L L Hansen

A randomised prospective study of treatment of non-ischaemic central retinal vein occlusion by isovolaemic haemodilution.

In a randomised study 25 patients over 50 years of age with non-ischaemic central retinal vein occlusion (CRVO) were assigned to either a treatment (14 patients, isovolaemic haemodilution) or a control group (11 patients, no treatment). After three months eight eyes in patients with haemodilution improved, whereas none of the untreated eyes had better visual acuity (p less than 0.01). Thirteen haemodiluted and 11 control patients could be observed for one year. Six eyes of the haemodiluted patients retained a better visual acuity, whereas no improvements had occurred in the control group (p less than 0.025). In fluorescein angiography the lowering of the packed cell volume to 35-32% accelerated the time of maximal venous filling (tmvf) from 17.4 (SEM 1.4) s to 11.4 (SEM 0.9) s (p less than 0.005). In patients with non-ischaemic CRVO without treatment the passage time did not change. The shortened tmvf reflects a higher blood velocity. Thus isovolaemic haemodilution improves the visual prognosis in non-ischaemic CRVO probably by inducing a higher blood fluidity, which results in higher blood velocity, at least in areas of compromised retinal microcirculation.

A randomised prospective study on treatment of central retinal vein occlusion by isovolaemic haemodilution and photocoagulation.

Thirty eight patients with ischaemic and non-ischaemic central retinal vein occlusion were evaluated for the effect of isovolaemic haemodilution. They were allocated at random to a haemodilution group (19 patients, panretinal photocoagulation and isovolaemic haemodilution) and a control group (19 patients, panretinal photocoagulation). Haematocrit was lowered in steps to 30 to 35% in the haemodilution group by repeated exchanges of whole blood for plasma and dextran (MW 40 000) and kept at this level for a period of six weeks. The haemodilution did not lead to serious complications. Three months after starting the treatment eight of 19 patients with haemodilution showed a better visual acuity, whereas only one of 19 control patients had improved. Seven of 17 patients with haemodilution, but only one of 17 control patients, retained a better visual acuity after one year. In the haemodilution group there were fewer patients with macular fibrosis and more with only minor foveal changes. The haemodilution seems to be more effective in patients with ischaemic than with non-ischaemic central retinal vein occlusion. It is concluded that isovolaemic haemodilution improves the visual outcome of patients with central retinal vein occlusion, probably mediated by enhanced retinal blood flow.

Haemorheological changes in patients with retinal vein occlusion after isovolaemic haemodilution.

In 83 patients with central retinal vein occlusion and branch vein occlusion we measured the haematocrit (HCT), plasma viscosity (PV), red cell aggregation (RCA), red cell filterability (RCF) and apparent whole blood viscosity (WBV). A control group (n = 41) was matched for sex, age, and cardiovascular risk factors. Measurements were performed before and after treatment with isovolaemic haemodilution (IHD). We found no significant differences between patients with retinal vein occlusion (RVO) and control subjects in haematocrit, plasma viscosity, red cell aggregation, and red cell filterability and no increased whole blood viscosity in the patient group. Patients with ischaemic retinal vein occlusion and non-ischaemic retinal vein occlusion did not show different haemorheological parameters either. After treatment with haemodilution, only the haematocrit and whole blood viscosity were significantly decreased, and there were no changes in plasma viscosity, red cell aggregation or red cell filterability.

Effect and Compatibility of Isovolaemic Haemodilution in the Treatment of Ischaemic and Non-ischaemic Central Retinal Vein Occlusion

In a prospective study, 48 eyes with non-ischaemic and 35 with ischaemic central retinal vein occlusion (CRVO) were treated by isovolaemic haemodilution (IHD). Two or more cardiovascular risk factors were present in 42% of patients with non-ischaemic and in 69% of patients with ischaemic CRVO (p less than 0.025). Nevertheless, IHD in no case caused serious cardiovascular complications. Minor problems were short fainting spells in 5% and a general weakness in 16% of the haemodiluted patients. The effect of IHD was measured by determining the time of maximal venous filling (tmvf) in fluorescein angiographies. Lowering the packed cell volume to 32-35% accelerated the tmvf from 18.4 +/- 1.61 to 13.1 +/- 1.0 s (p less than 0.001) in eyes with non-ischaemic CRVO and from 24.5 +/- 1.2 to 14.8 +/- 1.3 s (p less than 0.001) in eyes with ischaemic CRVO. After 3 months, an increase in visual acuity had occurred in 27% of eyes with non-ischaemic CRVO and in 48.5% with ischaemic CRVO. These improvement rates could nearly be maintained after 1 year. 59% of eyes with non-ischaemic and 25% with ischaemic CRVO were able to read (visual acuity greater than or equal to 6/15) after 1 year.

