Developing Healthcare Team Observations for Patient Safety (HTOPS): senior medical students capture everyday clinical moments.

BACKGROUND: Aviation has used a real-time observation method to advance anonymised feedback to the front-line and improve safe practice. Using an experiential learning method, this pilot study aimed to develop an observation-based real-time learning tool for final-year medical students with potential wider use in clinical practice. METHODS: Using participatory action research, we collected data on medical students' observations of real-time clinical practice. The observation data was analysed thematically and shared with a steering group of experts to agree a framework for recording observations. A sample of students (observers) and front-line clinical staff (observed) completed one-to-one interviews on their experiences. The interviews were analysed using thematic analysis. RESULTS: Thirty-seven medical students identified 917 issues in wards, theatres and clinics in an acute hospital trust. These issues were grouped into the themes of human influences, work environment and systems. Aviation approaches were adapted to develop an app capable of recording real-time positive and negative clinical incidents. Five students and eleven clinical staff were interviewed and shared their views on the value of a process that helped them learn and has the potential to advance the quality of practice. Concerns were shared about how the observational process is managed. CONCLUSION: The study developed an app (Healthcare Team Observations for Patient Safety-HTOPS), for recording good and poor clinical individual and team behaviour in acute-care practice. The process advanced medical student learning about patient safety. The tool can identify the totality of patient safety practice and illuminate strength and weakness. HTOPS offers the opportunity for collective ownership of safety concerns without blame and has been positively received by all stakeholders. The next steps will further refine the app for use in all clinical areas for capturing light noise.

Enhanced purinergic contractile responses and P2X1 receptor expression in detrusor muscle during cycles of hypoxia-glucopenia and reoxygenation.

Bladders from patients with detrusor overactivity have an increased atropine-resistant contractile response to nerve stimulation. The bladder has also been shown to be very susceptible to hypoxia-glucopenia and reperfusion injury, leading to the hypothesis that episodes of hypoxia-glucopenia and reoxygenation result in increased atropine-resistant responses to nerve stimulation in the detrusor muscle. Detrusor muscle strips were suspended in a Perspex organ bath chamber of volume 0.2 ml perfused with Krebs solution at 37°C aerated with 21% O2, 5% CO2 and the balance nitrogen. Hypoxia-glucopenia was induced by switching perfusion to Krebs solution without glucose, gassed with 95% nitrogen and 5% CO2. Atropine-resistant contractile responses increased by 40.5 ± 7.3% after four cycles of hypoxia-glucopenia (10 min) and reoxygenation (1 h), whereas α,ß-methylene ATP-resistant responses did not increase. Expression of P2X1 receptors in the bladder was increased after hypoxia-glucopenia and reoxygenation cycling, and ATP release from stimulated bladder strips during cycling was also increased. Other P2X receptor-mediated mechanisms may also be involved in the augmentation of bladder contraction during hypoxia-glucopenia and reoxygenation cycling, because a non-specific P2X antagonist blocked most of the augmented response, whereas a P2X1-specific antagonist prevented only part of the augmentation of contractile response induced by hypoxia-glucopenia and reoxygenation. In conclusion, four cycles of hypoxia-glucopenia and reoxygenation increased the purinergic, but not the cholinergic, contractile responses to nerve stimulation. Increased P2X1 receptor expression and ATP release may have contributed to the augmentation of contractile response induced by hypoxia-glucopenia and reoxygenation. Purinergic antagonists may, therefore, be a useful therapeutic option for the treatment of overactive bladder with increased purinergic-mediated contractions.

Reduced effectiveness of HMR 1098 in blocking cardiac sarcolemmal K(ATP) channels during metabolic stress.

