Intravenous nanosomes of quercetin improve brain function and hemodynamic instability after severe hypoxia in newborn piglets

Perinatal asphyxia is a major cause of death and neurological morbidity in newborns and oxidative stress is one of the critical mechanisms leading to permanent brain lesions in this pathology. In this context we have chosen quercetin, a natural antioxidant, known also by its brain protective effects to study its potential as a therapy for brain pathology provoked by severe hypoxia in the brain. To overcame the difficulties of quercetin to access the brain, we have developed lecithin/cholesterol/cyclodextrin nanosomes as a safe and protective vehicle.We have applied the nanosomal preparation intravenously to newborn piglets submitted to a severe hypoxic or ischemic/hypoxic episode and followed them for 8 or 72 h, respectively. Either towards the end of 8 h after hypoxia or up to 72 h after, electroencephalographic amplitude records in animals that received the nanosomes improved significantly. Animals receiving quercetin also stabilized blood pressure and recovered spontaneous breathing. In this experimental group mechanical ventilation assistance was withdrawn in the first 24 h while the hypoxic and vehicle groups required more than 24 h of mechanical ventilation. Three days after the hypoxia the suckling and walking capacity in the group that received quercetin recovered significantly compared with the hypoxic groups. Pathological studies did not show significant differences in the brain of newborn piglets treated with nanosomes compared with hypoxic groups. The beneficial effects of quercetin nanosomal preparation after experimental perinatal asphyxia show it as a promising putative treatment for the damaged brain in development.     

Nutrient-intake-level-dependent regulation of intestinal development in newborn intrauterine growth-restricted piglets via glucagon-like peptide-2

The objective of the present study was to investigate the intestinal development of newborn intrauterine growth-restricted (IUGR) piglets subjected to normal nutrient intake (NNI) or restricted nutrient intake (RNI). Newborn normal birth weight (NBW) and IUGR piglets were allotted to NNI or RNI levels for 4 weeks from day 8 postnatal. IUGR piglets receiving NNI had similar growth performance compared with that of NBW piglets. Small intestine length and villous height were greater in IUGR piglets fed the NNI than that of piglets fed the RNI. Lactase activity was increased in piglets fed the NNI compared with piglets fed the RNI. Absorptive function, represented by active glucose transport by the Ussing chamber method and messenger RNA (mRNA) expressions of two main intestinal glucose transporters, Na⁺-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2), were greater in IUGR piglets fed the NNI compared with piglets fed the RNI regimen. The apoptotic process, characterized by caspase-3 activity (a sign of activated apoptotic cells) and mRNA expressions of p53 (pro-apoptotic), bcl-2-like protein 4 (Bax) (pro-apoptotic) and B-cell lymphoma-2 (Bcl-2) (anti-apoptotic), were improved in IUGR piglets fed the NNI regimen. To test the hypothesis that improvements in intestinal development of IUGR piglets fed NNI might be mediated through circulating glucagon-like peptide-2 (GLP-2), GLP-2 was injected subcutaneously to IUGR piglets fed the RNI from day 8 to day 15 postnatal. Although the intestinal development of IUGR piglets fed the RNI regimen was suppressed compared with those fed the NNI regimen, an exogenous injection of GLP-2 was able to bring intestinal development to similar levels as NNI-fed IUGR piglets. Collectively, our results demonstrate that IUGR neonates that have NNI levels could improve intestinal function via the regulation of GLP-2.     

Effect of alpha adrenergic blockade on brain blood flow and ventilation during hypoxia in newborn piglets.

The influence of cardiovascular changes on ventilation has been demonstrated in adult animals and humans (Jones, French, Weissman & Wasserman, 1981; Wasserman, Whipp & Castagna 1974). It has been suggested that neonatal hypoxic ventilatory depression may be related to some of the hemodynamic changes that occur during hypoxia (Brown & Lawson, 1988; Darnall, 1985; Suguihara, Bancalari, Bancalari, Hehre & Gerhardt, 1986). To test the possible relationship between the cardiovascular and ventilatory response to hypoxia in the newborn, eleven sedated spontaneously breathing piglets (age: 5.9 +/- 1.6 days; weight: 1795 +/- 317 g; SD) were studied before and after alpha adrenergic blockade with phenoxybenzamine. Minute ventilation (VE) was measured with a pneumotachograph, cardiac output (CO) by thermodilution and total and regional brain blood flow (BBF) with radiolabeled microspheres. Measurements were performed while the animals were breathing room air and after 10 min of hypoxia induced by breathing 10% O2. Hypoxia was again induced one hour after infusion of phenoxybenzamine (6 mg/kg over 30 min). After 10 min of hypoxia, in the absence of phenoxybenzamine, the animals responded with marked increases in VE (P less than 0.001), CO (P less than 0.001), BBF, and brain stem blood flow (BSBF) (P less than 0.02). However, the normal hemodynamic response to hypoxia was eliminated after alpha adrenergic blockade. There were significant decreases in systemic arterial blood pressure, CO, and BBF during hypoxia after phenoxybenzamine infusion; nevertheless, VE increased significantly (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Induction of hyperglycemia in adult intrauterine growth-restricted rats: effects on renal function

