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Fructose superfused on the mesenteric venules of rats induces microvascular inflammation via oxidative stress. It is unknown whether intragastric fructose exerts a similar effect and whether fructose impairs postprandial hyperemia (PPH). The goals were to determine whether intragastric fructose administration promotes leukocyte adherence and whether fructose, owing to its oxidative properties, may also impair nitric oxide-dependent PPH in the mesenteric microcirculation of rats.Leukocyte adherence to mesenteric venules, arteriolar velocity, and diameter were measured in Sprague-Dawley rats before and 30 minutes after intragastric (1 mL 0.5 M, ~0.3 g/kg) dextrose (n = 5), fructose (n = 6), and fructose after intravenous injection of the antioxidant α-lipoic acid (ALA, n = 6).Only fructose increased leukocyte adherence: control 2.3 ± 0.3 per 100 µm; fructose 9.7 ± 1.4 per 100 µm (P.001). This effect was independent of changes in venular shear rate: control 269 ± 48 s(-1); fructose 181 ± 27 s(-1) (P.05, r(2) = 0.083 for shear rate vs leukocyte adherence). Dextrose had no effect on leukocyte adherence: control 1.52 ± 0.13 per 100 µm; dextrose 2.0 ± 0.7 per 100 µm (P.05). ALA prevented fructose-induced leukocyte adherence: control 1.9 ± 0.2 per 100 µm; fructose + ALA 1.8 ± 0.3 per 100 µm (P.05). Neither fructose nor dextrose induced PPH: arteriolar velocity: control 3.3 ± 0.49 cm/s, fructose 3.06 ± 0.34 cm/s (P.05); control 3.3 ± 1.0 cm/s, dextrose 3.15 ± 1.1 cm/s (P.05); arteriolar diameter: control 19.9 ± 1.10 µm, fructose 19.7 ± 1.0 µm (P.05); control 21.5 ± 2.6, dextrose 20.0 ± 2.7 µm (P.05).Intragastric fructose induced leukocyte adherence via oxidative stress. Neither dextrose nor fructose induced PPH, likely because of the inhibitory effect of anesthesia on splanchnic vasomotor tone.

Recent evidence indicates that fructose is a pro-inflammatory molecule. Oral fructose induces serum and kidney inflammatory intercellular adhesion molecule-1 (ICAM-1) in rats. Fructose also induces ICAM-1 expression in human aortic endothelial cells (HAEC) and monocyte chemoattractant protein-1 in proximal tubular renal cells. It is not known whether fructose may directly promote inflammation on the intestinal microcirculation. Accordingly, using intravital microscopy we studied the effect of topical fructose and dextrose on leukocyte adherence to the mesenteric venule of the rat. Leukocyte adherence was determined during a control period and after fructose was added to the mesentery, in the presence or absence of the NO donor spermine NONO-ate (SNO), and after i.v. injection of the antioxidant lipoic acid (LA). In separate experiments, we examined the effect of topical dextrose on leukocyte adherence to the mesenteric venule. Venular shear rate was calculated. Fructose, but not dextrose, induced significant inflammation independent of shear rate. This effect was completely blocked by SNO and LA, suggesting that fructose induces inflammation via reactive oxygen species (ROS) generation. These results suggest that fructose present in formulas may adversely affect the intestinal microcirculation of premature infants and potentially contribute to the pathogenesis of necrotizing enterocolitis (NEC).