ATP-sensitive K(+) (K(ATP)) channels are involved in ischemic cardioprotection induced by preconditioning (IPC), though the relative role of sarcolemmal (sK(ATP)) and mitochondrial (mitoK(ATP)) channels remains controversial. The sK(ATP)-selective sulphonylthiourea HMR 1098 has often been reported to be without effect on ischemic cardioprotection, suggesting minimal involvement of sK(ATP). Since some sulphonylureas show reduced potency under conditions of metabolic stress, we used patch clamp to assess the ability of HMR 1098 to block sK(ATP) currents of adult rat ventricular myocytes activated by metabolic inhibition (MI, NaCN+iodoacetate). In contrast to the prototype sulphonylurea glibenclamide, HMR 1098 (10 muM) was without effect on sK(ATP) currents, and also did not inhibit MI-induced action potential shortening. However, HMR 1098 blocked sK(ATP) current induced by the K(ATP) opener pinacidil (IC(50)=0.36+/-0.02 muM), and reversed pinacidil-induced action potential shortening. In inside-out patches, block by HMR 1098 was relieved by increasing MgADP concentrations (1-100 muM). HMR 1098 inhibited pinacidil-activated recombinant Kir6.2/SUR2A channels with a similar IC(50) (0.30+/-0.04 muM), but was less effective when channels were activated by low intracellular ATP. HMR 1098 displaced binding of the pinacidil analogue [(3)H]P1075 to native cardiac membranes with a biphasic inhibition curve. Our results show that HMR 1098 becomes a much less effective inhibitor of sK(ATP) during metabolic stress, and suggest that the lack of effect of HMR 1098 on ischemic cardioprotection reported in some studies may represent loss of block by the drug under these conditions rather than a lack of involvement of sK(ATP) channels.

SUR2A C-terminal fragments reduce KATP currents and ischaemic tolerance of rat cardiac myocytes.

C-terminal fragments of the sulphonylurea receptor SUR2A can alter the functional expression of cloned ATP-sensitive K(+) channels (K(ATP)). To investigate the protective role of K(ATP) channels during metabolic stress we transfected SUR2A fragments into adult rat cardiac myocytes. A fragment comprising residues 1294-1358, the A-fragment, reduced sarcolemmal K(ATP) currents by over 85% after 2 days (pinacidil-activated current densities were: vector alone 7.04 +/- 1.22; and A-fragment 0.94 +/- 0.07 pA pF(-1), n= 6,6, P < 0.001). An inactive fragment (1358-1545, current density 6.30 +/- 0.85 pA pF(-1), n= 6) was used as a control. During metabolic inhibition (CN and iodoacetate) of isolated myocytes stimulated at 1 Hz, the A-fragment delayed action potential shortening and contractile failure, but accelerated rigor contraction and increased Ca(2+) loading. On reperfusion, A-fragment-transfected cells also showed increased intracellular Ca(2+) and the proportion of cells recovering contractile function was reduced from 40.0 to 9.5% (P < 0.01). The protective effect of pretreatment with 2,4-dinitrophenol, measured from increased functional recovery and reduced Ca(2+) loading, was abolished by the A-fragment. Our data are consistent with a role for K(ATP) channels in causing action potential failure and reduced Ca(2+) loading during metabolic stress, and with a major role in protection by preconditioning. The effects of the A-fragment may arise entirely from reduced expression of the sarcolemmal K(ATP) channel, but we also discuss the possibility of mitochondrial effects.

Distribution of Kir6.0 and SUR2 ATP-sensitive potassium channel subunits in isolated ventricular myocytes.

The subcellular distribution of ATP-sensitive potassium (K(ATP)) channel subunits in rat-isolated ventricular myocytes was investigated using a panel of subunit-specific antisera. Kir6.1 subunits were associated predominantly with myofibril structures and were co-localized with the mitochondrial marker MitoFluor red (correlation coefficient (cc) = 0.63 +/- 0.05). Anti-Kir6.1 antibodies specifically recognized a polypeptide of 48 kDa in mitochondrial membrane fractions consistent with the presence of Kir6.1 subunits in this organelle. Both Kir6.2 and SUR2A subunits were distributed universally over the sarcolemma. Lower-intensity antibody-associated immunofluorescence was detected intracellularly, which was correlated with the distribution of MitoFluor red in both cases (cc, Kir6.2, 0.56 +/- 0.05; SUR2A, 0.61 +/- 0.06). A polypeptide of 40 kDa was recognized by anti-Kir6.2-subunit antibodies in western blots of both microsomal and mitochondrial membrane fractions consistent with the presence of this subunit in the sarcolemma and mitochondria. Similarly, SUR2A and SUR2B subunits were detected in western blots of microsomal membrane proteins consistent with a sarcolemmal localization for these polypeptides. SUR2B subunits were shown in confocal microscopy to co-localize strongly with t-tubules (cc, 0.81 +/- 0.05). Together, the results indicate that Kir6.2 and SUR2A subunits predominate in the sarcolemma of ventricular myocytes consistent with a Kir6.2/SUR2A-subunit combination in the sarcolemmal K(ATP)channel. Kir6.1, Kir6.2 and SUR2A subunits were demonstrated in mitochondria. Combinations of these subunits would not explain the reported pharmacology of the mitochondrial K(ATP) channel (Mol Pharmacol 59 (2001) 225) suggesting the possibility of further unidentified components of this channel.

