Long-term non-invasive measurement of intraocular pressure in the rat eye

To study the optic neuropathy associated with glaucoma, a system for accurate, reliable, and non-invasive monitoring of intraocular pressure (IOP) is required. Of particular interest is the effect of sampling frequency on IOP. To address this issue, ten adult male brown Norway rats (group 1) were acclimatized to a 12-h/12-h light/dark cycle. On 20 days over a 30-day period, rats were anesthetized with short-acting isoflurane (Forane) inhalant anesthesia and IOP for each eye was determined by averaging 15 valid individual readings obtained with a TonoPen 2 tonometer. The last 12 measurement sessions were performed on a daily basis. To determine the minimum tolerable interval between IOP measurement sessions, a second group of 10 animals (group 2) was acclimatized in the same manner as group 1, and IOP was measured every 4 days over a period of 80 days. Next, IOP was measured every 4 days over a period of 28 days, and finally, every 2 days over a period of 19 days. For all group 1 measurements, there was no statistically significant difference between the right and left eye IOP, 14.75 +/- 1.08 (SEM) and 14.90 +/- 1.09 mm Hg, respectively. However, daily measurements produced a steady decrease in IOP and gradual weight loss. For group 2, overall mean right and left eye IOPs were 15.24 +/- 1.28 (SEM) and 15.12 +/- 1.26, respectively and were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)     

Type B and type C natriuretic peptide receptors modulate intraocular pressure in the rabbit eye

We investigated (1) the in vivo functional significance of the type B (ANP(B)) and type C (ANP(C)) natriuretic peptide receptors in the rabbit eye by evaluating the effect of intracameral administration of C-type natriuretic peptide (CNP) and C-ANP-(4-23) on intraocular pressure, and (2) the action of CNP on guanylate cyclase activity in the rabbit ciliary process membranes. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were also studied for comparison. We demonstrated that the natriuretic peptides decrease intraocular pressure and stimulate guanylate cyclase activity, CNP being the most potent. The duration of the effect of C-ANP-(4-23) on intraocular pressure reduction was almost 9-fold that of the BNP and 20-fold that of ANP and CNP effect. This ligand increased threefold the immunoreactive natriuretic peptides levels in aqueous humour. Our data demonstrate the presence of functional ANP(A) and ANP(B) receptors in the rabbit eye and that the ANP(C) receptor modulates the concentration of the natriuretic peptides in the aqueous humour.     

Drug effects on cerebral blood flow in the baboon model--acetazolamide and nimodipine

The sensitivity of the baboon model under anaesthesia for single photon emission computed tomography (SPECT) of the brain with 99mTc-HMPAO, as recently developed by us to study cerebral blood flow patterns, was investigated using drugs that are known to increase cerebral blood flow, e.g. acetazolamide, the carbonic anhydrase inhibitor and nimodipine, the calcium channel blocker. Increases in cerebral blood flow for both acetazolamide and nimodipine were observed that correspond well with other studies. Statistically significant regional specificity was noted for acetazolamide and nimodipine. Interestingly a combination of these drugs did not enhance cerebral blood flow but rather decreased it in comparison with the individual drug responses. The results were correlated with arterial blood pressure, heart rate, pCO2 and pO2. A blood pressure decrease was noted for both drugs, while acetazolamide had a marked influence on pO2. The results indicate that the baboon model is sensitive for evaluation of drug effects on cerebral blood flow.     

Blood flow and vascular pressure in the dental pulp. Summary

The present summary is a review and a discussion of the following papers (I-V), submitted as partial fulfillment of the requirements for the degree of Doctor Odontologiae at the University of Bergen. I. Blood flow in the dental pulp in dogs measured by local H2 gas desaturation technique. Arch. Oral Biol. 1975, 20, 73-79. Co-author: K. Aukland II. The effect of variations in arterial blood pressure and baroreceptor reflexes on pulpal blood flow in dogs. Arch. Oral. Biol.1975, 20, 345-349 III. Effect of vasodilating drugs on external carotid and pulpal blood flow in dogs: "Stealing" of dental perfusion pressurE. Acta Physiol. Scand. 1976, 97, 75-87 IV. Nervous control of blood flow in the dental pulp in dogs. Acta Physiol. Scand. 1978, 104, 13-23. Co-author: G. Naess V. Microvascular pressure in the dental pulp and gingiva in cats. Acta Odontol. Scand. 1979, 37, 161-168. Co-author: G. Naess Other papers are referred to in the conventional manner.     