We recently observed that acute systemic hypoxia produces rapid increases in leukocyte adherence in the mesenteric microcirculation of the anesthetized rat Wood JG, Johnson JS, Mattioli LF, and Gonzalez NC. J Appl Physiol 87: 1734–1740, 1999; Wood JG, Mattioli LF, and Gonzalez NC. J Appl Physiol 87: 873–881, 1999. Hypoxia-induced leukocyte adherence is associated with an increase in reactive oxygen species (ROS) generation and is attenuated by antioxidants or interventions that increase tissue levels of nitric oxide (NO). These results suggest that the acute effects of hypoxia on leukocyte-endothelial interactions are caused by a change in the ROS-NO balance. The present experiments were designed to extend our observations of the initial microcirculatory response to hypoxia; specifically, we wanted to determine whether the response to systemic hypoxia involves increased microvascular permeability and leukocyte emigration and whether ROS generation and decreased NO levels contribute to these responses. At this time, there is conflicting evidence, from in vitro studies, regarding the effect of hypoxia on these indexes of vascular function. Our studies were carried out in the physiological setting of the conscious animal, in which a prolonged hypoxic exposure is possible without the adverse effects that may develop under anesthesia. The central observation of these studies is that conscious animals exposed for 4 h to environmental hypoxia show increased microvascular permeability and emigration of leukocytes into the extravascular space of the mesenteric circulation. Furthermore, these events are dependent on increased ROS generation and, possibly, a subsequent decrease in tissue NO levels during systemic hypoxia. Our results show that systemic hypoxia profoundly affects vascular endothelial function through changes in the ROS-NO balance in the conscious animal.

Although the effects of ischemia-reperfusion have received considerable attention, few studies have directly evaluated the microcirculatory response to systemic hypoxia. The overall objective of this study was to assess the effect of environmental hypoxia on adhesive interactions of circulating leukocytes with rat mesenteric venules by using intravital microscopy. Experiments were designed to 1) characterize the adhesive interactions of circulating leukocytes to venules during acute hypoxia produced by a reduction in inspired[Formula: see text], 2) evaluate the role of nitric oxide in these adhesive interactions, 3) determine whether the effect of hypoxia on leukocyte adhesive interactions differs between acclimatized and nonacclimatized rats, and 4) assess whether compensatory changes in nitric oxide formation contribute to this difference. The results showed that acute hypoxia promotes leukocyte-endothelial adherence in mesenteric venules of nonacclimatized rats. The mechanism of this response is consistent with depletion of nitric oxide within the microcirculation. In contrast, no leukocyte-endothelial adherence occurred during hypoxia in rats acclimatized to hypobaric hypoxia. The results are consistent with increased nitric oxide formation due to expression of inducible nitric oxide synthase during the acclimatization period. Further studies are needed to establish the cause of nitric oxide depletion during acute hypoxia as well as to define the compensatory responses that attenuate hypoxia-induced leukocyte-endothelial adherence in the microvasculature of acclimatized rats.

Dietary dextrose and fructose may promote vascular inflammation and endothelial dysfunction. In certain infant populations, altered postprandial mesenteric hyperemia (PPH) may increase risk for feeding intolerance.To compare superior mesenteric artery (SMA) PPH following feeds of lactose-containing (LC) formula vs lactose-free (LF; dextrose + sucrose) formula.In a 2 × 2 crossover study with 6 term newborns, 3 received LC first followed by LF 3 hours later. The remaining 3 received the reverse order. Ultrasound measures of pre- and postprandial SMA flow, diameter, and resistance were taken 5 minutes preprandial and 10, 30, and 40 minutes postprandial.Mean ± SD age and weight (n = 6) were 24.1 ± 2.3 hours and 3.1 ± 0.21 kg. Formula intake was similar for LC and LF (22.5 ± 2.8 mL and 25 ± 1.8 mL, respectively; P = .076). Both formulas increased SMA flow at 10 and 30 minutes. However, postprandial flow was greater for LC overall (P = .004) and especially at 30 minutes (LC 103 ml/min, 52% increase vs LF 92.7 ml/min, 31% increase; P = .014). For both formulas, vasodilation was seen at 10 and 30 minutes and was overall significantly greater following LC than following LF (9.1% VS 6.5%; P = .028). Both formulas elicited significant decreases in sma vascular resistance over the 10- to 30-minute period (overall P = .016). However, decreases did not differ across formulas (P = .672).The LC formula elicited a greater SMA PPH response than did LF. SMA flow for both formulas was within normal limits; thus, differences are likely inconsequential for a term newborn. However, in a vulnerable preterm infant, differences may become significant.

