RESUMEN

Atrial fibrillation is a well-known heart disease in horses. The common therapy consists of administration of quinidine. More potent antiarrhythmic drugs have become available for human therapy and the use of these as alternatives to quinidine for equine antiarrhythmic therapy is a matter of interest. Amiodarone (AMD) is used in human medicine for treatment of many arrhythmias, including atrial fibrillation. Its disposition in horses has not yet been investigated. The purpose of this study was to measure the effect of single intravenous doses of amiodarone (5 and 7 mg/kg) on the surface electrocardiogram (ECG) of healthy minishetland ponies during the first 2 days after drug administration and to calculate pharmacokinetic parameters with a physiologically based pharmacokinetic model (PBPK) using amiodarone and desethylamiodarone (DAMD) plasma levels that were determined by high-performance liquid chromatography (HPLC). As expected for a K(+)-channel-blocker, the main effect on the measured ECG could be seen on the ventricular complex, as the QT interval and the T wave showed statistically significant alterations. The doses investigated were well tolerated clinically. Results from the pharmacokinetic model were found to compare well with literature data of rats, dogs, and humans. It showed a rapid distribution in the tissue, beginning with the rapidly perfused tissue, like the heart, followed by slowly perfused tissues, and finally an accumulation in fat. The half-life for total elimination was calculated to be 16.3 days with 99% eliminated by 97 days. The model predicts that approximately 96% of amiodarone is eliminated as desethylamiodarone in urine, 2% eliminated as desethylamiodarone in bile, and 2% as other metabolites.

Asunto(s)

RESUMEN

Myometrial smooth muscle strips were collected from slaughtered cows in estrus and diestrus. Longitudinal and circular smooth muscle strips were mounted in organ baths and after equilibration time and 2g preload, their physiologic contractility was recorded for 3h. Area under the curve (AUC), mean amplitude (MA) and frequency of contractions (F) were studied. Differences between cycle phases, between muscle layers and over the recorded time period were statistically evaluated. In the cow, physiologic contractility patterns (measured as AUC and MA) of circular versus longitudinal myometrial strips are always different during the 3h recording. Significant differences between estrus versus diestrus are only found for circular layers, but not for longitudinal layers. Significant differences over time are only found for longitudinal layers.

Asunto(s)

RESUMEN

The effects of 5-hydroxytryptamine (5-HT), HTF 919, a new 5-HT(4) agonist, and the antagonists SB 203-186 (5-HT(4)) and tropisetron (5-HT(3)) on intestinal motility were tested in vitro on isolated preparations of horse ileum and pelvic flexure. Concentration-response curves were created by cumulative application of the agonists with or without preincubation of the antagonists. The 5-HT preparation induced a concentration-dependent contraction in equine ileum and pelvic flexure. The results indicate that 5-HT receptors are present in all parts of equine intestine investigated in this study. Tropisetron was found to act as a noncompetitive antagonist in all locations of the equine intestine. SB 203-106 was confirmed as an antagonist to 5-HT in the equine ileum circular muscle, in pelvic flexure circular and longitudinal muscle. Nevertheless, a discernible increase of smooth muscle contractions caused by HTF 919 could only be observed in pelvic flexure. In accordance with an earlier study in the guinea pig, in the equine gut HTF 919 acted as a partial agonist for the 5-HT(4) receptor with an affinity constant in the nanomolar range. It is concluded that 5-HT receptors, and especially their subtypes, may represent a promising target for the treatment and prevention of gastrointestinal (GI) motility disorders in horses.

Asunto(s)

