitreal oxygen tension measurements in the rat eye.

Oxygen tension measurements are presented for the first time for the vitreous body of the rat eye. Oxygen-sensitive microelectrodes were used to measure vitreal PO2 profiles for two breathing conditions: 20 and 100% O2. Results show that for ventilation with 20% O2 most of the vitreous body has a constant PO2 (mid vitreous PO2 of 22.6 +/- 1.9 mmHg (+/- S.E.; n = 6), except for a layer about 200 microns thick at the retinal surface where significant PO2 gradients exist, especially in the region of retinal arteries. Midvitreous PO2 is similar to the PO2 at retinal veins. All vitreal PO2 values increase if ventilatory oxygen is raised to 100% O2. After equilibration, the main body of the vitreous again has an almost constant PO2, a factor of 3.75 +/- 0.40 (n = 10), higher than for 20% O2 ventilation except for a region about 400 microns thick adjacent to the internal limiting membrane where the local geometry of the retinal circulation dictates PO2 distribution. When the electrode was oriented to make contact with the retina at different distances from the optic disk, venous PO2 was observed to decrease in more peripheral locations. This work opens the possibility of investigating the role of hypoxia in rat models of retinal vascular disease.

Animals↗

PubMed1991

Measurement of blood flow in rat eyes by hydrogen clearance.

Intraocular measurements of blood flow have been made in the rat eye using hydrogen-clearance polarography. Hydrogen was delivered by a bolus injection of hydrogen-saturated saline via a cannula in the lingual artery of the anesthetized rat. An intraocularly placed hydrogen-sensitive microelectrode monitored the arrival and clearance of hydrogen preretinally adjacent to retinal arteries, veins, and intervascular areas. The effect of stepwise penetration through the retina and into the choroid was also determined, and a map of hydrogen distribution in the retina during hydrogen delivery and clearance was produced. Intraocular measurements, which have the advantage that the electrode location can be clearly visualized, together with computer control of the bolus injection and data collection, have allowed highly repeatable measurements of local blood flow to be made. The mean blood flow in retinal tissue was 373 +/- 51 ml.min-1.100 g-1 (values are means +/- SD, n = 32). The correlation between the nature of the hydrogen clearance curve and the location of the electrode helps explain data from other studies in which the position of the electrode with respect to the vasculature was unknown.

Animals↗

PubMed1990

The validity of hydrogen clearance measurements of retinal blood flow.

Simultaneous measurements of retinal and either choroidal or long posterior ciliary artery (LPCA) flow have been made in the isolated perfused dog eye by hydrogen clearance polarography. If measurement of retinal flow is made by an electrode placed preretinally within the vitreous, many of the assumptions required by the mathematical theory describing clearance measurements of flow are not satisfied. This paper investigates the extent to which contamination of the clearance curve by diffusion of H2 from the choroidal circulation, or inaccurate placement of the electrode at varying distances from the internal limiting membrane, affects estimates of flow. A non-equilibrium method of administrating H2 is used, as this allows higher flows to be measured than can be achieved by the equilibrium method, and also means that measurements can be repeated every 5 min. Measurement of flow with an electrode placed at the LPCA gave flow estimates which were larger than could be measured with an equilibrium method of clearance. LPCA flow was proportional to total ocular flow, as was choroidal flow. This technique may have potential use clinically for estimating uveal flow. The estimate of retinal flow was not significantly affected by H2 diffusing from the choroidal circulation, but was greatly reduced as the electrode was placed at increasing distances from the internal limiting membrane.

Animals↗

PubMed1990

In vitro characterization of the mechanical properties of canine ophthalmociliary artery.

The form and magnitude of K+ Krebs-induced contractures has been measured for the dog ophthalmociliary artery. Ring segments of the vessel were mounted in a myograph after the method of Hogestatt, Andersson and Edvinsson (1983, Acta Physiol. Scand. 117, 49-61). For low passive tensions the K(-)-induced contractures show both a phasic and tonic component, with the tonic tension component being the smaller. As passive tension is increased, the phasic component grows and plateaus whilst the tonic component continues to increase. For high passive tensions the phasic component disappears and the tonic component reduces in magnitude and the contracture is not fully reversible. Comparison of the length tension curves measured during K+ Krebs-induced contractures and Ca2(+)-free Krebs-induced relaxation shows that the active tension generated by this vessel increases with increasing passive tension until a peak active tension of 3.1 mN mm-1 is reached at an effective radius of 357 microns. For greater values of passive tension the active tension decreases. The calculated transmural pressure required to maintain the vessel at this optimal radius is 51.9 mmHg, which is very similar to the only available measurements of ophthalmic artery pressure, viz. 51.8 mmHg (Grunwald, Sinclair and Riva, 1981, Invest. Ophthalmol. Vis. Sci. 20, 564-6). The optimal passive stretch to apply to these ring segments for further pharmacological or physiological work is discussed.

Animals↗