Effect of aldosterone on sodium and potassium transport in the kidney

Abstract (1) In adrenalectomized rats dietary potassium (and sodium) intake modifies the effect of aldosterone on electrolyte excretion. Speculations on mode and tubular site of action of aldosterone are misleading, if urinary excretion rates are the only data available. 1. (2) The main site of action of aldosterone on potassium transport is located at the distal tubular level. The distal tubule and the collecting duct are mainly responsible for changes in the excretion pattern of potassium. 2. (3) With electrophysiological methods it can be demonstrated that the transport number for potassium in the distal tubule of adrenalectomized rats is reduced significantly and is normalized by acute administration of aldosterone (2 μg/100gmb.w.). The data indicate that the relative permeability of the luminal membrane of the distal tubule is under the influence of mineralocorticosteroids. The impairment of distal potassium secretion in adrenal insufficiency is mainly due to a reduced permeability of the luminal membrane. Aldosterone stimulates potassium secretion by increasing the luminal permeability of the distal tubule.

Effect of Calcium, Furosemide and Chlorothiazide on Net Volume Reabsorption and Basolateral Membrane Potential of the Distal Tubule*

In the distal tubule of the isolated kidney of Amphiuma net volume reabsorption (split-oil droplet method) and basolateral membrane potential (Ψb) were measured. Luminal perfusion solution could be changed rapidly from 108 mmol·l−1 NaCl plus 0.1 mmol·l−1 calcium to solutions containing 103 or 97 mmol·l−1 NaCl plus 3.6 or plus 7.2 mmol·l−1 calcium. Furthermore, 10−4 mol·l−1 furosemide or chlorothiazide were applied luminally. (1) Addition of 7.2 mmol·l−1 calcium hyperpolarized Ψb from −73.4 mV to −108.3 mV and inhibited net volume reabsorption. (2) Similarly, when furosemide was injected, Ψb was hyperpolarized and net volume reabsorption reduced. Application of both high calcium and furosemide further inhibited volume reabsorption. (3) The effects of chlorothiazide were similar to those of furosemide. However, when both high calcium and chlorothiazide were administered Ψb and volume reabsorption were almost normalized. (4) The data are consistent with the hypothesis that calcium and the diuretics interfere primarly with chloride uptake across the luminal membrane and thus reduce sodium chloride transport. When chlorothiazide in the presence of high luminal calcium almost normalized chloride transport, it is likely that its effects were by stimulating calcium transport and thus increasing intracellular calcium activity.

Sodium Conductance Changes by Aldosterone in the Rat Kidney

SummaryTo asses passive permeability properties of distal, and proximal tubules of the rat kidney the tubular lumen was perfused with solutions of 1.5 and 150 mM Na/l while transtubular potential differences were recorded. Sodium transport numbers (TNa) were calculated.TNa in the distal tubule of adrenalectomized rats was acutely increased from 0.21 to 0.27 by aldosterone (5 μg/100 g B.W.). This effect of aldosterone could not be reduced by concomitant injection of cycloheximide (100 μg/100 g B.W.). Aldosterone was also effective in control rats. In the proximal tubule similar data were obtained. However, the aldosterone-induced increase of conductance was slightly reduced with cycloheximide.These measurements of transepithelial sodium conductance indicate that aldosterone, in addition to the already known stimulation of active sodium transport, increases overall permeability of the tubular wall to sodium. In the distal tubule this effect indicates an increase of the luminal membrane permeability whereas in the proximal tubule aldosterone may facilitate the diffusion of sodium through the intercellular shunt path and/or the luminal membrane. The passive components of transepithelial electrolyte transfer seem to be less sensitive to inhibition of protein synthesis than the active transport components.

Relationship between peritubular membrane potential and net fluid reabsorption in the distal renal tubule of Amphiuma.

