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Biomedical subjects

A F Leite-Moreira

Publications and source records attributed to A F Leite-Moreira.

At least 19 recordsLinked to original sources
PubMed2003

Distinct load dependence of relaxation rate and diastolic function in Oryctolagus cuniculus and Ratus norvegicus.

This study investigated potential differences on load dependence of relaxation rate and diastolic function between Oryctolagus cuniculus and Ratus norvegicus, which have constitutive differences in the mechanisms involved in myocardial inactivation. Load dependence of relaxation rate and diastolic function were evaluated with the response of left ventricular time constant tau and diastolic pressure-dimension relation to beat-to-beat aortic constrictions in open-chest rabbits and rats. Afterload levels were normalized, being expressed as a percentage of peak isovolumetric pressure (relative load). In control heartbeats, relaxation rate and diastolic function were similar in the two animal species. They presented, however, distinct responses to afterload elevations. In rabbits, time constant decreased approximately 7% and diastolic pressure-dimension relation remained unchanged when afterload was elevated to a relative load of 73-76%. Above this afterload level, a significant deceleration of relaxation rate (increase of time constant) and an upward shift of diastolic pressure-dimension relation were observed. In rats, afterload elevations accelerated pressure fall up to a relative load of 97-100% and no afterload-induced shift of the diastolic pressure-dimension relation was observed. This study provides, therefore, evidence that Oryctolagus cuniculus has lower afterload reserve of myocardial relaxation and diastolic function than Ratus norvegicus.

Analysis of Variance↗
PubMed2002

Modulation of myocardial function by pyruvate.

OBJECTIVES: Pyruvate is an intermediate product of glycolytic metabolism that has a positive inotropic effect in animal models and in failing human hearts. The main objective of the present work was to clarify the mechanisms underlying this inotropic effect. METHODS: Isotonic and isometric twitches were recorded before and after the addition of pyruvate (3, 10 and 15 mM) to rabbit papillary muscles (n = 10) and human atrial trabeculae (n = 6) degrading glucose 9 mM and acetate 5 mM as metabolic substrates. In another protocol, undertaken in rabbit papillary muscles (n = 8), pyruvate was added in the presence of an inhibitor of mitochondrial pyruvate uptake (alpha-cyano-4-hydroxycinnamate [HCm]; 0.5 mM), and using octanoate 5 mM as metabolic substrate. Calculated parameters: active tension (AT); maximum velocity of tension rise (dT/dtmax); maximum velocity of tension decline (dT/dtmin); peak shortening (PS); maximum velocity of shortening (dL/dtmax); maximum velocity of lengthening (dL/dtmin) and time to half relaxation (tHR). Values are presented as means +/- SEM. RESULTS: In rabbit papillary muscles, pyruvate caused an initial transient negative inotropic effect (maximum at 3 min), followed by a sustained increase in myocardial contractility that stabilized 15 min later. The maximum negative inotropic effect was observed with 3 mM of pyruvate, decreasing AT by 13 +/- 4%, dT/dtmax by 14 +/- 5%, dT/dtmin by 9 +/- 3%, PS by 13 +/- 4% and dL/dtmax by 13 +/- 5%. Maximum positive inotropic effect was observed with 10 mM, which increased AT by 45.0 +/- 9.5%, dT/dtmax by 20.5 +/- 7.4%, PS by 33.4 +/- 9.6%, dL/dtmin by 35.5 +/- 12.1, and tHR by 27.8 +/- 3.2%, without significantly altering dL/dtmax or dT/dtmin. In the presence of HCm, the positive inotropic effect was not only observed but even enhanced. In human atrial trabeculae the addition of pyruvate also induced a similar increase in contractility, but the transient negative inotropic effect was absent. CONCLUSIONS: The addition of pyruvate caused a dose dependent positive inotropic effect observed in rabbit papillary muscles as well as in human atrial trabeculae. The effect of pyruvate in rabbit papillary muscles does not depend on its mitochondrial uptake and metabolism. This may be particularly relevant during myocardial ischemia when pyruvate concentration is increased and mitochondrial function is impaired. These characteristics give pyruvate a suitable profile for the metabolic protection of the heart.