Inhibition of the contractile responses of isolated human and rat bladders by clenbuterol.

PURPOSE: We investigated the inhibition of the contractile responses of human continent and unstable detrusor muscle by the beta2 agonist clenbuterol as well as the inhibition of electrical field stimulation evoked contractile responses of isolated rat bladder muscle strips by orally administered clenbuterol. MATERIALS AND METHODS: The contractile responses of human continent and unstable detrusor muscle strips to electrical field stimulation (0.05 milliseconds, 0.5 to 80 Hz.) were measured before and after adding 10(-9) to 10(-4) M. clenbuterol in vitro. In addition, 6 rats per group were dosed orally with 2 microg x kg(-1) clenbuterol daily acutely (1 dose) or chronically (1 dose daily for 8 days), or with distilled water to serve as controls. The contractile response to electrical field stimulation of strips of isolated detrusor muscle was then measured. Serum clenbuterol levels were analyzed in duplicate by enzyme-linked immunosorbent assay and high performance liquid chromatography. RESULTS: In vitro clenbuterol significantly inhibited the electrical field stimulation evoked contractile responses of detrusor muscle strips from unstable but not continent human bladders. A significant inhibitory effect of clenbuterol on the electrical field stimulation evoked contractile response of rat detrusor muscle was observed after chronic but not acute oral dosing (p <0.01). Serum clenbuterol levels measured by enzyme-linked immunosorbent assay and high performance liquid chromatography were not significantly different. CONCLUSIONS: Clenbuterol or related beta2-adrenoceptor agonists may represent a useful therapeutic strategy for detrusor muscle overactivity.

K(ATP) channels mediate the beta(2)-adrenoceptor agonist-induced relaxation of rat detrusor muscle.

We propose that ATP-sensitive K(+) (K(ATP)) channels are normally inactive but involved in beta(2)-adrenoceptor stimulated relaxation of the rat bladder. Spontaneous detrusor muscle contractions were unaffected by glibenclamide (K(ATP) channel blocker) but were reduced when pinacidil (K(ATP) channel opener) concentrations exceeded 10(-5) M. Inhibition by beta(2)-adrenoceptor agonist clenbuterol [10(-6) M] of 1 Hz electrical field stimulated contractions was abolished by glibenclamide [10(-6) M]. Glibenclamide [10(-6) M] decreased forskolin-induced relaxation [10(-9)-10(-4) M] in bladder muscle stimulated with 1 Hz electrical field. In the presence glibenclamide (10(-6) M) or myristoylated protein kinase A inhibitor (2)x[10(-6) M], clenbuterol [10(-9)-10(-5) M] failed to inhibit bladder contraction in response to 1 Hz electrical field stimulation. Therefore, K(ATP) channel opening and the subsequent hyperpolarization of cell membranes in response to beta(2)-adrenoceptor activation is mediated by raised cyclic-AMP levels and activation of protein kinase A. This counteracts ATP-stimulated depolarization in bladder muscle, thereby reducing cell contraction.

Inhibition of the contractile response of the rat detrusor muscle by the beta(2)-adrenoceptor agonist clenbuterol.

The action of clenbuterol, beta(2)-adrenoceptor agonist, on the contractile response of isolated rat detrusor muscle strips was investigated in vitro. Clenbuterol (10(-5) M) inhibited the detrusor muscle frequency response (1-40 Hz, p<0.02) with a more pronounced effect at 1 Hz than 40 Hz. Clenbuterol (10(-6) M) significantly inhibited the contractile response to exogenous ATP (10(-4) to 10(-2) M, p<0.05) but not to carbachol (10(-9) to 10(-4) M). The presence of 10(-5) M ICI 118, 551, beta(2)-adrenoceptor antagonist, shifted significantly the clenbuterol dose-response to 1 Hz electrical field stimulation (EC(50) 3.4x10(-6) M (+/-2.2x10(-6) M) for clenbuterol alone, to 4.1x10(-4) M (+/-8.8 x10(-5) M), P<0.05). In conclusion, clenbuterol inhibits electrical field and ATP-stimulated contractions of detrusor muscle. Reversal of the clenbuterol inhibition of detrusor muscle contraction by ICI 118, 551 shows that clenbuterol is probably acting through postsynaptic beta(2)-adrenoceptors, which modulate the response to ATP released from purinergic nerves.

