Efficacy and safety of a hyperoxygenated fatty acid compound in improving the microcirculation of purpura fulminans in paediatric patients with sepsis: a pilot study.

INTRODUCTION: Purpura fulminans (PF) is a serious complication of sepsis resulting from a set of alterations characterised by the development of ecchymotic haemorrhagic lesions and skin necrosis. AIM: To analyse the efficacy and safety of the topical application of HOFA compound, in the cutaneous microcirculation of PF lesions in paediatric patients affected by sepsis. MATERIAL AND METHODS: A prospective quasi-experimental pre-test/post-test single-group conducted in a Paediatric Intensive Care Unit of a third level hospital was performed. Paediatric patients aged 0-18 years with sepsis were included. Somatic oximetry values were measured before and after application of HOFAs every 4h over the first three days of the patients' hospitalisation. Patient's socio-demographic and clinical variables and somatic oximetry by placing a sensor for measuring tissue perfusion on the area with PF were determined. RESULTS: Four patients were recruited, with a median age of 98 months. The purpuric lesions measured were mainly located on both feet and hands and, in two patients, also on the lateral malleoli and calves of both lower extremities. A total of 225 measurements were obtained, with mean pre-intervention scores of 71.17±15.65% versus 73.68±14.83% post-intervention. Statistical significance (p<0.001) was observed upon comparison of the pre- and post-intervention measurements. CONCLUSIONS: Early and continued application of HOFAs in the management of sepsis-induced PF is an effective and safe practice in the cases analysed. In more than half of the episodes analysed, an increase in tissue microcirculation was observed after the application of HOFAs, with no adverse events.

Economics of pressure-ulcer care: review of the literature on modern versus traditional dressings.

Published evidence suggests that some of the benefits of modern dressings--longer wear times and less frequent dressing changes--make them more cost-effective than traditional gauze dressings in pressure ulcer management.

Asignatura sobre el cuidado de las personas con lesiones cutáneas en el grado de enfermería: competencias y propuesta de contenidos / A course on care for people with skin lesions for the undergraduate nursing programme: competencies and proposed contents

El presente artículo pretende desarrollar una propuesta marco sobre una asignatura sobre el cuidado de las personas con lesiones cutáneas en el grado de enfermería. Esta ha sido realizada por consenso de expertos, profesores con experiencia en el cuidado de heridas y fue sometida a modificaciones en el marco del Segundo Encuentro Iberolatinoamericano de Facultades y Escuelas Universitarias con Programas Formativos en Heridas. Con ello se presenta una propuesta de competencias sobre el cuidado de las personas con lesiones cutáneas para la enfermera graduada, así como la propuesta curricular, con su estructura pedagógica basada en unidades didácticas y la propuesta de carga docente y ubicación de la asignatura de cuidados de las personas con lesiones cutáneas en el grado en enfermería. Finalmente se presentan documentos de apoyo al profesorado y estudiantado para la creación de la asignatura de cuidados de las personas con lesiones cutáneas para el grado en enfermería (AU)

This article aims to develop a framework proposal for a course on the care of people with skin lesions in the nursing degree. It has been developed by consensus of experts, professors with experience in wound care and was subject to modifications in the framework of the Segundo Encuentro Iberolatinoamericano de Facultades y Escuelas Universitarias con Programas Formativos en Heridas. This includes a proposal of competencies on the care of people with skin lesions for the graduate nurse, as well as the Curricular proposal, with its pedagogical structure based on didactic units and the proposed teaching load and location of the subject of care for people with skin lesions in the nursing degree. Finally, support documents are presented for the teaching staff and students for the creation of the subject of care of people with skin lesions for the degree in nursing (AU)

Molecular diagnosis of autosomal dominant early onset Alzheimer's disease: an update.

BACKGROUND: Autosomal dominant early onset Alzheimer's disease (ADEOAD) is genetically heterogeneous. Mutations of the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) genes have been identified. OBJECTIVE: To further clarify the respective contribution of these genes to ADEOAD. METHODS: 31 novel families were investigated. They were ascertained using stringent criteria (the occurrence of probable or definite cases of Alzheimer's disease with onset before 60 years of age in three generations). All cases fulfilled the NINCDS-ADRDA criteria for probable or definite Alzheimer's disease. The entire coding regions of PSEN1 and PSEN2 genes and exons 16 and 17 of APP gene were sequenced from genomic DNA RESULTS: PSEN1 mutations, including eight previously unreported mutations, were detected in 24 of the 31 families, and APP mutations were found in five families. In this sample, the mean ages of disease onset in PSEN1 and APP mutation carriers were 41.7 and 51.2 years, respectively. CONCLUSIONS: Combining these data with previously published data, yielding 65 ADEOAD families, 66% of the cases were attributable to PSEN1 mutations and 16% to APP mutations, while 18% remained unexplained.

