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T Gherezghiher

Publications and source records attributed to T Gherezghiher.

At least 19 recordsLinked to original sources
PubMed1994

Ocular effects of alpha 2-adrenoceptor activation in anesthetized cats.

The present study was undertaken to determine the effects of direct administration of the selective alpha 2-adrenoceptor stimulant, B-HT 933, on choroidal blood flow, intraocular pressure and pupil size in anesthetized cats. Anterior segment choroidal blood flow was measured using laser-Doppler flowmetry. B-HT 933 administered by intra-arterial, topical and intracameral routes produced a significant depression of ocular blood flow which was largely abolished by pretreatment with rauwolscine. B-HT 933 did not lower IOP in any of these preparations. The largest doses of B-HT 933 caused a modest mydriasis when given intracamerally. However, this pupillary dilation was not blocked by rauwolscine. These results demonstrate that alpha 2-adrenoceptor activation can produce pronounced depression of anterior segment choroidal blood flow but does not cause a concomitant lowering of IOP or mydriasis in anesthetized cats.

Adrenergic alpha-Agonists↗
PubMed1993

Adrenoceptor subtypes involved in neurally evoked sympathetic vasoconstriction in the anterior choroid of cats.

Electrical stimulation of the preganglionic cervical sympathetic nerve produced ocular vasoconstrictor responses as measured from the anterior choroid of anesthetized cats using laser-Doppler flowmetry. Ipsilateral nictitating membrane contractions were simultaneously measured as an established index of neural sympathetic activation. The frequency-response relationships for both effectors were nearly linear from 0.125-32 Hz. When elicited at 2-min intervals, submaximal evoked responses of both systems were stable for more than 1 hr. Ocular vasoconstrictor and nictitating membrane responses were blocked in a dose-dependent fashion by intravenous treatment with the non-selective alpha-adrenoceptor antagonist phentolamine (0.1-3.0 mg kg-1) and with phenoxybenzamine (3.0 mg kg-1) as well as with the selective alpha 1-adrenoceptor antagonist, prazosin (10-300 micrograms kg-1). In contrast, neither evoked response was antagonized by alpha 2-adrenoceptor blocker, yohimbine (10-300 micrograms kg-1), nor with rauwolscine (500 micrograms kg-1). No significant alteration in magnitude of ocular vasoconstriction was seen with blockade of either muscarinic (atropine, 1 mg kg-1) or beta-adrenergic (propranolol, 1 mg kg-1) receptors. These results demonstrate the usefulness of laser-Doppler flowmetry in studies of the choroidal circulation and suggest that, as previously established for the nictitating membrane, adrenergic neurogenic vasoconstriction in the anterior segment of the eye is mediated almost exclusively by alpha 1-adrenoceptor mechanisms.

Animals↗
PubMed1993

Ocular effects of topical administration of the phosphodiesterase III inhibitor milrinone in rabbits and cats.

Increases in intracellular cAMP levels have previously been shown to decrease intraocular pressure (IOP) and increase ocular blood flow (OBF). However, the ocular effects of milrinone, which increases intracellular cAMP levels via selective cAMP PDE III inhibition, have not been investigated. The purpose of this study was to investigate the ocular effects of topically administered milrinone at different concentrations in rabbits and cats. When compared to vehicle in conscious rabbits, topical administration of milrinone at 0.03% decreased IOP (-14.1 +/- 2.6% vs. -7.4 +/- 3.7%, max. changes expressed as mean +/- SEM), at 0.1% increased IOP (10.4 +/- 8.5% vs. -1.7 +/- 4.1%), and at 0.01% and 1% did not significantly affect IOP. Neither pupil size nor central corneal thickness were affected by milrinone. Additionally, there were no signs of inflammation and no effects on corneal clarity. In anesthetized cats, topical administration of milrinone at 0.01-0.3% increased OBF (38.9 +/- 6.0% for milrinone vs. -7.4 +/- 4.4% for vehicle), and at 0.03%-0.3% decreased mean arterial pressure (-19.0 +/- 5.6 vs. 3.0 +/- 4.1 mmHg) in a dose-related manner. The durations of OBF enhancement (1.5-2.5 h) and MAP reduction (less than 30 min to 2 h) were also dose-dependent. In conclusion, milrinone induced biphasic IOP effects: IOP was decreased at 0.03% but increased at 0.1%. Milrinone at 0.01% increased OBF, possibly via a local vasodilator effect, and at 0.03-0.3% increased OBF, possibly via local and systemic effects. These data suggest that cAMP PDE III inhibitors such as milrinone may have efficacy as agents which enhance ocular blood flow following topical ocular application.