RESUMEN

1. The influence of 5-hydroxytryptamine (5-HT) receptor agonists and antagonists on the ureter motility was investigated in vivo on intact ureters of anaesthetized pigs. Drugs were administered intravenously or topically. 2. 5-HT induced a dose-dependent increase in the frequency of ureter contractions in anaesthetized pigs when given intravenously (0.0001-1 mg kg(-1); ED(50) 0.066 mg kg(-1)) or topically (0.001-1 mg ml(-1); EC(50) 0.043 mg ml(-1)). Significant increases in heart rate and blood pressure were observed when the drug was given intravenously but not topically. 3. The 5-HT(2A) agonist, DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) increased the frequency of ureteral contractions in a dose-dependent manner (1-300 microg kg(-1) i.v.). Calculation of ED(50) indicated this compound to be about 1.5 times more potent with an efficacy of 23% compared to 5-HT. 4. The 5-HT(2A/2C) antagonist, ketanserin (0.5 mg kg(-1)) and the 5-HT(2C) antagonist, methysergide (1 mg kg(-1)) antagonized the 5-HT-induced ureter peristalsis when given intravenously. Contraction amplitude, blood pressure and heart rate were not affected by the antagonists. 5. Intravenous (0.0001-1 mg kg(-1)) and topical (0.0001-1 microg ml(-1)) ketanserin significantly decreased the frequency of spontaneous ureteral contractions to about 30% of controls, which could be partly reversed by 5-HT (0.3 mg kg(-1) i.v.). The contraction amplitude, contractions of the contralateral, saline perfused ureter, heart rate and mean arterial blood pressure were not affected. 6. Thus, contractility of porcine ureter is mediated by 5-HT(2) receptors. Their antagonists ketanserin and methysergide seem to be promising drugs for treatment of acute ureteric colic or in preparing the ureter for ureteroscopy.

Asunto(s)

RESUMEN

BACKGROUND: DPI 201-106 (DPI) was the first synthetic compound showing cardioselective modulation of voltage-gated sodium channels (VGSCs) resulting in a positive inotropic effect. Currently, the exact mode of action for this class of compounds is not known. METHODS: Effects of different natural and synthetic sodium channel modulators were investigated in cardiac tissue of several species with conventional electrophysiologic methods. RESULTS: In electrically driven cardiac tissues, all compounds investigated increased force of contraction (FC) and action potential duration (APD) with increasing concentrations except for DPI in cattle trabecular muscle, which demonstrated no effect. Interestingly, calculation of EC50 levels at 30% repolarization demonstrates that natural VGSC-ligands were highly potent in prolonging the APD in cattle whereas no positive trends could be obtained for DPI and SDZ 211-939 (SDZ) in cattle. CONCLUSIONS: These results demonstrate that the binding site for DPI and SDZ is distinct from sites 2 or 3 of the VGSC alpha-subunit. Moreover, this is the first time that these compounds show no effect or even shortening of APD. This finding will enable the characterization of the mode of action and probably the binding site for synthetic VGSC-modulators.

Asunto(s)

RESUMEN

PURPOSE: We searched for compounds that are pharmacologically active on ureteral motility for treating ureteral colic to ease retrograde access into the ureter and improve the clearance of stones or stone particles from the ureter. The effects of the alpha1-adrenergic receptor agonist phenylephrine, the nonselective beta and beta2-adrenergic receptor agonists isoproterenol and fenoterol, and the phosphodiesterase inhibitors papaverine (nonspecific) and rolipram (type IV) on the frequency and amplitude of ureteral contractions when administered intravenously or topically were investigated in pigs. MATERIALS AND METHODS: A total of 52 pigs were anesthetized. A double lumen 6Fr catheter was inserted through each renal pelvis and into the ureter, allowing perfusion of saline or drug solution into the renal pelvis and the recording of contractions from the mid portion of the ureter. RESULTS: The alpha1 and beta-adrenergic receptors of the ureter are not tonically activated by endogenous epinephrine or norepinephrine. Phenylephrine administered intravenously at a dose of 0.01 to 3 mg./kg. and topically at 0.1 to 3 mg./ml. per minute increased contraction frequency 10 and 4-fold, respectively, and contraction amplitude 2-fold each in a dose dependent manner. Arterial blood pressure increased markedly during intravenous administration of phenylephrine but was minimally affected during topical application. The phenylephrine effects were reversed by the antagonist prazosin. Isoproterenol administered intravenously at a dose of 0.01 to 10 mg./kg. and topically at 0.1 to 200 microg./ml. per minute decreased contraction frequency to 13% and 31% of controls, respectively. Contraction amplitude was not affected by intravenous administration but decreased to 59% of controls when applied topically. These effects were also observed with a slight delay in the saline perfused contralateral ureter. The heart rate also increased, suggesting absorption of the drug by the urothelium. The isoproterenol effects were blocked by the antagonist propranolol. Fenoterol administered intravenously at a dose of 0.1 to 30 microg./kg. and topically at 0.003 to 1 mg./ml. per minute decreased contraction frequency to 14% and 10% of controls, and contraction amplitude to 84% and 65%, respectively. These effects on the drug perfused ureter were also observed on the contralateral saline perfused ureter but to a lesser extent. The fenoterol effects were blocked by the antagonist propranolol. Papaverine administered intravenously at a dose of 0.001 to 3 mg./kg. decreased contraction frequency to 33% of controls. Topically administered papaverine as well as intravenous and topically administered rolipram had no relevant effect on ureteral motility. CONCLUSIONS: Intravenous phenylephrine increases, and isoproterenol and fenoterol decrease the frequency and amplitude of ureteral contractions in the pig. The same effects are observed with the topical administration of phenylephrine, which causes a significant local but not systemic side effect. Topical administration of isoproterenol and fenoterol produced local as well as systemic effects, suggesting absorption by the urothelium. However, to our knowledge a drug that relaxes ureteral peristalsis in pigs without causing systemic side effects has not yet been identified.