Amphiuma kidneys were isolated and perfused with modified Ringer solution and peritubular and transepithelial membrane potentials (p.d.s) in distal tubules measured with micro‐electrodes during rapid changes of luminal electrolyte concentrations. Peritubular membrane potential and net fluid reabsorption (split‐oil‐droplet method) were also measured with and without application of various drugs known to alter transport. Raising the luminal sodium concentration from 10 to 100 mM reversibly increased the peritubular p.d. The magnitude of the peritubular p.d. was a saturable function of luminal sodium concentration. In the presence of chloride in the lumen the peritubular hyperpolarization following increased luminal sodium could be inhibited by luminal amiloride (10(‐4)M). Sodium‐induced hyperpolarization of the peritubular p.d. could be completely inhibited by 10(‐5)M‐ouabain. Adding amiloride (10(‐4)M) to the luminal fluid rapidly and reversibly depolarized the peritubular p.d. and inhibited fluid reabsorption. Addition of amphotericin B (20 micrograms/ml) to the luminal perfusion solution had no effect on peritubular p.d. at 100 mM‐luminal NaCl but at 10 mM‐NaCl, peritubular p.d. hyperpolarized. Fluid reabsorption was stimulated (with 100 mM‐NaCl in the lumen). Addition of amphotericin when the tubule was perfused on both sides with solutions containing a constant potassium concentration of 78 mM and a variable sodium concentration ranging from 7.8 to 34.5 mM revealed strong dependence of the peritubular hyperpolarization on the sodium concentration. Luminal furosemide (10(‐4)M) and chlorothiazide (10(‐4)M) and peritubular ethacrynic acid (10(‐4)M) all reduced fluid reabsorption but hyperpolarized the peritubular p.d. The data suggest the presence of an electrogenic sodium transport process in the peritubular membrane that directly contributes to the generation of the peritubular potential. In addition, chloride transport has an important role in determining this potential.

Haemorheological parameters in patients with retinal artery occlusion and anterior ischaemic optic neuropathy.

The haemorheological parameters haematocrit (Hct), plasma viscosity (PV), red cell aggregation (RCA), red cell filterability (RCF), apparent whole blood viscosity (WBV), and fibrinogen were measured in 31 patients with retinal artery occlusion (RAO), 25 patients with anterior ischaemic optic neuropathy (AION), and 19 patients with giant cell arteritis (GCA). The patient groups were compared with controls of same age and similar prevalence of cardiovascular risk factors. Patients with RAO and AION have a significantly decreased RCF in comparison with controls. All other parameters showed no differences. Patients with GCA had significantly decreased Hct and RCF and increased PV and fibrinogen. After 2 weeks of systemic treatment with high dose steroids in patients with GCA the plasma viscosity had returned to normal and was even lower than in controls, and the Hct and fibrinogen had reached normal levels.

Intracellular potassium activity of isolated human and rabbit corneal epithelium.

Abstract Single-barrelled open tip microelectrodes containing a potassium-selective liquid ion exchanger (Corning 477 317) were used to determine intracellular K-activity a K i in squamous and basal cells of isolated rabbit and human corneal epithelium. The intracellular potassium activity a K i during the five hours of incubation in Ringer solution was 114·3±23·6 mmol/l and 107·6±26·2 mmol/l for the basal cell layer of rabbit and human epithelia respectively. The corresponding values for the squamous cells of the superficial cell layer were 41·2±14·2 mmol/l and 50·2±11·1 mmol/l. Based on intracellular chemical concentrations of potassium c K i an apparent activity coefficient could be calculated that is close to that of a dilute solution of the same ionic strength. This indicates that intracellular potassium is essentially free in both epithelia. Ouabain (5 × 10 −5 mol/l) added to the bathing solution of the rabbit cornea lowered the transmembranal voltage Ψ M as well as the intracellular K-activities of squamous and basal cells. Three hours after application of ouabain a K i of the basal cells had decreased to about one third of its initial value. Under all experimental conditions the potassium equilibrium potential E K considerably exceeded Ψ M . Our data indicate: (1) The high absolute values for a K i imply that almost no potassium is bound or sequestered within the epithelial cells. (2) An active potassium uptake is necessary to explain the high K-activity in relation to the transmembranal voltage Ψ M . (3) There is an intraepithelial gradient of a K i within the corneal epithelia.