Beta-blockers and mechanical dyssynchrony in heart failure assessed by radionuclide ventriculography.

BACKGROUND: Radionuclide ventriculography (RNVG) can be used to quantify mechanical dyssynchrony and may be a valuable adjunct in the assessment of heart failure with reduced ejection fraction (HFrEF). The study aims to investigate the effect of beta-blockers on mechanical dyssynchrony using novel RNVG phase parameters. METHODS: A retrospective study was carried out in a group of 98 patients with HFrEF. LVEF and dyssynchrony were assessed pre and post beta-blockade. Dyssynchrony was assessed using synchrony, entropy, phase standard deviation, approximate entropy, and sample entropy from planar RNVG phase images. Subgroups split by ischemic etiology were also investigated. RESULTS: An improvement in dyssynchrony and LVEF was measured six months post beta-blockade for both ischemic and non-ischemic groups. CONCLUSIONS: A significant improvement in dyssynchrony and LVEF was measured post beta-blockade using novel measures of dyssynchrony.

Radionuclide ventriculography phase analysis for risk stratification of patients undergoing cardiotoxic cancer therapy.

BACKGROUND: Accurate diagnostic tools to identify patients at risk of cancer therapy-related cardiac dysfunction (CTRCD) are critical. For patients undergoing cardiotoxic cancer therapy, ejection fraction assessment using radionuclide ventriculography (RNVG) is commonly used for serial assessment of left ventricular (LV) function. METHODS: In this retrospective study, approximate entropy (ApEn), synchrony, entropy, and standard deviation from the phase histogram (phase SD) were investigated as potential early markers of LV dysfunction to predict CTRCD. These phase parameters were calculated from the baseline RNVG phase image for 177 breast cancer patients before commencing cardiotoxic therapy. RESULTS: Of the 177 patients, 11 had a decline in left ventricular ejection fraction (LVEF) of over 10% to an LVEF below 50% after treatment had commenced. This patient group had a significantly higher ApEn at baseline to those who maintained a normal LVEF throughout treatment. Of the parameters investigated, ApEn was superior for predicting the risk of CTRCD. Combining ApEn with the baseline LVEF further improved the discrimination between the groups. CONCLUSIONS: The results suggest that RNVG phase analysis using approximate entropy may aid in the detection of sub-clinical LV contraction abnormalities, not detectable by baseline LVEF measurement, predicting a subsequent decline in LVEF.

Indoor PM2.5, VOCs and asthma outcomes: A systematic review in adults and their home environments.

INTRODUCTION: As the amount of time people spend indoors increases globally, exposure to indoor air pollutants has become an important public health concern. Asthma is a complex disease caused and/or exacerbated by increased exposure to diverse chemical, physical and biological exposures from multiple indoor and outdoor sources. This review aims to investigate the relationship between increased indoor PM and VOC concentrations (i.e. objectively measured) and the risk of adult asthma in higher-income countries. METHODS: Eleven databases were systematically searched on the February 1, 2019 and again on the February 2, 2020. Articles were limited to those published since 1990. Reference lists were independently screened by three reviewers and authors were contacted to identify relevant articles. Backwards and forward citation chasing was used to identify further studies. Data were extracted from included studies meeting our eligibility criteria by three reviewers and assessed for quality using the Newcastle-Ottawa scale designed for case-control and cohort studies. RESULTS: Twelve studies were included in a narrative synthesis. We found insufficient evidence to determine the effect of PM2.5 on asthma in the indoor home environment. However, there was strong evidence to suggest that VOCs, especially aromatic compounds, and aliphatic compounds, were associated with increased asthma symptoms. DISCUSSION & CONCLUSION: Although no single exposure appears to be responsible for the development of asthma or its associated symptoms, the use of everyday products may be associated with increased asthma symptoms. To prevent poor health outcomes among the general population, health professionals and industry must make a concerted effort to better inform the general population of the importance of appropriate use of and storage of chemicals within the home as well as better health messaging on product labelling.

Randomized, open-label, 5-way crossover study to evaluate the pharmacokinetic/pharmacodynamic interaction between furosemide and the non-steroidal anti-inflammatory drugs diclofenac and ibuprofen in healthy volunteers.

