Biomedical subjects

S J Cringle

Publications and source records attributed to S J Cringle.

68 records · Page 4Linked to original sources

PubMed1989

Fluorescein angiographic findings in three patients with long-term intravitreal liquid silicone.

The long-term retinal effects of intravitreal liquid silicone (ILS) remain controversial. In this study fundus fluorescein angiographic findings in three patients with long-term ILS are presented. Sluggish or absent blood flow was observed in retinal arterioles that lay in close proximity to the ILS, and the arterioles themselves appeared narrowed. It is suggested that ILS may have a long-term effect on the retinal vasculature, owing either to direct vascular damage, secondary to damage to the neuroretina, or to the ILS preventing diffusion of oxygen into the vitreous cavity.

Adult↗

PubMed1989

Intraretinal and preretinal PO2 response to acutely raised intraocular pressure in cats.

The effect of acutely raised intraocular pressure (IOP) on retinal oxygenation has been determined using oxygen-sensitive microelectrodes preretinally and intraretinally. Anesthetized cats were ventilated alternately with one of two oxygen concentrations, 21 or 100%, while the IOP was manipulated via a hydrostatic pressure head connected to the anterior chamber. Preretinal and inner retinal oxygen tension remained stable over a broad range of IOP for air breathing. In contrast, the outer retina was severely affected, with the PO2 reducing as IOP was raised, resulting in some areas becoming anoxic. Outer retinal oxygen consumption was reduced for perfusion pressures less than 50 mmHg. It is postulated that under air-breathing conditions the preretinal and inner retinal oxygen tension was stabilized by the autoregulatory capacity of the retinal circulation. The inability of the choroidal circulation to autoregulate was reflected in the reduction of outer retinal oxygen tension with increasing IOP. With 100% oxygen breathing, increases in IOP caused a significant reduction in PO2 throughout the entire retina and preretinal vitreous. It is proposed that the effect of the autoregulatory capacity of the retinal circulation on retinal oxygenation is reduced in hyperoxia.

Animals↗

PubMed1989

Pharmacokinetics of intravitreal injection. Assessment of a gentamicin model by ocular dialysis.

Intravitreal drug administration is the treatment of choice for bacterial endophtalmitis, but improved knowledge of vitreal pharmacokinetics is essential for the development of optimal antibiotic regimes. We used our recently developed sampling device to estimate vitreal gentamicin concentrations for up to 30 hr after an intravitreal bolus injection of gentamicin. The device is based on the principle of dialysis, whereby a constant flow rate of dialysate through a loop of dialysis fiber in the vitreous attains a gentamicin concentration proportional to the intravitreal gentamicin level around the fiber. The dialysate is continuously recovered and the collected samples then assayed for gentamicin. Normal cat eyes and those with induced bacterial endophthalmitis formed the two groups tested. Concentration-time data fitted well to an open single compartment pharmacokinetic model that incorporated the processes of transfer of drug from the injection site to the sampling site (a function of diffusion within the vitreous), and the elimination from the sampling site (a function of elimination from the vitreous). The initial phase of transfer between the injection and sampling site was rapid and rates were comparable in the two groups. Elimination rate constants were uniformly greater in infected eyes than in controls (0.107 hr-1 compared to 0.055 hr-1). Aqueous humor gentamicin concentrations in control eyes varied between 3 and 6 times those found in fellow infected eyes at the end of each experiment. Accelerated elimination of gentamicin from the vitreous body of eyes with endophthalmitis may be explained by increased permeability of the blood-retinal barrier.

Animals↗

PubMed1988

Ocular dialysis. A new technique for in vivo intraocular pharmacokinetic measurements.

A new technique, using the principle of dialysis, enables continuous determination of the concentration of compounds within the vitreous humor of the eye. A semipermeable catheter inserted into the cat vitreous cavity was continuously perfused with a normal saline solution. Gentamicin concentration in the dialysate, after subconjunctival or intravitreal injection, was used to calculate gentamicin concentration in the vitreous from the catheter's recovery ratio, as calibrated in vitro. After subconjunctival injection, no gentamicin was detected in the vitreous for up to eight hours. From four to eight hours after intravitreal injection of approximately 100 micrograms of gentamicin sulfate, its vitreal concentration ranged from 30 to 80 mg/L and from nine to 16 hours it fell from 26 to 22 mg/L. This method may prove useful for the study of the pharmacokinetics of many drugs and metabolites in the eye.