The effectiveness of a hyperoxygenated fatty acid compound in preventing pressure ulcers.

OBJECTIVE: To compare the effects of Mepentol, a hyperoxygenated fatty acid preparation, with a placebo treatment in preventing the development of pressure ulcers. METHOD: The research study consisted of a multicentre double-blind randomised clinical trial. The incidence of pressure ulcers, relative risk (RR), preventable fraction and number necessary to treat (NNT) were calculated. In addition, Kaplan-Meier survival curves, with log-rank test, and Cox's proportional hazards regression model were used to compare both groups. RESULTS: A total of 331 patients completed the study: 167 in the control group and 164 in the study group. Pressure-ulcer incidence during the study was 7.32% in the intervention group versus 17.37% in the placebo group (p 0.006). These results show that for each 10 patients treated with Mepentol one pressure ulcer was prevented (NNT = 9.95). Survival curves and the regression model showed a significant statistical difference for both groups (p < or = 0.001). The average cost of Mepentol during the study was 7.74 Euro. CONCLUSION: Mepentol is an effective measure for pressure ulcer prevention. It was more effective than a greasy placebo product, and was found to be cost-effective.

Optimal maintenance of constructed wetlands using an environmental decision support system.

Constructed wetlands (CWs) are artificial wastewater treatment systems appropriate for small communities because of their affordability, operability and reliability. These qualities are true whenever CWs are designed and constructed properly, and as long as the necessary operation and maintenance procedures are carried out correctly. Experience shows that the operation and maintenance procedures, and the frequencies with which these procedures are carried out, differ from one CW to another. With this in mind, and along with a projected increase in CWs in Catalonia, the Catalan Water Agency (Agència Catalana de l'Aigua) has developed an Environmental Decision Support System (EDSS) which proposes guidelines for monitoring and maintenance, according to the characteristics of each CW. This EDSS was developed following a methodology based on five steps: (i) problem analysis; (ii) collecting data and knowledge acquisition; (iii) model selection; (iv) model implementation and (v) validation. This paper describes the methodology followed to build the decision support system and presents some examples of the information provided by this EDSS.

Evaluating the application of a decision support system in identifying adequate wastewater treatment for small communities. A case study: the Fluvia River Basin.

The identification of adequate wastewater treatment for small communities is a complex problem since it demands a combination of data from different sources, such as aspects of the community and landscape, the receiving environment and the available wastewater treatment technologies. The Catalan Water Agency (Agència Catalana de l'Aigua) considered using an EDSS (Environmental Decision Support System) as a tool to help water managers select the most adequate treatment for the urban wastewater of nearly 3,500 small communities in Catalonia (Spain). From that moment, EDSS was applied to all the river basins in Catalonia. In this paper the authors present the results obtained for the 76 small communities located in one of these river basins: the Fluvia River Basin. The characteristics of the community used in the reasoning process of the EDSS, the list of selected wastewater treatment alternatives, the technical environmental justification for the selected treatments and the reasons for discarding, favouring or disadvantaging them are presented. Finally, some results for the Fluvia River Basin are compared with those obtained in other Catalan river basins with different characteristics in order to evaluate which are the significant features in identifying adequate wastewater treatments.

Involvement of enteric neurones in the response of guinea-pig ileum preparations to metoclopramide.

The role of myenteric neurones in mediating the stimulant effects of metoclopramide in vitro in the guinea-pig ileum has been investigated using the non-ionic surfactant Triton X-100. Histological examination of the ileum 30 days after application of Triton X-100 to the serosal surface demonstrated a marked reduction in the number of ganglion cells and nerve elements in the myenteric plexus. Longitudinal muscle-myenteric plexus (LM-MP) preparations from Triton X-100-treated animals were unresponsive to dimethylphenylpiperazinium and responded poorly or not at all to electrical field stimulation. Metoclopramide (30 microM) elicited small contractions in LM-MP preparations from control and sham-operated animals but failed to contract Triton X-100-treated tissues. However, tissues responded in a similar manner to exogenous acetylcholine (ACh). These results demonstrate the importance of a prejunctional site of action for metoclopramide in this tissue and suggest that contractile responses to the drug are mediated indirectly, probably by increased release of ACh from myenteric neurones.