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) can induce renal complications in patients taking loop diuretics. This study investigated the pharmacokinetic/pharmacodynamic effects and safety profile of orally administered diclofenac sodium, ibuprofen and diclofenac epolamine topical patch (DETP) on furosemide in healthy adult subjects. METHODS: This open-label, randomized, 5-way crossover study was conducted in 40 subjects (aged 19 - 45 y). Diclofenac (75 mg taken orally twice daily), DETP (1.3% applied topically twice daily), or ibuprofen (800 mg taken orally thrice daily) was administered for 3 consecutive days, followed by co-administration with furosemide (given intravenously as 20 mg/2 min). Plasma furosemide and NSAID concentrations, urine furosemide, sodium and potassium concentrations and urine output were determined throughout the 24 h period following furosemide administration. RESULTS: Orally administered ibuprofen significantly increased furosemide AUC(0-t) (37%) and AUC(0-inf) (36%) and decreased total body CL (27%), R(max) (19%) and CLR (23%) geometric mean ratios compared with furosemide control. Oral and topical diclofenac had no pharmacokinetic effects on furosemide. Ibuprofen increased sodium excretion (Ae(0-24), 16%) and decreased sodium R(max) (15%), and oral diclofenac decreased urine output (Vu(0-24), 15%). DETP had no effect on furosemide pharmacodynamics; total systemic exposure to diclofenac during DETP treatment was < 1% that of oral diclofenac. Treatments were generally safe, with 25 subjects reporting a total of 112 adverse events. CONCLUSIONS: Pharmacodynamic effects were seen with oral diclofenac (urine output) and ibuprofen (urine sodium excretion). Furosemide also affected plasma and urine pharmacokinetic profiles. Pharmacologic effects of DETP on furosemide were not observed under these conditions. Additional research is warranted to delineate the potential interactions of other NSAIDs with furosemide and other loop diuretics.

Nuclear magnetic resonance studies and water "ordering" in the crystalline lens.

Nuclear magnetic resonance studies of the relaxation times of the water in the crystalline lens show that, as in all interfacial systems, these parameters are markedly reduced from their values in pure water, that T(2) is less than T(1), and that both depend on water content. Determination of diffusion coefficients and studies on physiologically inert lenses indicate that reduced relaxation times do not provide direct evidence for ordering of the bulk of the cell water.

Mice lacking the vascular endothelial growth factor-B gene (Vegfb) have smaller hearts, dysfunctional coronary vasculature, and impaired recovery from cardiac ischemia.

Vascular endothelial growth factor-B (VEGF-B) is closely related to VEGF-A, an effector of blood vessel growth during development and disease and a strong candidate for angiogenic therapies. To further study the in vivo function of VEGF-B, we have generated Vegfb knockout mice (Vegfb(-/-)). Unlike Vegfa knockout mice, which die during embryogenesis, Vegfb(-/-) mice are healthy and fertile. Despite appearing overtly normal, Vegfb(-/-) hearts are reduced in size and display vascular dysfunction after coronary occlusion and impaired recovery from experimentally induced myocardial ischemia. These findings reveal a role for VEGF-B in the development or function of coronary vasculature and suggest potential clinical use in therapeutic angiogenesis.

Ocular inflammatory responses in the EP2 and EP4 receptor knockout mice.

PURPOSE: To examine the role of EP2 and EP4 receptors in murine ocular inflammation. METHODS: Prostaglandin EP2 and EP4 receptor knockout and wild-type mice were treated topically with prostaglandin E2, SDF-1, and RANTES and lipopolysaccharide by intravitreal injection. Paracentesis was performed by puncturing the cornea. The increase in the level of aqueous humor protein and the number of leukocytes were measured and the vascular leakage of protein was visualized using fluorescein angiography. RESULTS: In the EP2 receptor knockout mice, there was significant inhibition of the disruption of the blood-aqueous barrier caused by lipopolysaccharides, paracentesis, prostaglandin E2, SDF-1, and RANTES. Reductions in the disruption in the blood-aqueous barrier and leukocyte infiltration after lipopolysaccharide injection and paracentesis were significant, but there was no increase in the aqueous humor protein level after prostaglandin E2 treatment in EP4 receptor knockout mice. CONCLUSIONS: The results of the present experiments suggest that EP2 and EP4 receptors partly mediate the disruption of the blood-aqueous barrier and leukocyte infiltration induced by prostaglandin E2, SDF-1, RANTES, and lipopolysaccharides.

An electrogenic component of the potential difference in the rabbit lens.