To investigate the interobserver reliability and diagnostic validity of a commercial electronic stethoscope for pediatric telecardiology.Pairs of blinded pediatric cardiologists made independent diagnoses, recommendations concerning follow-up echocardiography, and specific judgments regarding heart sounds, murmurs, and congenital heart disease using an electronic (ES) or an acoustic (AS) stethoscope on 78 pediatric cardiology outpatients and at a distance of 450 km (280 miles) with 38 telemedicine cardiology outpatients. The kappa statistic (K) indexed the instruments' interexaminer reliabilities. The validity of ES was measured by K for ES versus AS and by the percentage of cases where the findings for ES and AS differed sufficiently to suggest an important ES screening error.For heart disease, AS, ES, and tele-ES reliabilities were satisfactory (K = 0.80, 0.67, and 0.80, respectively), as were AS agreement with hands-on ES (K = 0.65) and with tele-ES (K = 0.64). The AS and ES reliabilities and ES/AS agreement were also satisfactory for systolic regurgitant and diastolic pulmonic murmurs (K = 0.63-0.78) but were unsatisfactory for evaluable heart sounds and other murmurs (K = 0.16-0.60). The ES yielded clinically important disagreements with AS in 5.4% of the clinic cases and 10.5% of the telemedicine cases (P = 0.67). In determining the need for additional work-up (echocardiography) or follow-up appointments, hands-on ES and tele-ES had a combined accuracy of 92%, with a sensitivity of 88% and a specificity of 97%.Hands-on ES provided reliable and valid screening for congenital heart disease. Tele-ES was highly reliable but had reduced diagnostic validity. Examiner blinding, bandwidth limitations, and artificial restrictions on the remote assistant may have contributed to this reduced performance. As these factors are easily correctable, we regard the ES as a highly promising tool for pediatric telecardiology.

Objective. Wide-bandwidth electronic stethoscopy is reliable and accurate for pediatric telecardiology. We tested a much less expensive and more convenient system for the same purpose, a narrow-bandwidth telephonic stethoscope (TS). Methods. Seventy-six consecutive patients (mean age: 10.0; standard deviation: 6.5 years) in a pediatric cardiology outpatient clinic were studied. One pediatric cardiologist examined the patients with his acoustic stethoscope (AS); a second examined them within a few minutes using a remote TS. A nurse placed the TS chest piece as directed by the remote examiner via intercom, but neither video examination nor conversation with the parent/patient were permitted. Examiners independently recorded the stethoscope findings for all heart sounds, all murmurs, and heart disease (present/absent). TS accuracy was indexed using the κ statistic for TS/AS agreement and for TS agreement with auscultatory findings predicted from echocardiographic (echo) studies (N = 49). Results. TS/AS agreement was satisfactory for presence/absence of heart disease (κ = 0.63) and for organic, functional, vibratory, diastolic aortic, and diastolic pulmonic murmurs (κ range: 0.65–0.75). For other specific murmurs and all heart sounds, TS/AS agreement was either unsatisfactory (κ ≤ 0.60) or indeterminate because prevalence was 0. TS-AS agreement improved when the TS was used by the more-experienced TS examiner and with patients at least 5 years of age. When the older children were examined by the more TS-experienced examiner, the TS-echo comparison yielded κ = 0.90, raw agreement = 0.96, sensitivity = 0.94, and specificity = 1.00. Conclusions. In pediatric patients, a narrow-bandwidth telephonic stethoscope can accurately distinguish between functional and organic murmurs and thus can detect heart disease. Accuracy is greatest when the instrument is used by an experienced examiner with patients at least 5 years of age.

We report on a patient with Williams syndrome who suffered a cerebrovascular accident. Clinical evaluation demonstrated the presence of carotid and cerebral arterial stenoses. We believe these lesions led to acute cerebrovascular ischemia and a non-hemorrhagic cerebral infarction. It is possible the stenoses were exacerbated by a vasculitis. The stenoses were identified by both invasive and noninvasive imaging studies. These studies may have a role in the evaluation of persons with Williams syndrome. © 1994 Wiley-Liss, Inc.