Intrauterine growth restriction (IUGR) leads to a reduction in nephron endowment at birth and is linked to renal dysfunction in adulthood. The aim of the present study was to determine whether kidneys of IUGR rat offspring are more vulnerable to a secondary insult of hyperglycemia. IUGR was induced in Wistar-Kyoto rats by maternal protein restriction. At 24 wk of age, diabetes was induced in male IUGR and non-IUGR offspring by streptozotocin injection; insulin was injected daily to maintain blood glucose levels at either a mild (7-10 mmol/l; n=8/group) or a moderate (10-15 mmol/l; n=8/group) level. At 32 wk of age, renal function was assessed using ultrasound and [(3)H]inulin and [(14)C]para-aminohippurate clearance techniques. Conscious mean arterial blood pressure and heart rate were unchanged in IUGR offspring. Relative kidney length was increased significantly in IUGR offspring, and renal function was altered significantly; of importance, there was a significant increase in filtration fraction, indicative of glomerular hyperfiltration. Induction of hyperglycemia led to marked impairment of renal function. However, the response to hyperglycemia was not different between IUGR and non-IUGR offspring. Maintaining blood glucose levels at a mild hyperglycemic level led to marked improvement in all measures of renal function in IUGR and non-IUGR offspring. In conclusion, while the IUGR offspring showed evidence of hyperfiltration, the response to hyperglycemia was similar in IUGR and non-IUGR kidneys in adulthood. Importantly, maintaining blood glucose levels at a mild hyperglycemic level markedly attenuated the renal dysfunction associated with diabetes, even in IUGR offspring.     

Depressed ventilatory response to hypoxia in hypothermic newborn piglets: role of glutamate

To evaluatewhether changes in extracellular glutamate (Glu) levels in the centralnervous system could explain the depressed hypoxic ventilatory responsein hypothermic neonates, 12 anesthetized, paralyzed, and mechanicallyventilated piglets <7 days old were studied. The Glu levels in thenucleus tractus solitarius obtained by microdialysis, minute phrenicoutput (MPO), O₂ consumption, arterial blood pressure, heart rate, and arterial blood gases weremeasured in room air and during 15 min of isocapnic hypoxia (inspiredO₂ fraction = 0.10) at braintemperatures of 39.0 ± 0.5°C [normothermia (NT)]and 35.0 ± 0.5°C [hypothermia (HT)]. During NT, MPO increased significantly during hypoxia and remained above baseline. However, during HT, there was a marked decrease in MPOduring hypoxia (NT vs. HT, P < 0.03). Glu levels increased significantly in hypoxia during NT;however, this increase was eliminated during HT(P < 0.02). A significant linearcorrelation was observed between the changes in MPO and Glu levelsduring hypoxia (r = 0.61, P < 0.0001). Changes in pH, arterialPO₂, O₂ consumption, arterial bloodpressure, and heart rate during hypoxia were not different between theNT and HT groups. These results suggest that the depressed ventilatoryresponse to hypoxia observed during HT is centrally mediated and inpart related to a decrease in Glu concentration in the nucleus tractussolitarius.

     

Effect of glucose on adrenocortical activity of newborn piglets.

Adrenocortical function was followed in newborn piglets fasted for 36 hours and in piglets given only glucose or glucoplastic amino acids during this period. The greatest increase in relative adrenal weight, blood plasma 17-hydroxycorticosteroid (17-OHCS) levels and in the production of 17-OHCS by pig adrenals in vitro as compared with suckled controls was found in fasted piglets followed by amino acid-treated animals. The latter showed no significant differences in blood glucose between the initial and final values. The administration of glucose produced a transient hyperglycemia, failed to prevent the inhibition of body growth, resulted in a reduction in liver weight similar to that seen in fasted animals, and had a marked suppressive effect on the elevation of adrenocortical function. There were no significant differences in the production of 17-OHCS by adrenals in vitro per kg body weight between the glucose-treated and suckled piglets.     