The normal resting potential of the rabbit lens, -70mV, is altered to -59mV by ouabain concentrations up to 5-1- minus 6M, and to -52mV at 4 degrees C. Ouabain acts only at the anterior lens surface. The temperature effect id completely reversible. The Hodgkin-Katz-Goldman equation can be used with the measured lens potentials and Na+ and K+ levels in the lens and bathing medium to obtain alpha, the ration of the membrane permeabilities to Na+ and K+. The alpha-values obtained were 0.052 at 4 degrees C and 0.053 in 5-10 minus 6M ouabain. These data suggest that the change in potential due to cold and ouabain is caused by an inhibition of an electrogenic Na+ ump in the anterior lens epithelium.

The influence of calcium-free EGTA solution upon membrane permeability in the crystalline lens of the frog.

Potential difference, resistance, cation content, and 86Rb efflux were measured in frog lenses maintained in normal or calcium-free EGTA Ringer's solution. Exposure of the lens to calcium-free solution resulted in a rapid fall in potential and resistance, together with a twofold increase in 86Rb efflux rate. These rapid changes were not due to an alteration in cation distribution between the lens and its environment. However, the alteration in 86Rb efflux rate could be explained on the basis of the fall in potential. These findings suggested that removal of calcium from the bathing medium caused a rapid increase in sodium permeability alone. This suggestion was substantiated by the results of experiments where the response of the lens to low calcium solution was determined in a medium in which 90% of the sodium had been replaced by sucrose.

Effect of oxidation on Ca2+ -ATPase activity and membrane lipids in lens epithelial microsomes.

Membrane oxidation may contribute to cataractogenesis. In our pursuit to understand the etiology of cataracts, we assessed the effect of membrane oxidation products on the activity of the lens epithelium calcium pump. Microsome preparations from bovine lens epithelium were oxidized to varying degrees with a ferrous and ferric ascorbate system to generate hydrogen peroxide and superoxide. Ca2+ -ATPase activity was measured using a colorometric assay. Lipid oxidation was quantified by infrared spectroscopy. Ca2+ -ATPase activity decreased as a function of ascorbate concentration between 0 and 200 microM. The level of Ca2+ -ATPase inhibition was correlated to both the level of lipid oxidation and the degree of lipid hydrocarbon chain order. At 25 degrees C when lipids are more ordered, the Ca2+ -ATPase activity was similar to that observed in the oxidized system measured at 37 degrees C. Glutathione, mercaptoethanol, and iodoacetate were able to reverse the oxidative inhibition of the calcium pump, suggesting that the ascorbate/iron oxidant directly oxidized the protein sulfhydryl moieties. To further probe the mechanism of Ca2+ ATPase inhibition, hydrogen peroxide was used to oxidize muscle sarcoplasmic reticulum Ca2+ -ATPase reconstituted in its native lipid vesicles, egg phosphatidylcholine, and dihydrosphingomyelin, with saturated hydrocarbon chains. In these systems, oxidation inhibited the Ca2+ -ATPase pump by 60-80%. There was no statistical difference between the level of oxidative inhibition and the percentage of dihydrosphingomyelin. Because dihydrosphingomyelin cannot be oxidized, whereas egg phosphatidylcholine (PC) can, and because the percentage of inhibition was the same for reconstituted systems using either lipid, the mechanism of inhibition is likely not via a secondary process involving oxidation-induced lipid structural changes or products of lipid oxidation.

Prostaglandin E2 effects on corneal endothelial cyclic adenosine monophosphate synthesis and cell shape are mediated by a receptor of the EP2 subtype.

Corneal endothelial cells synthesize prostaglandin E2 (PGE2), and this synthesis is necessary for the maintenance of the normal polygonal shape of these cells. A series of experiments was done to examine the receptor-effector mechanism responsible for PGE2-mediated effects on cultured rabbit corneal endothelium. When challenged with exogenous PGE2, endothelial cells synthesized cyclic adenosine monophosphate (AMP) in a dose-dependent manner, and this synthesis was not antagonized by AH6809. The synthetic agonist 11-deoxy-PGE1, but not sulprostone, stimulated increased cyclic AMP synthesis. The pharmacologic profile of the endothelial PGE2 receptor is therefore consistent with that of an EP2 receptor linked to activation of adenylate cyclase. The prostaglandin agonists were also tested for their ability to prevent cellular elongation in response to indomethacin. The PGE2, 11-deoxy-PGE1, and 16,16-dimethyl PGE1 prevented elongation, but sulprostone and PGF2 alpha did not. The authors conclude that rabbit corneal endothelium in culture expresses a specific PG receptor of the EP2 subtype which is coupled to cyclic AMP synthesis and is involved in the regulation of cell shape.

