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Biomedical subjects

C Valenzuela

Publications and source records attributed to C Valenzuela.

At least 73 records · Page 4Linked to original sources
PubMed1991

Tonic and frequency-dependent Vmax block induced by (S)-nafenodone, a new antidepressant drug, in guinea-pig papillary muscles.

The effects of (S)-nafenodone, a new antidepressant, on transmembrane action potentials were studied in guinea-pig papillary muscles. In muscles driven at 0.02 and 1 Hz, (S)-nafenodone, 10(-6) mol/l and 10(-5) mol/l, produced a concentration-dependent decrease in the maximum upstroke velocity of the action potential, but it had no effect of the resting membrane potential. In the presence of 10(-5) mol/l (S)-nafenodone, trains of stimuli at rates between 0.5 and 2 Hz led to an exponential decline in maximum upstroke velocity to a new steady-state level [K = 0.152 +/- 0.03 (action potential)-1 at 2 Hz]. This frequency-dependent maximum upstroke velocity block increased at higher stimulation frequencies and at higher drug concentrations. (S)-Nafenodone also prolonged the time constant of recovery of maximum upstroke velocity from the frequency-dependent block to 2.3 +/- 0.6 s, this value being independent of the drug concentration. These values of onset and offset kinetics of (S)-nafenodone lie between those of drugs with fast and intermediate kinetic properties. (S)-nafenodone also shifted the curve relating membrane potential and maximum upstroke velocity in hyperpolarizing direction. All these results indicated that (S)-nafenodone produced a frequency- and voltage-dependent inhibition of the fast sodium channels similar to that exhibited with imipramine.

Action Potentials↗
PubMed1991

Voltage- and use-dependent modulation of calcium channel current in guinea pig ventricular cells by amiodarone and des-oxo-amiodarone.

Amiodarone is an effective antiarrhythmic drug handicapped by serious side effects. The mechanism of its antiarrhythmic activity is not known but is presumed to involve inhibition of current flowing through ion channels. Des-oxo-amiodarone, a close structural analogue of amiodarone, was synthesized based on the hypothesis that the toxic and therapeutic properties reside in different parts of the molecule and that chemical modification could result in a less toxic agent that yet preserved amiodarone's antiarrhythmic efficacy. We compared the effects of amiodarone and des-oxo-amiodarone on Ca current in enzymatically dispersed guinea pig ventricular myocytes using the whole-cell patch-clamp method. Amiodarone caused both a tonic and a phasic (use-dependent) reduction of the Ca current. The relationship between membrane potential and the availability for channel opening upon depolarization (inactivation curve) was shifted toward more negative membrane potentials by amiodarone (delta - 10.6 +/- 2.2 mV, n = 7). The use-dependent reduction of the Ca current was also dependent on the frequency of the voltage clamp steps (0.5 Hz, 40.2 +/- 7.9%; 1.0 Hz, 50.0 +/- 6.7%). Dex-oxo-amiodarone had a dual effect on the Ca current: After maintaining the membrane potential for several seconds at negative membrane potentials (less than -45 mV), the Ca current was increased by des-oxo-amiodarone. Des-oxo-amiodarone also shifted the Ca channel inactivation curve to more negative membrane potentials up to 16 mV. Consequently, Ca current could be increased or decreased depending on the experimental conditions. Enhancement of Ca current by des-oxo-amiodarone was transient and was supplanted entirely by the antagonistic effects of the drug after approximately 5 min. The antagonistic effects of des-oxo-amiodarone on Ca current were also use- and frequency-dependent.

Action Potentials↗
PubMed1991

Electrophysiological effects of the combination of mexiletine and flecainide in guinea-pig ventricular fibres.

1. The effects of flecainide alone, mexiletine alone and their combination at the Na+ channel level were studied in guinea-pig papillary muscles. The maximum upstroke velocity (Vmax) was used as an indirect index of the magnitude of the fast inward Na+ current (INa). 2. In muscles driven at 0.02 Hz, neither mexiletine (10(-5) M) nor flecainide (10(-6) M) nor the combination of both drugs modified the action potential characteristics. Mexiletine, but not flecainide, increased the effective refractory period/action potential duration ratio; this enhancement was greater when flecainide was also present. 3. Mexiletine or flecainide alone produced a frequency-dependent Vmax block. Although at 0.5 Hz the blockade induced by the combination of flecainide and mexiletine was similar to that produced by flecainide alone, in muscles driven at 1 and 2 Hz the combination increased the magnitude and the onset rate of the Vmax block. 4. The time constant of recovery of Vmax block was similar in the presence of flecainide or the combination mexiletine plus flecainide (tau re = 16.4 +/- 2.3 s and 16.7 +/- 2.7 s, respectively), but the combination decreased the magnitude of the slow component of reactivation induced by flecainide (93.8 +/- 1.5% versus 68.9 +/- 1.7%). Moreover, the combination of both drugs was more effective in inhibiting the Vmax of early test stimuli than either drug alone. 5. It is concluded that the combination of mexiletine and flecainide is synergistic at driving rates faster than 0.5 Hz without detracting from the characteristics of flecainide.