Animals↗

PubMed1988

Choroidal blood flow measured in the dog eye in vivo and in vitro by local hydrogen clearance polarography: validation of a technique and response to raised intraocular pressure.

Local choroidal flow has been measured using hydrogen (H2) clearance polarography in dog eyes in vivo and in vitro. The accuracy and reproducibility of the method was checked in the eye in vitro by demonstrating a linear relationship between flow measurements obtained by an absolute method and those obtained by the H2 clearance technique. The H2 electrode was placed through a scleral window and its current response to a bolus injection of H2-saturated saline into a proximal artery was measured. The clearance of H2 from the choroidal circulation in vitro was monoexponential and the reproducibility of the measurements at the same site and in the same eye was good. In vivo the technique was used to measure alterations in local choroidal blood flow produced by acute changes of intraocular pressure. A linear relationship between perfusion pressure and choroidal blood flow was obtained. H2 clearance polarography is shown to be an accurate and reproducible method for determining choroidal flow, with the advantage that localized repeated measurements of flow can be made.

Animals↗

PubMed1988

A new method for oxygen supply to acute ischemic retina.

This paper introduces a new method for supplying oxygen directly to ischemic inner retina, using an oxygen source in the vitreous. Acute retinal vascular occlusion was created in cat eyes by direct pressure on the optic disk and its margins with a glass probe. The satisfactory occlusion of the retinal vessels was documented by direct observation, and functionally by recording the ERG. The vascular occlusion caused a large decrease in the size of the ERG b wave, with no change in the a wave amplitude. The oxygen source was a catheter made of strands of an oxygen-permeable membrane which was inserted into the vitreal cavity. After successful vascular occlusion was documented, 100% gaseous oxygen was perfused through the catheter while recording the ERG. In response to the perfused oxygen the b wave partially recovered. Ventilating the animal with 100% oxygen when the retinal vessels were occluded also caused recovery of the b wave amplitude. Termination of the vitreal oxygen source caused a decrease in b wave amplitude to the level previously observed after the occlusion of the retinal vessels. When the retinal circulation was restored by removal of the glass probe the b wave recovered. The results show that it is possible to supply adequate oxygen to the inner retina via the vitreous to replace the oxygen normally supplied by the retinal circulation. Modification of this method may be useful for the treatment of recent and incomplete retinal vascular occlusion.

Acute Disease↗

PubMed1988

An explanation of the "supernormal" b-wave in vitro.

The isolated arterially perfused eye preparation has proven to be comparable to the in vivo model in many respects. However, the existence of "supernormal" b-wave amplitudes in the perfused eyes has remained an unexplained functional difference between the two preparations. The term "supernormal" reflected the observation that at high perfusate flow rates the amplitude of the b-wave from the perfused eyes was frequently larger than that recorded in vivo under the same stimulus and adaptation conditions. Recent investigations in this laboratory have demonstrated that the position of the scleral electrode on the isolated eye greatly influences the amplitude of the b-wave obtained. The simple comparison of b-wave amplitudes in vivo and in vitro was therefore not appropriate, due to the different electrode locations used in the two situations. In addition, the relationship between perfusate flow rate and b-wave amplitude at a fixed location has been reinvestigated. In our perfusion system the b-wave amplitude has been shown to saturate at moderate flow rates (1.5 ml/min), considerably lower than those required to maximize the b-wave amplitude in earlier studies. This difference is due to the higher oxygen tension of our perfusate at the entry point to the eye. It is concluded that b-wave stability with increasing perfusate flow can be achieved in vitro, and that the apparently supernormal b-wave amplitudes observed under these conditions can be explained in terms of the different electrode environment in the in vivo and in vitro preparations. The implications of these findings with regard to autoregulation of the retinal circulation are discussed.

Electroretinography↗

PubMed1987

The effect of a retinal lesion on the distribution of B wave potentials on the sclera.

