Effects of the dopamine D3 receptor agonist 7-hydroxy-2-(di-N-propylamino) tetralin in hyperthyroidism-induced premature ejaculation rat model.

Various factors are involved in the aetiology of premature ejaculation (PE). Hyperthyroidism is one of the causes of acquired PE, but the exact mechanism by which it causes the disorder is not yet understood. The aim of this study was to evaluate the role of the dopaminergic system in hyperthyroidism-induced PE by the intracerebroventricular microinjection of the preferentially active dopamine receptor agonist 7-hydroxy-2-(di-N-propylamino) tetralin (7-OH-DPAT) in a rat model of this disorder. Wistar rats were randomly divided into hyperthyroid and control groups, and ejaculation was induced by the ICV administration of 7-OH-DPAT. To evaluate the emission and expulsion phases of ejaculation, measurements of seminal vesicle pressure (SVP) and electromyographic recordings of the bulbospongiosus muscle were taken. The interval between the 7-OH-DPAT administration and the first ejaculation was significantly less in the hyperthyroid group (p < .01) than in the control group, and the maximum amplitude of the SVP values revealed a statistically significant difference between the groups (p < .01). The intervals between contractions of the seminal vesicle and bulbospongiosus muscles were also significantly less in the hyperthyroid group (p = .0187) than in the control group. No other results differed significantly between the groups. This study determined that hyperthyroidism altered only the emission phase of ejaculation.

Do penile haemodynamics change in the presence of hydrogen sulphide (H2 S) donor in metabolic syndrome-induced erectile dysfunction?

Erectile dysfunction (ED) is defined in relation to the metabolic syndrome (metS). Hydrogen sulphide (H2 S), a gasotransmitter, has been revealed to get involved in hypertension, insulin secretion and regulation of vascular tone especially in erectile physiology. This study aimed to investigate the effect of H2 S on metS-induced ED. Animals were divided into two groups as control and metS, which were fed with standard diet or 60% high-fructose diet for 10 weeks respectively. The metS model was evaluated with biochemical analyses, waist circumference/tibia length ratio and HOMA index. Penile hemodynamic parameters were evaluated by the measurement of intracavernous pressure/mean arterial pressure ratio during cavernous nerve stimulation in the presence and absence of intracavernous injection of NaHS (100 µg/50 µl) and its control 0.9%NaCl (50 µl) in both groups. H2 S levels were measured in penile tissues by methylene blue assay. H2 S levels were significantly decreased in the penile tissues of the metS group. Decreased intracavernous pressure/mean arterial pressure ratio improved after intracavernous administration of NaHS in the metS group. These results suggest the significant role of H2 S in the metS-induced erectile dysfunction that could be a new therapeutic target.

Time-course changes of nLDL-induced erectile dysfunction.

Hyperlipidemia is an important risk factor for atherosclerosis and is frequently seen in patients with erectile dysfunction (ED). This study was designed to evaluate whether the acute effect of native low-density lipoprotein (nLDL) on intracavernosal pressure (ICP) is reversible and related to plasma asymmetrical dimethylarginine (ADMA), endogenous inhibition of endothelial nitric oxide synthase (eNOS) levels and eNOS expression in cavernous tissues. Hyperlipidemia was induced by a single dose of intravenous 4 mg kg-1 nLDL. Experiments were performed 72 h (72H), 2 weeks (2W) and 8 weeks (8W) after nLDL injection. Endothelium-dependent relaxations, the ratio of ICP to mean arterial pressure (MAP; ICP/MAP), plasma ADMA levels and eNOS mRNA and protein levels were evaluated. The ICP/MAP ratio decreased in both the 2W and 8W groups. Endothelium-dependent relaxation responses to acetylcholine in the rat thoracic aorta were damaged in the 8W group. Plasma ADMA levels increased in the 8W group. mRNA expression of eNOS decreased in a time-dependent manner, whereas the protein expression increased. These results suggest that acute nLDL injection-induced impairments in erectile functions during an 8-week period are irreversible and might be related to an increase in ADMA levels and changes in the regulation of the eNOS/NO pathway.

Acute effect of rosiglitazone on relaxation responses in hypercholesterolemic corpus cavernosum.

