PubMed Health⌕ Search

Biomedical subjects

P Lorente

Publications and source records attributed to P Lorente.

At least 19 recordsLinked to original sources
PubMed1992

Analytical modeling of the hysteresis phenomenon in guinea pig ventricular myocytes.

In the present study, we have demonstrated hysteresis phenomena in the excitability of single, enzymatically dissociated guinea pig ventricular myocytes. Membrane potentials were recorded with patch pipettes in the whole-cell current clamp configuration. Repetitive stimulation with depolarizing current pulses of constant cycle length and duration but varying strength led to predictable excitation (1:1) and non-excitation (1:0) patterns depending on current strength. In addition, transition between patterns depended on the direction of current intensity change and stable hysteresis loops were obtained in stimulus:response pattern vs. current intensity plots in 14 cells. Increase of pulse duration and decrease of stimulation rate contributed to a reduction in hysteresis loop areas. Changes in amplitude and shape of the subthreshold responses during the transitions from one stable pattern to the other, suggested that activity led to an increase in membrane resistance, particularly in the voltage domain between resting potential, and threshold. Therefore, we modelled the dynamic behaviour of the single cells as a function of diastolic membrane resistance, using previously published analytical solutions. Numerical iteration of the analytical model equations closely reproduced the experimental hysteresis loops in both qualitative and quantitative ways. In particular, the effect of stimulation frequency on the model was similar to the experimental findings. The overall study suggests that the excitability pattern of guinea pig ventricular myocytes accounts for hysteresis and bistabilities when current intensity is allowed to fluctuate around threshold levels.

Action Potentials↗
PubMed1992

Slow inward current in single cells isolated from adult human ventricles.

Characteristics of the slow inward current (Isi) in human ventricular myocytes isolated from septal specimens obtained in patients undergoing corrective cardiac surgery were studied using the whole-cell clamp method. A first series of experiments was performed under normal standard superfusion. Clamping from -60 mV evoked an inward current with a threshold at about -35 mV, a maximum around +10 mV and an apparent reversal potential at about +55 mV. No overlapping transient or background outward currents were detected in the -60 to +30 mV potential range, but time-dependent and steady-state outward currents were elicited at potentials above +30 mV. An overlap of steady-state activation and inactivation curves was present between -30 and +10 mV and a slight relief from inactivation was observed for voltages positive to +10 mV. The time course of inactivation consisted of fast and slow phases with time constants differing by a factor of eight. Slow time constants of inactivation were shorter at potentials that elicited larger Isi, and longer at potentials inducing smaller Isi. Recovery from inactivation evolved slowly with 100% reactivation occurring in about 4000 ms. Switching the holding potential from -60 to -40 mV led to a reversible decline of Isi without any change of the decay time constants. Isi was significantly increased by 0.1 microM isoproterenol. Total or partial inhibition by inorganic (2 mM Mn2+, 3 mM Co2+, 1 mM Cd2+) and organic (1 microM methoxyverapamil, 5 microM diltiazem) calcium antagonists did not unmask any transient outward current. However, a consistent increase of Isi was reversibly observed with 3 mM 4-aminopyridine while using standard solutions. A second series of experiments carried out with K(+)- and Na(+)-free solutions did not demonstrate any significant change from data observed with standard solutions except a reduction of outward currents at steps above +30 mV and alteration of inactivation kinetics. In this experimental setting, 4-aminopyridine also increased Isi but to a lesser degree. We conclude that Isi, as compared to the outward currents, is dominant in the diseased human ventricular cells we have studied.

4-Aminopyridine↗
PubMed1991

Hysteresis in the excitability of isolated guinea pig ventricular myocytes.