In the experiments presented here we have used the isolated perfused eye technique to investigate the distribution of ERG potentials on the sclera over local retinal lesions induced by xenon arc photocoagulation. Three lesioned dog eyes were examined. In two cases the lesion was allowed 28 days to stabilize, whilst in the third the experiment was performed two hours after treatment. Immediately after enucleation, the eyes were placed in a perfusion system capable of maintaining retinal function for many hours. The scleral ERG profile was then measured on the scleral surface over both treated and untreated areas of retina in the same eye. It was found that the ERG amplitudes were consistently lower over the treated areas of retina when compared to the untreated side of the same eye. More surprising was the discovery that the ERG distribution on the untreated side was significantly different to that observed in control eyes. In particular it was found that the limbal areas of sclera on the untreated side now had significant ERG amplitudes present, whereas the control eyes had close to zero amplitude in this region. It is concluded that the induced retinal lesions caused a widespread redistribution of ERG potentials around the entire surface of the globe. The potential applications of these results in the assessment of local retinal function is discussed. A schematic model is presented for the distribution of ERG potentials on the surface of control and lesioned eyes.

Animals↗

PubMed1987

The effect of regional retinal photocoagulation on vitreal oxygen tension.

PO2 measurements have been made for the first time within the retina and vitreous of cat eyes to compare normal and photocoagulated areas. This was done to test the hypothesis that the observed beneficial effects of pan-retinal photocoagulation therapy in the treatment of retinal vascular diseases with an ischemic origin, may be due to more oxygen becoming available to the remaining functioning retina. A xenon arc photocoagulator was used to photocoagulate large areas of cat retinas served by one major set of vessels while leaving the remaining retina untouched. After 6 months an acute experiment was performed in which retinal and vitreal oxygen tension profiles were measured using oxygen-sensitive microelectrodes to compare PO2 profiles in normal and photocoagulated regions, for two ventilation conditions: air and 100% O2. The only differences in PO2 values were found for the 100% O2 breathing condition, where values within the retina and in the overlying vitreous were larger in photocoagulated areas. It is proposed that any differences in PO2 distribution which occur for air breathing are masked by the autoregulatory capacity of the retinal circulation and the PO2 buffering capacity of hemoglobin.

Animals↗

PubMed1986

Effect of scleral recording location on ERG amplitude.

The isolated arterially perfused eye preparation has become a valuable tool in the investigation of ocular function. Normal retinal function can be maintained for several hours with the measurement of the gross electroretinogram (ERG) serving as a useful monitor of the electrophysiological condition of the preparation. This paper deals with the manner in which the amplitude of the ERG is affected by the electrode recording locations and describes the characteristic distribution of potentials on the surface of the isolated arterially perfused dog eye. The ERG is recorded between a fixed corneal contact lens electrode and a movable electrode on the uppermost surface of the sclera. The scleral electrode is moved in small increments parallel to the optic axis and lowered onto the uppermost surface of the sclera on a line from the corneal limbus to the optic nerve. The resulting ERG profile is characterised by minimal b-wave amplitude at the corneal limbus and little growth until a point 5 or 6 mm from the corneal limbus is reached, followed by a region of rapidly increasing amplitude up to a maximum at the point where the optic nerve exits from the globe. There follows a region of large but stable signal amplitude along the optic nerve. The ERG profile is largely unaffected by a reorientation of the globe about the optic axis, demonstrating that the potential distribution on the surface of the globe may be described in terms of points equidistant from the limbus being isopotential.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Vitreal oxygen tension gradients in the isolated perfused cat eye.

Pre-retinal partial pressure of oxygen (PO2) profiles have been measured for the first time in the isolated arterially perfused eye of the cat. The perfusate, fed to the eye under a constant pressure head, contained no haemoglobin or haemoglobin analogue so that the only source of oxygen was in the dissolved form. Maximum oxygen supply is provided by raising perfusate PO2 by equilibration with 100% O2. Periodic measurements of the DC corneal electroretinogram were used as a check on preparation viability. Using oxygen sensitive microelectrodes, oxygen tension profiles were measured in the vicinity of retinal vessels and also in vessel free areas, to determine the effect of the retinal circulation on the local oxygen environment of the vitreous. Results showed that large PO2 gradients exist near retinal arteries whereas more than 1mm away from the retina the PO2 gradient is very shallow. These results are in agreement with those obtained for the in vivo cat eye where the animal is breathed on 100% oxygen. Thus it can be concluded that the isolated perfused eye behaves similarly to the in vivo eye with respect to oxygen distribution and function.

