Fructose, but not dextrose, induces leukocyte adherence to the mesenteric venule of the rat by oxidative stress.

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).

Effects of lactose-containing vs lactose-free infant formula on postprandial superior mesenteric artery flow in term infants.

BACKGROUND: 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. OBJECTIVE: To compare superior mesenteric artery (SMA) PPH following feeds of lactose-containing (LC) formula vs lactose-free (LF; dextrose + sucrose) formula. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Effects of intragastric fructose and dextrose on mesenteric microvascular inflammation and postprandial hyperemia in the rat.

OBJECTIVES: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Effectiveness of teaching cardiac auscultation to residents during an elective pediatric cardiology rotation.

This study aimed to assess the effectiveness of randomized tracks of prerecorded cardiac sounds as a teaching tool for cardiac auscultation. The study focused on recognizing murmurs when present, distinguishing functional from organic murmurs, and detecting heart disease by auscultation. At both pre- and posttesting, 26 residents listened to 15 randomized tracks of live-recorded cardiac sounds and identified key features. The results indicate that the residents improved at detecting any murmur (66% vs 76%, p = 0.007) and functional murmur (37% vs 54%, p = 0.048), and marginally improved at detecting organic murmur (75% vs 84%, p = 0.129). Detection of absence of murmur declined slightly (69% vs 62%, p = 0.723). The posttest difference in identifying organic versus functional murmurs was striking (84% vs 54%, p < 0.001). Detection of heart disease (sensitivity) improved significantly (76% to 86%, p = 0.016), but there was scant improvement in detecting no disease (specificity) (55% vs 59%, p = 0.601). The residents increased in their ability to detect heart disease when present. However, the false-positive rate for a diagnosis of heart disease remained quite high. To ensure that appropriate referrals will be made, teaching should specifically target the confident recognition of functional murmurs.

Accuracy of analog telephonic stethoscopy 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 kappa 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 (kappa = 0.63) and for organic, functional, vibratory, diastolic aortic, and diastolic pulmonic murmurs (kappa range: 0.65-0.75). For other specific murmurs and all heart sounds, TS/AS agreement was either unsatisfactory (kappa < or = 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 kappa = 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.