Investigation into the role of phosphodiesterase IV in bronchorelaxation, including studies with human bronchus.

1. We have investigated the role of cyclic nucleotide phosphodiesterase IV (PDE IV) in the relaxation of human bronchus and guinea-pig trachea in vitro and in guinea-pigs in vivo. 2. Functional studies showed that the selective PDE IV inhibitors, rolipram and denbufylline, relaxed human and guinea-pig preparations in vitro. 3. Two clinically used xanthine non-selective PDE inhibitors, theophylline and pentoxifylline, were also effective in these preparations, but were much less potent than the selective agents used. 4. The rank order of potency for the four PDE inhibitors in both species was similar. 5. Biochemical studies indicated that PDE IV was the major PDE isoform present in the human bronchial tissue. PDEs I, II and V were also identified. 6. Theophylline and pentoxifylline were, as expected, non-selective inhibitors of the human enzymes, but there was a good correlation between PDE IV inhibitory and bronchorelaxation potencies, suggesting that PDE IV inhibition is important for the clinical bronchodilator activities of the two xanthine compounds. 7. We have confirmed the ability of selective PDE IV inhibitors to cause bronchodilatation in guinea-pigs in vivo. 8. We conclude that our study has provided further evidence that selective PDE IV inhibitors could act as bronchodilators in the clinic.

Studies on the cardiac actions of flosequinan in vitro.

1. We have investigated the in vitro cardiac actions of flosequinan and of its major metabolite in man, BTS 53554. 2. Positive inotropic activity was seen with flosequinan in guinea-pig isolated ventricles, the threshold concentration for effect being less than 1 x 10(-5) M. BTS 53554 was approximately half as potent as the parent compound. 3. In guinea-pig working whole hearts flosequinan increased left ventricular dp/dtmax, indicating a positive inotropic action. This effect was accompanied by increases in heart rate, cardiac output and stroke volume. 4. The virtual complete inhibition of inotropic responses to flosequinan and BTS 53554 by carbachol suggests that these responses are adenosine 3':5'-cyclic monophosphate (cyclic AMP)-mediated. 5. Flosequinan was shown to increase calcium inward current in guinea-pig ventricle, an action consistent with a cyclic AMP involvement in the response. 6. The inotropic activity of flosequinan was not potentiated by the selective phosphodiesterase (PDE) III inhibitor SK&F 94120, a result which indicates that flosequinan does not increase cyclic AMP concentrations via stimulation of adenylate cyclase. 7. Flosequinan inotropic responses were potentiated by rolipram, a selective PDE IV inhibitor, a result consistent with flosequinan being itself a PDE III inhibitor. 8. Biochemical studies with purified enzymes confirmed that flosequinan and BTS 53554 are relatively selective inhibitors of PDE III. 9. A comparison of pharmacological and biochemical data for both flosequinan and BTS 53554 indicates that their PDE III inhibitory potency is sufficient to account for their inotropic activity.

Characterization of 5-HT receptors on human pulmonary artery and vein: functional and binding studies.

