RESUMEN

Boophone disticha (Amaryllidaceae) are mainly used in Southern Africa for inflammatory conditions. It is also known for its toxic effects. Because of the putative effects on components of the immune system and inflammatory response the effects of extracts of the bulb of Boophane disticha were investigated on ATP production in isolated human neutrophils. Furthermore, one possible mechanism of Boophone disticha's therapeutic properties might be its inhibition of superoxide release from neutrophils. The effect of the extracts on superoxide production of human neutrophils was also investigated. Aqueous and ethanol extracts of the outer and inner scales of the bulb of Boophone disticha was investigated for their effect on human neutrophils. It was decided to test the dry other scales separately from the fleshy inner scales as the parts are also used separately by traditional healers for different applications. ATP production was significantly decreased by ethanol extracts of the inner scales of the bulb. Superoxide production was significantly inhibited by aqueous extracts of the inner and outer scales of the bulb.

Asunto(s)

Asunto(s)

RESUMEN

Scales from the bulb are traditionally used as wound dressing after circumcision and as general wound dressing. Concoctions of the bulb taken orally cause sedation, analgesia, visual hallucinations, irrational behaviour, coma or death. A man ingested 150 ml of a concoction to see who placed a spell on him. He started to hallucinate, thinking that somebody was attacking him. He pulled his gun and fired shots randomly, killing one person and injuring others. A gas chromatograph/mass spectrometer was used to analyze a sample of the concoction. The sample contained buphandrin, buphanine and crinamidine (alkaloids) and eugenol. Buphanine has a pharmacological action similar to that of hyoscine and, when ingested in toxic quantities, leads to excitement, agitation, hallucinations and coma. Eugenol is a volatile oil with analgesic properties. Although itcould not be proved that the concoction was only from Boophane disticha, the components were similar to those found in Amaryllidaceae to which Boophane belongs. The man's behaviour could be ascribed to the ingestion of compounds found in B. disticha.

Asunto(s)

RESUMEN

The arrhythmogenic effect of adenosine triphosphate (ATP)-sensitive potassium channel openers is controversial and may be dependent on the type of animal model used. Information on the effect of these drugs in the normal primate model is limited. The purpose of this study was first to determine the arrhythmogenic properties of cromakalim in the baboon and second to determine whether N-omega-nitro-L-arginine methyl ester (L-NAME) has any effect on the induced arrhythmia. Adult (2-4 years old) baboons (Papio ursinus) were anesthetized with a continuous i.v. infusion of ketamine (100 mg/ ml), diazepam (5 mg/ml), and saline (ratio 2:2:50) at a rate of 40-60 ml/h. Sympathetic responses were inhibited by administration of propranolol (1 mg/kg) before the start of the experiments. Cromakalim (30 microg/kg) was administered before and after L-NAME (7.5 mg/kg), and the parameters were monitored for 15 min after each intervention. A Millar double-tipped microcatheter was used to record left ventricular and aortic pressures. Lead II of the ECG was monitored. During a 15-min period after administration of cromakalim, 22.3 +/- 6.0 abnormal ventricular complexes were recorded. L-NAME administration significantly reduced these abnormal complexes to 4.5 +/- 2 (paired t test, p < or = 0.05). We therefore conclude that cromakalim has arrhythmogenic properties in the baboon and that these can be attenuated by L-NAME.

Asunto(s)

RESUMEN

The stability of cardiodynamic and some blood parameters during a slow, continuous infusion of a combination of ketamine and diazepam is reported. Contractility (dP/dt), myocardial relaxation (Tln), left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), arterial blood pressure and certain blood parameters were assessed in 3 male and 3 female juvenile baboons (Papio ursinus). Anaesthesia was induced with 15 mg/kg ketamine i.m. and maintained with a continuous i.v. infusion (40-60 ml/h) of ketamine and diazepam. The mixture consisted of 2 ml ketamine (100 mg/ml), 2 ml diazepam (5 mg/ml) and 50 ml saline. A period of 75 +/- 10 min was allowed for preparation of the animals, after which lead II of the ECG, femoral artery blood pressure and left ventricular pressure were recorded at 15-min intervals for a period of 2 h: the total duration of anaesthesia was 195 min. Arterial blood samples were analysed at 30-min intervals for blood gases, electrolytes, glucose and insulin. Left ventricular parameters were derived from the left ventricular pressure curve. Tln, LVSP and LVEDP showed small fluctuations. Contractility decreased (p < 0.037) at the 195-min interval. No arrhythmias or ECG changes were seen, while blood pressure decreased gradually. Serum calcium concentration decreased and blood glucose levels increased gradually over time. Anaesthesia and analgesia were sufficient and no other drugs were necessary. The animals appeared sedated and dazed 60-80 min after the procedure. A continuous infusion of a combination of ketamine and diazepam for a duration of 150 min can provide stable anaesthesia for cardiodynamic measurements.