Hysteresis phenomena were demonstrated in the excitability of single, enzymatically dissociated guinea pig ventricular myocytes. Membrane potentials were recorded with patch pipettes in the whole-cell current-clamp configuration. Repetitive stimulation with depolarizing current pulses of constant cycle length and duration but varying strength led to predictable excitation (1:1) and nonexcitation (1:0) patterns depending on current strength. However, transition between patterns depended on the direction of current strength change, and stable hysteresis loops were obtained in stimulus-response pattern versus current strength plots in 31 cells. Increase of pulse duration and decrease of stimulation rate contributed to a reduction in hysteresis loop areas. In addition, at the abrupt transitions from 1:0 to 1:1 patterns, a latency adaptation phenomenon was consistently observed. Bath application of tetrodotoxin (30 microM) produced no change of hysteresis, whereas hysteresis was substantially decreased in cobalt (2 mM) superfusion experiments. Analysis of the changes in amplitude and shape of the subthreshold responses during the transitions from one stable pattern to the other suggested that activity led to an increase in membrane resistance, particularly in the voltage domain between resting and threshold potentials. We therefore modeled the dynamic behavior of the single cells, using an analytical solution aimed at calculating the recovery of activation latency as a function of diastolic membrane resistance. Numerical iteration of the analytical model equations closely reproduced the experimental hysteresis loops in both qualitative and quantitative ways. The effect of stimulation frequency on the model was similar to the experimental findings. The overall study suggests that the excitability pattern of guinea pig ventricular myocytes is responsible for hysteresis and bistabilities when current intensity is allowed to fluctuate around threshold levels.

Adaptation, Physiological↗
PubMed1991

Dynamics of the background outward current of single guinea pig ventricular myocytes. Ionic mechanisms of hysteresis in cardiac cells.

Subthreshold potentials are thought to be mediated by time-independent, "passive" background currents. In this study, we show that the background current-voltage (I-V) relation of guinea pig ventricular myocytes is changed significantly by repetitive stimulation, in such a way that cell excitability becomes enhanced. Myocytes were used for whole-cell voltage-clamp experiments. A voltage-clamp ramp (100 mV/sec) to -50 mV was applied from a holding potential of -100 mV. Subsequently, a train of square voltage-clamp pulses to +10 mV (duration, 300 msec; interpulse interval, 300 msec) was delivered from a holding potential of -85 mV. A new ramp was applied again immediately after the train, and the resulting I-V curve was compared with that obtained before the train. Pulsing displaced the I-V relation to the right, the zero-current point becoming 1-2 mV less negative, and increased the degree of inward-going rectification. These changes were insensitive to tetrodotoxin (30 microM); disappeared during superfusion with cobalt (2 mM), verapamil (22 microM), or ryanodine (5 microM); and could not be mimicked by agonists of the protein kinase C system. In the presence of cesium (8 mM), pulsing still displaced the I-V curve to the right. However, the linear portion of the curve became steeper after the train. Subtraction of the cesium-sensitive current from control revealed that, although the zero-current point remained constant, the I-V relation showed a stronger inward-going rectification after pulsing. In accordance with these results, we have demonstrated hysteresis of excitability in ventricular myocytes. We conclude that the observed changes are mediated by an increase in intracellular calcium, which leads to an increase in rectification of IK1, as well as to activation of another membrane-conductance system, perhaps the Na-Ca exchange or the Ca(2+)-activated, nonselective current.

Animals↗
PubMed1990

Bistabilities and annihilation phenomena in electrophysiological cardiac models.