We recently demonstrated that systemic hypoxia during reduced inspired [Formula: see text] produces a rapid increase in leukocyte adherence to rat mesenteric venules. Evidence suggests that the mechanism of this response involves decreased nitric oxide (NO) levels. One possible pathway for NO depletion could involve increased reactive oxygen species (ROS) generation resulting in inactivation of NO. The overall goal of the present study was to examine the role of ROS in promoting leukocyte-endothelial adherence during systemic hypoxia. Experiments were designed to 1) evaluate changes in ROS generation in the mesenteric microcirculation during systemic hypoxia, 2) determine how the ROS signal changes when [Formula: see text] levels return to normal after a period of systemic hypoxia, 3) assess the effect of antioxidants on ROS generation during hypoxia, and 4) utilize antioxidants to examine the functional relationship between ROS generation and leukocyte adherence during hypoxia. The major findings from this study are that systemic hypoxia increases ROS generation within the mesenteric microcirculation and that antioxidants prevent the increase in leukocyte-endothelial adhesive interactions observed in hypoxia.

Nitric Oxide Depletion during Acute Hypoxia Causes Leukocyte Adherence to the Rat Mesenteric Venule

1. 1. The llama has markedly lower levels of in vitro angiotensin-I (A-I) converting enzyme activity and angiotensin-II (A-II) than nine other species tested. 2. 2. In vivo conversion of A-I to A-II in the llama is similar to that of other species. 3. 3. Resting levels of other components of the renin-angiotensin system, i.e. renal renin granulation, A-I and plasma renin activity, are normal. 4. 4. Acute alveolar hypoxia increased the levels of A-II in four out of five experiments.

Summary A 6-wk-old infant born with large hepatic hemangioma underwent successful ligation of the common hepatic artery with marked clinical and hemodynamic improvement of her profound cardiac failure. No alteration of liver enzymes was noted. At 2 yr of age, this infant is clinically normal. We feel on the basis of this case and of two other previously reported cases that ligation of the common hepatic artery is a safe and effective means of therapy for cardiac failure due to diffuse intrahepatic arteriovenous fistulas in the newborn.

The following is the first case of anatomically corrected malposition of the {S, L, D} type clinically diagnosed antemortem and only the second case recorded in the literature. The {S, L, D} notation indicates the segmental set of situs solitus of viscera and atria (S), ventricular l -loop (L), and d -malposition of the great arteries (D). This rare anomaly has the physiologic findings of complete d -transposition. Attempted surgical palliation was unsuccessful.

Two cases of obstructive asymmetric septal hypertrophy with biventricular outflow obstruction in childhood are presented. Both patients were treated first with propranolol and later by ventriculoseptal myotomy-myectomy. The first patient died two and one-half years following surgery, and the second patient died in the immediate postoperative period. In the first patient the 690 gm. heart had an interventricular septum to posterior left ventricular wall ratio of 1.9, and in the second patient the ratio in the 460 gm. heart was 1.8. In both cases the posterobasal left ventricular free wall was rounded and hypertrophied, as has been reported grossly in obstructive asymmetric septal hypertrophy. However, in both cases, the bizarre disoriented cardiocytes typical of asymmetric septal hypertrophy were present in both ventricular free walls as well as in the interventricular septum, as has been reported in the nonobstructive variety. In these two cases, previously reported morphologic criteria for the differentiation of obstructive and nonobstructive disease are not considered reliable.

primary hypertension and the more common forms of secondary hypertension in the pediatri c age patient. In the second part; the therapeutic approach, based on an understanding Of the mechanisms of hypertension is discussed. NO attempts are made to discuss the differential diagnosis of hypertension noi: the Various approaches to diagnosis, except as possibly related to pathophysiology and treatment. These aspects have been recently reviewed in detail for both children and adults?' ', ~, 9

Ten infants under 6 months of age in congestive heart failure have been studied and were proved to have only a large patent ductus arteriosus. Auscultation and phonocardiography of the chest wall showed only a systolic murmur along the left sternal border. Intracardiac phonocardiography revealed a continuous murmur inside the pulmonary artery in 9 out of the 10 cases. The role of intracardiac phonocardiography in the diagnosis of large patent ductus arteriosus in early infancy is emphasized.