Asunto(s)

RESUMEN

The relaxant effects of gammalinolenic acid (GLA) and dihomo gammalinolenic acid (DGLA) were compared to the relaxant effect of arachidonic acid (AA). The effect of the combination of ascorbate to form the novel drugs ascorbyl-6-gammalinolenic acid (ascorbyl-6-GLA) and ascorbyl-6-dihomo gammalinolenic acid (ascorbyl-6-DGLA) were investigated and the role of the epithelial cells was determined. Salbutamol was used as control. The isolated tracheas of six to eight guinea pigs were used in each experiment and suspended in organ baths filled with Krebs-Henseleit solution and aerated with 95% O2 and 5% CO2. The relaxant effects produced for histamine-contracted preparations were as follows: AA=71.2+/-0.2%, GLA=55.2+/-4.2%, DGLA=69.8+/-3.9%, ascorbyl-6-GLA =26.2+/-5.1% and ascorbyl-6-DGLA=54.5+/-2.4%. For methacholine-contracted preparations: AA=46.6+/-3.2%, GLA=55.0+/-9.5%, DGLA=61.8+/-2.7%, ascorbyl-6-GLA=40.0+/-8.0% and ascorbyl-6-DGLA=88.0+/-15.3%. Ascorbyl-6-GLA and ascorbyl-6-DGLA had mainly a decreased relaxant effect compared to GLA and DGLA, except ascorbyl-6-DGLA after methacholine-induced contraction, which showed a significant increased relaxant effect. The removal of the epithelium showed decreased relaxant effects for the drugs except AA, which showed increased values after methacholine contraction. Histamine-contracted preparations showed varied results. Ascorbyl-6-GLA showed an increased relaxant effect, DGLA was unaffected with no additional effect, and AA, GLA and ascorbyl-6-DGLA showed decreased relaxant effects. In conclusion, it is clear that the contractant and the availability of epithelial cells could ultimately determine the results, though the mechanism remains very complex. The benefit of added ascorbate is still unclear and warrants more investigation.

Asunto(s)

RESUMEN

The cardiodynamic effects of prostaglandin E(2) (PGE(2)) were studied in both healthy sheep and in animals with congestive heart failure (CHF). Merino ewes were equipped surgically with high fidelity micromanometers and left ventricular pressures measured. Heart rate, left ventricular systolic and end-diastolic pressures, +dP/dt and T(ln) were calculated on a computer from the recorded pressure curves. The paired t-test was used to determine the statistical significance of the differences. PGE(2) (25 mu g/kg) significantly improved the cardiac contractility and relaxation rate of healthy sheep and significantly reduced the heart rate, while the loading conditions under which the heart operates were not significantly affected. In contrast to healthy sheep, PGE(2) significantly reduced the contractility and relaxation rate of sheep with congestive heart failure and significantly increased the preload while heart rate and afterload were significantly reduced. The study suggests that despite the promising vasodilatory, positive inotropic and relaxation rate actions of PGE(2) in normal hearts, PGE(2) might not be a suitable therapeutic agent for CHF, because of the worsening effect it has on the cardiodynamics and loading conditions of the failing heart.

Asunto(s)

RESUMEN

The effects of low and high doses of atropine on respiratory sinus arrhythmia were assessed to ascertain whether any differences exist in the degree of parasympathetic control on cardiac rhythm between two ethnic groups. The standard deviation of the R-R interval (the R peak-to-peak interval of two QRS complexes of an electrocardiogram) has been used as a noninvasive parameter to measure the degree of parasympathetic cardiac control. Nine black and nine white healthy male volunteers took part in study after approval by the Research and Ethics Committee of the Medical University of South Africa. Thirty consecutive electrocardiographic complex were recorded during each of the following: 3 deep inspirations and expirations, incremental cumulative atropine injections of 0.001 mg/kg until 0.005 mg/kg, followed by two injections of 0.01 mg/kg and 0.015 mg/kg of atropine each. After each of the last two injections the deep inspiration and expiration procedure was repeated. No significant differences could be found at any stage for any parameter between the groups. In both groups the R-R interval variation increased threefold during voluntary induced respiratory sinus arrhythmia. This effect was blocked after 0.01 mg/kg of atropine. The degree of parasympathetic control was not affected by any respiratory maneuver, but was affected by atropine. A significant inverse quadratic relationship was found between parasympathetic control and heart rate change (R = .984 for whites, and R = .905 for blacks). A poor correlation was found between the R-R interval variation and heart rate changes. In conclusion, ethnicity does not affect parasympathetic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

