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J Correia-Pinto

Publications and source records attributed to J Correia-Pinto.

At least 19 recordsLinked to original sources

Ghrelin as a novel locally produced relaxing peptide of the iris sphincter and dilator muscles.

Ghrelin is a recently described acylated peptide, which works as a somatosecretagogue and has described effects on the smooth, skeletal and cardiac muscle. We examined the production and effects of ghrelin on relaxation of the iris muscles. Contractile effects of 1-5 human ghrelin (frGhr, 10(-9)-6 x 10(-5)M) and 1-5 human des-octanoyl-ghrelin (d-frGhr; 10(-9)-6 x 10(-5)M) were tested on iris rabbit sphincter (n=11 frGhr; n=7 d-frGhr), dilator (n=6 frGhr; n=6 d-frGhr) and rat sphincter (n=6 frGhr; n=8 d-frGhr) precontracted muscles. On rabbit sphincter the effect of frGhr was also tested in presence of: i) L-NA (10(-5)M; n=7); ii) indomethacin (10(-5)M; n=7); iii) DLys(3)GHRP6 (10(-4)M; n=6); and iv) apamin+carybdotoxin (10(-6)M; n=6). Furthermore, on rabbit dilator the effect of frGhr was tested in presence of DLys(3)GHRP6 (10(-4)M; n=7). Finally, ghrelin mRNA production was assessed by "in situ" hybridization in Wistar rat eyes (n=8). In all muscles, frGhr promoted a concentration-dependent relaxation, maximal at 6 x 10(-5)M, 1.5-3 min after its addition, decreasing tension by 34.1+/-12.1%, 25.8+/-4.8% and 52.1+/-10.3% in the rabbit sphincter, dilator and rat sphincter, respectively. In the rabbit sphincter the relaxing effects of frGhr were: (i) enhanced in presence of DLys(3)GHRP6 (118.1+/-21.1%); (ii) blunted by indomethacin; and (iii) not altered by apamin+carybdotoxin (36.4+/-14.4%) or L-NA (52.4+/-11.4%). Relaxing effects of d-frGhr in rabbit (43.3+/-5.2%) and rat (77.1+/-15.3%) sphincter muscles were similar to those of frGhr. In rabbit dilator muscle, d-frGhr did not significantly alter active tension and the relaxing effect of frGhr was blunted by GHSR-1a blockage. Ghrelin mRNA was identified in iris posterior epithelium. In conclusion, ghrelin is a novel, locally produced, relaxing agent of iris dilator and sphincter muscles, an effect that is mediated by GHSR-1a in the former, but not in the latter. Furthermore, in the sphincter it seems to be mediated by prostaglandins, but not by NO or K(Ca) channels.

Animals↗

Pattern of right ventricular pressure fall and its modulation by afterload.

Pattern of right ventricular pressure (RVP) fall and its afterload dependence were examined by analyzing ventricular pressure curves and corresponding pressure dP/dt phase planes obtained in both ventricles in the rat heart in situ. Time and value of dP/dt(min), and the time constant tau were measured at baseline and during variable RV afterload elevations, induced by beat-to-beat pulmonary trunk constrictions. RVP and left ventricular pressure (LVP) decays were divided into initial accelerative and subsequent decelerative phases separated by corresponding dP/dt(min). At baseline, LVP fall was decelerative during 4/5 of its course, whereas only 1/3 of RVP decay occurred in a decelerative fashion. During RV afterload elevations, the absolute value of RV-dP/dt(min) and RV-tau increased, whilst time to RV dP/dt(min) decreased. Concomitantly, the proportion of RVP decay following a decelerative course increased, so that in highly RV afterloaded heartbeats RVP fall became more similar to LVP fall. In conclusion, RVP and LVP decline have distinct patterns, their major portion being decelerative in the LV and accelerative in the RV. In the RV, dP/dt(min), tau and the proportional contribution of accelerative and decelerative phases for ventricular pressure fall are afterload-dependent. Consequently, tau evaluates a relatively much shorter segment of RVP than LVP fall.

Animals↗

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↗

Neonatal splenic necrosis not related to wandering spleen.

Splenic necrosis is extremely rare in neonates, the cases recorded so far being secondary to torsion of wandering organs. A newborn with an abdominal mass who underwent exchange transfusions through an umbilical catheter is presented here. Comprehensive investigation led to the suspicion of enteric duplication, but a splenic necrosis with no features of wandering spleen was found at laparotomy. The pathogenesis and preoperative diagnostic work-up of splenic necrosis are emphasised.

Humans↗

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↗

Neonatal perforation of a Y-shaped sigmoid duplication.

Tubular colonic duplications are exceedingly rare; the "Y"-shaped forms are exceptional. In the absence of associated low vertebral or urogenital malformations (often fistulas), the tubular colonic malformations frequently stay hidden for several years until a complication develops. The authors report a case of a spontaneous perforation of a Y-shaped tubular colonic duplication during the neonatal period.

Anastomosis, Surgical↗

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↗

[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↗

[Prognostic indexes derived from ventricular morphology in congenital diaphragmatic hernia induced by nitrofen].

BACKGROUND: Some indices derived from cardiac morphology have been proposed as prognostic factors in fetuses and newborns with congenital diaphragmatic hernia (CDH). These would be of interest in evaluating the risk of pulmonary hypoplasia and the need for surgery in the fetus. The aim of this study was to evaluate the heart-related indices in the nitrofen-induced CDH rat model. METHODS: At day 9 1/2 of gestation dated pregnant female Wistar rats received 100 mg of nitrofen. Fetuses were harvested at day 21 1/2 by laparotomy. The fetuses exposed to nitrofen without CDH were defined as the control group (n = 38) while the fetuses exposed to nitrofen with CDH were defined as the CDH group (n = 30). The hearts from both groups were weighed, processed for paraffin embedding and fragmented in serial 7 microns thick transverse sections. In the hearts without cardiac morphological defects the right and the left ventricular cavity volumes were estimated. These allowed calculation of cardioventricular and left-ventricular mass indices. RESULTS: In the fetuses without cardiac malformations, no significant difference was found regarding heart-to-body weight ratio, cardioventricular index or left ventricular mass between the study groups. CONCLUSION: In this model the presence of CDH was not associated with any alteration in cardiac dimension, in the absence of structural malformations. These results suggest that the indices derived from ventricular morphology should not be used to evaluate the prognosis in fetuses and newborns with CDH.

Animals↗

Prenatal diagnosis of abdominal enteric duplications.

Alimentary tract duplications are rare congenital malformations with few reports of the antenatal sonographic appearance. Early diagnosis is of paramount importance to prevent complications. We present a case of a cystic gastric duplication diagnosed antenatally at 31 weeks' gestation, which was treated successfully. Simultaneously, we review all published cases of prenatally diagnosed enteric duplications.

Adult↗

Acute gastric volvulus secondary to a Morgagni hernia.

Gastric volvulus (GV) is a rare surgical emergency in infancy and childhood. The first case of a child with an acute GV secondary to a Morgagni hernia (MH) is reported. The authors briefly discuss the etiology, clinical features, and management of acute GV and review the scattered reports of strangulated MHs in children.

Child, Preschool↗

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↗

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↗

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↗