Animals↗

PubMed1985

The effect of the retinal circulation on vitreal oxygen tension.

Detailed measurements have been made of the pre-retinal partial pressure of oxygen (PO2) in the cat eye to determine the effect of the local geometry of the retinal circulation on vitreal PO2 values. Measurements were made with oxygen sensitive microelectrodes for two ventilation conditions: air and 100% O2 breathing. PO2 gradients, which may extend as far as 800 micron from the internal limiting membrane, have been shown to exist in the vicinity of retinal arteries. Close to a retinal vein there is either a very shallow PO2 gradient or none at all. Coarse vitreal PO2 profiles which were measured out to the "mid vitreous" show that the gradients are very shallow to within 1 mm of the retina. The close agreement between "mid vitreous" PO2 and retinal venous PO2 implies that the retinal venous PO2 sets the PO2 value of the main bulk of the vitreous. Absolute PO2 values indicate that the retinal arterial walls offer easy diffusion for oxygen, and that at 100% O2 breathing almost all the oxygen offloaded from the retinal circulation is from dissolved oxygen. Alterations in the physiological condition of the eye such as those due to changes in the ventilation gas, blood pressure or intraocular pressure may cause relative movement between the microelectrode and the retina. This movement can lead to apparent changes in vitreal PO2 when it occurs in a region in which substantial PO2 gradients exist.

Air↗

PubMed1983

The retinal oxygen profile in cats.

This study records for the first time the retinal tissue oxygen partial pressure as a function of location within the retina of the domestic cat. Tissue pO2 was recorded with oxygen sensitive microelectrodes that use the polarographic principle. The mean vitreal pO2 close to the internal limiting membrane was 20.2 +/- 2.3 mmHg. The internal limiting membrane does not act as a diffusion barrier for oxygen. As the electrode was advanced into the inner retina, the tissue pO2 rose gradually to a value of 24.6 +/- 2.3 mmHg and then fell to a minimum of 12.0 +/- 5.5 mmHg before rising again to a value of 29.2 +/- 2.5 mmHg. Further insertion resulted in a sudden steep rise of tissue pO2 values to 72.0 +/- 5.1 mmHg, after which there was no further alteration in measured values. Although the exact location within the retina of the recording electrode was not known, it is probable that the tissue pO2 minimum occurs at about the level of the inner nuclear layer. Therefore, it is probable that the retinal avascular layers receive their oxygen supply primarily from the choroidal circulation in the cat.

Animals↗

PubMedDate not supplied

Diabetic retinopathy: early functional changes.

1. The present review reports some of the earliest physiological changes that occur in the diabetic retina prior to any clinical or anatomical changes in an animal model of diabetes. 2. Using chemically induced diabetes (by streptozotocin) in rats, retinal blood flow and vitreal and retinal oxygen tension were determined after 5 weeks of sustained hyperglycaemia. Blood flow was greater and was also redistributed in the diabetic group compared with values for the control group. At the same time, oxygen tension distribution was altered around retinal arterioles, implying an increase in retinal oxygen consumption in these early diabetic retinas. 3. The possibility that the blood flow changes could be due to altered control mechanisms in the retinal vasculature was confirmed using an isolated, perfused eye preparation. In diabetic eyes an altered reactivity to test pharmacological agents was demonstrated after 4 weeks of diabetes. 4. To further explore these vascular response changes we developed an isolated, perfused retinal arteriolar preparation in which individual segments of the vasculature can be tested. The possibility that insulin has a direct vasodilator effect on retinal arterioles was confirmed and was demonstrated to act via nitric oxide released from the vascular endothelial cells. These data may implicate the diabetic-induced insulin changes in early retinal changes. 5. Evidence is presented that although early glucose control may be vital in stopping the onset of diabetic retinopathy, there comes a stage in the induced diabetic cascade where if the retinopathy has commenced, good glucose control cannot stop the further progression of the retinopathy.

Animals↗