RESUMEN

1. The hypokalaemic effect of salbutamol after more than 30 min of administration has been well described. A hyper-and-hypokalaemic effect for adrenaline has been reported, but no such hyperkalaemic effect for salbutamol. 2. The possible hyper-and-hypokalaemic effects of salbutamol with the concomitant potential for pro-arrhythmia were assessed in the baboon (Papio ursinus). 3. Male and female baboons were anaesthetized with ketamine (15 mg kg-1) and maintained with 6% pentobarbitone as spontaneously breathing animals. Six baboons in each group received either 10, 100 or 500 micrograms kg-1 salbutamol i.v. Lead II of the ECG and femoral i.a. blood pressure were recorded continuously for 10 min. Arterial blood samples were collected at 0 min and then after 3 and 10 min of salbutamol administration. 4. All the animals developed sinus tachycardia (above 200 beats min-1) within 30 s of each dose of salbutamol administration and the high heart rate persisted throughout the experiment. All the animals were hyperkalaemic after 3 min and hypokalaemic after 10 min for each dose of salbutamol. Left ventricular conduction defects were seen in 3 animals during the hyperkalaemic phase. No arrhythmia was seen during the hypokalaemic phase. 5. Salbutamol has a transient hyperkalaemic and a more prolonged hypokalaemic effect in the baboon. The hypokalaemia could not be associated with arrhythmia although conduction defects were associated with the hyperkalaemia. 6. Since salbutamol is used as a bronchodilator in asthmatic patients and to treat acute hyperkalaemia, it is suggested that caution should be exercised when using salbutamol in high doses to treat acute asthma especially during the first few minutes of administration. The finding of hyperkalaemia with salbutamol questions its use in the treatment of hyperkalaemia.

Asunto(s)

RESUMEN

In this study eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were given in a cumulative manner, every 6 weeks, starting with 10 mg, then 100 mg, 1000 mg and 10,000 mg EPA daily to mild to moderate essential hypertensive black patients. The corresponding DHA doses were 3, 33, 333 and 3333 mg. A control group was given olive oil as placebo for the entire 24 weeks. The placebo group had lower diastolic and systolic blood pressures after 24 weeks than the EPA and DHA group. No effect was seen on plasma triglycerides, cholesterol, HDL-cholesterol and gamma-glutamyltranspeptidase at any stage of the trial. In the EPA group plasma free-EPA increased significantly from 1000 mg onwards and plasma free-arachidonic acid (AA) decreased after 1000 mg EPA. No other plasma free essential fatty acid changed during the trial, although the HDL:cholesterol increased slightly but non-significantly with an increase in EPA and DHA. No significant changes in diet pattern or body mass was observed. It is therefore concluded that EPA and DHA supplementation had no beneficial effects in mild to moderate essential hypertensive black patients except for a lowering of plasma AA.

Asunto(s)

RESUMEN

Animal studies suggest that for the same inotropism hydrophilic cardiac glycosides produce greater depression of atrioventricular (AV) conduction than lipophilic ones. This has been explained on the basis of a greater vagomimetic effect with hydrophilic agents and a greater sympathomimetic effect with lipophilic agents. In this randomized, cross-over study we investigated the effects of placebo, digoxin (relatively hydrophilic), and digitoxin (relatively lipophilic) in twelve healthy volunteers. For both drugs steady-state serum concentrations in the mid-therapeutic range were achieved. Both drugs produced the same positive inotropic effect as measured by systolic time intervals (QS2c). There was a trend for digoxin to have a greater effect on AV conduction than digitoxin. After atropine or propranolol there was no difference between the effect of the two cardiac glycosides on AV conduction. No significant effects on colour vision were seen. We conclude that, there do not seem to be pharmacodynamic differences between digoxin and digitoxin at mid-therapeutic serum concentrations.