Effects on intraocular pressure and aqueous flow of various dose regimens of latanoprost in human eyes

A "new" syndrome was identified by McPherson and Clemens [1996: Am J Med Genet 62:58-60] in a brother and sister with bilateral cleft lip and palate, hypertelorism, flat facial profile, flat occiput, and complex heart defects. The brother also had a bilobed tongue and the sister had malrotation of the intestine and bifid thumbs. We describe three brothers with similar anomalies apart from the bilobed tongue, malrotation of the intestine, and bifid thumbs. McPherson and Clemens [1996: Am J Med Genet 62:58-60] suggested autosomal recessive inheritance. Our observation of three affected brothers also raises the possibility of X-linked recessive inheritance.     

Effect of pulmonary blood flow on microvascular pressure profile determined by micropuncture in perfused cat lungs

To clarify the role of the pulmonary microvasculature in adjusting to increased pulmonary blood flow, we measured arteriolar and venular pressure by the servo-null micropuncture method while changing the pulmonary blood flow in isolated perfused cat lungs. We divided the lung vasculature into three longitudinal segments: 1) arterial (pulmonary artery to 30- to 50-microns arteriole), 2) microvascular (between 30- to 50-microns arteriole and venule), and 3) venous (30- to 50-microns venule to left atrium). The vascular resistance was calculated by dividing the pressure gradient by the flow. The pressure gradient of the microvascular segment did not increase, whereas the pressure gradient of the arterial and venous segments increased simultaneously with flow rate. Total and microvascular resistance decreased with increase of flow rate. Resistances of the arterial and venous segments did not change with increase in flow. We conclude that the microvasculature plays a crucial role in preventing pulmonary hypertension with increases in flow by decreasing microvascular resistance.     

Modeling the effects of anterior chamber fluid viscosities on intraocular pressure following glaucoma filtering surgery

BACKGROUND: Hypotonia, flat anterior chamber, and choroidal effusion are not infrequent and undesirable consequences of glaucoma filtering surgery. Methods developed so far to prevent or combat these complications have only been moderately successful. Viscous fluids admixed to the aqueous humor are known to influence fluid dynamics and hence intraocular pressure during variable time intervals following surgery. It was the intention of the authors to develop a mathematical model which predicts the influence of sodium hyaluronate determining the intraocular pressure following injection into the anterior chamber. METHODS: The model is based on first-order approximations and derives from the theory of rheology and fluid dynamics in narrow tubes, and is essentially based on Hagen-Poiseuille's law. RESULTS: The predictions of the model (to be published in a paper to follow) were verified in experiments on owl monkeys and showed a high degree of predictive power. CONCLUSIONS: One may conclude that sodium hyaluronate, injected once or repeatedly with fine canulas into the anterior chamber, qualifies as an important tool to maintain normal on near-normal intraocular pressure in the immediate and late postoperative phase following surgery.     

The effects of vasoconstrictors on distribution of ischemic tissue flow in isolated perfused rat liver

Discusses plans of marriage among students and the problems of student families. Comprehensive sociohygienic study of the health status and communal conditions was carried out among the students of the Russian Peoples' Friendship University, including married students with children. This social group is characterized by a peculiar life style, intensive intellectual and social activity; moreover, it is the most favorable period for marriage and childbirth. Special attention is paid to difficulties (material, communal, educational, etc.) experienced by the female students becoming mothers in the course of studies. Specific medicodemographic tendencies brought the authors to a conclusion that development and introduction of programs of medicosocial support for student families, specifically, mothers, is needed, which should be aimed at the soonest possible solution of the acute problems of maintaining the health of mothers and their children.     

Tracing attention and the activation flow in spoken word planning using eye movements.

The flow of activation from concepts to phonological forms within the word production system was examined in 3 experiments. In Experiment 1, participants named pictures while ignoring superimposed distractor pictures that were semantically related, phonologically related, or unrelated. Eye movements and naming latencies were recorded. The distractor pictures affected the latencies of gaze shifting and vocal naming. The magnitude of the phonological effects increased linearly with latency, excluding lapses of attention as the cause of the effects. In Experiment 2, no distractor effects were obtained when both pictures were named. When pictures with superimposed distractor words were named or the words were read in Experiment 3, the words influenced the latencies of gaze shifting and picture naming, but the pictures yielded no such latency effects in word reading. The picture-word asymmetry was obtained even with equivalent reading and naming latencies. The picture-picture effects suggest that activation spreads continuously from concepts to phonological forms, whereas the picture-word asymmetry indicates that the amount of activation is limited and task dependent. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of dihydro-ouabain on vascular tone on the perfused cannine hindlimb

