Linda Fornell

Effect of unilateral testicular torsion on blood flow and histology of contralateral testes

BACKGROUND/PURPOSE Infertility occurs in 25% of patients after unilateral testicular torsion; hence, the authors examined hemodynamic and histological changes in both testes after acute testicular torsion in neonatal piglets. METHODS The animals were anesthetized, intubated, ventilated, catheterized, and assigned randomly to a sham group or one of three experimental groups undergoing 720 degrees torsion of the left testis for 8 hours after which it was untwisted in group I and removed in group II. In group III, both testes were removed. Data were collected at baseline (T = 0), 4 hours (T = 4), and 8 hours of torsion (T = 8) and at the ninth hour of the experiment (T = 9). Testicular blood flow was determined by using radiolabeled microspheres. The testes also were examined blindly with routine and electron microscopy. RESULTS In group I, testicular blood flow decreased in the affected testis during torsion and increased significantly after detorsion, whereas blood flow to the contralateral testis increased significantly after detorsion. Sham-operated animals showed no histological abnormality in either testis. In all torsion groups, the affected testis showed extensive changes caused by hemorrhagic necrosis. The contralateral testis only showed changes in group I. CONCLUSION Unilateral testicular torsion resulted in ipsilateral damage caused by a decrease and subsequent increase in blood flow while in the contralateral testis; damage was the result of a significant increase in blood flow after detorsion.

New animal model to evaluate testicular blood flow during testicular torsion

BACKGROUND/PURPOSE Unilateral testicular torsion is known to cause infertility because of damage to the contralateral testis. Testicular damage has been attributed to many different mechanisms, one of which is altered contralateral blood flow. In our experiment, in an effort to identify the reason for contralateral testicular injury, the authors developed an accurate method of measuring blood flow in both testes before, during, and after unilateral torsion. METHODS Four- to 6-week-old piglets weighing 4 to 6 kg were studied. The animals were anesthetized, intubated, ventilated, and catheterized for vascular access. Piglets were assigned randomly to a sham group or a group undergoing 360 degrees or 720 degrees torsion of the left testis (n = 5 per group) for 8 hours, after which it was untwisted. Data were collected at baseline (T = 0), 8 hours of torsion (T = 8), and 1 hour after detorsion (T = 9). Mean arterial blood pressure and heart rate were monitored continuously. Testicular blood flow was determined using radiolabeled microspheres. Blood flow data were evaluated by analysis of variance. RESULTS In the 360 degrees torsion group, blood flow changes were insignificant during torsion and after detorsion. In the 720 degrees torsion group, blood flow to the twisted testis was reduced significantly, whereas the contralateral testis was unaffected. One hour after detorsion, blood flow to both testes was increased significantly. CONCLUSIONS The authors describe a new animal model to evaluate testicular blood flow during and after testicular torsion. Increased blood flow after detorsion may be the cause of testicular damage in patients with unilateral testicular torsion.

Correlation of Flow Probe Determinations of Common Carotid Artery Blood Flow and Internal Carotid Artery Blood Flow with Microsphere Determinations of Cerebral Blood Flow in Piglets

We investigated whether blood flow determined by a flow probe situated on one common carotid artery provided an accurate estimation of unilateral cerebral blood flow (CBF) in piglets. In eight anesthetized, mechanically ventilated piglets, blood flow determined by an ultrasonic flow probe placed on the right common carotid artery was correlated with CBF determined by microspheres under two experimental conditions: 1) before ligation of the right external carotid artery with both the right external and internal carotid circulations intact [common carotid artery blood flow (CCABF) condition], and 2) after ligation of the right external carotid artery (ipsilateral to the flow probe) with all residual right-sided carotid artery blood flow directed through the right internal carotid artery [internal carotid artery blood flow (ICABF) condition]. The left carotid artery was not manipulated in any way in either protocol. Independent correlations of unilateral CCABF and ICABF with microsphere-determined unilateral CBF were highly significant over a 5-fold range of CBF induced by hypercarbia or hypoxia (r = 0.94 and 0.92, respectively; both p < 0.001). The slope of the correlation of unilateral CCABF versus unilateral CBF was 1.68 ± 0.19 (SEM), suggesting that CCABF overestimated CBF by 68%. The slope of the correlation of unilateral ICABF versus unilateral CBF did not differ significantly from unit (1.06 ± 0.15), and the y intercept did not differ significantly from zero [-1.3 ± 5.2 (SEM) mL]. Consequently, unilateral ICABF determined by flow probe accurately reflected unilateral CBF determined by microspheres under these conditions. Flow probe assessments of CCABF and ICABF in piglets may provide information about dynamic aspects of vascular control in the cerebral circulation that has heretofore been unavailable.

Metabolic syndrome in pediatric renal transplant recipients: Comparing early discontinuation of steroids vs. steroid group

Maduram A, John E, Hidalgo G, Bottke R, Fornell L, Oberholzer J, Benedetti E. Metabolic syndrome in pediatric renal transplant recipients: Comparing early discontinuation of steroids vs. steroid group. Pediatr Transplantation 2010:14:351–357.