Cardiopulmonary function was studied at rest and during exercise in 17 patients with Fallot's tetralogy who had systemic-pulmonary anastomoses to determine the factors which limit their work capacity (Wmax) and produce their limiting symptoms. The patients stopped exercise at a mean work rate of 355 kg-M·min-1 because of dyspnea or leg pain. The average pattern observed in room air was: a fall in arterial pO2 from 64 mm Hg at rest to 47 mm Hg during exercise due to increased right-to-left shunting; alveolar hyperventilation at rest (arterial pCO2 = 31.6 mm Hg) and during exercise (arterial pCO2 = 35.2 mm Hg); a progressive fall in arterial pH during exercise to pH = 7.369; and increased levels of wasted ventilation (VD:VT = 50.6) during exercise. Wmax was directly related to pulmonary blood flow, anaerobic threshold, and O2 pulse, and inversely related to the size of right-to-left shunt during exercise. Exercise response during O2 breathing in 16 patients studied showed decreased hypoxemia, decreased acidosis, and decreased minute ventilation. These results suggest that the excessive ventilation observed in these patients when they breathed room air was partly due to a chemoreceptor drive. Exercise response in the supine posture in seven patients studied was improved with decreased dyspnea, decreased minute ventilation, and decreased wasted ventilation without changes in the right-to-left shunt. These results suggest that the excessive ventilation observed was partly due to an increased wasted ventilation. Dyspnea appeared to be related to the inappropriateness of the level of ventilation relative to the metabolic needs of exercise.

SUMMARY 1.Thirteen patients with pulmonary artery branch stenosis proved by angiography have been presented. 2.All patients, except one, had systolic murmurs audible throughout both lung fields. One patient had a continuous murmur radiating to the entire left lung field. 3.Intracardiac phonocardiography was done in 12 patients and systolic murmurs localized distal to the stenotic site were recorded. Similarity was found between murmurs recorded on the chest wall and within the stenotic vessel. 4.Main pulmonary artery pressure curves were thought to be strongly suggestive of the diagnosis in all the cases of bilateral or multiple peripheral pulmonic stenosis. 5.Simultaneous pressure and sound recordings have been used to study the mechanisms involved in the production of stenotic murmurs within the pulmonary vasculature in experimental preparations in dogs. Systolic and continuous murmurs were produced by graded constriction of one or both pulmonary artery primary branches. The timing and intensity of these murmurs were found to be a function of the magnitude and duration of the pressure gradient created across the stenotic sites.

Renal artery stenosis accounts for 12% of secondary causes of hypertension1 and must be considered in the evaluation of a child with sustained hypertension. The surgical treatment for renal artery stenosis is preferably renovascular reconstruction or partial or complete nephrectomy if the former procedure is not possible.2 In recent years, percutaneous angioplasty has been performed in adult patients with renal artery stenosis with encouraging results.3,4 However, there has been little experience with this procedure in pediatric patients. This report describes the successful use of this technique in a 4½-year-old boy with recurrent hypertension following renal artery reconstruction for unilateral stenosis.

Morphometric analyses of the right ventricular papillary muscle, as well as measurements of right ventricular pressure and weight, were carried out in the rat during the development and recovery of hypoxic pulmonary hypertension. Animals were divided into hypoxic and normobaric control groups. The hypoxic rats were placed in hypobaric chambers for 1, 2, and 3 wks; and after 3 wks exposure, subgroups of hypoxic rats were allowed to recover in normoxia for 1 to 9 wks. Hematocrit (HCT) and right ventricular systolic pressure (RVSP) were measured prior to sacrifice. The heart was perfused, and the right ventricle (RV) was separated from the left ventricle and septum (LV+S) and weighed. The papillary muscles were dissected and processed for ultrastructural morphometry. Results showed that HCT, RVSP, and RV weight increased in the rats during the hypoxic exposure and then gradually returned to control levels after 3 to 4 wks of normobaric recovery. The papillary muscle of the hypoxic rats showed increased volume density of interstitium, increased diameter and cross sectional area of the cardiac myocytes, reduced volume density of mitochondria, and reduced mitochondria to myofilament ratio. During normoxic recovery, these morphometric indices returned toward control values at various periods of time ranging from less than 3 wks to 9 wks. The results indicate that the adaptive ultrastructural changes of the papillary muscle in RV hypertrophy paralleled the RVSP changes, and also demonstrate the reversibility of these changes in ambient oxygen.