Asunto(s)

Asunto(s)

RESUMEN

Voltage-gated sodium channels (VGSCs) are responsible for the initial inwards current during the depolarisation phase of action potential in excitable cells. Therefore, VGSCs are crucial for cardiac and nerve function, since the action potential of nerves and muscle cannot occur without them. Their importance in generation and transmission of signals has been known for more than 40 years but the more recent introduction of new electrophysiological methods and application of molecular biology techniques has led to an explosion of research on many different ion channels, including VGSCs. Their extraordinary biological importance makes them logical and obvious targets for toxins produced by animals and plants for attack or defence. The action of these and similar substances modulating the function of the VGSCs is interesting with respect to their possible use in medicine or use as tools in the study of these molecules. This review summarises recent progress in this research field and, in particular, considers what is known about the relationship of the structure to function, including a current understanding of the pharmacological modulation of VGSCs.

Asunto(s)

RESUMEN

Bovine hereditary dilated cardiomyopathy (bCMP) is endemic in Switzerland and hearts from diseased animals display important clinical and biochemical similarities to human DCM. Recent research has identified at least one protein (myoglobin) to be significantly reduced in bovine DCM. Using a proteomic approach, we have separated over 1125 protein species from bovine ventricular tissue. Gel analysis and protein characterisation have identified a number of proteins whose abundance is significantly altered in bovine DCM. Twenty-four proteins are of decreased abundance in diseased tissue, whilst 11 proteins are of increased abundance in the diseased state. A combination of amino acid compositional analysis, peptide mass profiling, N-terminal microsequencing and MultiIdent (http://www.expasy.ch/sprot/multiident. html) has been employed in order to elucidate the identities of the differentially expressed proteins. Using these techniques we have currently determined the identity of 12 of the 35 altered proteins. We have also detected three proteins that are differentially expressed in genotypically diseased but phenotypically normal animals, identifying a possible mechanism for the onset of the disease. The possibility that inappropriate ubiquination of proteins plays an important role in the disease is discussed. A database of bovine proteins is currently being established. The identity of the proteins affected, together with a comparison of the human and bovine expression patterns, is displayed.

Asunto(s)

RESUMEN

OBJECTIVE: To compare concentrations of acetic, propionic, butyric, and i- and n-valerianic acids in digesta samples obtained from the rumen, cecum, proximal loop of the ascending colon (PLAC), and rectum of healthy cows and cows with cecal dilatation or dislocation (CDD). ANIMALS: 20 cows with CDD and 20 healthy cows. PROCEDURE: Samples were collected from all sites during surgical correction of CDD and also from the rectum 1, 2, and 3 days after surgery (group CDD). Samples from healthy (control) cows, matched on the basis of diet and milk yield, were obtained at a slaughterhouse. Concentrations of volatile fatty acids (VFA) were analyzed by use of gas chromatography. Absolute concentration of each VFA was additionally corrected for pH to allow calculation of the concentration of undissociated VFA. RESULTS: Absolute concentration and concentration of the undissociated form of all analyzed VFA were significantly increased in samples collected from the cecum and PLAC of cows in group CDD, compared with concentrations for control cows. Within 3 days after surgery, significant decreases of the absolute concentration of butyric, i- and n-valerianic acids, and undissociated i- and n-valerianic acids were evident in samples obtained from the rectum of group-CDD cows. Concentrations of VFA in samples obtained from the rectum during surgery correlated with corresponding VFA concentrations in samples obtained from the PLAC. CONCLUSIONS: Concentrations of VFA are increased in the cecum and PLAC of cows with CDD. However, the role of increased concentrations of VFA in the etiopathogenesis of CDD is unknown.

