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Biomedical subjects

C Valenzuela

Publications and source records attributed to C Valenzuela.

At least 55 records · Page 3Linked to original sources
PubMed1994

Effects of lisinopril on cardiac contractility and ionic currents.

1. The effects of lisinopril, an angiotensin-converting enzyme inhibitor, were studied on cardiac contractile force, action potential characteristics and membrane ionic currents. 2. In guinea-pig atria, lisinopril (0.001-1 microM) exerted a negative inotropic effect which was accompanied by a shortening of the time to peak tension and time for total contraction. However, it did not modify atrial rate or the characteristics of the ventricular action potentials recorded either in normally polarized or in depolarized papillary muscles. 3. In isolated guinea-pig ventricular myocytes, lisinopril had no effect on the inward L-type Ca2+ (ICa,L), the inward rectifier (IK1) or the delayed rectifier K+ currents (IK), but abolished the stimulation-dependent facilitation of the ICa,L. Furthermore, it did not alter a cloned human cardiac K+ current (hKv1.5) expressed in a mouse L cell line (Ltk-). 4. The absence of negative inotropic effects in patients with congestive heart failure can be explained by the potent arterial vasodilator action of lisinopril which reduced left ventricular afterload overriding the expected direct cardiodepressant effects of the drug.

Action Potentials↗
PubMed1994

Gating of cardiac Na+ channels in excised membrane patches after modification by alpha-chymotrypsin.

Single cardiac Na+ channels were investigated after intracellular proteolysis to remove the fast inactivation process in an attempt to elucidate the mechanisms of channel gating and the role of slow inactivation. Na+ channels were studied in inside-out patches excised from guinea-pig ventricular myocytes both before and after very brief exposure (2-4 min) to the endopeptidase, alpha-chymotrypsin. Enzyme exposure times were chosen to maximize removal of fast inactivation and to minimize potential nonspecific damage to the channel. After proteolysis, the single channel current-voltage relationship was approximately linear with a slope conductance of 18 +/- 2.5 pS. Na+ channel reversal potentials measured before and after proteolysis by alpha-chymotrypsin were not changed. The unitary current amplitude was not altered after channel modification suggesting little or no effect on channel conductance. Channel open times were increased after removal of fast inactivation and were voltage-dependent, ranging between 0.7 (-70 mV) and 3.2 (-10 mV) ms. Open times increased with membrane potential reaching a maximum at -10 mV; at more positive membrane potentials, open times decreased again. Fast inactivation appeared to be completely removed by alpha-chymotrypsin and slow inactivation became more apparent suggesting that fast and slow inactivation normally compete, and that fast inactivation dominates in unmodified channels. This finding is not consistent with a slow inactivated state that can only be entered through the fast inactivated state, since removal of fast inactivation does not eliminate slow inactivation. The data indicate that cardiac Na+ channels can enter the slow inactivated state by a pathway that bypasses the fast inactivated state and that the likelihood of entering the slow inactivated state increases after removal of fast inactivation.

Animals↗
PubMed1994

Class I and III antiarrhythmic actions of prazosin in guinea-pig papillary muscles.