The first case of tricuspid atresia with a double-outlet left ventricle, l -transposition of the great arteries {S,D,L}, and bilateral conus in levocardia diagnosed correctly during life is reported. This case is unique and differs from the classic double-outlet left ventricle in that there is a bilateral conus.

Plasma levels of angiotensin II were determined by radioimmunoassay in unanesthetized white rabbits exposed to acute hypoxia (FIO2 10% for 10 min),chronic hypoxia (0.5 atm up to 16 days), or hypovolemic stress (bleeding 20ml/kg). Angiotensin II levels significantly decreased after 10 min of acutehypoxia in normal rabbits and significantly increased when the same procedure was applied to animals previously exposed to hypoxia by 6–8 days of permanence in the hypobaric chamber or sodium deprivation. Chronic hypoxia resulted in a temporary increase of angiotensin II already evident on the 3rd day, but maximal at the 9th day with return to normal values within 16 days.Hypovolemic stress resulted in the expected rise of angiotensin II levels 10 min postbleeding both in normal and acclimatized rabbits. The responseof the renin-angiotensin-aldosterone system to hypoxic and hypovolemic stress is different. The direction and magnitude of the response to hypoxia depends on the underlying state of activation of the system and the cardiovascular condition of the animal at the time of hypoxic stress.

SummaryMice exposed to chronic alveolar hypoxia showed elevations of serum and lung angiotensin I converting enzyme activity during the second week of exposure. The increment of activity of the lung and serum converting enzyme was of the same order of magnitude and occurred at approximately the same time. An increase in renal renin granules was closely correlated with both lung and serum converting enzyme activity.

Serum angiotensin-I-converting enzyme activity was found to be elevated in infants with idiopathic respiratory distress syndrome when compared with healthy premature infants, normal infants, and acutely ill full-term infants. Serum and lung CE activity has been found to be elevated in mice exposed to hypobaric alveolar hypoxia which also stimulated renal renin production. These findings suggest that alveolar hypoxia stimulates the renin-angiotensin-aldosterone system and this system may be involved in the response to the stress of IRDS.

In 11 healthy, normotensive young women taking contraceptive medication (Enovid) for at least one year, plasma levels of angiotensin II were significantly higher than in healthy male and female controls. No significant difference was seen in the serum activity of angiotensin I-converting enzyme measured in vitro. Although serum angiotensin I converting enzyme activity is stimulated in several conditions in which other components of renin-angiotensin-aldosterone system are increased, this is not the case during administration of estrogens.

A family has been studied in which a man and four of his male adolescent children are affected with the Noonan syndrome. Four of the five family members have pulmonic stenosis confirmed by...

Fifteen infants with an angiographie or autopsy diagnosis, or both, of pulmonary valvular atresia with intact ventricular septum (type I) were treated by various surgical procedures. An angiographie right ventricular cavity-intramyocardial sinusoid method was used to assess the “true” right ventricular size. The clinical, electrocardiographic and roentgenographic findings as well as the cardiac catheterization data were similar to those of other observers. A 2-stage palliative surgical approach is proposed. The first stage consists of combined Waterston-Cooley (ascending aorta to right pulmonary artery anastomosis) and Blalock-Hanlon (surgical atrial septectomy) procedures at the time of initial diagnosis. In the second stage a transventricular pulmonary valvotomy is performed 3 to 4 months after the initial palliative surgery. A definite improvement in morbidity and mortality was achieved. Furthermore, evidence is presented to demonstrate the capability for growth of the right ventricle.

Summary This report involved 7 infants with IRDS who were treated with acetylcholine. In 3 of them the drug was infused directly into the pulmonary artery, and a temporary rise in PaO2 was accompanied by fall in pulmonary artery pressure and partial correction of acidosis. However, both pressure and blood-gas tensions reverted to original levels during the course of the infusion, and no lasting beneficial effect was evident.

In an autopsy-proven case of left aortic arch with hypoplastic retro-esophageal segment, right descending aorta and right patent ductus arteriosus forming a vascular ring, the clinical course was characterized by profound congestive heart failure secondary to the large left-to-right shunts at ductal and ventricular levels. This is the first such anomaly with associated aortic arch hypoplasia.