Action Potentials↗
PubMed1991

[Pepsanurin in congestive heart failure].

We have identified a plasmatic substance, "pepsanurin" (PU) obtained by pepsin hydrolysis which inhibits the renal effects of the atrial natriuretic factor (ANF). To investigate whether patients with congestive heart failure (CHF) have increased plasma levels of PU we prepared PU from 10 patients with CHF class IV (NYHA), 9 patients with CHF class II or III and 16 healthy controls. Anesthetized rats were used to test the effects of ANF, 0.5 ug/100 g body weight i.v., before and following the intraperitoneal injection of 0.5 ml of PU. The inhibition of the diuretic and natriuretic effects of ANF was 40.9 +/- 11.9% and 49.8 +/- 12% respectively for control subjects. Corresponding figures for class IV CHF patients were 62.3 +/- 3.1% and 73.8 +/- 3.5% (p less than 0.02) and for class II-III patients 39.2 +/- 7.0% and 53.1 +/- 8.2% (NS). Accordingly, an increased capacity to generate PU may underlie the decreased sensitivity to ANF in patients with advanced CHF.

Adult↗
PubMed1991

Intraarticular progesterone inhibits 3H-dexamethasone binding to synovial cells from patients with rheumatoid arthritis. A study by dry radioautographic technique.

Glucocorticoids are known to exert their antiinflammatory effects through an interaction with specific hormone receptors. Progesterone is able to bind to these glucocorticoid receptors exerting either agonistic or antagonistic actions. We have reported that a single intraarticular injection of progesterone exerts a local antiinflammatory action in patients with rheumatoid arthritis (RA), suggesting an agonistic effect of progesterone on local glucocorticoid receptors. To corroborate this possible mechanism of action, we investigated the binding of 3H-dexamethasone to local glucocorticoid receptors in synovial tissue from 3 patients with active RA, before and 14 days after a single intraarticular injection of progesterone. Both cytoplasmic and nuclear 3H-dexamethasone binding sites were observed within synoviocytes, macrophages, fibroblasts, lymphocytes and endothelial cells. Dry radioautograms of biopsied synovial tissue demonstrated a marked decrease of 3H-dexamethasone binding following progesterone treatment in all patients (p less than 0.001 for each comparison). Although the number of cases is not large enough to draw definitive conclusions, our data confirm the marked anti-inflammatory effect of intraarticular progesterone and support the hypothesis of an agonistic effect of progesterone (or its metabolites) on glucocorticoid receptors.

Arthritis, Rheumatoid↗
PubMed1990

Tonic and frequency-dependent Vmax block induced by imipramine in guinea pig ventricular muscle fibers.

The effects of imipramine (IMI) on transmembrane action potentials were studied in isolated guinea pig papillary muscles. In muscles driven at 0.02 and 1 Hz, IMI (10(-7) to 5 X 10(-5) M) produced a concentration-dependent decrease in the maximum upstroke velocity (Vmax) of the action potential, but it had no effect on the resting membrane potential. In the presence of 10(-5) M IMI, trains of stimuli at rates between 0.5 and 2 Hz led to an exponential decline in Vmax to a new steady-state level (K = 0.230 +/- 0.09 AP-1 at 2 Hz). This frequency-dependent Vmax block was augmented at higher stimulation frequencies and at higher drug concentrations. The time constant of the recovery of Vmax from the frequency-dependent block was 2.5 s, this value being independent of the drug concentration. These values of onset and offset kinetics of IMI lie between those of drugs with fast and intermediate kinetic properties. IMI also shifted the curve relating membrane potential and Vmax in hyperpolarizing directions. These results suggested that IMI exhibited a frequency- and voltage-dependent inhibition of the fast sodium channels similar to that exhibited by other class Ib antiarrhythmics. The possible role of this frequency- and voltage-dependent Vmax inhibition in the pro-antiarrhythmic effects of IMI is discussed.

Action Potentials↗
PubMed1990

[Beta adrenergic receptors in circulating lymphocytes of patients with chronic heart failure].