Administration, Topical↗
PubMed1991

Choroidal and ciliary body blood flow analysis: application of laser Doppler flowmetry in experimental animals.

Laser Doppler flowmetry (LDF) measures the flux of red blood cells in a vascular network embedded in tissue. In the present report, choroidal and ciliary body blood flow was measured continuously using an LDF technique in pentobarbital anesthetized cats. Blood flow measurements were made from the choroid beneath the lateral and superior rectus muscles and from the surface above the ciliary body 2-3 mm posterior to the limbus. In some experiments, the sympathetic nerve to the eye was stimulated; in others, intraocular pressure (IOP) was monitored manometrically with a controlled saline infusion delivered into the anterior chamber to gradually elevate IOP. Norepinephrine (NE) and methacholine (MC) also were tested for their effects on choroidal blood flow when given intravenously and intra-arterially. Transient bilateral carotid artery occlusions produced a significant drop in blood flow, but flow did not decrease to zero probably due to collateral contribution of the vertebral circulation. Sympathetic nerve stimulation produced a frequency-dependent decrease in both choroidal and ciliary body blood flow with the latter exhibiting a lower threshold and a greater magnitude of effect. Gradual elevation of IOP produced a proportional decrease in choroidal blood flow. The level of intraocular pressure required to decrease blood flow was dependent on the existing ocular perfusion pressure. Both intravenous and intra-arterially administered NE produced dose-dependent decreases of choroidal blood flow despite graded increases of systemic arterial blood pressure. In contrast, MC produced dose-dependent increases of choroidal blood flow in conjunction with graded decreases of systemic blood pressure. The results of the present report demonstrate the validity of the LDF technique for performing continuous reading of blood flow changes in the choroid and ciliary body of experimental animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Parasympathetic nervous control of intraocular pressure.

Electrical or chemical activation of the oculomotor nucleus (ONC) was performed in pentobarbital anesthetized cats to determine the role of parasympathetic nervous input to the eye in modulating intraocular pressure (IOP). In all animals, the vagosympathetic nerve trunks were sectioned bilaterally at the mid-cervical level. Intracranial stimulation of the ONC produced miosis and a bilateral sustained rise in IOP with little or no cardiovascular response. During stimulation, IOP increased by approximately 35-40%, with an additional small rise seen when the current was turned off. The secondary rise in IOP probably represents the actual pressure level reached which was otherwise masked by intense accommodation due to stimulation. The rise in IOP was not antagonized with gallamine triethiodide. However, both IOP and pupillary responses were blocked by either hexamethonium (1.5 mg kg-1, i.v.) or atropine (0.5 mg kg-1, i.v.). These results provide evidence for a neural parasympathetic mechanism for increasing IOP in cats. In another group, activation of ONC following electrolytic lesion of the preganglionic parasympathetic nerve to one eye, produced a rise in IOP and miosis only on the side with intact oculomotor nerve indicating that the rise in IOP is in part mediated by nerve fibers that travel to the eye along the oculomotor nerve trunk. Microinjection of L-glutamate (2.5 x 10(-7) M) into the ONC produced a bilateral rise in IOP that lasted for more than 15 min. This increase in IOP was greater than 50% of control levels and was accompanied with miosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Ocular effects of dipivalyl esters of epinephrine and alpha-methylepinephrine.

The intraocular pressure (IOP) and pupillary effects of dipivalyl esters of epinephrine and alpha-methylepinephrine were compared after topical application in conscious rabbits. Both dipivalyl-alpha-methylepinephrine (DP alpha meE) and dipivalylepinephrine (DPE) produced a dose-dependent pupillary dilation (PD) and decrease in IOP. The onset of PD was approximately 30 min for both agents and reached maximal plateau within 1 and 2 hr for DPE and DP alpha meE, respectively. Duration of mydriatic effect was also dose-related, although more prolonged with DP alpha meE. This probably reflects differences in rate of inactivation of these compounds. The onset of IOP lowering effect of DP alpha meE was more rapid (35-45 min) when compared with DPE (1.5-2 hr) which may be due to the initial ocular hypertensive response seen with DPE. The initial rise in IOP was prevented by transection of three rectus muscles. DP alpha meE produced initial ocular hypertension only at the highest doses. The decrease of IOP lasted more than 6 hr for both drugs, returning to normal by 24 hr. No pupillary or IOP effects were seen in the contralateral eye. Denervation supersensitivity to both the pupillary and IOP responses to DP alpha meE was seen after superior cervical ganglionectomy. These findings are consistent with the hypothesis that the pupillary and IOP responses to DP alpha meE do not require intact adrenergic innervation to the eye, and that these effects are mediated by activation of postjunctional alpha-adrenoceptors. It is concluded that DP alpha meE is a potent adrenergic ocular hypotensive agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Characterization of adrenergic receptors of the cat iris and nictitating membrane.