Thiazolidinediones (TZDs) improve vascular endothelial dysfunction through non-genomic effects of peroxisomal proliferator-activated receptor γ. This study investigated the acute effect of one of the TZD, rosiglitazone, on endothelium-dependent relaxation response of corpus cavernosum (CC) in hypercholesterolemic rabbits. New Zealand rabbits were divided into two groups randomly as control and cholesterol groups. Hypercholesterolemia was induced by feeding rabbits with 2% cholesterol diet (w/w) for 6 weeks. Endothelium-dependent and -independent relaxation response of CC were evaluated in the presence of rosiglitazone by organ bath studies with cumulative doses of acetylcholine (Ach) and sodium nitroprusside (SNP). Maximal relaxation (Emax) response to Ach significantly decreased owing to hypercholesterolemia in CC tissues. However, in vitro incubation of rosiglitazone with different concentrations (0.1, 1 and 10 µm) did not improve the Ach-dependent Emax responses in hypercholesterolemic rabbit CC. Surprisingly, rosiglitazone caused a significant decrease in Ach-dependent relaxation in healthy CC. Emax responses to SNP did not differ in the presence of rosiglitazone in both the control and hypercholesterolemic groups. Rosiglitazone does not improve hypercholesterolemia-induced endothelial dysfunction in CC tissues while it dose-dependently impairs endothelium-dependent relaxation in healthy CC tissue.

The role of calcium entry on the relaxation response of rho-kinase inhibitor in rabbit renal artery.

This study was performed to clarify the role of extracellular and intracellular Ca2+ on rho-kinase enzyme inhibition-induced relaxation in rabbit renal arteries. The response to rho-kinase inhibitor (Y-27632) was studied in isolated renal artery segments precontracted with phenylephrine in the presence of voltage-gated calcium channel blocker nifedipine and in the absence of intracellular or extracellular Ca2+. Cumulative addition of rho-kinase inhibitor Y-27632 (10-8-10-5 M) produced a concentration-dependent relaxation in renal artery rings precontracted with phenylephrine. Preincubation with nifedipine (1µM) resulted in a significant increase in relaxation response to rho-kinase inhibitor Y-27632 compared with preincubation with DMSO; the solvent of nifedipine. The maximal relaxation to Y-27632 in renal arteries precontracted with phenylephrine was significantly increased in the Ca-free Krebs containing 100 µmol/l ethylene glycol tetraacetic acid (EGTA) but after depletion of intracellular stores with 20 mmol/l caffeine and 1mmol/l EGTA in Ca2+ free Krebs there was no significant difference between the relaxation to Y-27632 from control response in 2.5 mmol/l Ca2+ Krebs in the renal artery. These results suggest the involvement of extracellular Ca and L-type voltage-operated Ca2+ channels in phenylephrine-induced rho-kinase activation (Fig. 3, Ref. 20).

Evaluation of vascular smooth muscle and corpus cavernosum on hypercholesterolemia. Is resveratrol promising on erectile dysfunction?

The aim of this study is to evaluate the effects of hypercholesterolemia in thoracic aorta (TA), mesenteric artery (MA), renal artery (RA), and corpus cavernosum (CC) isolated from cholesterol-fed rabbits. For determination of the maximum detrimental effect, vasorelaxation and vasoconstriction results of arteries and CC have been compared. Animals were fed with a diet that contained 2% w/w cholesterol and 2% w/w high cholesterol plus resveratrol (4 mg kg(-1) per day) for 6-week duration. Total cholesterol levels in the plasma were measured. Vascular and endothelial functions in RA, TA, MA, and CC were assessed by isolated tissue bath with cumulative doses of acetylcholine and sodium nitroprusside. The statistical significance of differences of groups was analyzed by means of one-way ANOVA or Student's t-test. P-values <0.05 were considered significant. There have been no significant changes on plasma total cholesterol levels between cholesterol and cholesterol + resveratrol-treated groups. Vasorelaxation responses to acetylcholine in resveratrol-treated group showed significant changes when compared with hypercholesterolemic group. No statistically significant differences were seen between non-receptor-mediated vasorelaxation responses between the three groups. Resveratrol might be an effective treatment in the prevention of atherosclerotic changes in arteries and CC. The initial effects of hypercholesterolemia on erectile dysfunction and endothelial dysfunction may be precluded with resveratrol. This protective effect may also ensure the prevention of coronary arterial diseases and renovascular diseases in hypercholesterolemic patients.

Effect of verapamil on responses to endothelin-1 in aortic rings from streptozotocin-induced diabetic rats.