Severe decompensated chronic heart failure is associated to increased levels of circulating catecholamines and decreased density of myocardial beta-adrenergic receptors. In 14 patients with stable, class II-III heart failure we studied circulating lymphocytes to determine the number of beta adrenergic receptors, the dissociation constant of 3H dihydroalprenolol (kd) and the intracellular content of cyclic AMP (AMPc). Results (mean +/- SEM) were compared to those obtained in 10 healthy controls. The number of beta receptors was significantly decreased (105 +/- 16 vs 185 +/- 24, fmol/mg of membrane protein, p less than 0.01). No differences were found in Kd (1.65 +/- 0.2 vs. 1.36 +/- 0.28 nm) nor the level of AMPc (7.9 +/- 2.1 vs 7.1 +/- 2.9 pmol/mg protein), respectively. The decreased number of beta adrenergic receptors in the circulating lymphocytes may be related to the increased level of circulating catecholamines that have been shown to be present during exercise in these patients.

Adult↗
PubMed1990

[Growth patterns in height and weight in children aged 0 to 17 years and cranial circumference in children aged 0 to 2 years from medium-high and high socioeconomic status in Santiago. Comparison with growth in children from medium-low and low status in the Northern area of Santiago].

The results of a semi-longitudinal growth study of children from an upper socioeconomic stratum (SES), 0 to 17 years of age, are reported. Medical records of 6,000 boys and girls who were seen in the pediatric outpatient department of Clínica Las Condes, Santiago, during the period January 1983-December 1987 were reviewed. Data of height (H), weight (W) and head circumference (HC) of 4,800 normal children were obtained; the totals of recorded measurements were 13,000 for H, 13,000 for W and 5,800 for HC. The information is presented in 13 Tables and 32 Figures and it was compared to that from a longitudinal study in children of lower SES in Northern Metropolitan Santiago. Females of the upper stratum are taller at all ages, but W for H ratio is higher in girls of the low stratum. H and W for age values are higher in boys of the upper stratum, but W for H ratio is similar in both socioeconomic groups. The age of peak height velocity is the same in both groups for both sexes. We conclude that the stated differences in growth and weight gain between these two socioeconomic groups are better explained by genetic than by nutritional factors.

Adolescent↗
PubMed1990

[Age of menarche and genetic blood markers].

In 160 girls from low and middle socio-economic class of Santiago we correlated the age at menarque with genetic markers such as ABO blood group, Rh, MN, Xg, haptoglobins, Esterase D and Phosphoglucomutase. No significant association of these markers and age at menarque was found.

Adolescent↗
PubMed1990

[Paratyphoid B fever in 2 areas of Santiago. An analysis of the epidemiological significance].

Salmonella isolates from 3920 patients with typhoid fever from 2 areas in Santiago were analyzed to determine the frequency of association with S paratyphi B infection. This was demonstrated in 18.8% of subjects in both areas, a figure significantly higher than the 8-10% previously reported. The association with S paratyphi B was higher for females, especially for the younger age group. These findings suggest an infectious agent-gender-age interaction which may explain the discrepancy with previously reported rates of infection. Their possible relation to the chronic salmonella carrier state and association with biliary tract lithiasis and cancer is discussed.

Adolescent↗
PubMed1989

Electrophysiologic interactions between mexiletine and propafenone in guinea pig papillary muscles.

The effects of propafenone alone, mexiletine alone, and their combination at the sodium channel level were studied in isolated guinea pig papillary muscles. The maximum upstroke velocity (Vmax) was used as an indirect index of the magnitude of the sodium inward current. In muscles driven at 0.02 Hz, neither mexiletine (10(-5) M) nor propafenone (5 X 10(-6) M) had any effect on action potential characteristics, but their combination decreased Vmax. In the presence of mexiletine and propafenone, trains of stimuli at 1 Hz led to a use-dependent block (onset rate 0.11 +/- 0.008 and 0.19 +/- 0.02 per action potential, respectively). The combination of mexiletine plus propafenone increased the onset rate of the use-dependent Vmax block (0.32 +/- 0.04 per action potential), but did not modify the time-constant of recovery of Vmax block or the magnitude of the slow component of reactivation induced by propafenone. Moreover, the combination of both drugs was more effective in suppressing early test stimuli than either drug alone. We conclude that the combination of mexiletine and propafenone is a synergistic one that affects only the onset kinetics of use-dependent Vmax block without detracting from the characteristics of the propafenone.

Action Potentials↗
PubMed1989

Electrophysiologic interactions between mexiletine-quinidine and mexiletine-ropitoin in guinea pig papillary muscle.