Asunto(s)

RESUMEN

Torsades de Pointes (TdP) is a polymorphic ventricular arrhythmia which can degenerate into ventricular fibrillation. The most typical symptom of TdP is the ECG morphology where QRS complexes seem to rotate around the isoelectric baseline. Bradycardia and delayed repolarization are regarded as pathophysiologic predispositions. For better understanding of the pathophysiology and the evaluation of therapeutic or proarrhythmic potential of drugs, a functional experimental model is needed. In the present study, an experimental model of polymorphic tachyarrhythmias taken as TdP equivalents in isolated guinea pig hearts was developed. The hearts were perfused by the Langendorff technique. Bradycardia was induced by dissection of the sinus node, and prolongation of the QT interval by infusion of two inhibitors of the sodium channel inactivation, veratridine and DPI 201-106. TdP equivalents were triggered reproducibly by application of electrical single stimuli at the end of the T wave. Experiments with different concentrations of the channel active substances alone and in combination, with different perfusion times and mode of electrical stimulation (single pulse versus train stimulation), showed the highest incidence for TdP equivalents by means of an initial 30 min long infusion of 0.5 microM each veratridine and DPI 201-106 in combination with electrical single stimuli. After finishing the infusion with the channel active substances but still with lasting effects from them. TdP equivalents were triggered repeatedly in five of six experiments. The reasons for this increased TdP susceptibility after finishing the infusion are not known. In a separate series of six similarly arranged experiments, the incidence for TdP equivalents could be decreased from 83% to 12.5% (p < 0.001) by increasing the concentration of magnesium in the perfusate from 1.17 to 5.0 mM. With these experiments, the clinically known therapeutic effect of magnesium suppressing TdP could be demonstrated in an in vitro model for the first time. The results suggest that this model could be used as a base for further studies of clinical relevant drugs, especially antiarrhythmic agents, to obtain hints of possible risks of proarrhythmic effects or of suitability for therapeutic use at TdP attacks.

Asunto(s)

RESUMEN

Acute pharmacodynamic effects of the alpha2-adrenoceptor agonists, xylazine and guanfacine, were investigated in nine healthy calves in an open crossover trial. Xylazine (100 microg/kg body weight intravenously (i.v.)) and guanfacine (20 microg/ kg body weight i.v.) were equi-effective in lowering heart rate by 25-30%, at 5 min. Under these conditions, xylazine induced strong sedation and increased plasma growth hormone levels, indicating central nervous system mediated actions, whereas guanfacine was not sedative and did not induce release of growth hormone. Oxygen consumption was decreased by both drugs, but respiratory exchange ratio decreased only in response to xylazine. However, in response to both drugs, plasma levels of noradrenaline, adrenaline, insulin and non esterified fatty acids decreased similarly and glucose increased comparably. These results demonstrate marked differences in the central nervous system-mediated effects of the two alpha2-adrenoceptor agonists, whereas peripheral actions are similar.

Asunto(s)

RESUMEN

Following the application of permethrin or cyhalothrin to cattle for the control of ectoparasites, the occurrence and persistence of these chemicals was assessed on the animals and in their environment. The release of permethrin from ear tags containing 1 g of the drug on cattle was followed for 65 days and lead to concentrations of 5 to 35 micrograms of permethrin per gram of hair on the shoulders. On the flanks of the animals, the corresponding values were 10 times lower. Across the 1.5 acre pasture, high concentrations of permethrin were measured at various locations and long after treatment: 6 micrograms/g on bark of a birch after one week, 5 micrograms/g on a pole of the fence after two weeks, 1 microgram/g in grass from a resting site of the animal after six weeks, and 0.5 microgram/g in bark of a pine tree after three month and two weeks after the animals had left the pasture. In similar assays, cyhalothrin applied to milk cows as a pour-on preparation was monitored. One week following treatment with 0.2 g/animal, hair cut from the shoulders contained 5 micrograms/g of the insecticide, which disappeared with a half-life of 12 days. Dust collected two weeks after the pour-on treatment from the milk barn where the cows were milked twice daily contained 47 micrograms/g of cyhalothrin, which disappeared with a half-life of 44 days. These results show that synthetic pyrethroids used on farm animals can be the source of widespread and persistent contamination.