We have investigated the oscillatory behavior of cardiac cellular elements simulated by two electrophysiological models: the van Capelle and Durrer (VCD) model and the sinoatrial node cell model of Yanagihara, Noma, and Irisawa (YNI). The VCD model behavior was examined systematically by using continuation-bifurcation analysis. Bifurcation diagrams were constructed as a function of Qit1, an intrinsic parameter of the model, which sets both maximum diastolic potential and depolarization threshold of the cell. The existence of stable high amplitude oscillations was evidenced between two Hopf bifurcation points (HB). Near each HB, a zone of bistability was detected. Close to the HB that corresponded to high values of Qit1, a high amplitude periodic stable state coexisted with a stable steady state. Close to the other HB, in a narrow range of lower Qit1 values, a relatively high amplitude periodic stable state coexisted with a low amplitude periodic stable state. There was no stable steady state in the latter bistability zone. Through the use of phase-plane representations and the determination of separatrices between the different attractor basins, we could deduce the conditions of timing, polarity, and strength needed for a pulse perturbation to send the system from one state to another and vice versa. The YNI model was analyzed by numerical simulation, and the oscillatory behavior of the sinoatrial node cell was explored while applying a depolarizing bias current of various strengths. Results were similar to those obtained from the VCD model in that there were two bistability regions for two different ranges of applied bias current. Depending on current intensity, annihilation of pacemaker activity could be achieved in both zones. However, the coexistence of two oscillatory stable states was never observed in the YNI model. From the behavioral similarities of these different models, we can conclude that bistabilities and annihilation phenomena can be found in transitional zones between quiescence and rhythmic activity.

Animals↗
PubMed1989

[Mortality of dilated myocardiopathies as a function of continuation of alcohol drinking. Multivariate analysis concerning 236 patients].

A retrospective study was conducted in 236 consecutive patients with dilated cardiomyopathy to determine the characteristics of the disease in heavy alcohol drinkers (n = 110) and to study its outcome, using a Cox model, according to whether the patients were abstainers (n = 49) or continued to indulge drinking (n = 61). At the time of diagnosis, pulmonary pressures were higher in heavy drinkers than in abstainers. During a mean follow-up period of 39 +/- 27 months, 80 patients died of heart disease, viz.: 46 out of 127 non-alcoholic patients (36.2 per cent), 31 out of 61 heavy drinkers (50.8 per cent) and 3 out of 49 patients who had given up alcohol (6.12 per cent). Thus, independently of other parameters, abstinence is a highly significant (P less than 0.001) factor of favourable prognosis in dilated cardiomyopathy.

Adult↗
PubMed1988

Rate dependence of ventricular extrasystoles: computer identification and quantitative analysis.

A new computer program was designed to identify and quantify the rate dependence of arrhythmias using 24 hour Holter tape recordings. The program was used in 10 untreated apparently healthy patients with fixed, coupled, isolated monomorphic ventricular extrasystoles. The second cycles of two consecutive sinus cycles were grouped according to whether or not they were followed by a ventricular extrasystole. Each of these sinus cycles was further analysed by cycle length during successive one hour periods. From the number of cycles in each cycle length class, identification and quantification of an upper or lower limit, or both, of cycle length beyond which ventricular extrasystoles disappeared were possible. Upper and lower limits were observed in 10 and eight of the 10 patients respectively. An upper and a lower limit were identifiable (mean(SD) 9.3(5.1) and 8.4(5.8) times per recording respectively). Values of both types of limits varied throughout tape recording. A positive significant correlation was found between the values of upper and lower limits and the mean sinus cycle length during the corresponding hour in nine of the 10 and eight of the eight patients respectively. The type of relation observed suggests that heart rate directly alters limits or that heart rate and limits are under the same influence of the autonomic nervous system. It is concluded (a) that identification and quantification of the rate dependence of arrhythmias is possible using this computer program; and (b) that, in patients with ventricular extrasystoles and apparently normal hearts, upper and lower limits vary and are related to heart rate.

Adolescent↗
PubMed1988

Deferoxamine reduces neutrophil-mediated free radical production during cardiopulmonary bypass in man.