Digitalis compounds are known to cause contraction of vascular smooth muscle. However, it has been reported by Kahn and colleagues (J. Pharmacol. Exp. Ther. 142: 215-222, 1963) that dihydro-ouabain has no effect on vascular tone in dogs. The purpose of our study was to reassess the vasoconstrictor activity of dihydro-ouabain. This was done by monitoring perfusion pressure of the canine hindlimb preparation perfused at a constant rate of blood flow and administering intra-arterial injections of dihydro-ouabain. Increasing doses of this drug (i.e., 25, 50, 100, 200 and 300 mug) produced significant dose-dependent increases in perfusion pressure. Pretreatment with phentolamine prevented the effect of dihydro-ouabain on perfusion pressure. These results indicate that dihydro-ouabain causes contraction of vascular smooth muscle by an adrenergic mechanism.     

Reflex vascular responses to alterations in abdominal arterial pressure and flow in anaesthetized dogs

The existence of abdominal arterial baroreceptors has long been controversial. Previously difficulties have been encountered in localizing a stimulus to abdominal arteries without affecting reflexogenic areas elsewhere. In these experiments, using anaesthetized dogs, the abdomen was vascularly isolated at the level of the diaphragm, perfused through the aorta, and drained from the inferior vena cava to a reservoir. Changes in abdominal arterial pressure were effected by changing the perfusion pump speed. During this procedure the flow back to the animal from the venous outflow reservoir was held constant. Increases and decreases in abdominal arterial pressure resulted, respectively, in decreases and increases in perfusion pressure to a vascularly isolated hind-limb and in some dogs also a forelimb. Responses were significantly larger when carotid sinus pressure was high (120-180 mmHg) than when it was low (60 mmHg). Responses were still obtained after cutting vagus, phrenic and splanchnic nerves, but were abolished by spinal cord lesion at T12. These experiments provide evidence for the existence of abdominal arterial baroreceptors. The afferent pathway for the reflex vasodilatation appears to run in the spinal cord.     

The effect of excimer laser photorefractive keratectomy on intraocular pressure measurements using the Goldmann applanation tonometer

PURPOSE: The authors determined whether photorefractive keratectomy (PRK) affects Goldmann applanation readings in human eyes. METHODS: The intraocular pressure (IOP) of 111 patients was measured using Goldmann applanation tonometry at baseline and 12 months after PRK. Ultrasonic corneal thickness measurements and keratometry were also obtained. Contralateral eyes were used as controls. RESULTS: There was a statistically significant decrease in mean tonometer readings in the treated eyes when compared with the control eyes (0.5 +/- 2.1 mmHg, P = 0.01) accompanied by a significant reduction in mean central pachymetry in the treated eyes (23 +/- 23 microns, P < 0.001). In the treated eyes, the mean spherical equivalent and mean central keratometry readings were significantly reduced by 3.3 +/- 1.5 and 2.2 +/- 1.2 diopters, respectively (P < 0.001). CONCLUSION: Photorefractive keratectomy causes a mild lowering of the Goldmann tonometer readings. The reduction in IOP measurement is probably not enough to alter a therapeutic decision in an individual patient known to have glaucoma, but it may delay recognition and treatment of glaucoma.     

The effects of unoprostone isopropyl 0.12% and timolol maleate 0.5% on diurnal intraocular pressure

PURPOSE: To compare the effect of unoprostone isopropyl 0.12% to that of timolol maleate 0.5% solution given twice daily on the diurnal curve of intraocular pressure (IOP) in patients with primary open-angle glaucoma or ocular hypertension. METHODS: In this investigator-masked, single-center, parallel-group comparison, 36 patients with primary open-angle glaucoma or ocular hypertension were randomized in a 2:1 ratio to receive either unoprostone isopropyl 0.12% or placebo/timolol maleate 0.5% solution, respectively. A placebo-controlled diurnal curve on day 0 and active-controlled diurnal curves at weeks 2 and 4 were performed at 0, 2, 4, 6, 8, 10, 12, and 24 hours. At week 2, administration of unoprostone isopropyl twice daily was compared with administration of timolol maleate twice daily. At week 4, administration of unoprostone isopropyl three times daily was compared with administration of timolol maleate twice daily. RESULTS: At the 24-hour 8:00 AM trough at week 2, administration of unoprostone isopropyl twice daily decreased IOP from 23.4 +/- 2.0 mmHg at baseline to 19.3 +/- 4.4 mmHg, and timolol maleate reduced IOP from 24.4 +/- 2.6 mmHg to 17.5 +/- 2.9 mmHg. At the 8:00 AM trough at week 4, unoprostone isopropyl given three times daily produced an IOP of 19.6 +/- 3.3 mmHg and timolol maleate resulted in an IOP of 19.4 +/- 3.0 mmHg. No statistical differences between groups were observed at any time point during either diurnal curve. Safety was similar in the two treatment groups, with no differences between groups in conjunctival hyperemia, anterior segment inflammation, or iris color change. CONCLUSION: Results of this short-term pilot trial indicate that unoprostone isopropyl may be safe and effective in reducing IOP from baseline when given twice or three times daily.     