Animals↗
PubMed2001

A new fetal rat model of gastroschisis: development and early characterization.

BACKGROUND/PURPOSE: The perinatal management and pathophysiology of gastroschisis remain controversial. Large animal experimental models of gastroschisis are inherently limited by expense and length of gestation, making multiple studies and statistical analysis difficult. To address these limitations the authors have developed a model of gastroschisis in the fetal rat. METHODS: Twenty-one time-dated pregnant rats underwent laparotomy at 18 (1/2) day's gestational age. The exposed uterus was bathed in ritodrine for tocolysis. The right posterior leg was exteriorized through a hysterotomy, and under a dissecting microscope (16x) the fetal small bowel was exteriorized through a small incision performed on the right lower abdominal quadrant. The amniotic fluid was restored with saline solution and the hysterotomy closed with a purse-string suture. Control fetuses underwent hysterotomy and leg manipulation only. The surgical time was uniformly less than 60 minutes. Fetuses were harvested by cesarean section at 21 (1/2) days' gestational age. Fetal intestine was assessed by microscopic examination, and fetal weight, intestinal length, and intestinal weight per unit length were evaluated. RESULTS: There was a significant surgical and anesthetic learning curve, which is not included in this report. After this, the authors achieved a maternal survival of 100% (n = 21). We created gastroschisis in 64 fetuses (58 survivors, 90.6%), and 33 fetuses were only manipulated (30 survivors, 90.9%). The number of induced gastroschisis per pregnant rat varied between 2 and 5 with median of 3. On gross examination, eviscerated intestine appeared dilated, edematous, and covered by peel when compared with control intestine. Fetuses with gastroschisis had significantly reduced body weight (4.1+/-0.5 v 5.6 g +/- 0.5 g) and intestinal length (102+/-19 v 210+/-17 mm) relative to controls, whereas the intestinal weight per unit length (1.75+/-0.29 v 0.71 +/- 0.1 mg/mm) was markedly increased (P<.001). CONCLUSIONS: The pathophysiology observed in this experimental model appears to resemble human gastroschisis. In comparison with large animal models, the rat model offers the advantages of low expense, short gestation, littermate controls, and high maternal and fetal survival rates. In addition, there are specific probes and reagents available for application of molecular methodology to clarify the mechanisms responsible for the intestinal damage. This model appears appropriate for future experimental studies on gastroschisis.

Animals↗
PubMed2001

Load as an acute determinant of end-diastolic pressure-volume relation.

Afterload-induced changes in myocardial relaxation are a mechanism for diastolic dysfunction when afterload is elevated beyond certain limits. The present study investigated the effects of acute afterload and preload changes on the position of the end-diastolic (ED) pressure-volume (P-V) relation. Beat-to-beat afterload elevations were induced in seven open-chest rabbits by gradually occluding the ascending aorta to increase peak left ventricular pressure (LVP) from baseline to isovolumetric level. Afterload elevations were performed at three ED LVP: 2.0 +/- 0.2 (low), 5.7 +/- 0.2 (mid), and 9.6 +/- 0.6 (high) mmHg. Preload was altered with caval occlusions and/or intravenous dextran. Afterload elevations induced an upward shift of the diastolic P-V relation, which became more important as afterload and/or preload increased. For instance, maximal afterload elevations shifted this relation upward 2.2 +/- 0. 5, 5.1 +/- 0.8, and 12.1 +/- 1.7 mmHg at low, mid, and high preload, respectively. These effects were partially due to changes in relaxation rate and time available to relax. In conclusion, load is an acute determinant of the ED P-V relation, which, therefore, does not provide a load-independent assessment of diastolic function.

Animals↗
PubMed2001

[Interaction between load and beta-adrenergic stimulation in the modulation of diastolic function].