The effect of ascorbic acid on experimental acid burns of the rabbit cornea.

The corneas of albino rabbits were subjected to 45 sec, 12 mm, 2.3N hydrochloric acid burns. Of 18 eyes in nine rabbits receiving no treatment (controls), 11 (61%) developed ulceration sometimes progressing to descemetoceles and perforation. Of 17 eyes in nine rabbits receiving a daily subcutaneous injection of ascorbic acid (0.5 gm/kg), only one eye (5.9%) developed an anterior stromal ulcer. The difference in incidence of ulceration between the control and ascorbate-treated eyes was statistically significant (p less than 0.01). The aqueous humor level of ascorbate in untreated animals was 6.0 +/- 0.6 mg/dl compared to 33.0 +/- 2.7 in the treated group. This study therefore demonstrates that subcutaneous administration of ascorbic acid significantly raises the aqueous humor level of ascorbic acid in severely acid-burned eyes, thereby largely preventing the characteristic development of corneal ulceration. The mechanism of this effect is presumably the same as previously described for alkali-burned eyes.

PMN accumulation in aqueous humor and iris-ciliary body during intraocular inflammation.

The accumulation of polymorphonuclear leukocytes (PMNs) was determined in the aqueous humor and iris-ciliary body following an intravitreal injection of endotoxin in the albino rabbit. PMN accumulation in the iris-ciliary body was quantified by measuring myeloperoxidase (MPO) activity in homogenates of this tissue. Leukocyte appearance in the aqueous humor was determined by counting the number of PMNs in diluted aspirates of aqueous humor and also by measuring MPO activity in the same aspirates. Twenty-four hours following an intravitreal injection of endotoxin, there was marked vasodilatation in the iris, breakdown of the blood-aqueous barrier, and infiltration of PMNs into the aqueous humor. There was, however, no correlation between MPO activity in the iris-ciliary body and the number of PMNs or the MPO activity in the aqueous humor. Furthermore, the number of PMNs in the aqueous humor did not increase with increasing amounts of intravitreally injected endotoxin, whereas MPO activity in the iris-ciliary body increased in a dose-dependent manner. The results of this study suggest that quantification of leukocytes in the aqueous humor does not represent a meaningful index of intraocular inflammation.

Responses of intraocular pressure and the pupil of feline eyes to prostaglandin EP1 and FP receptor agonists.

PURPOSE: Previous studies suggested that FP receptors do not mediate the relaxation of the ciliary muscle and reduction of intraocular pressure in cats by prostaglandin (PG) F2alpha. The present study was undertaken to determine whether the reduction of intraocular pressure in cats induced by PGF2alpha is mediated by FP or other prostaglandin receptors. METHODS: One eye of each cat was treated topically with prostaglandin F2alpha, fluprostenol (FP receptor agonist), or 17-phenyl trinor PGE2 (EP1 receptor agonist) in a dose range of 12.5 to 50 microg. The effects of SC19220 and SC51089 (EP1 receptor antagonists), BWA868c, and SQ29548 (DP and TP receptor antagonists, respectively) on the intraocular response to PGF2alpha were also examined. At intervals up to 6 hours after treatment, intraocular pressure was measured with a pneumotonometer, and pupil diameters were measured with a millimeter ruler. RESULTS: In the dose ranges used, PGF2alpha and 17-phenyl trinor PGE2 decreased intraocular pressure and pupil diameter. The greatest reduction of intraocular pressure by 50.0 microg PGF2alpha was 5.0+/-1.4 mm Hg, whereas that by 50 microg 17-phenyl trinor PGE2 was 6.2+/-1.5 mm Hg. The isopropyl ester of PGF 2alpha at a dose of 1.25 microg reduced intraocular pressure by 3.75+/-0.25 mm Hg at 2 hours. At doses up to 100 microg, fluprostenol did not decrease intraocular pressure but did reduce pupil diameter. SC19220, a weak but selective EP1 receptor antagonist, inhibited the intraocular pressure response to both PGF2alpha and 17-phenyl trinor PGE2. The more potent EP1 receptor antagonist SC51089 had a greater inhibitory effect than SC19220 on the intraocular pressure response to PGF2alpha. Both of these antagonists had a small but non-dose dependent and statistically insignificant effect on the pupil response to PGF2alpha. These observations suggest that in cats, intraocular pressure and pupil responses to PGF2alpha, are mediated by EP1 and FP receptors, respectively. However, SC19220 significantly and dose-dependently inhibited the pupil response to 17-phenyl trinor PGE2alpha suggesting that EP1 receptors mediate pupil response to this agonist. DP and TP receptor antagonists at doses 5- to 20-fold greater than the IC50 values had no effect on the ocular hypotensive response to PGF2alpha. The concurrent administration of 12.5 microg of each of PGF2alpha and 17-phenyl trinor PGE2 did not produce an additive effect on intraocular pressure, indicating that in cats PGF2alpha and 17-phenyl trinor PGE2 act on the same receptor type. CONCLUSIONS: These results suggest that a significant proportion of the ocular hypotensive action of PGF2alpha in cats is mediated by EP1 but not by FP receptor. Evidence was also provided to show that 17-phenyl trinor PGE2 is an ocular hypotensive agent in cats.