The ocular blood flow tonograph: a new instrument for the measurement of intraocular pressure in rabbits

OBJECTIVES: To determine the intraprostatic pathologic changes following accurately measured doses of transurethral microwave thermal energy in patients with benign prostatic hyperplasia. METHODS: Eight patients scheduled for prostate surgery were treated for approximately 1 hour without anesthesia using a newly designed microwave treatment catheter that allows a close impedance match to prostate tissue and concentrates thermal energy preferentially in the anterior and lateral prostate gland. Interstitial, urethral, and rectal temperatures were continuously measured using a novel stereotactic thermal mapping technique. Serial sections of prostate tissue harvested during subsequent surgery were evaluated pathologically with prostate mapping. RESULTS: Microwave treatment resulted in marked and continuous intraprostate temperature elevation, while urethral and rectal temperatures remained low. Peak intraprostate temperatures in individual patients reached as high as 80 degrees C. Mean temperature reached a maximum of 54 degrees C at a radial distance of approximately 0.5 cm from the urethra and remained 45 degrees C or higher up to a distance of 1.6 cm. The predominant pathologic findings were uniform hemorrhagic necrosis and tissue devitalization without significant inflammation. The mean distance from the urethra to the viable-necrotic tissue border was 1.6 +/- 0.2 cm (range, 0.5 to 2.5). At this border, no more than 1 mm in thickness, temperature averaged 45.7 +/- 0.6 degrees C, and there was a suggestion that pure stromal nodules were more resistant to thermal injury. CONCLUSIONS: Microwave treatment can destroy obstructive prostate tissue while maintaining innocuous urethral and rectal temperatures. Temperatures of 45 degrees C or higher for approximately 1 hour cause uniform thermoablation of prostate tissue.     

Drug distribution in the vitreous humor of the human eye: the effects of intravitreal injection position and volume

PURPOSE: The purpose of this study was to determine how the position and volume of an intravitreal injection affect the distribution and elimination of drug from the vitreous humor. METHODS: A mathematical model that had been developed and used previously to study drug distribution in the vitreous humor of the rabbit eye was modified to match the physiology of the human eye. Fluorescein and fluorescein glucuronide were used as the model compounds for these studies. Four extreme injection locations were considered: a central injection, an injection displaced towards the retina, an injection displaced towards the lens, and an injection displaced toward the hyaloid membrane. Injections containing an equal mass of drug dissolved in volumes of either 15 microL or 100 microL were compared. RESULTS: The location of an intravitreal injection was found to have a substantial effect on elimination and distribution in the vitreous. Peak concentrations at different vitreous locations varied by over three orders of magnitude, depending on the injection location. The mean concentration of drug remaining in the vitreous 24 hours after the intravitreal injection varied by up to a factor of 3.8, depending on the injection location. Changing the volume of the injection from 15 microL to 100 microL dampened the effects of the initial injection location; however, meant concentrations at 24 hours still varied by up to a factor of 2.5. CONCLUSIONS: Careful control of the conditions of an intravitreal injection could reduce treatment variability, improve bioavailability, and reduce the possibility of retinal toxicity.     