We assessed the effects of the iron chelator deferoxamine in 24 adult patients (12 controls, 12 treated) undergoing cardiopulmonary bypass for various cardiac operations. Deferoxamine was given both intravenously (30 mg/kg of body weight, starting 30 minutes before and ending 30 minutes after bypass) and as an additive to the cardioplegic solution (250 mg/L). Right atrial blood samples were taken before, during, and after bypass, and isolated polymorphonuclear neutrophils were evaluated for their capacity to generate superoxide radicals after stimulation with N-formyl-methionyl-leucyl-phenylalanine (FLMP, 10(-7) mol) and phorbol myristate acetate (100 ng/ml). At the same sampling times, measurement of the plasma levels of 6-keto-prostaglandin F1 alpha, the stable derivative of prostacyclin, was used as an index of membrane phospholipid breakdown. The two groups were not significantly different with regard to age, duration of bypass, and quantitative changes in polymorphonuclear neutrophil counts during the operation. Before bypass, the superoxide production of FMLP-stimulated polymorphonuclear neutrophils was comparable in the two groups. Conversely, after bypass, polymorphonuclear neutrophils harvested from deferoxamine-treated patients produced significantly fewer superoxide radicals than those of control patients (1.9 +/- 0.3 versus 3.7 +/- 0.2 nmol/10(6) polymorphonuclear neutrophils per minute, p less than 0.05). Stimulation of polymorphonuclear neutrophils by phorbol myristate acetate yielded similar changes, as the postbypass superoxide production was 12.6 +/- 2.5 nmol/10(6)/min in control patients and 7.1 +/- 0.9 nmol/10(6)/min in those receiving deferoxamine (p less than 0.05). In contrast, plasma levels of 6-keto-prostaglandin F1 alpha were not significantly different between the two groups. We conclude that deferoxamine-exposed polymorphonuclear neutrophils have a decreased oxidative responsiveness, compatible with the fact that they may have been less "primed" by secretagogues released during bypass, as compared with cells of untreated patients. Our results are consistent with the hypothesis that deferoxamine, by inhibiting iron-catalyzed free radical production, may limit the free radical-mediated amplification of the inflammatory response to bypass and as such could be effective in reducing the harmful effects of extracorporeal circulation.

Cardiopulmonary Bypass↗
PubMed1987

Hysteresis phenomena between periodic and stationary solutions in a model of pacemaker and nonpacemaker coupled cardiac cells.

We were interested in investigating the behaviour of a cardiac electrophysiological model including coupled pacemaker (PM) and nonpacemaker (NPM) cells. To this aim, a modified version of the model of Van Capelle and Durrer was used. First, few discrete values were assigned to coupling resistance (CR) and respective cell sizes and numerical simulations versus time showed three possible kinds of response pattern: sustained rhythmic activity, subthreshold oscillations, and complete inhibition. Then, after setting a fixed value to PM cell size, we undertake a thorough study of the system by using bifurcation-continuation techniques and CR was chosen as the continuation parameter. On the maximum action potential--CR plane representation, we could describe five behavioural zones: complete inhibition, coexistence of complete inhibition and NPM large oscillations, NPM large oscillations, coexistence of NPM large oscillations and subthreshold oscillations, subthreshold oscillations. Within the zones of qualitatively different coexisting solutions, a detailed exploration clearly demonstrated the presence of hysteresis cycles. Indeed, the status of the system depended on its immediate previous story within narrow ranges of CR values. Such a coexistence of stable solutions for identical values of CR may suggest an explanation of the intermittant activity elicited from abnormal ectopic foci observed in certain ventricular rhythm disturbances. In addition, a Hopf bifurcation point, from which emerged stationary and periodic solutions, was followed on the PM cell size--CR plane and from this representation we could deduce that the smaller the PM cell, the higher the CR must be for the PM cell to escape from the NPM cell inhibition.

Cell Membrane↗
PubMed1987

Alpha-myosin heavy chain isoform and atrial size in patients with various types of mitral valve dysfunction: a quantitative study.