Ca-ATPase activity in the rabbit and bovine lens.

Membrane-rich vesicle preparations of rabbit and bovine lenses were prepared in such a manner as to preserve ATPase activity. The lipid:protein ratio of these preparations was increased 22- to 33-fold with a 94% recovery of total phospholipid. Using this preparation, calcium stimulated ATPase was routinely determined in both individual lenses and in pooled specimens. The pattern of stimulation of ATPase activity by a range of calcium concentrations was found to be similar in membrane preparations of epithelium and cortex, from rabbit and bovine lenses. The concentration of calcium necessary for half-maximal stimulation of ATPase activity was approximately 10(-6) M. Calcium concentrations in excess of 10(-4) M reduced the ATPase activity. Calcium-ATPase was undetectable in the lens nuclear region of both species. The regional distribution of sodium-potassium ATPase was also measured.

Oxidative inhibition of Ca2+-ATPase in the rabbit lens.

Hydrogen peroxide inhibition of maximum Ca2+-ATPase and Na+,K+-ATPase activity was measured in a membrane-enriched preparation of rabbit lens cortical fibers and epithelium. At 5 X 10(-6) M hydrogen peroxide maximum Ca2+-ATPase activity was inhibited by 39%, while maximum Na+,K+-ATPase activity was stimulated. Ca2+-ATPase activity was almost completely inhibited at 5 X 10(-4) M hydrogen peroxide, in comparison to Na+,K+-ATPase activity, which was only inhibited by 28% at a concentration of hydrogen peroxide an order of magnitude larger. The addition of catalase to hydrogen peroxide-pretreated samples did not reverse the inhibition of Ca2+-ATPase by hydrogen peroxide.

Prostaglandin E2 binding sites in bovine iris-ciliary body.

In the eye, prostaglandins (PGs), in particular PGE2 and PGF2 alpha, may induce vasodilation, disruption of the blood-aqueous barrier, and biphasic effects on intraocular pressure, depending on the species. The initial event leading to many of these physiologic responses is the interaction between the PG and a receptor. We have explored the specificity and selectivity of PGE2 receptors in bovine iris-ciliary body (ICB) membrane preparations. Pigment-free bovine ICB membranes were prepared by high-speed sucrose density-gradient centrifugation. Membranes were incubated with 1 nM 3H-PGE2 in the presence or absence of varying concentrations of unlabeled PGE2 or F2 alpha. Binding of 3H-PGE2 to membranes at 37 degrees C increased linearly with protein concentration, and binding reached equilibrium in 30 min. Specific PGE2 binding represented 80% of total 3H-PGE2 binding. Studies with unlabeled PGE2 or F2 alpha, as competing ligands, showed a dose-dependent inhibition of 3H-PGE2 specific binding. The IC50 for unlabeled PGE2 and F2 alpha was 3 and 379 nM, respectively, which suggests a 100-fold greater selectivity of the binding sites for PGE2 over F2 alpha. Scatchard analysis of saturation data revealed a mean Kd value of 13.3 nM with a Bmax of 156 fmoles bound/mg protein. The general linearity of our Scatchard plots tends to suggests a single class of binding sites for PGE2, although more than a single binding site could be present. These results indicate that binding sites selective for PGE2 exist in the bovine ICB.

Prostaglandin E2 and F2 alpha binding sites in the bovine iris ciliary body.