Effect of controlled ventilation on renal and splanchnic blood flows during severe arterial hypoxia

The present study was undertaken to evaluate the extent that the lung inflation reflex attenuates vasoconstrictor responses in renal cortex and splanchnic beds during severe arterial hypoxia. Hypoxia was induced by inspiration of a 3-5% oxygen gas mixture in three groups of chloralose-anesthetized dogs: Group I, free breathing; Group II, controlled ventilation; Group III, free breathing with arterial PCO2 held constant. Regional vascular conductances (VC) were calculated from regional blood flows measured with 15-microns radioactive microspheres. In Group I, hypoxia caused marked hyperventilation, which was accompanied by no significant change in VC in renal cortex, and by reductions in VC in spleen (-36%), pancreas (-56%), and duodenum (-28%). In Group II, hypoxia caused reduction in VC in renal cortex (-70%), and reductions in VC in spleen, pancreas, and duodenum similar to those in Group I. In Group III, hypoxia again caused marked hyperventilation, but reductions in VC in renal cortex, spleen, pancreas, and duodenum were similar to those in Group II. Results indicate that during severe arterial hypoxia activation of lung inflation reflex does not attenuate or reverse vasoconstriction in renal cortex, spleen, pancreas, and duodenum.     

Shivering and cardiorespiratory responses during normocapnic hypoxia in the pigeon

To study the inhibitory effect of hypoxia on the cold defense mechanism, pigeons were exposed at low ambient temperature (5 degrees C) to various inhaled gas mixtures: normoxia [0.21 fractional concentration of O2 (FIO2)], hypoxia (0.07 FIO2), and normocapnic hypoxia (0.07 FIO2 + 0.045 FICO2). Electromyographic (EMG) activity indicative of shivering thermogenesis was inhibited during hypoxia, and body temperature (Tre) fell by 0.09 degrees C/min. Respiratory frequency (f) and minute ventilation (VE) increased by 143 and 135%, respectively, compared with normoxia, but tidal volume (VT) was not changed. PO2, PCO2, and O2 contents in the arterial and mixed venous blood were decreased and pH was enhanced. During normocapnic hypoxia, shivering EMG was present at approximately 50% of the normoxic intensity; Tre fell by only 0.04 degrees C/min. Arterial and mixed venous PCO2 and pH were the same as during normoxia, but VE increased by 430% because of twofold increases in both f and VT. During normocapnic hypoxia, arterial PO2 and O2 content were higher than during hypoxia alone. We conclude that the persistence of shivering during normocapnic hypoxia is due to maintenance of critical levels of arterial PO2 and O2 content.     

Quantification of compensatory processes of postnatal hypoxia in newborn piglets applying short-term nonlinear dynamics analysis

Background

Acute Respiratory Distress Syndrome (ARDS) patients require mechanical ventilation (MV) for breathing support. Patient-specific PEEP is encouraged for treating different patients but there is no well established method in optimal PEEP selection.

Methods

A study of 10 patients diagnosed with ALI/ARDS whom underwent recruitment manoeuvre is carried out. Airway pressure and flow data are used to identify patient-specific constant lung elastance (E _lung ) and time-variant dynamic lung elastance (E _drs ) at each PEEP level (increments of 5cmH ₂ O), for a single compartment linear lung model using integral-based methods. Optimal PEEP is estimated using E _lung versus PEEP, E _drs -Pressure curve and E _drs Area at minimum elastance (maximum compliance) and the inflection of the curves (diminishing return). Results are compared to clinically selected PEEP values. The trials and use of the data were approved by the New Zealand South Island Regional Ethics Committee.

Results

Median absolute percentage fitting error to the data when estimating time-variant E _drs is 0.9% (IQR = 0.5-2.4) and 5.6% [IQR: 1.8-11.3] when estimating constant E _lung . Both E _lung and E _drs decrease with PEEP to a minimum, before rising, and indicating potential over-inflation. Median E _drs over all patients across all PEEP values was 32.2 cmH ₂ O/l [IQR: 26.1-46.6], reflecting the heterogeneity of ALI/ARDS patients, and their response to PEEP, that complicates standard approaches to PEEP selection. All E _drs -Pressure curves have a clear inflection point before minimum E _drs , making PEEP selection straightforward. Model-based selected PEEP using the proposed metrics were higher than clinically selected values in 7/10 cases.