In this study, we investigated the constrictor responsiveness to endothelin-1 (ET-1, 10-30 n m) of aortic rings (under 1 g resting tension in Krebs-Bicarbonate solution) from 8-weeks streptozotocin (STZ, 65 mg kg-1, i.p)-induced diabetic rats and vehicle-treated control rats. The maximum ET-1-induced contraction of the aorta in diabetic rats was increased by 150%, but the EC50 of ET-1 remained unchanged. Although in both groups, verapamil reduced the constrictor responses to ET-1 (diabetic group P<0.001, control group P<0.05), there were not any significant differences between PD2 values. These results suggest that verapamil inhibits ET-1-induced Ca2+ entry through the L-type channel and this effect did not change in diabetes mellitus.

Pharmacological analysis of 5-hydroxytryptamine effects on human isolated ureter.

5-Hydroxytryptamine (5-HT) induced concentration-dependent contractions in human isolated ureteral strips in vivo. On the basis of available selective 5-HT agonists and antagonists, we have further investigated the receptors involved. At concentrations from 10 n m to 1 m m, 5-HT induced concentration-dependent contractions. Significant contractions were not observed with 5-HT1Aagonist 8-OH-DPAT (10(-9)-10(-4)m), 5-HT1Dalphaagonist sumatriptan (10(-9)-10(-4)m), 5-HT2agonist DOI (10(-9)-10(-4)m), 5-HT3agonist 2-methyl 5-HT (10(-9)-10(-3)m) and 5-HT4agonist renzapride (10(-9)-10(-3)m) on the human isolated ureter. On the other side, a 5-HT1-likeagonist 5-CT (10(-9)-10(-3)m) produced contractions on the isolated samples. The Emaxdeveloped by 5-CT was significantly smaller than that of the 5-HT (29% of 5-HT). Methithepin, the less selective 5-HT1/2antagonist (10(-9)-10(-6)m), 5-HT3antagonist, ondansetron (10(-9)-10(-5)m) and 5-HT4antagonist DAU 6285 (10(-8)-10(-6)m) did not antagonise the contractile responses to 5-HT. 10(-7)m ketanserin antagonised 5-HT induced contractile responses in ureteral strips. Additionally, combined administration of 5-HT4antagonist DAU 6285 (10(-6)m) and 5-HT1/2antagonist methithepin (10(-6)m) caused a rightward shift of the CRC of 5-HT yielding pEC50values of 4.68+/-0.15. 5-HT-induced contractile responses that were not abolished by TTX and atropine, thus supporting the suggestion that in the human, the contractile responses to cumulative addition of 5-HT of the ureter are not mediated by excitation of cholinergic neurons. In the present study the receptor mediating the contractile response to 5-HT in the human upper ureter could not be clearly designated 5-HT1-like, 5-HT2, 5-HT3or 5-HT4. This study suggests that contractile response to 5-HT in the upper segments of the human ureter appear to be mediated by an atypical 5-HT receptor subtype.

Circadian rhythmicity in serotonin-induced acute gastric mucosal injury in rats.

Time-dependent patterns in the susceptibility of the rat gastric mucosa to ulcerogenic stimuli involving stress or chemical injury have been described. The purpose of this study was to evaluate whether serotonin (5-HT)-induced gastric mucosal injury is produced in a circadian fashion in the rat model. In fasted Wistar rats (adapted for 3 weeks to a standard 12-h light-dark cycle), 5-HT administered subcutaneously (20 mg/kg, 4 h before autopsy) produced gastric mucosal injury. The stomachs were removed and the ulcers were scored for intensity, using a scale of 0-4. In studies performed at 4-h intervals, beginning 1 h after lights-on, most of the mucosal injury occurred at 2000 h, i.e. early in the dark phase. Likewise, serum corticosterone levels were also found to be high at the same time period. The time of 2000 h is approximately determined to be the beginning of the rats' active period. These results suggest that the extent of acute 5-HT-induced gastric mucosal injury varies with the time of day and that elevations in corticosterone concentrations might be responsible for the 5-HT-induced gastric mucosal injury.

Contractility changes of the deep dorsal penile vein due to serotonin.

