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Biomedical subjects

J Correia-Pinto

Publications and source records attributed to J Correia-Pinto.

At least 19 recordsLinked to original sources

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↗

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↗

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↗

[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↗

[Patent ductus arteriosus in neonatal intensive care].

OBJECTIVE: In this study we evaluated the prevalence of symptomatic patent ductus arteriosus (PDA) in newborns, admitted to a neonatal intensive care unit (NICU), as well as the clinical features and the outcome of medical or surgical treatment. METHODS: We carried out a retrospective medical chart review of 42 newborns admitted to an NICU between May 1996 and May 1998. Data regarding birth weight, sex, gestational age, prenatal corticotherapy and surfactant needs were gathered. Clinical evolution was assessed based on mechanical ventilation, morbidity and mortality. The therapeutic options and their results where analysed. RESULTS: Of the 1,195 newborns admitted to an NICU, 42 had symptomatic PDA. The prevalence was higher in newborns with a low birth weight. There was no significant difference regarding the administration of steroids prenatally in the newborns with PDA compared to the remaining newborns without PDA. Surfactant therapy, mechanical ventilation, bronchopulmonary dysplasia, necrotizing enterocolitis and intraventricular hemorrhage were found to be more frequent in patients with PDA, especially among those with a lower birth weight, with statistical significance for newborns weighing less than 2,500 g (p < 0.05). The therapy most frequently used was indomethacin, with a success rate of 22/23 (95.6%) and with two cases of acute renal failure as side effects. Only one infant required surgical ligation of PDA. Mortality was similar in both groups (PDA vs. no PDA). CONCLUSION: PDA was probably underdiagnosed in our NICU. Morbidity, but not mortality, was higher in newborns with symptomatic PDA. We conclude that treatment with indomethacin is preferred to surgical ligation as an initial approach in those infants. Our data show the importance of early screening with echocardiogram for "silent" PDA in low birth weight neonates.

Birth Weight↗

[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↗

Gastric inflammatory myofibroblastic proliferation in children.

Gastric inflammatory myofibroblastic proliferation (IMP) is an extremely rare entity in children, which to our knowledge has only been mentioned in case reports. We describe the ninth pediatric case and review the literature concerning the etiology, clinical and laboratory features, pathology, treatment, and outcome. There has been a predominance in preschool females. Abdominal pain, upper gastrointestinal hemorrhage, and an abdominal mass, either isolated or associated, have been the main clinical features. Iron-deficiency anemia has been a constant finding. Lesions are elevated and involve the full thickness of the gastric wall, usually with ulceration of the luminal surface; extragastric extension suggesting malignancy is frequent. Diagnosis is made by histology after surgical excision. There was no mortality directly related to gastric IMP, and only one case recurred after surgical excision. The pathogenesis is controversial, but the finding of Helicobacter pylori in our case may indicate an inflammatory origin. Awareness of this benign lesion and its mimicry of malignancy is important so that inappropriately aggressive therapy can be avoided.

Cell Division↗

[Evolution in the management of splenic trauma. Retrospective study in children].

BACKGROUND/PURPOSE: The treatment of blunt splenic lesions had changed in the last years with an increasing trend to conservative management. In the absence of national surveys, this paper is aimed to evaluate the results of this therapeutic approach in a group of Portuguese children. MATERIALS AND METHODS: Patients with blunt splenic lesions, admitted over a period of 7 years, (n = 54) were retrospectively analysed. A group submitted to surgical treatment 'ab initio' (group A, from 1990 to 1992 incl.) was compared with a group managed by a conservative approach (group B, from 1993 to 1996 inclusive). Age, sex, associated lesions, treatment, need of a blood transfusion and length of hospital stay were studied. RESULTS: The frequency of splenic lesions was relatively stable (6 to 10 years) in both periods. Group A (n = 24) was similar to group B (n = 30) regarding gender and age. In group A, 23 (97%) splenectomies were performed. In group B, only six (20%) children underwent laparotomy and 4 (13%) of them were submitted to splenectomy (A vs. B, p < 0.001). The need of a blood transfusion was similar in the two groups and so were the associated lesions. The great majority of transfused children presented associated lesions (10/11, 91%). In group B, associated lesions did not significantly alter the effectiveness of the conservative treatment. Hospital stay was significantly longer in group B (B vs. A: 12.5 +/- 2.5 vs. 9.8 +/- 1.8, p = 0.017). CONCLUSIONS: The conservative approach was viable in the great majority of patients with blunt splenic lesions, resulting in a drastic reduction in splenectomies. The need for transfusions did not increase, but the length of hospital stay increased. These results are concordant with other series from major centres, justifying this approach and constituting the challenge of its application in adults.

Child↗