Inhibition of isolated rat and human detrusor muscle contraction by disopyramide.

1. The aim of this study was to investigate the effect of in vitro and in vivo disopyramide treatment on human and rat isolated detrusor muscle contractile response. Muscle strips were suspended in an organ bath chamber containing Kreb's solution at 37 degrees C aerated with 95% oxygen and 5% carbon dioxide. 2. Disopyramide antagonized significantly the contractile response of isolated human detrusor muscle to carbachol stimulation, shifting the concentration-response curve to the right in a parallel manner. The pA2 for competitive inhibition was estimated to be 6.4 with a slope of 0.64 for disopyramide. 3. Rat detrusor muscle contractile response to electrical field stimulation (EFS) was inhibited by 28% (P < 0.01) after in vitro administration of disopyramide (7.5 x 10(-6) M). Disopyramide had no effect on the atropine-resistant component of the response to EFS or on spontaneous contractions of isolated rat detrusor muscle strips. The concentration-response curve to carbachol was competitively antagonized by disopyramide with a pA2 of 6.3 and a Schild curve a slope of 0.85. 4. Disopyramide (7.5 x 10(-6) M) had no effect on rat detrusor contractile response to low concentrations of KCl but at high concentrations contraction was reduced significantly by 16% (P < 0.01). 5. In vivo treatment of rats with disopyramide for 8 days or with a single dose had a significant inhibitory effect on the contractile response of detrusor muscle strips. 6. In conclusion, disopyramide had a significant anticholinergic effect on isolated human and rat detrusor muscle contraction.

Characterisation of Kir2.0 proteins in the rat cerebellum and hippocampus by polyclonal antibodies.

Rabbit polyclonal antibodies were raised to rat Kir2.0 (Kir2.1, Kir2.2 and Kir2.3) inwardly rectifying potassium ion channel proteins. The antibody specificities were confirmed by immunoprecipitation of [35S]-methionine-labelled in vitro translated channel proteins and western blotting. Immunohistochemistry revealed a different patterns of expression of Kir2.0 subfamily proteins in the rat hind-brain (cerebellum and medulla) and fore-brain (hippocampus). Notably, only Kir2.2 protein was detected in the cerebellum and medulla, Kir2.1, Kir2.2 and Kir2.3 proteins were expressed in the hippocampus and immunostaining was not limited to neuronal cell types. Anti-Kir2.1 (fore-brain only) and anti-Kir2.2 (fore- and hind-brain) antibodies showed positive staining in macroglia, endothelia, ependyma and vascular smooth muscle cells. In contrast, anti-Kir2.3 (fore-brain only) immunostaining was limited to neurons, macroglia and vascular smooth muscle. These results indicate that specific regions within the rat fore- and hind-brain have differential distributions of inwardly rectifying potassium ion channel proteins.

Raised affinity for extracellular sodium of the sodium-lithium countertransporter is associated with a family history of hypertension and uraemia in patients with renal disease.

1. Increased affinity for sodium (Km) at an external site of the sodium-lithium countertransporter and altered membrane microviscosity in the surface regions of the lipid bilayer identifies a group of essential hypertensive patients with a genetic predisposition to hypertension. The present study investigated the kinetic properties of the sodium-lithium countertransporter and membrane microviscosity in patients with hypertension, renal disease and impaired renal function. 2. Sixty patients with renal disease (28 chronic renal failure, 30 hypertensive, 23 family history of hypertension) were investigated. Standard erythrocyte sodium-lithium countertransport activity, sodium affinity constant (Km), maximum reaction velocity (Vmax) and membrane microviscosity were measured. 3. Patients with renal disease and a family history of hypertension had significantly lower Km (P < 0.05) values and raised membrane microviscosity measured by 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene anisotropy (P < 0.05) compared with patients without a family history of hypertension. 4. Uraemic subjects had low K(m) values compared with patients with renal disease and normal renal function (P < 0.05). However, there was no significant difference in membrane microviscosity between uraemic and non-uraemic subjects. 5. In patients with a family history of hypertension, sodium-lithium countertransport activity and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene anisotropy are important markers of cellular changes in essential hypertension, independent of renal disease. Uraemia, independently of hypertension, produces an alteration in the function of the sodium-lithium countertransporter which has previously been associated with a genetic predisposition to hypertension and cardiovascular disease.