PURPOSE: Penile erection is a complex neurovascular phenomenon that takes place with the active contribution of arterial and sinusoidal structures. However, some authors claim that larger veins including the deep dorsal veins that produce contractions, might be involved in the physiology of erection. This study was designed to clarify the contractile properties of deep dorsal penile veins (DDPV). MATERIALS AND METHODS: The effect of serotonin (5-HT), noradrenaline (NA), adenosine triphosphate (ATP) and acethylcholine (Ach) on the isolated DDPVs of 16 impotent men, 9 with veno-occlusive dysfunction and 7 without venous leakage, and 5 potent men (controls) who underwent radical prostatectomy, were examined in vitro. RESULTS: Although NA, ATP and Ach had no effect, 5-HT produced concentration-dependent contractions. Emax and pEC50 of 5-HT were 411 +/- 10 mg., 5.92 +/- 0.25; 1020 +/- 260 mg., 5.83 +/- 0.24 and 160 +/- 40 mg., 6.4 +/- 0.22 in controls and patients who had venous leakage and no venous leakage, respectively. Samples of controls were contracted only with 5-HT2 agonist, DOI (pEC50 = 5.63 +/- 0.02), and these contractions were antagonized with 5-HT2 antagonist ketanserin. On the other hand, both DOI (pEC50 = 6.30 +/- 0.77) and 5-HT1 agonist, 5-CT (pEC50 = 6.23 +/- 0.21) produced venoconstriction in patients with veno-occlusive dysfunction. CONCLUSIONS: The present findings suggest that 5-HT receptor functions in the DDPVs are of 5-HT2 subtype in potent men and the altered response to 5-HT in patients with veno-occlusive disease may play a role in the pathophysiology of impotence.

The effects of amrinone and glucagon on verapamil-induced myocardial depression in a rat isolated heart model.

1. We measured the ability of glucagon and amrinone, used alone and in combination, to improve the myocardial function in a rat isolated heart model of calcium channel blocker (CCB) cardiotoxicity. 2. Verapamil 10(-4) mol consistently decreased heart rate and cardiac contractile force in our Langendorff rat isolated heart preparations. Glucagon increased the heart rate in a dose-dependent fashion. Amrinone increased the heart rate only at the 1 x 10(-1) mol concentration, and had no significant effect on cardiac contractility. 3. A positive linear correlation was found between the glucagon concentration and the percent recovery of baseline contractile force. 4. Although complete reversal of verapamil-induced myocardial depression occurred at glucagon concentrations of > 3 x 10(-6) mol, amrinone produced only 23.8 +/- 3.6% recovery from baseline at its highest concentration (4 x 10(-3) mol). 5. When glucagon and amrinone were administered together, there was no additional increase over glucagon alone in the increase in contractile force. 6. Glucagon, and not amrinone, is an appropriate agent, capable of reversing verapamil-induced myocardial toxicity in this rat isolated heart model. In vivo studies should be performed to assess whether this may be a reliable therapy in clinical cases.

Gastric antisecretory effect of serotonin: quantitation of release and site of action.

Despite many reports that serotonin (5-HT) inhibits gastric acid output, the role and mechanism of action of endogenous 5-HT to modulate gastric secretion remain unclear. Vagal stimulation enhanced the basal rate of 5-HT release into both the gastric lumen (600%) and the portal circulation (265%) of the rat. The peak rate of 5-HT release into the portal circulation was 1,000-fold higher that luminal release (12 micrograms/min and 1.2 ng/min, respectively). To elucidate site(s) of action of 5-HT to inhibit acid secretion, several approaches were taken. Intraluminal perfusion of exogenous 5-HT to encompass enhanced levels seen after vagal stimulation did not reduce gastric acid output. In contrast, administration of systemic 5-HT, which raised portal venous 5-HT to similar levels as vagal stimulation, had a marked antisecretory effect. Chemical or surgical ablation of enteric or sympathetic nerves innervating the stomach did not attenuate the inhibitory effect of exogenous 5-HT on gastric acid output. The antisecretory effect of systemic 5-HT was insensitive to pretreatment with piroxicam, doxantrazole, close gastric intra-arterial sodium nitroprusside, somatostatin monoclonal antibody, or bilateral adrenalectomy. The results suggest that 5-HT is released from endogenous stores into the portal circulation in sufficient quantities after vagal stimulation to alter gastric physiology and that its action is independent of the autonomic nervous system, gastric mucosal prostaglandins or somatostatin, mucosal mast cell or adrenal constituents, or changes in gastric mucosal blood flow.

The effect of acute bilateral adrenalectomy on serotonin-induced inhibition of gastric acid secretion and acute gastric mucosal injury in rats.