Conclusion

Continuous monitoring of the patient-specific E _lung and E _drs and minimally invasive PEEP titration provide a unique, patient-specific and physiologically relevant metric to optimize PEEP selection with minimal disruption of MV therapy.     

Effect of hyperventilation on oxygenation of the brain cortex of newborn piglets

A new phosphorescence imaging method (Rumsey et al. Science Wash. DC 241: 1649-1651, 1988) has been used to continuously monitor the PO2 in the blood of the cerebral cortex of newborn pigs. A window was prepared in the skull and the brain superfused with artificial cerebrospinal fluid. The phosphorescent probe for PO2, Pd-meso-tetra(4-carboxyphenyl)porphine, was injected directly into the systemic blood. The phosphorescence of the probe was imaged, and the lifetimes were measured using flash illumination and a gated video camera. The PO2 in the blood of the veins and capillary beds of the cortex was calculated from the lifetimes. Systemic blood pressure was continuously monitored while the systemic arterial PCO2, PO2, and blood pH were measured periodically. The PO2 in the blood was quantitated for 60- to 200 microns2 regions within the image (from a total field of approximately 3 mm diam). The PO2 in the microvasculature was not uniform across the viewing field but increased or decreased in each region independently of the other regions. Thus at any point in time the PO2 in a region could be substantially above or below the average value. During hyperventilation, which lowered arterial PCO2 and increased pH of the blood, the average PO2 decreased in proportion to the decrease in arterial PCO2. For example, hyperventilation, which decreased arterial PCO2 from its normal value of 40 Torr to 10 Torr, caused a rapid (within 5 min) decrease in PO2 in the blood of capillaries and veins to approximately one-third of normal.     

Changes in upper airway resistance during progressive normocapnic hypoxia in normal men

The effects of normocapnic progressive hypoxia on nasal and pharyngeal resistances were evaluated in nine normal men. To calculate resistances, upper airway pressures were measured with two low-bias flow catheters; one was placed at the tip of the epiglottis and the other in the posterior nasopharynx, and we measured flow with a Fleish no. 3 pneumotachograph connected to a tightly fitting mask. Both resistances were obtained during a baseline period and during progressive normocapnic hypoxia achieved by a rebreathing method. We collected the breath-by-breath values of upper airway resistances, minute ventilation, O2 and CO2 fractions, arterial O2 saturation (SaO2), and changes in functional residual capacity (inductance vest). The central respiratory drive was evaluated by the mouth occlusion pressure 0.1 s after the onset of inspiration (P0.1), and breath-by-breath P0.1 values were estimated by intrapolation from the linear relationship between P0.1 and SaO2. In each subject both resistances decreased during the hypoxic test. The slope of the decrease in resistance with decreasing SaO2 (%baseline/%SaO2) was steeper for pharyngeal resistance than for nasal resistance [2.67 +/- 0.29 and 1.61 +/- 0.25 (SE), respectively; P less than 0.05]. The slope of the decrease in resistance with increasing P0.1 (%baseline/cmH2O) was -0.24 +/- 0.05 for nasal resistance and -0.39 +/- 0.07 for pharyngeal resistance (P less than 0.05). Functional residual capacity progressively increased during the test, but the decrease in resistance was greater than expected from an isolated increase in lung volume. We conclude that nasal and pharyngeal resistances decrease during progressive normocapnic hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adipose tissue proteomes of intrauterine growth-restricted piglets artificially reared on a high-protein neonatal formula

The eventuality that adipose tissues adapt to neonatal nutrition in a way that may program later adiposity or obesity in adulthood is receiving increasing attention in neonatology. This study assessed the immediate effects of a high-protein neonatal formula on proteome profiles of adipose tissues in newborn piglets with intrauterine growth restriction. Piglets (10th percentile) were fed milk replacers formulated to provide an adequate (AP) or a high (HP) protein supply from day 2 to the day prior weaning (day 28, n=5 per group). Adipocytes with small diameters were present in greater proportions in subcutaneous and perirenal adipose tissues from HP piglets compared with AP ones at this age. Two-dimensional gel electrophoresis analysis of adipose tissue depots revealed a total of 32 protein spots being up- or down-regulated (P<.10) for HP piglets compared with AP piglets; 18 of them were unambiguously identified by mass spectrometry. These proteins were notably related to signal transduction (annexin 2), redox status (peroxiredoxin 6, glutathione S-transferase omega 1, cyclophilin-A), carbohydrate metabolism (ribose-5-phosphate dehydrogenase, lactate dehydrogenase), amino acid metabolism (glutamate dehydrogenase 1) and cell cytoskeleton dynamics (dynactin and cofilin-1). Proteomic changes occurred mainly in dorsal subcutaneous adipose tissue, with the notable exception of annexin 1 involved in lipid metabolic process having a lower abundance in HP piglets for perirenal adipose tissue only. Together, modulation in those proteins could represent a novel starting point for elucidating catch-up fat growth observed in later life in growing animals having been fed HP formula.     