Asunto(s)

RESUMEN

The synthetic pyrethroid derivatives permethrin and cyhalothrin are widely used insecticides that are considered to be relatively nontoxic to higher animals. However, a variety of toxic effects on mammals have been reported. We investigated the effect of these drugs on energy coupling by mitochondria and on the activity of the individual respiratory complexes. Using isolated rat liver mitochondria, a concentration-dependent inhibition of glutamate and succinate sustained state 3 respiration was found for both compounds in the micromolar range. The effect of pyrethroids on the activities of the complexes I to V were assessed individually in submitochondrial particles (complex I) and in freeze-thawed mitochondria (complexes II-V). Complex I (EC 1.6.5.3) was found to be the most sensitive link within the electron transport chain. Half-maximal inhibition was observed at 0.73 microM permethrin and 0.57 microM cyhalothrin, respectively, and exhibited sigmoidal inhibition kinetics. Complexes II, III, IV and V (EC 1.3.5.1, 1.10.2.2, 1.9.3.1, 3.6.1.34) were not significantly inhibited by up to 50 microM of these drugs. Thus, our results reveal a model of action of synthetic pyrethroid insecticides not previously reported.

Asunto(s)

RESUMEN

Myoglobin levels are decreased in various animal models of heart failure, a change that has been associated with compromised energy supply. The underlying mechanisms by which myoglobin content decreases in failing myocardium are unknown. Bovine hereditary cardiomyopathy (bCMP) displays several characteristics of human dilated cardiomyopathy with a marked desensitization of the beta-adrenoceptor signal cascade. The aim of the present study was to investigate whether a similar reduction of myoglobin can be seen in this animal model, and to elucidate the possible mechanism of this reduction. Myoglobin protein concentration was decreased by 46-47% (P < 0.05) in left and right ventricular myocardium of failing hearts (n = 9) compared to control hearts (n = 11). No difference was found between atria of diseased and control animals. Immunohistochemistry with a polyclonal antibody against myoglobin revealed a strong and uniform labeling in cardiomyocytes of non-failing hearts. Using microscopic densitometry, immunosignals were significantly decreased in ventricular myocytes of bCMP hearts (168 +/- 5.3 v 118 +/- 8.6 arbitrary units, P < 0.05). Moreover, myoglobin was heterogeneously distributed in bCMP hearts, with single myocytes showing no staining. Slot blot analysis of total RNA demonstrated a 40-50% reduction (P < 0.05) of myoglobin mRNA levels in ventricular but not in atrial myocardium of bCMP hearts. The results support the view that a decrease of myocardial myoglobin is a general phenomenon in end-stage heart failure. It appears to be primarily due to reduced gene expression but may be aggravated by leaking from single myocytes. The decrease of myoglobin may contribute to the imbalance between energy production and energy expenditure in heart failure.

Asunto(s)

RESUMEN

The effects of the new class III antiarrhythmic agent E-4031 were investigated in different guinea pig cardiac preparations. In left atria, E-4031 (10(-8)-10(-5) M) prolonged the functional refractory period up to 45% and reduced the frequency of spontaneously beating right atria by 32%. In papillary muscles, E-4031 (3 x 10(-8)-3 x 10(-7) M) reversibly prolonged the action potential duration (APD70) of fast and slow APs by 68 and 51%, respectively. Vmax, resting potential, and AP amplitude (APA) were not altered. In isolated ventricular myocytes, E-4031 reversibly prolonged the APD90 from 275 ms (control) to 1,496 ms (10(-6) M), pD2 value 6.5. The current changes that underlie the AP-prolonging effect were also studied in ventricular myocytes: in concentrations up to 10(-5) M), E-4031 did not affect the Na+ or Ca2+ inward current but reduced the delayed rectifier (IK) tail current by 76% (10(-7) M). Contractility was enhanced by E-4031 in isolated atria by 20% (3 x 10(-7) M) and increased cell shortening in ventricular myocytes. Thus, the class III antiarrhythmic action of E-4031 is due to a selective reduction of outward currents.