Serotonin (5-hydroxytryptamine, 5-HT) produces many changes in gastric functional parameters, including the inhibition of gastric acid secretion and changes in mucosal blood flow. Exogenous 5-HT has also been shown to induce gastric erosion. The influence of adrenalectomy on experimental lesions in the rat gastric mucosa remains controversial. The aim of this study was to see the effects of adrenalectomy on pentagastrin stimulated gastric acid secretion in anaesthetized male Wistar rats. Gastric acid was collected via cannulae placed in the stomach. 5-HT (3.5 mumol/kg, i.v.) inhibited pentagastrin stimulated acid output by 54% and produced haemorrhagic gastric lesions with a mean ulcer index of 2 +/- 0.3. Adrenalectomy prevented both 5-HT induced inhibition of gastric acid secretion and mucosal injury. The results suggest that the effects of 5-HT require an intact adrenal gland.

The effect of extracorporeal electromagnetic shock waves on the morphology and contractility of rabbit ureter.

PURPOSE: Although extracorporeal shock wave lithotripsy (ESWL) is known to cause pathologic changes in various organs, little is known about its effects on the ureter, the target organ in ESWL of ureteral stones in situ. In this study, we sought to determine the short-term effects of ESWL on the ureter. MATERIALS AND METHODS: Left lower ureteral segments of 21 rabbits were removed to serve as the control group and 2000 shocks were applied to the right lower ureters. Groups of 7 rabbits were sacrificed 1, 3 and 5 days after shock wave exposure. While histomorphological alterations were examined under light and transmission electron microscopy, contractility of all ureters was determined in organ baths. RESULTS: The epithelial cells disclosed no change after shock wave application. Histologically the muscular layer was the most affected part of the ureter. There was interstitial and intracellular edema on light microscopy and marked chromatin and mitochondrial changes at the subcellular level. The adventitial layer was also edematous. These changes were prominent on days 1 and 3 and returned to normal on day 5. The contractility of the ureters on day 1 was significantly reduced (p < 0.05). However, the contractility of the samples on days 3 and 5 were not significantly different from controls. CONCLUSION: Our findings demonstrate that electromagnetic shock waves produce reversible morphological and functional changes in rabbit ureteric muscle.

8-OH-DPAT stimulates gastric acid secretion through a vagal-independent, adrenal-mediated mechanism.

Serotonin (5-hydroxytryptamine, 5-HT) is a neuroendocrine component of the gastrointestinal tract. 5-HT1A receptors exist both in the brain and have been demonstrated autoradiographically in high density in the rat stomach. However, the physiologic role of 5-HT1A receptors in modulating gastric function is not known. The effect of the selective 5-HT1A receptor agonist, (+/-)-8-hydroxy-2-(n-dipropylamino)tetralin (8-OH-DPAT), on gastric acid secretory function was compared to 5-HT in acute, urethane-anesthetized gastric-fistulated rats during pentagastrin infusion. 5-HT inhibited, but 8-OH-DPAT stimulated, gastric acid secretion in a dose-dependent manner. Bilateral cervical vagotomy or celiac ganglionectomy did not reverse the effect of 8-OH-DPAT on acid secretion. However, the enhancement of acid by 8-OH-DPAT was attenuated by acute adrenalectomy or close intra-arterial administration of spiperone, but not idazoxan. Thus, the data suggest that the selective 5-HT1A receptor agonist 8-OH-DPAT may augment gastric secretory function via an adrenal-dependent mechanism.

Serotonin causes acute gastric mucosal injury in rats, probably via 5HT1D receptors.

5-HT-induced acute gastric mucosal injury was assessed in rats by using 5HT1, 5HT2, 5HT3, 5HT4 or muscarinic receptor related drugs. Rats were treated with antagonists i.p. and 30 minutes later either vehicle, 5-HT (20 mg/kg) or other agonists were administered s.c. The stomachs were removed 4 hours after the last injection and mucosal integrity was assessed by light microscopy using a histological ulcer index (HUI). The HUI was found to be significantly increased following 5-HT administration (1.57 +/- 0.3) when compared with controls (0.14 +/- 0.1). 5HT1 agonist 5-carboxamidotryptamine (20 mg/kg) produced acute gastric erosion and increased the HUI (P < 0.05). The HUI in the animals receiving 5-HT1D agonist sumatriptan (7 mg/kg) was found to be 1.62 +/- 0.24. 5HT2 antagonist ketanserine (2.5-15 mg/kg), 5HT3 antagonist ondansetron (1-5 mg/kg), 5HT4 antagonist DAU 6285 (1-10 mg/kg) and atropine (1.5-30 mg/kg) exerted no effect whereas 5HT1/2 antagonist metitepine (0.05-0.5 mg/kg) caused a dose dependent inhibition of the effect of 5-HT. The results from this study demonstrate that 5-HT causes acute gastric mucosal injury and this injury is probably due to the activation of the 5-HT1D receptors.