PURPOSE: To determine the regional distribution and selectivity of prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) specific binding sites in membrane preparations from bovine iris ciliary body. METHODS: Bovine eyes were obtained fresh from a local abattoir. Whole irides were separated into sphincter muscle, ciliary body, and remaining iris tissue then homogenized in 50 mM tris buffer, pH 7.5, containing cyclooxygenase, protease, and soybean trypsin inhibitors. Membranes were obtained after three-stage high-speed centrifugation then reconstituted in buffer. Aliquot portions were incubated with 3H-PGE2 or 3H-PGF2 alpha at 37 degrees C for 30 min in a final volume of 500 microliters. Competition studies were performed in the presence of up to 1000-fold excess unlabeled ligand. At the end of a 30-min incubation period, free and membrane bound ligand were separated by rapid filtration through a type HA millipore filter preequilibrated with buffer. The radioactivity bound to the membranes retained on the filter was quantitated in a scintillation counter. RESULTS: The equilibrium dissociation constant and maximum number 3H-PGE2 saturable binding sites were determined by Scatchard analysis. The data best fit to a single binding site model for all three membrane preparations. The majority of the 3H-PGE2 specific binding sites were in sphincter muscle (65%), followed by iris (17%), and ciliary body (18%). 3H-PGE2 alpha binding sites were not measurable in either iris or ciliary body and PGF2 alpha was less competitive than PGE2 in all tissues. The rank order of potency for agonist displacement by both 3H-PGE2 and 3H-PGF2 in sphincter muscle membrane was PGE2 > PGF2 alpha > PGD2 > Iloprost. It was determined that 3H-PGE2 and 3H-PGF2 alpha binding in the bovine sphincter was primarily to EP not FP, DP, or IP prostaglandin receptor types. CONCLUSIONS: The characteristics of PGE2 and PGF2 alpha specific binding sites in the bovine sphincter correlate with its in vitro contractile response to these prostanoids. The inability of PGF2 alpha to effectively compete with PGE2 for specific binding sites in the sphincter and lack of high affinity PGF2 alpha specific binding sites in the iris and ciliary body suggests that this prostaglandin may exert its in vivo effects through PGE2 specific binding sites.

The influence of calcium on the rabbit lens sodium pump.

PURPOSE: Experiments were conducted to examine how elevation of calcium in the lens impairs the lens sodium pump. METHODS: Rabbit lenses were incubated in the presence or absence of calcium ionophore A23187. 86Rb uptake by the intact lens was measured as an index of sodium pump activity. Na,K-ATPase (ouabain-sensitive adenosine triphosphate [ATP] hydrolysis) activity was determined in membrane material isolated from the lens. Lens ion content and ATP content also were determined. RESULTS: Rabbit lenses gained calcium after exposure to calcium ionophore A23187 or ionomycin. Ionophore-treated lenses also gained sodium and lost potassium. A diminished rate of 86Rb uptake observed in ionophore-treated lenses suggests that elevation of lens calcium leads to sodium pump inhibition. In contrast, the rate of 86Rb efflux was not altered by A23187, indicating that elevated lens calcium causes little change in passive cation permeability. Membranes isolated from A23187-treated lenses were found to have normal Na,K-ATPase activity. However, calcium had a small direct inhibitory effect upon the Na,K-ATPase activity measured in freshly prepared lens membranes isolated from control (nonionophore-treated) lenses. Using a luciferase assay, A23187-treated lenses were found to have a normal ATP content. CONCLUSIONS: Calcium may impair the ability of the lens, Na,K-ATPase to pump ions in the intact lens, but appears to leave the ATP-hydrolyzing capability of the isolated enzyme unchanged.

Na,K-ATPase in simulated eye bank and cryoextracted rabbit lenses, and human eye bank lenses and cataracts.

In the rabbit, cryoextraction of the lens and subsequent storage in Tyrode's solution did not alter the Na,K-ATPase activity from that determined in immediately excised rabbit lenses. Similarly, the procedures employed with the rabbit eye to simulate collection and storage of normal human eyes (eye banking) had no effect upon the Na,K-ATPase activity of the lens. These results permitted the investigation of human lenses with the knowledge that measured Na,K-ATPase activity had not been altered grossly by any manipulation procedures. Analysis of Na,K-ATPase activity in 44 eye bank lenses, 14 primary nuclear cataracts, 11 primary cortical cataracts, 18 primary posterior subcapsular cataracts, and 31 mixed cataracts revealed no significant difference in the enzyme activity between these groups. Similarly, there was no correlation between electrolyte levels and Na,K-ATPase in a further 18 mixed cataracts. It is concluded that, despite an often pronounced electrolyte imbalance, human cataract can develop without significant alteration in Na,K-ATPase activity.