INTRODUCTION AND OBJECTIVES: Excessive afterload induces an upward shift of the diastolic pressure-volume relation. This diastolic dysfunction was attributed to the concomitant slowing of relaxation. The present study investigated to what extent beta-adrenergic stimulation could influence this effect. METHODS: Beat-to-beat afterload elevations were induced in anaesthetised open-chest rabbits (n = 7) by narrowing the ascending aorta, to increase peak left ventricular pressure (LVPmax) from control up to isovolumetric. Afterload elevations were performed at baseline and during infusion of isoproterenol (0.15 mg/kg/min). RESULTS: At baseline, LVPmax increased from 84 +/- 7 in the control beat to 154 +/- 10 mmHg in the isovolumetric beat, while during isoproterenol it increased from 88 +/- 4 to 184 +/- 11 mmHg (p < 0.01). After an isovolumetric beat, diastolic dysfunction was 7.9 +/- 1.5 mmHg at baseline and 2.6 +/- 0.5 mmHg during isoproterenol (p < 0.01). At all afterload levels, isoproterenol accelerated LVP fall (decreased the time constant tau), decreased the predicted time to completion of relaxation but did not influence the time available for the ventricle to relax. CONCLUSIONS AND IMPLICATIONS: Afterload induced diastolic dysfunction was attenuated by beta-adrenergic stimulation. These results, along with the inotropic and lusitropic effects of isoproterenol, may contribute to the acute improvement of cardiac function induced by beta-adrenergic stimulation. It may also help to explain the response to physical exercise and the pathophysiology of diastolic dysfunction in heart failure.

Animals↗
PubMed2001

[Mechanisms underlying endothelin-1 effects on myocardial function].

INTRODUCTION: Endothelin-1 (ET-1) has potent vasoconstrictor, growth promoting and positive inotropic properties. Its effects on the intrinsic properties of the myocardium were recently described. The present study investigated the mechanisms underlying those effects. METHODS: The myocardial effects of 1 and 10 nM of ET-1 were evaluated in isolated rabbit papillary muscles (n = 9) and human atrial trabecula from CABG patients (Krebs-Ringer; 1.8 mM CaCl2; 35 degrees C). In papillary muscles the effects of 1 nM ET-1 were also studied in the presence of: (i) a selective ETA receptor antagonist, BQ-123 (0.1 microM; n = 9); (ii) a selective ETB receptor antagonist, BQ-788 (0.1 microM; n = 6); and (iii) an Na+/H+ exchanger inhibitor, methyl-isobutyl-amiloride (MIA; 1 microM; n = 6). Only significant results (mean +/- SE, p < 0.05) are given, expressed as delta % baseline. RESULTS: In AT by papillary muscles, 1 nM of ET-1 increased 64 +/- 16%, dT/dtmin 39 +/- 13% and decreased PT by 11 +/- 2%. The analysis of atrial strip contractions yielded similar results. In papillary muscles the effects of ET-1 were not affected by BQ-788, yet they were abolished by BQ-123, and reduced by 44% by MIA. CONCLUSIONS: The action of ET-1 on myocardial function is similar in human and non-human myocardium. The myocardial effects observed in the present study are mediated by the binding to ETA receptors, and partially dependent on Na+/H+ exchanger activation.

Animals↗
PubMed2000

Load dependent diastolic dysfunction in heart failure.

Congestive heart failure may result from cardiovascular overload, from systolic or from diastolic dysfunction. Diastolic left ventricular dysfunction may result from structural resistance to filling such as induced by pericardial constraint, right ventricular compression, increased chamber stiffness (hypertrophy) and increased myocardial stiffness (fibrosis). A distinct and functional etiology of diastolic dysfunction is slow and incomplete myocardial relaxation. Relaxation may be slowed by pathological processes such as hypertrophy, ischemia and by asynchronous left ventricular function. The present contribution analyses the occurrence of slow and incomplete myocardial relaxation in response to changes in systolic pressure and in response to changes in venous return. The regulation of myocardial relaxation by load is critically dependent on the transition from myocardial contraction to relaxation, which occurs in dogs when 82% of peak isovolumetric pressure has developed or at a relative load of 0.82. This corresponds to early ejection in normal hearts, but is situated even before aortic valve opening in severely diseased hearts. When load is developed beyond this transition, relaxation becomes slow and even incomplete. This is load dependent diastolic dysfunction. Load dependent diastolic dysfunction occurs in normal hearts facing heavy afterload and in severely diseased hearts even with normal hemodynamic parameters. This dysfunction should contribute to elevating filling pressures in most patients with severe congestive heart failure. This dysfunction can be reverted by decreasing systolic pressures or by decreasing venous return. Load dependent diastolic dysfunction gives us an additional reason to aggressively treat CHF patients with diuretics and vasodilators.