The cardiac myosin phenotype, an important determinant of myocardial contractility, is modified by chronic increases in hemodynamic load. To quantify the proportion of atrial alpha-myosin heavy chain in various types of left atrial overload and to assess the possible relation between this proportion and atrial size, 34 patients were studied, 4 with Wolff-Parkinson-White syndrome, 29 with various types of mitral valve dysfunction and 1 with an atrial septal defect. Four normal autopsy hearts were also studied. The proportion of alpha-myosin heavy chain among total (alpha plus beta) myosin heavy chains was determined in each atrial sample, using an enzyme-linked immunosorbent assay. The size of the left atrium was assessed by one- and two-dimensional echocardiography. Alpha-myosin heavy chain was the main isoform present in the normal atria (85.5 +/- 9% of total myosin heavy chains). Patients with pure tight mitral stenosis (n = 9), mitral stenosis plus mild regurgitation (n = 8) and severe mitral regurgitation (n = 8), who had a higher indexed left atrial transverse diameter than those with Wolff-Parkinson-White syndrome (33 +/- 6, 39 +/- 10 and 46 +/- 5 versus 19.5 +/- 2 mm/m2, p less than 0.01, p less than 0.001 and p less than 0.001, respectively), also demonstrated a much smaller percent of alpha-myosin heavy chain content (28 +/- 20, 23.5 +/- 13 and 12 +/- 10 versus 58 +/- 18%, p less than 0.01, p less than 0.01 and p less than 0.001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Decreased incidence of supraventricular arrhythmias achieved by selective atrial cooling during aortic valve replacement.

Inadequate atrial hypothermia and subsequent ischemic injury have been recognized as the major causes of supraventricular arrhythmias (SVAs) and conduction defects following cold chemical cardioplegia. This study was designed to assess the effects of right atrial cooling (15 degrees-20 degrees C) during cardioplegic arrest upon the incidence of postoperative SVAs and conduction defects in 40 consecutive patients undergoing isolated aortic valve replacement. Atrial preservation was ensured by combining systemic (24 degrees C) and topical hypothermia with snared double caval cannulation during arrest. Myocardial temperatures in the right atrial septum and anterior wall of the right ventricle were recorded before and after each cardioplegic infusion and upon release of caval tapes. Postoperatively, the incidence of SVAs and conduction defects was assessed by continuous rhythm monitoring, bipolar atrial electrograms and, in ten patients, 24-h Holter recordings during the first postoperative day. With the venae cavae snared, temperatures in the right atrial septum were not significantly different from those measured simultaneously in the right ventricle. Release of caval tapes resulted in right atrial temperatures increasing to systemic temperature (from 17.1 +/- 2.9 degrees C to 25.9 +/- 5.6 degrees C [m +/- SD]; P less than 0.01). Atrial rewarming between cardioplegic infusions did not exceed 2.9 degrees +/- 3.2 degrees C. Postoperatively, four patients (10%) developed sustained atrial fibrillation. One additional patient had a single episode of paroxysmal atrial fibrillation and two patients experienced asymptomatic episodes of junctional rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

[Comparative assessment of cardiac and psychologic results of aortocoronary bypass].

Two categories of criteria are used to evaluate the cardiological and psychological results of aortocoronary bypass (ACB): objective criteria, which support the clinician's judgement, and subjective criteria, which contribute to the patient's comfort. Numerous studies have revealed major discrepancies between these two modes of evaluation. A prospective study was undertaken to compare the cardiological and psychological results of ACB at 1 year. The study was based on 24 parameters collected in an ordinary cardiology consultation and from an open discussion between the patient and his (or her) partner and a psychiatrist. In the first phase of the study the results observed in 51 patients were classified as "good" in 40 and "poor" in 11 by the cardiologist, as against "good" in 32 and "poor" in 19 by the psychiatrist. The psychiatrist's assessment differed from that of the cardiologist on 22 patients, being better in 7 and not as good in 15. The second phase of the study has been devised to validate the results obtained in the first phase and to evaluate the contribution of ergonometric test to the cardiological classification of 37 new patients. This study makes it possible to analyze the reasons for the difference in assessment of the cardiological and psychological benefits of ACB, and to develop a method for measuring the impact on these results of new therapeutic measures, such as rehabilitation.

Adult↗
PubMed1986

Prolonged responsiveness to ouabain in hypertrophied rat heart: physiological and biochemical evidence.