1. The electrophysiological effects of prazosin, a highly specific alpha 1-adrenoceptor antagonist, on transmembrane action potential characteristics were studied in guinea-pig papillary muscles. 2. At concentrations between 10(-6) M and 10(-5) M, prazosin produced a concentration-dependent decrease in the maximum upstroke velocity (Vmax) and a progressive lengthening of the action potential duration at 50% (APD50) and 90% (APD90) of repolarization. The prolongation of the APD50 and APD90 values was independent of the frequency of stimulation. The prolongation of the ADP90 was accompanied by a parallel lengthening of the effective refractory period (ERP) and thus, the ERP/APD90 ratio remained unaltered at all drug concentrations tested. 3. In the presence of prazosin, 5 x 10(-6) M, the percentage of Vmax block increased with the frequency of stimulation, the inhibitory effect being more marked at fast driving rates (frequency-dependent Vmax block). At 3 Hz, the onset kinetics of the frequency-dependent Vmax block was better fitted by a biexponential function, the K values of the fast (K1) and slow components (K2) being 0.254 +/- 0.037 AP-1 and 0.045 +/- 0.010 AP-1, respectively. However, prazosin did not produce tonic Vmax block. 4. The recovery time constant (tau re) from the frequency-dependent Vmax block was prolonged from 19.6 +/- 2.5 ms to 24.4 +/- 5.5 s. This result indicated that prazosin can be considered as a slow kinetics Na channel blocker. 5. Prazosin, 5 x 10(-6) M, shifted the membrane responsiveness curve in a hyperpolarizing direction, which indicated that the blockade of sodium channels increased at less negative potentials (voltage-dependent Vmax block). 6. It is concluded that in guinea-pig papillary muscles, prazosin inhibited the Vmax and lengthened the duration of the action potentials, thus exhibiting both class I and class III antiarrhythmic actions,respectively, that were possibly unrelated to blockade of myocardial alpha l-adrenoceptors.

Action Potentials↗
PubMed1994

Imipramine blocks rapidly activating and delays slowly activating K+ current activation in guinea pig ventricular myocytes.

Imipramine is a tricyclic antidepressant drug that also exhibits antiarrhythmic effects and whose clinical spectrum of activity is similar to that of quinidine. It has been previously demonstrated that imipramine inhibits the aggregate time-dependent outward K+ current (IK). IK is composed of at least two components: a slowly activating La(3+)-resistant delayed rectifying current (IK,s) and a rapidly activating La(3+)-sensitive current (IK,r). To assess the effects of imipramine on IK,r and IK,s, single guinea pig ventricular myocytes were studied using the nystatin-perforated patch-clamp technique in the absence and in the presence of La3+. Imipramine inhibited IK,r and IK,s in a concentration-dependent manner. The effects of imipramine on the aggregate time-dependent outward current were more marked than those on IK,s alone. Thus, 1 mumol/L imipramine decreased the tail currents elicited on return to -30 mV after long depolarizing pulses (5 seconds, from -40 to +50 mV) in the absence and in the presence of La3+ by 27 +/- 4% and 15 +/- 3% (n = 6), respectively. Moreover, the inhibition induced by imipramine was greater after short (0.5-second) pulses than after 5-second depolarizing pulses, both in the absence and in the presence of La3+ (53 +/- 3% and 30 +/- 5%, respectively; n = 6; P < .05). Imipramine did not significantly modify either the activation midpoint or the slope factor of the aggregate IK and IK,s activation curves. The reduction of IK,s by imipramine was voltage dependent and was more marked at negative membrane potentials. In the presence of 1 mumol/L imipramine, the ratio of tail current to time-dependent current remained constant at 0.37 +/- 0.03, regardless of the test pulse duration at +50 mV. Thus, the envelope-of-tails test was satisfied in the presence of 1 mumol/L imipramine, which indicates that imipramine, at this concentration, blocks IK,r. Imipramine (1, 5, and 10 mumol/L) had no effect on the kinetics of the later phase of IK activation but delayed the beginning of the activation of IK,s by 62 +/- 22, 74 +/- 23, and 155 +/- 53 milliseconds in the presence of 1, 5, and 10 mumol/L imipramine, respectively. These results suggest that imipramine preferentially blocks rapidly activating K+ channels. In addition, experiments performed in the presence of 30 mumol/L La3+ suggest that the drug preferentially binds, but maybe not exclusively, to a closed state of the slowly activating K+ channel.

Action Potentials↗
PubMed1993

The sequence of eruption of the permanent dentition in a Chilean sample with Down's syndrome.