Animals↗
PubMed2000

Heart-related indices in experimental diaphragmatic hernia.

BACKGROUND: Heart-related indices have been suggested as useful tools to evaluate left ventricular (LV) hypoplasia, which might predict the outcome of fetuses and infants with congenital diaphragmatic hernia (CDH). The current study analyzed the behavior of such indices in the nitrofen-induced CDH rat model. METHODS: Dated pregnant Wistar rats received at day 9.5 of gestation either a dose of 100 mg of nitrofen or just the vehicle. Body, lung, and heart weights were measured in 12 newborn rats not exposed to nitrofen (Ctrl group) and 68 animals exposed to nitrofen: 30 without CDH (non-CDH group) and 38 with left CDH (CDH group). Each heart was fragmented in 7-microm thick sections. Only hearts with no evidence of cardiac morphologic defects (CMD) were studied further to estimate right and left ventricular cavity volumes, septal, right, and left ventricular free wall masses. These parameters allowed the calculation of the cardio-ventricular (CVindex) and LV mass indices. The aorta-to-pulmonary artery ratio also was calculated. RESULTS: Excluding fetuses with CMD, the heart-to-body weight ratio was reduced significantly in animals exposed to nitrofen, whereas no significant differences were observed between non-CDH versus CDH groups. Although the left and right ventricular cavity volumes were both reduced significantly in nitrofen-treated rats, they were not changed significantly by the existence of CDH, and the calculated CVindex was similar in the 3 groups. Estimated septal and LV masses were reduced markedly in the nitrofen-treated animals and further reduced by the presence of CDH. However, when LV mass was normalized (LV mass index) the difference became restricted to the animals exposed to nitrofen but was not influenced by the presence of CDH. Finally, the aorta-to-pulmonary artery ratio was similar in all studied groups. CONCLUSIONS: The results of the current study suggest that, although nitrofen had been responsible by global heart hypoplasia, the presence of CDH was not associated with significant underdevelopment of the heart or of the LV in rat fetuses without CMD. Based on these results, we think that the evidence for prenatal counseling based on heart-related indices should be critically reconsidered.

Animals↗
PubMed2000

[The effects of endothelin-1 on myocardial function].

INTRODUCTION: Endothelin-1 (ET-1) has potent vasoconstrictor, growth promoting and positive inotropic properties, with increased plasma levels in heart failure (HF). With regard to the cardiac effects of ET-1, most studies have not been able to differentiate its effects on the intrinsic properties of the myocardium from the secondary effects resulting from load changes and coronary vasoconstriction. This study investigated the myocardial effects of ET-1. METHODS: The study was performed on isolated rabbit papillary muscles (n = 9), before and after the addition of ET-1 (10 nM) to the superfusing solution (Krebs-Ringer; 1.25 nM Ca2+; 35 degrees C). One isotonic, one isometric and two afterloaded-isotonic twitches were recorded and analyzed. Only significant results (mean +/- SE, p < 0.05) are given, expressed as delta % baseline. RESULTS: ET-1 induced an increase of AT (147 +/- 33%), dT/dtmax (154 +/- 39%) and dT/dtmin (145 +/- 38%), while the duration of the twitch did not vary significantly. In addition, after ET-1, RT at the end of the isometric twitch decreased by 19 +/- 3%, when compared with the control and to its value at the beginning of the twitch. CONCLUSIONS: This study showed that, in addition to the well-known positive inotropic effect, ET-1 improves diastolic function by accelerating relaxation rate (dT/dtmin) and decreasing RT. These results may have important implications in the pathophysiology of HF.

Animals↗
PubMed2000

[Indexes for the evaluation of scientific publications: what they are and what they are used for].