Graded pupillary dilations and nictitating membrane (NM) contractions were elicited in anesthetized cats by electrical stimulation of the preganglionic sympathetic nerve or by i.a. administration of norepinephrine (NE) or phenylephrine into the carotid artery. Pupil and NM responses were measured simultaneously from the same side. Alpha-adrenoceptor antagonists were administered intravenously. All of the alpha 1-adrenoceptor blockers tested produced a dose-related reduction of NM responses to both neural and agonist activation; the potency rank order was prazosin greater than WB-4101 greater than phentolamine greater than phenoxybenzamine (PBZ). In contrast, responses of the iris dilator were antagonized only by WB-4101 and PBZ. The iris was almost totally refractory to doses of prazosin and phentolamine that blocked NM responses by more than 75% of control. Neither alpha 2- nor beta-adrenoceptor antagonism produced significant inhibition of neural or agonist activation of either organ (with the exception of high doses of yohimbine on the NM). These results suggest that the postjunctional adrenoceptors of the NM are exclusively of the alpha 1-adrenoceptor subtype. In contrast, those of the iris dilator muscle cannot be easily classified pharmacologically as either alpha 1 or alpha 2-adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed1989

Argon laser-induced ocular hypertension: animal model of ocular inflammation.

There is substantial evidence that prostaglandins (PG's) mediate acute elevations of intraocular pressure (IOP) due to laser irradiation of the iris. In the present study, we determined the optimal laser parameters needed to produce the maximal rise in IOP in anesthetized rabbits. Application of argon laser (0.75 watts, 0.5 sec. duration, and 8 spots of 500 micron size) to the iris of pigmented rabbits elicited an acute rise in IOP and miosis accompanied by an increase in aqueous protein concentration. This response was followed by a delayed ocular hypotension that lasted for more than 3 days and returned to baseline by day 5. The onset of ocular hypertension occurred within 15 min. and remained elevated for at least 90 min. The laser induced rise in IOP was related more to the number of laser spots applied to the iris than to the intensity of the total laser energy utilized. Pretreatment with either indomethacin or flurbiprofen produced a dose dependent inhibition of ocular hypertensive response and significantly reduced aqueous protein concentration. Indomethacin (0.01-30 mg/kg) was administered intraperitonially 1 hr. before laser treatment and flurbiprofen (0.03-0.3%) was administered topically 45 and 15 min. prior to laser application. The hypertensive response was reduced by more than 90% of control after both drugs, whereas the delayed hypotension was significantly antagonized only at the highest dose of indomethacin. Neither indomethacin nor flurbiprofen altered the maximum miotic response to laser irradiation of the iris. However, 0.3% flurbiprofen and 30 mg/kg indomethacin significantly increased the recovery rate of the miotic pupil. The results of this study support the contention that argon laser induced ocular hypertension may provide a quantitative assessment of inhibition of prostaglandin mediated responses.

Animals↗
PubMed1988

Pharmacological characterization of alpha-adrenoceptors involved in nictitating membrane and pupillary responses to sympathetic nerve stimulation in cats.

Electrical stimulation of the preganglionic cervical sympathetic nerve produced frequency-related contraction of the nictitating membrane (NM) and dilation of the pupil in anesthetized cats. Observations of the effects of alpha-adrenoceptor blockade on these effectors were made simultaneously from the same preparations. All of the alpha 1-adrenoceptor antagonists tested produced a dose-related blockade of the NM with the relative potencies being prazosin greater than WB-4101 greater than phentolamine greater than phenoxybenzamine. In contrast, the iris dilator response was blocked by WB-4101 and phenoxybenzamine but was almost totally refractory to antagonism by doses of prazosin and phentolamine that reduced the evoked NM responses by more than 75% in these same preparations. Neither alpha 2-adrenoceptor (yohimbine or rauwolscine) nor beta-adrenoceptor (propranolol) antagonism produced significant inhibition of the activation of either organ. These results suggest that: 1) neural activation of the nictitating membrane is solely due to stimulation of alpha 1-adrenoceptors; 2) neither beta- nor alpha 2-adrenoceptors contribute significantly to nerve activation of either the nictitating membrane or iris dilator muscle in vivo; 3) the alpha-adrenoceptors on the dilator muscle that are activated neurally can not be classified pharmacologically as either alpha 1 or alpha 2 receptors.