Anaesthetic potency of inhalation agents is independent of membrane microviscosity.

The decrease in membrane microviscosity of erythrocyte ghosts in the presence of clinically relevant concentrations of seven inhalation anaesthetic agents was studied using fluorescence polarization anisotropy of the membrane incorporated fluorescent probes 1,6-diphenyl-1,3,5-hexatriene and 1-[4-trimethylammoniumphenyl]-6-phenyl-1,3,5-hexatriene. All anaesthetic agents produced a dose-dependent decrease in anisotropy of both probes, indicating decreased membrane microviscosity. The reduction in anisotropy measured at the minimum alveolar concentration (ED50) for anaesthesia was related inversely to the anaesthetic potency of the agent and was directly proportional to the hypothetical concentration of agent in the membrane calculated from lipid-water partition coefficients. These findings do not support the hypothesis that volatile anaesthetic agents act by increasing membrane microviscosity of the bulk lipid bilayer to produce anaesthesia.

Effect of treatment with calcium antagonists in vitro and in vivo on the contractile response of isolated rat and human detrusor muscle.

1. The effect of calcium antagonists on the contractile response of human and rat isolated detrusor muscle in vitro was investigated. The effect of treatment with nimodipine on rat detrusor muscle in vivo was also examined. 2. Nimodipine 0.1 mumol/l, nifedipine 0.1 mumol/l, nifedipine 0.25 mumol/l and verapamil 1.5 mumol/l reduced the maximum contractile response of isolated human detrusor muscle to carbachol by 42%, 35%, 41% and 28% respectively (P < 0.01). Verapamil 0.1 mumol/l had no significant effect on contractile response. 3. Nimodipine 0.1 mumol/l reduced the maximum contractile response of isolated rat detrusor muscle in vitro to electrical field stimulation and carbachol by 53% and 84% respectively (P < 0.01). 4. Rats were pretreated with nimodipine for 8 days (5 mg day-1 kg-1) or with a single dose. Serum nimodipine concentrations were higher in rats treated for 8 days. In rats treated with nimodipine for 8 days there was no significant difference in detrusor contractile response compared with controls. However, after one dose of nimodipine the maximum contractile response was significantly reduced compared with controls (P < 0.05). 5. At the concentrations studied, nimodipine had a greater inhibitory effect on the contractile response of isolated human detrusor muscle. Nimodipine significantly reduced the contractile response of rat detrusor muscle in vitro and after a single dose in vivo, but had no significant effect after 8 days' treatment in vivo. It is possible that chronic oral treatment with nimodipine caused an up-regulation of 1,4-dihydropyridine-sensitive calcium channels, which may explain the lack of clinical effect of chronic treatment with calcium antagonists in patients with detrusor instability.

Cyclic AMP-dependent protein kinase phosphorylates residues in the C-terminal domain of the cardiac L-type calcium channel alpha1 subunit.

The molecular basis of the regulation of cardiac L-type calcium channel activity by cAMP-dependent protein kinase (cA-PK) remains unclear. Direct cA-PK-dependent phosphorylation of the bovine ventricular alpha1 subunit in vitro has been demonstrated in microsomal membranes, detergent extracts and partially purified (+)-[3H]PN 200-110 receptor preparations. Two 32P-labeled phosphopeptides, derived from cyanogen bromide cleavage, of 4.7 and 9.5 kDa were immunoprecipitated specifically by site-directed antibodies against the rabbit cardiac alpha1 subunit amino acid sequences 1602-1616 and 1681-1694, respectively, consistent with phosphorylation at the cA-PK consensus sites at Ser(1627) and Ser(1700). No phosphopeptide products consistent with phosphorylation at three other C-terminal cA-PK consensus phosphorylation sites (Ser(1575), Ser(1848) and Ser(1928)) were identified using similar procedures suggesting that these sites are poor substrates for this kinase. Ser(1627) and Ser(1700) may represent sites of cA-PK phosphorylation involved in the physiological regulation of cardiac L-type calcium channel function.

Inhibition by halothane of potassium-stimulated acetylcholine release from rat cortical slices.