The eruption of the permanent teeth in Down's individuals is reportedly delayed. The extent of such delay in comparison to normal children has been little studied. The eruption characteristics of the permanent teeth in a sample of Chilean individuals with Down's syndrome were here compared with those of the normal Chilean population. The sample consisted of 240 Down's individuals (all with trisomy 21), 116 males and 124 females. The chronological sequence of eruption in Down's children was not completely different from the normal. The least affected teeth were upper and lower first molars and central and lateral incisors. Alterations of the eruption sequence were not necessarily a consequence of alterations in the time of eruption. Asymmetries between sides of the jaw were mainly in canines and premolars. Alterations in sequence timing and asymmetry seem to be age dependent, being less frequent between 7 and 9 yr of age and more frequent between 10 and 14 yr of age. This may also reflect the larger variances of age of eruption observed in Down's individuals. Despite this, Down's children maintained a certain similarity in sequence and symmetry in comparison to normals.

Adolescent↗
PubMed1993

Electrophysiological effects of the combination of imipramine and desipramine in guinea pig papillary muscles.

The electrophysiological effects of imipramine and its active metabolite desipramine, alone or in combination, were studied in isolated guinea pig papillary muscles. The maximum upstroke velocity (Vmax) of the action potential was used as an indirect index of the magnitude of the sodium inward current. In muscles driven at 0.02 Hz, imipramine alone (5 x 10(-6) M), desipramine alone (5 x 10(-6) M), or their combination had no effect on action potential characteristics. However, in the presence of imipramine or desipramine, trains of stimuli at rates between 0.5 and 3 Hz led to a frequency-dependent Vmax block that was augmented at higher stimulation rates. At each driving rate, the Vmax block produced by desipramine was significantly greater than that produced by imipramine. The combination of imipramine and desipramine increased the onset rate of the frequency-dependent Vmax block, but the total amount of Vmax block was similar to that produced by desipramine alone. In the presence of imipramine alone, the recovery of Vmax was a monoexponential process, the time constant (tau re) being 2.3 +/- 0.4 s, whereas in the presence of desipramine, it was better defined by a biexponential function (tau re = 1.5 +/- 0.4 and 15.8 +/- 2.8 s). In the presence of the combination, the recovery process was also defined by a biexponential function and the tau re values were similar to those found in the presence of desipramine alone. Thus, according to their onset and offset kinetics of the frequency-dependent Vmax block, imipramine and desipramine can be classified as sodium channel blockers with intermediate and slow kinetics, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1993

Effects of lisinopril on electromechanical properties and membrane currents in guinea-pig cardiac preparations.

1. The effects of the angiotensin-converting enzyme inhibitor, lisinopril, were studied in guinea-pig atria and papillary muscles and in single isolated ventricular cells. 2. In isolated right atria, lisinopril (0.001-10 microM) decreased the amplitude and rate of the spontaneous contractions. In electrically driven left atria this negative inotropic effect was accompanied by a shortening of the time to peak tension and time for total contraction. 3. Lisinopril did not modify the electrophysiological characteristics of the ventricular action potentials recorded in papillary muscles perfused with normal Tyrode solution or elicited by isoprenaline in papillary muscles perfused with 27 mM K Tyrode solution. 4. In single ventricular cells, lisinopril (10 microM) had no effect on the inward L-type Ca2+ (ICa,L), the inward rectifier (IK1) or the delayed rectifier K+ currents (IK). However, it abolished the stimulation-dependent facilitation of the L-type Ca2+ current. 6. These results indicate that the negative inotropic effect of lisinopril cannot be explained by a decrease in Ca2+ entry through L-type channels and suggest that lisinopril may possibly act at an intracellular site to reduce contractile force.

Action Potentials↗
PubMed1993

[Tilt test: hemodynamic responses in patients with syncope or presyncope of unknown etiology].