Adrenergic alpha-Antagonists↗
PubMed1988

Alpha-adrenoceptor activation of nictitating membrane and iris in cats.

Intra-arterial administration of (+)- and (-)-isomers of adrenaline and noradrenaline produced dose-related contraction of the nictitating membrane (NM) and dilation of the pupil in anesthetized cats. The relative potencies were (-)-adrenaline greater than (+)-adrenaline = (-)-noradrenaline greater than (+)-noradrenaline. Observations of the effects of alpha-adrenoceptor antagonists on (-)-noradrenaline activation of these two effectors were made simultaneously. All of the alpha 1-adrenoceptor antagonists tested produced a dose-related blockade of the NM with the relative potencies being prazosin greater than WB-4101 greater than phentolamine greater than phenoxybenzamine. In contrast, the iris dilator was blocked by WB-4101 and phenoxybenzamine but was refractory to antagonism by doses of prazosin and phentolamine that reduced the (-)-noradrenaline evoked NM response by 75-80% in the same animals. The alpha 2-adrenoceptor antagonist, yohimbine, produced significant inhibition of the NM only at high dose (1 mg/kg) but even at this level had no effect on pupil diameter. These results suggest that activation of the NM by exogenous noradrenaline is due solely to stimulation of alpha 1-adrenoceptors. alpha 2-adrenoceptors do not seem to significantly contribute to noradrenaline induced activation of either the NM or iris dilator muscle in vivo. In contrast, the alpha-adrenoceptors on the iris dilator muscle that are stimulated by exogenous noradrenaline can not easily be classified pharmacologically as either alpha 1- or alpha 2-adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed1988

Systemic blood pressure and intraocular pressure relationship.

The relationship between intraocular pressure (IOP) and arterial blood pressure (BP) was analyzed in response to two pressor agents (norepinephrine and angiotensin II) and two depressor agents (methacholine and isoproterenol) in pentobarbital anesthetized cats. Both IOP and BP were measured manometrically in the same animals. Intravenous norepinephrine and angiotensin II produced dose-dependent increases, whereas intravenous methacholine and isoproterenol produced dose-dependent decreases of both BP and IOP. The IOP response to methacholine was biphasic, with an initial decrease followed by an increase above the pre-drug level. In some experiments a cannula loop was inserted into a carotid artery in order to separate the direct ocular effect of drugs on IOP from that contributed by the changes in systemic BP. Intravenous administration of norepinephrine and angiotensin II produced a larger increase in IOP on the side where drugs were delayed by the loop. Conversely, methacholine produced a larger fall in IOP on the cannulated side while the effect of isoproterenol was essentially unchanged. In other experiments injections were made directly into the ocular arterial blood supply. Norepinephrine and angiotensin II produced a decrease in IOP, methacholine produced a rise of IOP and isoproterenol was not active by this route. The present findings indicate that IOP is largely influenced by arterial BP changes in the acute phase and that the IOP response to drugs is the algebraic sum of effects on systemic BP and their direct ocular effects.

Angiotensin II↗
PubMed1988

Atypical alpha-adrenoceptor mediates phenylephrine-induced mydriasis in anesthetized cats.

Pupillary dilation and nictitating membrane (NM) contraction were elicited by pharmacological activation of alpha-adrenoceptors in vivo in anesthetized cats. A constant intravenous infusion of the alpha 1-adrenoceptor selective agonist phenylephrine (150 micrograms/min) was administered to produce a near maximal activation of both organs. Steady-state responses were attained about 15 minutes after starting the phenylephrine infusion. Administration of the alpha 1-adrenoceptor selective antagonist prazosin produced a dose-dependent blockade of NM contractions without altering phenylephrine-induced mydriasis when given as pretreatment (1.0 mg/kg i.v.) or post-treatment (0.01-1.0 mg/kg i.v.). In contrast, post-treatment with the alpha 1-adrenoceptor selective antagonist WB-4101 (0.1-1.0 mg/kg i.v.) or pretreatment with phenoxybenzamine (3.0 mg/kg i.v.) blocked both the NM and pupillary responses. These results suggest that the in vivo pupillary response to phenylephrine is mediated by an atypical alpha-adrenoceptor that cannot be readily classified as an alpha 1- or alpha 2-adrenoceptor. In contrast, the alpha-adrenoceptors of the NM appear to be of the classical alpha 1 subtype.

Adrenergic alpha-Antagonists↗
PubMed1987

Rapid and sensitive method for measurement of hyaluronic acid and isomeric chondroitin sulfates using high-performance liquid chromatography.