Individual variability in the diurnal intraocular pressure curve

BACKGROUND: Reduction of intraocular pressure (IOP) is a primary goal of most glaucoma treatments. However, because the IOP varies during the day, single measurements performed in an ophthalmologist's office do not necessarily provide information on the peak level and fluctuation of the IOP. METHODS: Home tonometry was performed to gain more information on the nature of the diurnal IOP curves and on their variability. One hundred seventy-six patients with open-angle glaucoma (OAG), 55 subjects with ocular hypertension (OHT), and 18 control individuals measured their IOP five times daily at home for 4 to 8 consecutive days using a self-tonometer. RESULTS: Well-defined diurnal IOP variations were observed in all three groups with a predominance of curves with morning or mid-day maxima. Erratic IOP curves without a diurnal rhythm were present in OHT (22%) and OAG (16%) patients but not in control subjects. Differences between the curves of the two eyes of an individual were frequent in OHT (33%) and OAG (36%) patients but not in control subjects (6%). Finally, the majority of OHT (72%) and OAG (66%) patients showed a difference in their diurnal curve patterns on repeat home tonometry performed months apart. CONCLUSION: The authors indicate that it is difficult to rely on one eye as a control for the other. They also indicate that changes in IOP observed in the office at different visits often may be due to a shift in the type of diurnal curve rather than to a true change in the mean IOP. Monitoring of the diurnal IOP may be necessary in some cases if the clinician relies, even partially, on the level of IOP when making a decision on patient management.     

Circadian rhythm of intraocular pressure in the rat

In order to investigate the relationship between the bioactive conformation of a peptide and its set of thermodynamically accessible structures in solution, the conformational profile of the tetrapeptide Ac-Pro-Ala-Pro-Tyr-OH was characterized by computational methods. Search of the conformational space was performed within the molecular mechanics frame-work using the AMBER4.0 force field with an effective dielectric constant of 80. Unique structures of the peptide were compared with its bioactive conformation for the protein Streptomyces griseus Protease A, as taken from the crystal structure of the enzyme-peptide complex. The results show that the bound conformation is close to one of the unique conformations characterized in the conformational search of the isolated peptide. Moreover, the lowest energy minimum characterized in the conformational search exhibits large deviations when compared to the bound conformation of the crystal structure.     

The effects of intra-arterial and intraportal injections of vasopressin on the simultaneously perfused hepatic arterial and portal venous vascular beds of the dog

The hepatic arterial and hepatic portal venous vascular beds of the chloralose-urethane anesthetized dog were perfused simultaneously in situ. Vasopressin (10 mU = 1 unit) was injected in graded increasing doses into the hepatic artery and into the portal vein. Both intra-arterial and intraportal vasopressin elicited both hepatic arterial vasoconstriction and hepatic venous dilation; the delay in onset of both hepatic vascular effects was significantly shorter than that for any succeeding systemic effects (a rise in systemic arterial pressure and fall in heart rate), showing that they were not attributable to recirculation or to arterial baroreceptor reflexes. Injections of vasopressin into the inferior vena cava at the level of the hepatic veins consistently produced smaller hepatic vascular effects than either intra-arterial or intraportal injections of the same doses. The results are discussed in the context of the therapeutic role of vasopressin in controlling gastrointestinal bleeding and portal hypertension.     

Effect of mitomycin C on aqueous humor flow, flare and intraocular pressure in eyes with glaucoma 2 years after trabeculectomy

BACKGROUND: The purpose of this study was to determine the intraocular pressure (IOP), aqueous humor flow, flare and ocular side effects in eyes with a history of hypotony after trabeculectomy with adjunctive mitomycin C (MMC). METHODS: Thirty-six eyes with primary or secondary open-angle glaucoma and IOP < or = 8 mmHg during the postoperative period were studied 745 +/- 315 days after surgery. MMC (0.2 or 0.5 mg/ml) was applied to the episclera with a cellular sponge. Flare was studied with the Kowa Laser Flare Meter 500. Aqueous humor flow was measured in the afternoon (Fluorotron Master II). IOP, visual fields and best corrected visual acuity were also examined. Twenty-two contralateral eyes without surgical intervention served as controls. RESULTS: The mean age of patients was 44.5 +/- 16.8 years. The mean IOP was significantly lower in the MMC group than in the control group: 9.6 +/- 6.4 mmHg vs 18.0 +/- 13.6 mmHg at 2 years (P < 0.001). Aqueous flow was significantly lower in subjects treated with MMC than in controls (P < 0.001). The flare values were significantly higher in the MMC-treated group, with a mean of 12.0 +/- 7.7 photon counts/ms, than in the control group, mean 7.9 +/- 4.6 photon counts/ms (P < 0.019). CONCLUSION: Our data suggest that MMC is a useful ocular hypotensive agent which seems to participate in a change in aqueous humor dynamics when applied topically as an aqueous solution.