The effects of quinidine alone, ropitoin alone, and in combination with mexiletine at the sodium channel level were studied in isolated guinea pig papillary muscles using a sucrose gap technique. The maximum upstroke velocity (Vmax) was used as an indirect index of the magnitude of the sodium current. With quinidine (24 microM) and ropitoin (1 microM) added, trains of stimuli led to an exponential decline of Vmax to a new steady-state level (use-dependent block). The combination of mexiletine and quinidine decreased use-dependent Vmax block and magnitude of the slow component of reactivation induced by quinidine without modifying its time-constant of recovery. When we studied the interaction between mexiletine and ropitoin, we obtained similar results. Therefore, we conclude that mexiletine, quinidine, and ropitoin may bind to the same receptor site in the sodium channel. In addition, these antagonistic effects appeared only at frequencies greater than 0.5 Hz, whereas at very slow frequencies of stimulation we observed a synergistic effect in both interactions studied.

Action Potentials↗
PubMed1989

Electrophysiological effects of E-3753, a new antiarrhythmic drug, in guinea-pig ventricular muscle.

1. The electrophysiological effects of E-3753, a new antiarrhythmic drug, were studied in guinea-pig papillary muscles. 2. E-3753 (10(-7) - 10(-4) M) produced a concentration-dependent decrease in the action potential amplitude and Vmax of the upstroke, shortened the action potential duration (APD) and shifted the resting membrane potential to less negative values. E-3753 also shortened the effective refractory period (ERP), lengthening the ERP relative to APD. 3. E-3753 (10(-5) M) shifted the membrane responsiveness curve along the voltage axis to more negative potentials. 4. In the presence of E-3753 (10(-5) M) trains of stimuli at rates between 0.5 and 3 Hz led to an exponential decline in Vmax (onset rate at 3 Hz, 0.05 +/- 0.009 per action potential), to a new steady-state level. This use-dependent Vmax block was augmented at higher rates of stimulation. The time constant for the recovery of Vmax from the use-dependent block was 41.1 +/- 4.8 s. 5. E-3753 (10(-5) - 10(-4) M) had no effect on the characteristics of the slow action potentials elicited by isoprenaline in ventricular fibres depolarized by 27 mM KCl. 6. The slow onset of use-dependent block during repetitive activity and the slow offset kinetics of use-dependent Vmax block suggest that E-3753 exhibits class Ic antiarrhythmic actions in ventricular muscle fibres but does not exhibit class IV (Ca antagonist) antiarrhythmic actions.

Action Potentials↗
PubMed1988

Tonic and phasic Vmax block induced by 5-hydroxypropafenone in guinea pig ventricular muscles.

The effects of 5-hydroxypropafenone (5-OH-P) on transmembrane action potentials were studied in isolated guinea pig papillary muscles. 5-Hydroxypropafenone, 10(-7) M to 5 X 10(-5) M, produced a dose-dependent decrease in the Vmax and amplitude of the action potential and a depolarization of the resting membrane potential, whereas the action potential duration was not affected by the drug. In the presence of 5-OH-P, trains of stimuli at rates between 0.2 and 2 Hz led to an exponential decline in Vmax (onset rate at 1 Hz 0.07 +/- 0.01 per action potential) to a new steady-state level. This phasic, use-dependent Vmax block was augmented at higher stimulation frequencies. The time constant for the recovery of Vmax from the phasic block (offset) was 200.0 +/- 9.3 s. In papillary muscles depolarized with 10 mM K the inhibitory effect of 5-OH-P on Vmax of the first action potential after a long quiescent period (tonic block) was markedly increased, but the rates of onset and offset of the phasic block were similar to those found in normally polarized fibers under 5.4 mM K. 5-OH-P also shifted the curves relating membrane potential and Vmax in the hyperpolarizing direction. These findings suggest that 5-OH-P exhibited similar phasic inhibitory action of the fast sodium channels than other class Ic antiarrhythmic drugs. This phasic Vmax block, and its greater inhibition of Vmax in depolarized muscles through the increase of tonic block, would play a major role for the antiarrhythmic effect of the drug.

Action Potentials↗
PubMed1988

Comparison of six new antidepressants on isolated rat atria.

The effects of six new antidepressants were studied and compared as to their electromechanical properties on isolated rat atria. All of the compounds reduced rate and amplitude of contractions, depressed atrial excitability and prolonged the sinus node recovery time. They also inhibited the amplitude of the slow contractions elicited by isoprenaline in K-depolarized atria. In decreasing order, the relative order of potency found was: mianserin approximately equal to maprotiline approximately equal to lofepramine greater than nomifensine approximately equal to trazodone greater than viloxazine. On atrial transmembrane action potentials mianserin, maprotiline and viloxazine decreased amplitude and maximum rate of depolarization and shortened the duration and depolarized the resting membrane potential. All these effects are similar to those previously reported with imipramine and amoxapine. Thus, differences between the cardiodepressant effects of the newer and older antidepressants are only quantitative but not qualitative. Possible explanations of the lower incidence of cardiovascular complications with the newer compounds are discussed.

Action Potentials↗