Influence of serotonin on the human ureter: an in vitro pharmacological study.

The influence of serotonin (5-hydroxytryptamine, 5-HT) on human ureteral smooth muscle was explored in a series of in vitro experiments. 5-HT evoked a dose-dependent contraction of the ureter. The effect of 5-HT was unaltered by blockade of 5HT3 and 5HT4 receptors and muscarinic cholinergic receptors. The 5HT2 receptor antagonist ketanserin (KT; 10(-5)-10(-4) M) and mixed 5HT1/5HT2 receptor antagonist methysergide (MS; 5 x 10(-5) M) inhibited the effect of 5-HT. Since the antagonist dissociation constant at 5HT2 receptors for both KT and MS is found to be approximately 10(-9) M, it is concluded that this contractile effect may have been mediated by some other, as yet uncharacterized 5-HT receptor. We believe that 5-HT is a potential neurotransmitter in the human upper ureteral smooth muscle.

A comparison of the serum concentration time-curves of amikacin-administered patients before and after open heart surgery.

The effects of open heart surgery on amikacin concentration time-curves were investigated in eight patients who were scheduled for open heart surgery at a Thoracic and Cardiovascular Surgery Department. A 500 mg single dose of amikacin was administered parenterally to the volunteers pre- and postoperatively and the serum concentration time-curves were compared. Serum amikacin levels after pre-operative intramuscular (IM) administration did not reach therapeutic values. By comparison, preoperative and postoperative IM or intravenously (IV) administration resulted in therapeutic serum amikacin levels. It was concluded that IM administration preoperatively was not appropriate. Serum levels of amikacin were also shown to fall below therapeutic values 8 h after administration. It is recommended that dosing intervals with amikacin should not exceed 8 h.

In vitro adsorption of dichlorvos and parathion by activated charcoal.

Accidental and suicidal ingestions of organophosphate compounds continue to be a common occurrence in Turkey. Activated charcoal administration without gastric emptying has been advocated as primary therapy in most acute poisoning cases, although some references do not recommend activated charcoal use in organophosphate poisoning. This study was performed to determine the in vitro adsorption of dimethyl dichlorovinyl phosphate (dichlorvos) and parathion by activated charcoal over a wide range of charcoal:organophosphate ratios (1:1, 2.5:1, 5:1, 10:1 and 20:1, g:g). The charcoal binding ability of dichlorvos and parathion were studied in both pH 1.2 and pH 7 environments. The supernatant was extracted with n-hexane and then analyzed by gas chromatography. Each incremental increase in charcoal dose increased the percent adsorption of dichlorvos and parathion. At the 20:1 ratio, 82.8 +/- 2.0/87.3 +/- 2.9% (pH 1.2/7.0) of dichlorvos and 59.3 +/- 4.5/64.5 +/- 6.1% (pH 1.2/7.0) of parathion were bound by activated charcoal. There were no significant differences in amounts of compound bound in the acid and neutral solutions. Large doses of activated charcoal effectively bind dichlorvos and parathion in vitro. In vivo research should be performed to determine activated charcoal's role in organophosphate poisoning cases.

A comparison of digoxin concentration--time curves before and after open-heart surgery.

The effects of open heart surgery on serum digoxin concentration--time curves were investigated in 10 cardiac patients receiving 0.25 mg/day digoxin. Blood samples were obtained from the patients immediately before and 1, 2, 3, 5, 8, 16 and 24 h after digoxin administration, both before open-heart surgery and 7 days after surgery. Serum digoxin concentrations, determined by fluorescence polarization immuno-assay, significantly (P < 0.05) increased after surgery, as did the maximum serum concentrations and the areas under the concentration-time curves. After surgery there was a significant increase in the serum gamma-glutamyl transferase concentration and a significant reduction in the total protein concentration. A reduction of digoxin dose may be appropriate for patients who have undergone open-heart surgery.