Asunto(s)

Asunto(s)

RESUMEN

The inotropic actions of various drugs known to increase force of contraction in isolated mammalian cardiac muscle were investigated in electrically driven (1 Hz) guinea-pig left atria under both normal [K+]o (4.7 mM) and high [K+]o (22 mM). Under normal [K+]o a concentration-dependent increase in force of contraction could be confirmed with the beta-adrenoceptor agonist, isoprenaline, the cyclase activator, forskolin, the inhibitors of the cyclic AMP-phosphodiesterase (PDE), amrinone, IBMX, and OPC 8212, the Na+ channel activators, DPI 201-106, SDZ 210-921, veratridine, and ATX II, the Na(+)-ionophore monensin, the inhibitor of Na+/K(+)-ATPase, ouabain, and the Ca2+ channel activators, Bay K 8644, CGP 28 H 392, and SDZ 202-791. Partial depolarization of the muscle preparations by increasing [K+]o in the organ bath to 22 mM completely abolished the positive inotropic action of the Na+ channel-activating drugs. In contrast, the effects of the other compounds were still present, although changes in the maximal force development were observed. The efficacy of the PDE inhibitors amrinone and IBMX were slightly increased; the maximal effects of isoprenaline, monensin, forskolin, and OPC 8212 were unchanged; the effect of ouabain decreased to about half maximal values; while the efficacy of the Ca2+ channel activators were either unchanged (CGP 28 392) or decreased (Bay K 8644 and SDZ 202-791). The results suggest that inactivation of cardiac fast Na+ channels by partially depolarizing isolated, electrically driven atria is a suitable model to distinguish between cardiotonic agents acting through activation of Na+ channels and those with other mechanisms of action.

Asunto(s)

RESUMEN

The present experiments were carried out to investigate the cardiovascular effects of endothelin 1 (ET) in pithed spontaneously hypertensive (SH) rats and to evaluate its mechanism of action. The results show that ET (0.1-3 nmol/kg i.v.) is a powerful vasoconstrictor agent in the pithed rat. However, at a dose of 3 nmol/kg i.v. all the pithed animals "died" following a gradual decrease in mean arterial blood pressure and pulse pressure and changes in the form of the electrocardiogram (ECG). The predominant feature of the change in the ECG was a progressive decrease in the amplitude of the T wave resulting in a depression of the curve representing repolarization. Investigations in isolated perfused SH rat hearts showed that ET powerfully reduces coronary flow concentration-dependently (IC50 2.1 +/- 0.3 nM) an effect associated with sinus bradycardia and a decrease in coronary pressure amplitude. No overt ECG changes were seen. Control experiments with mechanical flow restriction suggest that bradycardia is a consequence of reduced coronary flow and that the ECG changes observed in vivo can be explained on the basis of coronary insufficiency and resulting myocardial hypoxia. Vasoconstrictor responses to angiotensin II (0.4 microgram/kg i.v.), phenylephrine (8 micrograms/kg i.v.) and ET (0.5 nmol/kg i.v.) were antagonised by around 70% by isradipine (0.03 mg/kg i.a.). The results suggest that endothelin-induced vasoconstriction may involve receptor operated channel activation and opening of voltage sensitive Ca2+ channels.

Asunto(s)

RESUMEN

Guanfacine (Estulic, Tenex), a centrally acting antihypertensive, was investigated for its effects on the heart using isolated cardiac preparations and in patients for antiarrhythmic properties. The tachycardic effects of sympathetic nerve stimulation in spontaneously beating atria were concentration-dependently suppressed by guanfacine. A 50% inhibition was observed in atria from Syrian hamsters, guinea-pigs and rabbits with 1, 5.4 and 20 nmol/l, respectively. In guinea-pig atria the concentration-response curve of guanfacine was shifted to the right in a parallel manner by rauwolscine (pA2 8.58) but was not displaced by prazosine 1 mumol/l. In rabbit right papillary muscles guanfacine 1 to 10 mumol/l increased force of contraction by 13 to 91%. The positive inotropic effect was antagonized by prazosine 1 mumol/l but was not influenced by cimetidine 1 mumol/l or rauwolscine 1 mumol/l. It is concluded that guanfacine activates cardiac postsynaptic a1- and neuronal presynaptic a2-adrenoceptors with a preference to the latter of about 2 orders of magnitude. Direct membrane stabilizing effects in guinea-pig atria were negligible. In 4 patients with coronary heart disease associated with arrhythmia guanfacine 1 mg per day during 10 days decreased ventricular premature contractions, couplets and abolished appearance of ventricular tachycardias. These preliminary clinical results indicate that guanfacine may reduce cardiac risk factors.

Asunto(s)