The aim of this work was to assess the hemodynamic responses to the tilt test of 51 patients with syncope (n = 31) or presyncope (n = 20) of unknown etiology. A protocol with an inclination of 70 degrees (20 min) with or without isoproterenol (mean dose of 3.6 +/- 0.3 ug/min), was used. Forty five percent of patients had a positive test, 18 with isoproterenol at 70 degrees (group 1A) and 5 without isoproterenol (group 1B); 28 patients had a negative test (group 2). These groups did not differ in age or sex distribution. Basal heart rate was 76.2 +/- 2x'. At the end of the test it was 73.4 +/- 5.7 in group 1A, 78.0 +/- 7.5 in group 1B and 120.4 +/- 3.3 in group 2 (p < 0.01). Systolic blood pressure decreased to 78.1 +/- 4.8 mmHg in group 1A, to 76.2 +/- 9.9 in group 1B and did not decrease in group B (130.0 +/- 5.7 mmHg, p < 0.01). The required dose of isoproterenol was higher in group 1A than in group 2 (4.4 +/- 0.3 vs 3.1 +/- ug/min, p < 0.01). It is concluded that the tilt test reproduced symptoms and accompanying hemodynamic mechanisms in a high proportion of patients with syncope of unknown etiology. This test should be incorporated in the diagnostic workup of these patients.

Adolescent↗
PubMed1993

[2 solutions for estimating odds ratios with zeros].

Two solutions are proposed for the estimation of odds ratios (OR) when one or the two elements of the principal (A, D) or secondary (B, C) diagonals of a 2 x 2 matrix (A, B, C, D) are 0. The OR estimate is AD/BC. If A or D are 0, OR = 0; if B or C are 0, the OR is undefined. Analytical solution. This solution conserves the marginal totals. If B = 0 and C = 0, the OR cannot be less than AD/1 (the minimal acceptable value), then the equation (A-X) (D-X)/X2 = KAD/1 searches for that X which subtracted to A and B and added to B (0) and C (0) yields an OR K times AD; if B = 0 and C > 0 then (A-X) (D-X)/X (C+X) = AD/C; if B > 0 and C = 0, then B replaces C in the latter equation. If A and D are 0, X2/(B-X) (C-X) = 1/KBC; if A = 0 and D > 0, X (D+X)/(B-X) (C-X) = D/KBC; if A > 0 and D = 0, A replaces D in the latter equation. K can be taken at the maximum Chi squared value. Probabilistic solution. Zeros are replaced by ones and the elements of the diagonal without zeros are increased proportionally until the exact probability (Fisher) of this new matrix is equal or the nearest less than the exact probability of the original matrix. Since small numbers increase the estimation bias, the Haldane's correction should be always applied. This correction adds 0.5 to A, B C and D to estimate the OR (In OR) and adds 1 to these elements to estimate their variance.

Odds Ratio↗
PubMed1993

[Molecular genetic study of cystic fibrosis in the Chilean population. Relationship to its clinical expression].

Aiming to establish a genotype-phenotype relationship and to search a clinical expression in heterozygotes, 25 Chilean subjects with Cystic Fibrosis and 165 relatives were subjected to a clinical-molecular study. The most common mutations found worldwide were studied: delta F-508, G-542X, N-1303K, R-553X and G551D. Clinical and laboratory assessment comprised chest X-rays, spirometry, clinical evaluation, nutritional assessment, sweat test and carotenemia. Age at diagnosis was lower among homozygotes for the mutation delta F-508. In this group, Brasfield and Schawchman scores were better, probably due to an earlier initiation of treatment. No other differences were found among genotypic groups or relatives. Genetic markers indicated a higher european component of the sample, compared to the general Chilean population.

Adolescent↗
PubMed1993

Treatment of left ventricular hypertrophy in hypertensive patients.