Today, medicine lives the paradigm of Evidence-Based Medicine, which integrates the most recent discoveries of Research in day-to-day Clinical Practice. Simultaneously, there is an exponential growth in biomedical scientific knowledge, and, with it, of the number of scientific papers and biomedical journals. Currently, the assessment of the quality of biomedical scientific information is based on the peer review method, which also has different types of bias. In this setting, quantitative indexes are increasingly being used to assess it. Three of these indexes are the quotation rate, the impact factor and the Immediacy Index that, despite their objectivity, have several limitations. The impact factor, which is a valid tool to estimate the quality of a scientific journal, is not suited to evaluate single articles, scientists or research groups. In these cases, the best methodology is quotation analysis. No method, however, can replace the individual reading and study of the contents of the scientific work. Of the new potentialities of biomedical information, the possibility of discussing scientific articles before their publication is particularly promising. With this purpose, the netprints servers, which are new sites on the Internet, were created. Other sites where we can have access to databases with summaries of guidelines have also been created in an attempt to reduce the gap between research and clinical practice.

Abstracting and Indexing↗
PubMed2000

The physiology of left ventricular pressure fall.

Left ventricular pressure (LVP) fall is the hemodynamic manifestation of myocardial relaxation. This paper reviews the most important aspects of LVP fall and its regulation by load, inactivation and nonuniformity. This regulation is explained in terms of calcium transients and cross-bridge mechanics. Specific effects of systolic pressure on LVP fall and their relation to systolic cardiac function are emphasized. These data constitute a conceptual framework for the analysis of myocardial relaxation in cardiovascular research and in the cardiac patient. Comparison of clinical and experimental data during manipulation of afterload should lead to an improved understanding of relaxation disturbances and to a therapeutic approach which is relevant from the pathophysiological point of view. LVP fall may provide useful and quantitative information on systolic LV function if measurements are performed under different conditions of systolic load.

Blood Pressure↗
PubMed1999

Afterload induced changes in myocardial relaxation: a mechanism for diastolic dysfunction.

BACKGROUND: Diastolic left ventricular (LV) dysfunction manifests as an upward shift of the diastolic pressure-volume relation. One of the possible causes of diastolic LV dysfunction is incomplete myocardial relaxation. It is well known that high afterload slows myocardial relaxation. This contribution investigated to what extent afterload elevation could also affect LV filling pressures including end-diastolic LV pressure (LVP). METHODS: Selective, beat-to-beat elevations of afterload were induced in anaesthetised open-chest rabbits (n = 9) by abrupt narrowing of the ascending aorta during the diastole of the preceding heartbeat. This was performed with physiological heart rate and blood pressure. RESULTS: These interventions increased systolic LVP from 90 +/- 3 mm Hg at baseline to 103 +/- 4, 123 +/- 5, 139 +/- 5 and 154 +/- 6 mm Hg. The last intervention was a total aortic occlusion inducing a first beat isovolumetric contraction. Smaller afterload elevations decreased tau (accelerated LVP fall) and did not elevate diastolic pressure-internal diameter relation (P-ID). Larger afterload elevations increased tau (decelerated LVP fall), induced an upward shift of the diastolic P-ID and increased end-diastolic LVP. Effects of afterload on end-diastolic LVP were correlated with effects on tau (r = 0.89; P < 0.01). Incomplete relaxation or load-dependent residual active state appeared to be the mechanism for this diastolic dysfunction. Similar findings were made retrospectively in dogs instrumented with circumferential segment length gauges (n = 16). CONCLUSIONS: Diastolic LV dysfunction was induced by elevated afterload in healthy hearts of rabbits and dogs. If this mechanism could be shown to be operative in the failing heart, reversal of diastolic dysfunction should contribute to the beneficial effects of vasodilating and inotropic therapy on pulmonary congestion.

Analysis of Variance↗
PubMed1999

Load dependence of left ventricular contraction and relaxation. Effects of caffeine.