1. This study aimed to investigate the 5-hydroxytryptamine (5-HT) receptors mediating contraction of ring preparations isolated from human pulmonary arteries and veins. In functional studies, the responses to 5-HT, sumatriptan, ergotamine, serotonin-O-carboxymethyl-glycyl-tyrosinamide (SCMGT), alpha-methyl 5-HT (alpha-Me) and 2-methyl 5-HT (2-Me) were studied with WAY100635, GR127935, ritanserin, zacopride and SB204070 as antagonists. 2. All agonists produced concentration-dependent contractions of human pulmonary artery and vein preparations. The order of potency (-log ECS0 values) was ergotamine (6.88) > 5-HT (6.41) > or = SCMGT (6.20) = sumatriptan (6.19) > or = alpha-Me (6.04) in the artery, and ergotamine (7.84) > 5-HT (6.96) > sumatriptan (6.60) = alpha-Me (6.56) > SCMGT (6.09) in the vein. The potency of each agonist, except for SCMGT, was greater in vein than in artery preparations. Contractile responses to 5-HT were similar in intact and endothelium-denuded preparations but responses to sumatriptan were enhanced in artery rings without endothelium. 3. GR127935 (1 nM to 0.5 microM) produced an unsurmountable antagonism of the response to 5-HT, sumatriptan, ergotamine and SCMGT. Ritanserin (1 nM to 1 microM) also reduced the maximum contractile responses to 5-HT, ergotamine and alpha-Me in artery and vein preparations without affecting those to sumatriptan and SCMGT. In endothelium-denuded preparations, surmountable antagonism of sumatriptan by GR127935 (in the presence of ritanserin) and of alpha-Me by ritanserin (in the presence of GR127935) allowed for the calculation of the apparent pK(B) values of GR127935 (9.17+/-0.11 in artery and 9.11+/-0.05 in vein) and ritanserin (8.82+/-0.09 in artery and 8.98+/-0.12 in vein). 4. WAY100635 (1 nM to 1 microM), zacopride (1 nM to 1 microM), or SB204070 (1 nM) did not significantly alter the concentration-response curves for 5-HT, sumatriptan, ergotamine, SCMGT or 2-Me in human pulmonary artery or vein thus indicating that 5-HT1A, 5-HT3 and 5-HT4 receptors are presumably not involved in the contractile response to these agonists. 5. Binding studies using selective radioligands for different 5-HT receptors could not detect the presence of 5-HT1A receptor binding in human pulmonary blood vessels whereas the 5-HT(1B/1D) radioligand [3H]-5CT significantly labelled a population of specific binding sites in both vessel types. The presence of 5-HT2A receptors could also be inferred from the level of binding of [3H]-ketanserin to membranes obtained from human pulmonary vessels, although significance could not be reached for arteries. 5-HT4 specific receptor binding was scarce in veins and absent in the case of arteries. 6. These findings indicate that the human pulmonary artery and vein have a mixed functional population of 5-HT(1B/1D) and 5-HT2A receptors mediating the contractile response to 5-HT which is consistent with results of the binding studies.

Effect of diltiazem upon contractile responses to phenylephrine, cirazoline, Sgd 101/75, St 587 and B-HT 920 in rabbit aorta and dog saphenous vein preparations.

Diltiazem (10 microM) did not significantly affect concentration-response curves to the full, relatively selective alpha 1-adrenoceptor agonists phenylephrine and cirazoline in rabbit aorta and dog saphenous vein preparations. The effects of these 2 agonists remained resistant to diltiazem even in tissues pretreated with phenoxybenzamine (0.03 or 0.1 microM, 20 min) to reduce the alpha-adrenoceptor reserve. Sgd 101/75 and St 587 were partial agonists in both vascular preparations. The concentration-response curves to these relatively selective alpha 1-adrenoceptor agonists were also unaffected, or only slightly attenuated, by diltiazem. B-HT 920 at low concentrations preferentially stimulated the dog saphenous vein preparation and only at high concentrations elicited small contractions of the rabbit aorta. The responses to B-HT 920 were mediated by alpha 2-adrenoceptors in the vein and by alpha 1-adrenoceptors in the aorta yet concentration-response curves to this agonist were significantly attenuated by diltiazem in both tissues. The results indicate that the resistance of certain alpha-adrenoceptor-mediated responses in vascular preparations to calcium entry blockers need not be associated with the presence of a significant receptor reserve and that calcium dependency of a response may be determined by the agonist.

Phenoxybenzamine-induced inhibition of cirazoline pressor responses in pithed rats pretreated with organic or inorganic calcium entry blocking drugs.

In groups of propranolol-treated pithed rats pretreatment with either verapamil (1 mg/kg i.a., 20 min) or the inorganic calcium entry blocker (CEB), cobalt (23.8 mg/kg i.a., 20 min) reduced maximum obtainable pressor responses to the relatively selective alpha 2-adrenoceptor agonist B-HT 920 (0.1-1000 micrograms/kg i.v.) equally, by approximately 50%. Verapamil and cobalt at these doses had little or no effect upon pressor responses induced by the relatively selective alpha 1-adrenoceptor agonist cirazoline (0.1-1000 micrograms/kg i.v.). Phenoxybenzamine (0.1 mg/kg i.v., 15 min) displaced to the right and reduced by 44% the maximum obtainable pressor responses to cirazoline. Treatment of animals with the combination of either verapamil or cobalt followed by phenoxybenzamine, at the dose levels and pretreatment times given above, produced significantly greater inhibitions of cirazoline pressor responses (83% and 88% reduction in the maximum obtainable pressor responses to cirazoline respectively) than were observed following administration of phenoxybenzamine alone. Since yohimbine (1 mg/kg i.v.) did not significantly affect the residual responses to cirazoline following treatment with phenoxybenzamine the mechanism responsible for this interaction between CEBs and phenoxybenzamine is not mediated via postjunctional alpha 2-adrenoceptors. Additional studies are required to assess the involvement of a possible subtype of alpha 1-adrenoceptors which appear to mediate vascular responses sensitive to CEBs.