Asunto(s)

RESUMEN

The cardiodynamic effects of Prostaglandin E1 were studied in sheep with congestive heart failure. Six Merino ewes were equipped surgically with high fidelity micromanometers and left ventricular pressures measured. Heart rate, left ventricular systolic and end-diastolic pressures, [+dP/dt]max and a single-exponential time constant (T) were calculated on a computer from the recorded pressure curves and the Wilcoxon signed rank test used to determine the statistical significance of the differences. Prostaglandin E1 (20 micrograms.kg-1) significantly improved left ventricular contractility and relaxation rate as seen respectively from [+dP/dt]max and the single-exponential time-constant and reduced the afterload conditions under which the heart operated, during various stages of congestive heat failure, without significant tachycardia during the more advanced stages of the disease. The results show that [+dP/dt]max increased between 16% (stage 4) and 38% (stage 1); T shortened between 14% (stage 4) and 25% (stage 1) and left ventricular systolic pressure decreased between 14% (stage 4) and 21% (stage 1) when prostaglandin E1 was administered during four stages of left ventricular pump failure, which ranged from a 20% decrease in [+dP/dt]max (congestive heart failure stage 1) to a 50% decrease in [+dP/dt]max (congestive heart failure stage 4). In contrast to normal animals, prostaglandin E1 caused an increase in left ventricular end-diastolic pressure during the more advanced stages of pump failure. Nevertheless the favourable cardiodynamic changes brought about by prostaglandin E1 administration might contribute, together with afterload reduction, to a general haemodynamic improvement during congestive heart failure.

Asunto(s)

RESUMEN

The antihypertensive effects of penbutolol, a nonselective beta-adrenoceptor antagonist with intrinsic sympathomimetic activity, was assessed in nonobese black South Africans aged 25 to 65 years with uncomplicated mild to moderate essential hypertension. After a 4-week placebo run-in period 50 patients entered a randomized placebo-controlled study with a crossover design. For 8 weeks they received a once daily dose of 40 mg penbutolol (or placebo) which was increased to 80 mg per day for the next 4 weeks in poor responders. This was followed by a 4-week placebo washout period after which a crossover of treatment was achieved and a second 12-week period of treatment initiated. Thirty-five patients completed the whole study and in 15 patients diastolic blood pressure was reduced below 95 mm Hg. The mean systolic pressures of these patients decreased by 21 mm Hg and their mean diastolic pressure decreased by 11 mm Hg during treatment with penbutolol. These results suggest that penbutolol monotherapy is an alternative therapeutic approach to hypertension in black South Africans.

Asunto(s)

RESUMEN

The underlying mechanism for the cardiac responses to PGE1 has not yet been fully elucidated. In order to investigate a possible role for cyclic AMP in the positive inotropic and chronotropic actions of prostaglandin E1 (PGE1) in conscious sheep, theophylline-ethylenediamine was used to inhibit phosphodiesterase activity. Any significant potentiation or the lack of potentiation of the measured cardiac response to PGE1 was then used as a criterion to establish whether the cardiac actions of PGE1 were produced by an alteration in the intracellular levels of cyclic AMP. The results suggest that PGE1 produced positive inotropic and chronotropic actions in conscious sheep, which is neither caused by the autonomic nervous system (baroreflexes) nor by changes in intracellular cyclic AMP levels. Further research seems warranted to establish whether a relationship exists between Ca2+ and the contractile response of PGE1. Such a relationship could then possibly explain the positive inotropic action of PGE1 in conscious sheep.

Asunto(s)

RESUMEN

The aim of this study was to determine the validity of regression equations relating RR interval and heart rate to systolic time intervals in sheep. Regression equations were compiled employing the RR interval to correct systolic time intervals for heart rate in six Merino ewes. A range of heart rates was obtained by means of pharmacological intervention as well as electrical pacing. Heart rate did not affect the pre-ejection period, isovolumetric contraction time, the pre-ejection period to left ventricular ejection time ratio, the ratio QS2/QT, electrical delay (Q1), or the PR interval. Heart rate did, however, affect the duration of electromechanical systole (QS2), left ventricular ejection time and mechanical systole (S1S2). The study showed that it was preferable to correct the systolic time intervals using the RR interval rather than the heart rate. Bazett's equation to correct electrical systole (QT) for heart rate in humans was also validated in sheep.

Asunto(s)

RESUMEN

Eight healthy volunteers were studied to ascertain the effect of digoxin and the relatively more lipophylic cardiac glycoside, acetyl-digitoxin on ventilation. Baseline ventilation as well as the response to the inspiration of 2.2% and 4.8% carbon dioxide were assessed. Digoxin produced a depression of minute volume and oxygen consumption whereas acetyl-digitoxin produced the opposite effect. This could be the result of a relatively greater vagomimetic effect with digoxin and a greater symphatomimetic effect with acetyl-digitoxin. These findings might have clinical implications in cardiac patients who have pulmonary disease.

Asunto(s)