1. Cholinergic neurones in the basal forebrain are linked to cortical activation and arousal. 2. The present study was designed to examine the hypothesis that clinically relevant doses of halothane (0.1 to 5%) would significantly reduce depolarization-evoked acetylcholine (ACh) release from rat cortical slices. 3. ACh release was measured from rat cortical slices by a chemiluminescent technique. 4. Depolarization-evoked ACh release was inhibited significantly by halothane with an IC50 of 0.38%. This value equates to 0.3 MAC (the minimum alveolar concentration at which no movement occurs to a standard surgical stimulus in 50% of subjects) for the rat. 5. The potent effect of halothane on ACh release suggests that this mechanism may be a target for the action of volatile anaesthetic agents. This in vitro effect on ACh release is consistent with effects of halothane reported in vivo.

Use of site-directed antibodies to probe the topography of the alpha 2 subunit of voltage-gated Ca2+ channels.

Polyclonal antibodies were raised against peptides corresponding to residues 1-15, 469-483 and 933-951 of the rabbit skeletal muscle L-type calcium channel alpha 2/delta primary translation product, for use as topological probes. Immunocytochemical comparison of the abilities of the antibodies to bind to the alpha 2 and delta subunits in intact and detergent-permeabilised rat dorsal root ganglion cells enabled the membrane orientation of these regions to be established. The resultant data indicate that the regions containing residues 1-15 and 469-483 of the alpha 2 subunit, and residues 1-17 of the delta subunit, are exposed on the extracellular surface of the membrane, findings consistent with a model that proposes alpha 2 to be entirely extracellular.

Human erythrocyte membrane fluidity and calcium pump activity in primary combined hyperlipidaemia.

1. Human erythrocyte membrane cholesterol, fluidity and basal and calmodulin-stimulated calcium pump (Ca(2+)-Mg(2+)-ATPase) activities were compared in 24 patients with primary combined hyperlipidaemia and 20 age-matched normolipidaemic control subjects. 2. There was no correlation between serum and membrane cholesterol. Despite the differences in serum cholesterol levels between the two groups, membrane cholesterol levels were similar. 3. 1,6-Diphenyl-1,3,5-hexatriene anisotropy was lower in the hyperlipidaemic group, suggesting increased fluidity in the hydrocarbon core of the phospholipid membrane bilayer. 4. Basal calcium pump activity was lower in the hyperlipidaemic group with increased membrane fluidity. 5. These results suggest that membrane adaptive mechanisms can maintain membrane cholesterol within a narrow range, that serum triacylglycerol is more important than serum cholesterol in determining membrane fluidity and that increased membrane fluidity reduces basal calcium pump activity.

Altered membrane microviscosity in essential hypertension: relationship with family history of hypertension and sodium-lithium countertransport activity.

OBJECTIVE: To investigate the alterations in erythrocyte ghost membrane microviscosity in essential hypertensive patients and to determine the relationship between these changes and the sodium-lithium countertransport activity as a sensitive marker of membrane function. SUBJECTS: Forty-three normolipidaemic essential hypertensive patients (23 treated, 20 untreated) and 27 normotensive controls were studied. Patients were attending the hospital hypertension clinic or a local general practitioner's surgery. METHODS: Erythrocyte sodium-lithium countertransport activity was measured. The Michaelis constant (Km) for extracellular sodium and maximal reaction velocity for sodium-lithium countertransport were measured in a subgroup consisting of 22 essential hypertensive patients and 11 normotensive controls. Erythrocyte membrane microviscosity was measured using fluorescence polarization anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-[4-trimethylammoniumphenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH). RESULTS: There was no significant difference in the fluorescence polarization anisotropy of DPH or TMA-DPH between normotensive and essential hypertensive patients. However, the fluorescence polarization anisotropy of TMA-DPH was increased significantly (reflecting increased membrane microviscosity) in hypertensive patients with a family history of hypertension compared with in patients without a family history of hypertension. The standard sodium-lithium countertransport activity was elevated in essential hypertensive patients compared with normotensive controls, and the Km for sodium was significantly lower in patients with a family history of hypertension than in patients without a family history of hypertension. Patients with a family history of hypertension were clustered, with significantly lower Km for sodium and higher TMA-DPH anisotropies than either hypertensive patients without a family history of hypertension or normotensive controls. CONCLUSIONS: These findings suggest that a high membrane microviscosity affecting the outer region of the lipid bilayer is associated with altered sodium-lithium countertransport kinetics in a subgroup of essential hypertensive patients consisting of those with a family history of hypertension.