Functional profile of almotriptan in animal models predictive of antimigraine activity.

Almotriptan is a new 5-HT(1B/1D) receptor agonist whose clinical efficacy for the treatment of migraine attacks has been demonstrated in Phase III clinical trials. We now compare the functional profile of almotriptan (assessed using animal models) with that of sumatriptan. Almotriptan selectively increased carotid vascular resistance in anaesthetised cats after intravenous or intraduodenal administration (ED(100)=11 microg/kg, i.v.; ED(50)=339 microg/kg, i. d.) and in anaesthetised beagle dogs following intravenous administration (ED(50)=116 microg/kg). A study in anaesthetised cats also demonstrated that almotriptan acts by selectively increasing the resistance of the carotid arteriovenous anastomoses without adversely affecting brain irrigation. In addition, almotriptan inhibited meningeal extravasation produced by electrical stimulation of the trigeminal ganglion in anaesthetised guinea pigs in the dose range of 0.3-3 mg/kg, i.v. In conclusion, almotriptan is both a selective constrictor affecting intracranial blood vessels and an inhibitor of neurogenically evoked plasma protein extravasation of the dura mater.

Pancopride, a potent and long-acting 5-HT3 receptor antagonist, is orally effective against anticancer drug-evoked emesis.

Pancopride ((+-)N-(1-azabicyclo-[2,2,2]-oct-3-yl)-2-cyclopropylmethoxy-4-ami no-5-chlorobenzamide) is a new potent and selective 5-HT3 receptor antagonist, orally and parenterally effective against cytotoxic drug-induced emesis. In vitro, pancopride displayed high affinity (Ki = 0.40 nM) for [3H]GR65630-labelled 5-HT3 recognition sites in membranes from the cortex of rat brains. In vivo, pancopride antagonized 5-HT-induced bradycardia in anaesthetized rats when administered i.v. 5 min (ID50 = 0.56 microgram/kg) or p.o. 60 min (ID50 = 8.7 micrograms/kg) before 5-HT challenge. A single oral dose (10 micrograms/kg) of pancopride produced a significant inhibition of the bradycardic reflex over an 8-h period. Pancopride dose dependently inhibited the number of vomiting episodes and delayed the onset of vomiting induced by cisplatin in dogs (ID50 = 3.6 micrograms/kg i.v. and 7.1 micrograms/kg p.o.). Pancopride was also effective in blocking mechlorethamine- and dacarbazine-induced emesis. Unlike metoclopramide, pancopride was shown to lack any measurable antidopaminergic activity both in vitro and in vivo. These results support clinical data, indicating that pancopride will be a useful drug for treating cytostatic-induced emesis in humans.

Pharmacological characterization of almotriptan: an indolic 5-HT receptor agonist for the treatment of migraine.

Almotriptan (3-[2-(dimethylamino)ethyl]-5-(pyrrolidin-1-ylsulfonylmethyl )-1H-indo le) has been studied in several models predictive of activity and selectivity at 5-HT receptors. Almotriptan showed low nanomolar affinity for the 5-HT(1B) and 5-HT(1D) receptors in several species, including the human, while affinity for 5-HT receptors other than 5-HT(1B/1D) was clearly less. Affinity for 5-HT(7) and 5-HT(1A) receptors was approximately 40 and 60 times lower than that for 5-HT(1B/1D) receptors, respectively. Almotriptan did not exhibit significant affinity for several non-5-HT receptors studied up to 100 microM. Almotriptan inhibited forskolin-stimulated cyclic AMP accumulation in HeLa cells transfected with 5-HT(1B) or 5-HT(1D) human receptors. In this model, almotriptan had the same efficacy as serotonin and an affinity in the low nanomolar range. It induced vasoconstriction in several vessels in which it was compared with sumatriptan. In isolated dog saphenous veins, almotriptan elicited concentration-dependent contractions with an EC(50) of 394 nM. In both these systems, almotriptan behaved as a full agonist. Infusion of almotriptan into the porcine meningeal vasculature induced vasoconstriction. In contrast, in the pig renal and rabbit mesenteric arteries, it had a very low maximal efficacy even at 100 microM, with similar results obtained in the rabbit renal artery. The results suggest that almotriptan is a potent and selective 5-HT(1B/1D) receptor agonist, with selectivity for the cranial vasculature as compared with peripheral vessels.