Left ventricular hypertrophy (LVH), as detected by electrocardiography or echocardiography, constitutes a powerful risk factor for cardiovascular morbidity and mortality. Antihypertensive drugs that modulate the sympathetic or renin-angiotensin-aldosterone systems or the intracellular free Ca concentration (i.e. beta-blockers, postsynaptic alpha 1-blockers, centrally acting adrenergic drugs, calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors) can prevent or cause regression of LV mass after short-term therapy, this effect being more pronounced with ACE inhibitors. Diuretics and arterial vasodilators also cause regression of LVH provided that they are used for long enough to effect long-term control of arterial pressure. However, clinical studies also indicate that despite their equipotent blood-pressure lowering effects, there are marked differences not only in the ability of the different types of antihypertensive drugs to prevent or reverse LV mass but also within the same class of pharmacological drugs. Decreased LV mass in hypertensive patients may be associated with an improvement in diastolic function and has not been found to produce adverse effects on LV systolic performance.

Antihypertensive Agents↗
PubMed1993

[MNSs system mother-newborn segregation distortions].

We present segregation distortions for the MNSs system and for the sex ratio found among 400 mother-newborn pairs, from the northern Area of Santiago and the middle-low and low socioeconomic strata. Three subsamples were taken: from the non private patients of the Clinical Hospital of the University of Chile; from the Hospital San José, a public hospital of this Area; controls of malformed newborns belonging to an international study from the Clinical Hospital of the University of Chile. In spite of the almost homogeneity of socioeconomic strata and area, the differences among these subsamples did not allow us to take them as only one sample. We found excess of heterozygous individuals for the MN locus, specially among mothers. Ss heterozygotes had a higher sex ratio than ss homozygotes. Several distortions could not be dealt with as having a regular pattern in the three subsamples. A possible technical error is discussed.

Chile↗
PubMed1992

Electrophysiological effects of CRE-1087 in guinea-pig ventricular muscles.

1. The electrophysiological effects of CRE-1087, a new antiarrhythmic drug, were studied in guinea-pig papillary muscles. 2. CRE-1087 (10(-7) M-10(-4) M) produced a concentration-dependent decrease in the action potential amplitude and Vmax of the upstroke without altering the action potential duration or the resting membrane potential. 3. At 5 x 10(-6) M, CRE-1087 produced a 5.0 +/- 1.0% tonic Vmax block and this value was not modified at the different rates of stimulation tested. In the presence of CRE-1087, trains of stimuli at rates between 0.5 and 3 Hz led to an exponential decline in Vmax (frequency-dependent Vmax block) which augmented at higher rates of stimulation. At 2 Hz the onset kinetics of the frequency-dependent Vmax block was fitted by a monoexponential function being the K value 0.099 +/- 0.012 AP-1. The time constant for the recovery of Vmax from the frequency-dependent block was prolonged to 18.3 +/- 1.5 s. 4. CRE-1087 (5 x 10(-6) M) did not shift the membrane responsiveness curve. 5. CRE-1087 had no effect on the characteristics of the slow action potentials elicited by isoprenaline in ventricular fibres depolarized by 27 mM KCl, which suggested that CRE-1087 did not exhibit class IV (Ca antagonist) antiarrhythmic actions. 6. The slow onset and the slow offset kinetics of frequency-dependent Vmax block during repetitive activity suggested that in guinea-pig ventricular muscle fibres CRE-1087 exhibited class Ic antiarrhythmic actions.

Action Potentials↗
PubMed1992

[Borderline personality disorder: a comparative study between the clinical diagnosis and the Rorschach test].

Diagnostic concordance among Rorschach Test, clinical approach and DSM-III-R criteria for BPD is studied in an inpatient sample. A low degree of concordance among the three diagnostic systems was found. Two among 8 DSM-III-R criteria (physically self-damaging acts, and unstable-intense relationships) were the most discriminating symptoms for diagnosing BPD. The importance of considering the diagnostic efficiency of each DSM-III-R criterion is discussed. The most frequent concurrent diagnosis along with BPD were: Affective, and psychotic disorders. Their relationship is analyzed.

Adult↗