OBJECTIVE: Load dependence of left ventricular (LV) contraction and relaxation was investigated at baseline and after alteration of intracellular calcium handling by caffeine. METHODS: Afterload was increased by aortic clamp occlusions (n = 281) in anesthetized open-chest dogs (n = 7). Control and first heartbeat after the intervention were considered for analysis. RESULTS: Caffeine (50 mg/kg, iv) had no inotropic effect. The systolic LV pressure (LVP), developed in response to aortic occlusion, decreased as ejection proceeded and this pressure generating capacity was not affected by caffeine. Late-systolic aortic occlusions induced premature onset and accelerated rate of initial LVP fall at baseline and similarly after caffeine. Graded diastolic aortic occlusions induced systolic LVP elevations of various magnitudes. Smaller LVP elevations prolonged ejection and accelerated LVP fall, while larger elevations had opposite effects. The transition from acceleration to deceleration was observed at 83.1 +/- 1.1% of peak isovolumetric LVP at baseline and at lower loads, at 77.6 +/- 1.2%, after caffeine (p < 0.01). Isovolumetric heartbeats prolonged the time constant tau by 238 +/- 70% at baseline and only by 155 +/- 44% after caffeine (p < 0.01). The relaxation-systolic pressure relation, which describes afterload dependence of relaxation, was also modified by caffeine. CONCLUSIONS: Caffeine affected LV relaxation without altering contractility. As a consequence contraction-relaxation coupling was modified by caffeine. These results might help to understand load dependence of relaxation in conditions where intracellular calcium handling is altered.

Animals↗
PubMed1999

[Diastolic function modulation by load. Physiological basis and clinical implications].

INTRODUCTION AND OBJECTIVES: Diastolic heart failure has emerged over the last decade as a separate clinical entity, but its pathophysiology is still largely unknown. Left ventricular (LV) relaxation is considered an important determinant of early, but not late, LV filling. We recently showed that a substantial afterload elevation induces a marked slowing of relaxation. In this study we investigated the repercussion of such slowing on late LV filling. METHODS: The study was carried out on 7 open-chest, anaesthetised, New Zealand white rabbits, fully instrumented to evaluate cardiac function. The load was manipulated by transient occlusions of the ascending aorta and/or of the inferior vena cava. RESULTS: We observed that the afterload elevations had a biphasic effect on the relaxation rate and diastolic pressure-dimension (P-D) relation: small elevations accelerated relaxation and did not affect the diastolic P-D relation, while greater elevations progressively decreased the relaxation rate and induced a divergent upward shift of the diastolic P-D. The magnitude of this upward shift was related to the relaxation rate and the time available for the ventricle to relax. CONCLUSIONS AND IMPLICATIONS: Small to moderate afterload elevations are easily compensated by the normal ventricle, while greater elevations induce diastolic dysfunction even in normal hearts, which leads us to the concept of afterload reserve. This concept helps explain why diastolic dysfunction and pulmonary congestion, present in heart failure, may be reverted by decreasing the load (e.g. vasodilators and diuretics).

Animals↗
PubMed1999

[Absence of cardiac hypoplasia in an experimental model of congenital diaphragmatic hernia].

INTRODUCTION: Congenital diaphragmatic hernia (CDH) is a rare malformation in newborns. Amongst the various prenatal prognostic criteria, it is suggested that heart weight could be useful in evaluating the severity of lung hypoplasia. In this work we studied heart development in a rat model with nitrofen-induced CDH. MATERIAL AND METHODS: Pregnant female Wistar rats were treated on day 9 1/2 of gestation with 100 mg of nitrofen dissolved in 1 ml of olive oil. The control group was only treated with 1 ml of olive oil. The foetuses were delivered by caesarean section on day 21 1/2 of gestation. The weight of the foetuses was recorded. Under microscopy, the foetuses were dissected and the diaphragm was inspected. The wet weight of the heart and lung were recorded. The results are presented as a mean +/- standard deviation. A statistical analysis was made with the one-way ANOVA test on Ranks, and the Dunn test for post-test analysis. The statistical significance was set at a p < 0.05. RESULTS: The foetuses with CDH (n = 16) were lighter and had a smaller left lung/body weight ratio when compared with animals exposed to nitrofen without CDH (n = 18) and with controls (n = 12) (p < 0.05). The heart/ body weight ratio was smaller in foetuses exposed to nitrofen (p < 0.05), but we could not find any differences between nitrofen-treated treated foetuses with vs without CDH (n.s.). CONCLUSIONS: In spite of the lung hypoplasia, we could not demonstrate the presence of heart hypoplasia in rats with CDH when compared to nitrofen-treated foetuses without CDH.

Animals↗