Early effects of lipopolysaccharide on cytokine release, hemodynamic and renal function in newborn piglets

Background: Gram-negative sepsis in newborns is associated with high mortality and morbidity. Lipopolysaccharide (LPS) and cytokines released upon exposure to gram-negative sepsis are well known to be involved in the pathophysiology. Objective: In this report we investigate cytokine release, hemodynamic, and renal function induced by LPS in a newborn animal model with the intention to further examine early changes in gram-negative sepsis. Methods: Five 7- to 10-day-old domestic piglets were anesthetized and catheters placed in the jugular veins, left ventricle, and femoral artery. Urine output was monitored via suprapubic cystostomy. Mean arterial pressure, heart rate, and arterial blood gases were continuously monitored. Thirty minutes after line placement and obtaining baseline values, 0.06 µg/kg LPS were administered intravenously. One, 2, and 3 h later samples were taken to monitor tumor necrosis factor (TNF)-α, interleukin (IL)-1β, endothelin, and nitric oxide (NO)/nitrate via ELISA. In addition, blood flow was assessed by the microsphere method. Results: Our data show an initial surge of TNF-α and IL-1β at 1 h after exposure to LPS. NO/nitrate, endothelin, and hemodynamic as well as metabolic changes became apparent mostly 3 h after exposure, by which time TNF-α and IL-1β fell back to baseline. Conclusions: Our sepsis model suggests a brief initial TNF-α and IL-1β surge following LPS challenge; however, their effects become apparent by the time the levels are already subsiding. The emergence of vasoactive substances, NO and endothelin, precedes the first substantial clinical symptoms.

Renal effects of low to moderate doses of dopamine in newborn piglets

PURPOSE Administration of dopamine to adult animal and human subjects results in increased renal blood flow, and it may also enhance the glomerular filtration rate. However, renal hemodynamic effects of exogenous dopamine in the neonate are unclear. In this study, we examined the renal actions of low to moderate doses of exogenous dopamine in newborn piglets. METHODS The animals were anesthetized, catheterized for vascular access and urine collection, and assigned randomly to a control group or treatment groups receiving dopamine infusion at 2, 5, or 10 microg/kg/min. Data were collected at baseline, during dopamine infusion, and 1 hour after cessation of infusion. Mean arterial blood pressure (MAP) and heart rate (HR) were monitored. Glomerular filtration rate (GFR), cardiac index (CI), and renal blood flow (RBF) were determined. Fractional excretion of sodium (FENa) was calculated. RESULTS Dopamine did not alter renal blood flow nor did it significantly alter CI in spite of a modest increase in heart rate and mean arterial blood pressure. There was a statistically significant increase in GFR at 10 microg/kg/min and in FENa at all doses. CONCLUSIONS Low doses of dopamine produce significant natriuresis probably by direct action on renal tubules and at moderate doses via, both, increase in GFR and a direct tubular effect. Low and moderate doses of dopamine do not increase RBF as seen in adult animals, possibly because of immaturity of dopaminergic receptors in newborn piglets.

Estimation of urine specific gravity in neonates with a reagent strip

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Significance of fractional excretion of sodium and endothelin levels in the early diagnosis of renal failure in septic neonatal piglets.

PURPOSE This experiment was designed to help understand the cascade of events that end in renal impairment in septic animals. METHODS Twenty 3- to 8-day-old piglets were anesthetized and the femoral artery, jugular and femoral veins, and bladder were catheterized. After stabilization under anesthesia with ventilatory support, they were divided into a control group and three groups that received endotoxin (ETX) in doses of 0.01 mg/kg, 0.025 mg/kg, and 0.05 mg/kg. Blood pressure and blood gases were monitored continuously. Blood and urine samples were obtained before (B), 1 hour (E1), and 3 hours (E3) after the bolus of ETX to determine glomerular filtration rate (GFR), fractional excretion of sodium (FENa), tumor necrosis factor (TNF), and endothelin-1 (ET-1) levels. RESULTS Incremental doses of ETX induce greater release of ET-1 with an early proportionate increase in FENa (P< .05) and late decrease in GFR (P< .05). TNF release is dose and time dependent after ETX injection (P < .05). CONCLUSION ET-1 and FENa are the best tests to evaluate renal failure during early sepsis in neonatal piglets.

Effect of ultrafiltration on peritoneal dialysis drug clearances

To determine the effect of dialysate osmolarity on peritoneal dialysis drug transfer, peritoneal dialysis clearances of theophylline, phenobarbital, and tobramycin were determined in 10 rabbits using dialysate containing 1.5 and 4.25% glucose. Urea and creatinine clearances were also obtained for comparison. Under similar dialysis conditions, the peritoneal clearances of the three drugs remained unchanged for the two types of dialysate. In contrast, the peritoneal clearances of urea and creatinine were significantly higher with the use of 4.25% glucose dialysate (p less than 0.001). Thus, peritoneal dialysis clearances of theophylline, phenobarbital and tobramycin are not significantly affected by hypertonicity-induced ultrafiltration during acute peritoneal dialysis.

Endotoxemia and the effects of dopamine on renal functions of neonatal piglets.

In this study, we observed the effects of moderate and high doses of dopamine on the renal functions of neonatal piglets during endotoxic shock. We found that fluid therapy alone was better at maintaining cardiac index and preventing elevation of systemic vascular resistance, than dopamine at 10 and at 20 µg/kg/min. Furthermore, urine output and glomerular filtration rate were reduced by dopamine. Following endotoxin administration dopamine decreased SVR and maintained a CI better than fluid alone. However, in spite of a better CI, greater deterioration in renal functions occurred in the dopamine groups as compared to the fluid group.