A high-performance liquid chromatographic method for the separation and analysis of the unsaturated tetrasaccharide and hexasaccharide from Streptomyces hyaluronidase (S.HAase) enzyme digestion products of hyaluronic acid (HA) and standard unsaturated disaccharides 2-acetamido-2-deoxy-3-O-(beta-D-gluco-4-enepyranosyluronic acid)-D-galactose (delta Di-0S), 2-acetamido-2-deoxy-3-O-(beta-D-gluco-4-enepyranosyluronic acid)-4-O-sulfo-D-galactose (delta Di-4S) and 2-acetamido-2-deoxy-3-O-(beta-D-gluco-4-enepyranosyluronic acid)-6-O-sulfo-D-galactose (delta Di-6S) is described. An amino phase chemically bonded to silica with a particle diameter of 6 micron was used as the column. The composition and the pH of the mobile phase were systematically varied to determine the optimal chromatographic conditions for separation and analysis of the compounds. For HA, a complete separation was accomplished in less than 12 min with a practical detection limit of 100 ng. Separation of the disaccharides also required less than 15 min with detection limits of 10 ng for delta Di-0S and 25 ng each for delta Di-4S and delta Di-6S. This chromatographic method represents a significant improvement over existing methods. It allows the simultaneous separation and analysis of HA and chondroitin sulfate isomers (after digestion of the latter with chondroitinase) at a higher speed, and with more sensitivity and efficiency.

Chondroitin↗
PubMed1987

Safety of high-energy neodymium:YAG laser pulses in YAG sclerostomy.

YAG sclerostomy was performed in 15 eyes of nine cynomolgus monkeys. Individual pulse energies ranged between 10 and 135 millijoules. Total pulse energy ranged between 2,000 and 36,000 millijoules in order to test the extreme range of energy that might be required. Both acute effects and chronic effects were studied in the corneal endothelium, the lens capsule, the iris, the ciliary body, the retina, and the sclera. Techniques included flat preparations of the corneal endothelium, paraffin sections for light microscopy, and scanning and transmission electron microscopy. Our conclusion is that individual pulse energies of up to 135 millijoules with a total of up to 36 joules of energy are safe in monkey eyes when performing YAG sclerostomy.

Animals↗
PubMed1987

Silver oxide in YAG sclerostomy.

YAG sclerostomy is a filtering procedure performed entirely with the neodymium:YAG laser through a goniolens as an alternative to trabeculectomy in the treatment of glaucoma. Extremely large pulse powers have been required in the past to complete the procedure. We found that an injection of silver-stabilized protein intrasclerally prior to the procedure makes it possible to perform the procedure with low total power.

Animals↗
PubMed1987

Role of norepinephrine in the rabbit ganglionectomy response.

Superior cervical ganglionectomy (SCG) produced delayed mydriasis and ocular hypotension in rabbits. Norepinephrine (NE) was lost from the iris-ciliary body exponentially with onset of about 11 h. NE in aqueous humor peaked at twice control levels (from 7 to 14 ng/ml) at 16.5 h and subsequently declined to below control levels by 24 h. Intracameral administration of radiolabeled NE (150 ng) to control eyes resulted in a calculated outflow of 1.6 microliter/min, comparable to that seen with fluorescein (1.7 microliter/min). NE administered to ganglionectomized eyes (26 h after surgery) resulted in a calculated outflow of 3.1 microliter/min. These results suggest that mydriasis following SCG may be due to NE released from degenerating sympathetic nerve endings. However, NE concentration in the aqueous humor appears inadequate to produce the delayed increase in outflow observed in rabbits after SCG.

Animals↗
PubMed1986

Laser-induced glaucoma in rabbits.

Argon laser energy was applied to the trabecular meshwork of pigmented rabbits in an attempt to develop an animal model of 'glaucoma'. Laser energy was varied to determine the optimal level needed to produce sustained ocular hypertension. An initial response of ocular hypertension followed by hypotension was observed in all of the animals tested. Approximately half of the laser-treated rabbits developed a secondary buphthalmus and sustained ocular hypertension. In these animals outflow facility was decreased by approximately 60%. Histologic examination at 4- and 8 weeks after laser treatment demonstrated a wound-healing response resulting in closure of the intertrabecular spaces and obstruction of outflow to injected carbon particles. Optic nerve cupping and a loss of ganglion cells were also observed. Topical application of L-timolol (0.5%), pilocarpine (2.0%) and forskolin (1.0%) were found to be effective in decreasing intraocular pressure in the laser-treated, hypertensive eye with no significant effect in control non-laser-treated eyes, suggesting that this model can be a useful tool for screening potential antiglaucoma medications.

Animals↗