The inotropic effect of ouabain on cardiac hypertrophy was evaluated on an isolated Langendorff rat heart preparation with performances registrated by means of an intraventricular balloon. These effects were compared with the drug action on the sarcolemma-bound Na+-K+-ATPase activity. On both normal and pressure-overload induced hypertrophied rat hearts (ventricular wt-to-body wt ratios of 2.1 and 3.3, respectively) the inotropic effect of ouabain (10(-9)-10(-4) M) was evaluated at 0.25 mM external Ca2+. Compared with normal hearts, the recovery of a normal contractile function after the inotropic response was significantly slower in hypertrophied hearts. This was valid with the two protocols applied. During a 30-min washout period, the inotropic response remained nearly unchanged in hypertrophied hearts, whereas it was almost completely reversed in control groups. Sarcolemmal vesicles from both heart groups exhibited high Na+-K+-ATPase activities (sp. act.: 105 +/- 16 mumol X h-1 X mg-1). In both normal and hypertrophied cardiac sarcolemmal preparations, the Na+-K+-ATPase was heterogeneous, with high- and low-sensitivity forms. Their relative proportion was two-to-one. In both heart groups, their respective apparent affinities for ouabain were similar (inhibitory concentration of 50% = 10(-8) and 10(-6) M, respectively). The release of ouabain from these two sites was measured, in washout experiments, by the rates of enzyme relief from inhibition. High- and low-sensitivity forms in hypertrophied heart preparations released ouabain at seven- and threefold lower rates, respectively, than the corresponding forms present in normal cardiac sarcolemmal vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Limitations of fluorocarbons in reducing myocardial infarct size.

The effects of the oxygen-carrier fluorocarbons on myocardial infarct size were assessed in non-exchange-transfused dogs subjected either to a 3-hour occlusion of the left anterior descending coronary artery (LAD) followed by 2 hours of reperfusion (protocol I) or to a 5-hour permanent LAD occlusion (protocol II). Fluorocarbon administration was begun 30 minutes after LAD occlusion and was continued over the entire period of ischemia. After 5 hours, the hearts were excised and areas of necrosis were visualized by triphenyl tetrazolium chloride staining while risk regions were assessed by radiolabeled microspheres injected after coronary occlusion just before the onset of therapy, and further, in protocol I, by thallium-201 perfusion imaging performed at the end of fluorocarbon administration. In protocol I experiments, the ratio of necrotic area to area at risk was 81 +/- 35% (mean +/- standard deviation) in control saline-treated dogs (n = 6) and 67 +/- 27% in fluorocarbon-treated dogs (n = 6) (difference not significant). There was no significant difference between risk regions measured after and before fluorocarbon treatment. In protocol II, the ratio of necrotic area to area at risk was 47 +/- 30% in control dogs (n = 5) and 63 +/- 29% in fluorocarbon-treated dogs (n = 5) (difference not significant). However, in control dogs, the ratio of necrotic area to area at risk increased from 47 +/- 30% in the dogs that underwent permanent occlusion to 81 +/- 35% in the group that underwent reperfusion (p less than 0.001) while this ratio was similar in the corresponding subsets of fluorocarbon-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Relationships between single-vessel coronary artery obstructions and wall motion dysfunction analyzed by four computer-based methods.

We analyzed regional wall motion in 238 patients by using cineangiograms recorded in the 30 degrees right anterior oblique projection. The sample was divided into three groups: a normal group (n = 71), a group with isolated obstruction of the left anterior descending coronary artery and previous anterior myocardial infarction (n = 85), and a group with isolated obstruction of the right coronary artery and previous inferior myocardial infarction (n = 82). Both anterior and inferior groups also had motion abnormality within the corresponding anterior or inferior wall as judged by the qualitative analysis of cineangiograms. Four quantitative methods were compared: a long axis method and a center of mass method using internal reference systems, a method derived from the Stanford model and an area-based method using external reference systems. Normal regional values were determined from the normal group to evaluate the specificity and sensitivity of the methods. The area-based method was the most sensitive in the anterior infarction group, whereas the center of mass method was the most sensitive in the inferior infarction group. We conclude that there is no evidence that any method, among those tested, is superior to others for every expected location of wall motion abnormality.

Adult↗