A specific chromophoric substrate for activity assays of 1,3-1,4-beta-D-glucan 4-glucanohydrolases.

The synthesis of 4-methylumbelliferyl 3-beta-O-cellobiosyl-beta-D-glucopyranoside (3a) and its use as specific substrate to monitor enzyme activity of 1,3-1,4-beta-D-glucan 4-glucanohydrolases are described. The chromophoric substrate 3a is prepared by a chemoenzymatic approach starting from barley grain, whose beta-D-glucan polysaccharide is degraded down to a tri- and tetrasaccharide by an extracellular extract of recombinant E. coli expressing and secreting Bacillus licheniformis 1,3-1,4-beta-glucanase. The trisaccharide 1 is further chemically transformed into the title compound. Its use as substrate for an enzyme activity assay, the specificity of cleavage, and kinetic parameters are reported. As it undergoes a single glycosidic bond hydrolysis with release of 4-methylumbelliferone, direct UV monitoring of the reaction provides a sensitive kinetic assay of the enzyme action.

Allometry of the limb long bones of insectivores and rodents.

In an attempt to investigate the relationships between allometry and locomotory adaptations, we studied the long limb bones of 45 species of insectivores and rodents. Animals ranged from a few grams to about 50 kilograms. Diameter and length of the bones and body mass (when known) were recorded. Regressions of diameter to length, diameter to body mass, and length to body mass were calculated by the least-squares and Model II, or major axis, methods. The results obtained do not agree with the predictions of either the theory of geometric similarity or the theory of elastic similarity. The discrepancies could be due to the fact that animals studied exhibit various modes of locomotion. Moreover, the allometric relationships of the different locomotor patterns are better reflected in insectivores and rodents than in other groups of mammals. The use of a single regression analysis seems to be inadequate when the sample includes a large range of body sizes.

On the allometry of long bones in dogs (Canis familiaris).

The allometric relations of diameter and length of humerus, ulna, femur, and tibia of 108 specimens, from 63 different breeds of dogs and 12 specimens of wolves, were calculated by means of model II of regression or major axis method. Only for the tibia were the values of wolves included in the cluster formed for dog breeds. Consequently, separate lines of regression were calculated for the other bones. Results agree in general with the exponents predicted by the theory of geometric similarity; however, the slope obtained for femur (0.865) differed significantly from this. Morphology of the long bones of the legs does not differentiate dogs and wolves; this probably reflects secondary convergence among wolves with relatively modern breeds of dogs.

Cardiovascular effects of LAS 30538, a new vascular selective Ca(2+)-channel blocker.

A new compound, 1-[2-(2,6-dimethylphenoxy)ethyl]-alpha,alpha-bis-(p-fluorphenyl)-4 -piperidine methanol (LAS 30538), was found to have potent vasodilator effects. Its vasorelaxant activity was demonstrated in rat perfused hindlimbs contracted with 80 mM K+, having an IC50 value of 40 nM. In conscious spontaneously hypertensive rats, LAS 30538 administered orally, caused dose-dependent sustained falls in systolic blood pressure with an ED30 value of 11 mg kg-1. In pithed rats, LAS 30538, strongly inhibited vasoconstriction induced by the alpha 2-adrenoceptor agonist B-HT 933 and the calcium agonist compound Bay K8644 with ED50 values of 4 mg kg-1 p.o. and 1.3 mg kg-1 i.v., respectively. Results from electrophysiological studies carried out using guinea-pig papillary muscles partially depolarized by 22 mM K+ are consistent with LAS 30538 acting as a Ca(2+)-channel blocker. When compared with verapamil, in guinea-pig and rabbit isolated heart preparations, LAS 30538 caused less cardiodepression and bradycardia. The results suggest that LAS 30538 may have some advantages over other Ca(2+)-channel blockers such as verapamil in causing less myocardial depression for a given level of vasodilatation.