Ventilatory response to hypercapnia and hypoxia after extensive lesion of medullary serotonergic neurons in newborn conscious piglets.

Acute inhibition of serotonergic (5-HT) neurons in the medullary raphé (MR) using a 5-HT(1A) receptor agonist had an age-dependent impact on the "CO(2) response" of piglets (33). Our present study explored the effect of chronic 5-HT neuron lesions in the MR and extra-raphé on the ventilatory response to hypercapnia and hypoxia in piglets, with possible implications on the role of 5-HT in the sudden infant death syndrome. We established four experimental groups. Group 1 (n = 11) did not undergo any treatment. Groups 2, 3, and 4 were injected with either vehicle or the neurotoxin 5,7-dihydroxytryptamine in the cisterna magna during the first week of life (group 2, n = 9; group 4, n = 11) or second week of life (group 3, n = 10). Ventilation was recorded in response to 5% CO(2) (all groups) and 12% O(2) (group 2) during wakefulness and sleep up to postnatal day 25. Surprisingly, the piglets did not reveal changes in their CO(2) sensitivity during early postnatal development. Overall, considerable lesions of 5-HT neurons (up to 65% decrease) in the MR and extra-raphé had no impact on the CO(2) response, regardless of injection time. Postlesion raphé plasticity could explain why we observed no effect. 5,7-Dihydroxytryptamine-treated males, however, did present a lower CO(2) response during sleep. Hypoxia significantly altered the frequency during sleep in lesioned piglets. Further studies are necessary to elucidate the role of plasticity, sex, and 5-HT abnormalities in sudden infant death syndrome.     

Programmed obesity in intrauterine growth-restricted newborns: modulation by newborn nutrition

The degree of nutrient enhancement during the newborn period may modulate programming of appetite-regulating hormones, body composition, and propensity to adult obesity in intrauterine growth-restricted (IUGR) newborns. Pregnant rats received, from day 10 to term gestation and throughout lactation, ad libitum food (AdLib) or 50% food restriction (FR) to produce IUGR newborns. AdLib vs. FR offspring were studied at day 1, and, to create two distinct groups of newborn catch-up growth (immediate, delayed) among the IUGR newborns, cross-fostering techniques were employed. The four groups of pups at 3 wk were IUGR immediate catch-up growth (FR/AdLib), IUGR delayed catch-up growth (FR/FR), control (AdLib/AdLib), and lactation FR control (AdLib/FR). From 3 wk to 9 mo, all offspring had AdLib rat chow. Maternal FR during pregnancy resulted in IUGR pups (6.0 +/- 0.3 vs. 7.1 +/- 0.3 g, P < 0.01) with decreased leptin (0.66 +/- 0.03 vs. 1.63 +/- 0.12 ng/ml, P < 0.001) and increased ghrelin (0.43 +/- 0.03 vs. 0.26 +/- 0.02 ng/ml, P < 0.001). Maternal FR during lactation (FR/FR) further impaired IUGR offspring growth at 3 wk. However, by 9 mo, these pups attained normal body weight, percent body fat, and plasma leptin levels. Conversely, IUGR offspring nursed by AdLib dams (FR/AdLib) exhibited rapid catch-up growth at 3 wk and continued accelerated growth, resulting in increased weight, percent body fat, and plasma leptin levels. Thus the degree of newborn nutrient enhancement and timing of IUGR newborn catch-up growth may determine the programming of orexigenic hormones and offspring obesity.     

Effect of hypobaric hypoxia on immune function in albino rats

 The effect of exposure to hypoxia on macrophage activity, lymphocyte function and oxidative stress was investigated. Hypoxia enhanced peritoneal macrophage activity as revealed by enhanced phagocytosis and free radical production. There was no significant change in antibody titres to sheep red blood cells in either serum or spleen during hypoxia. However, there was a considerable reduction in the delayed-type hypersensitivity response to sheep red blood cells, indicating the impairment of T-cell activity. Hypoxia decreased the blood glutathione (reduced) level and increased plasma malondialdehyde by a factor of about 2. It is therefore speculated that hypoxia imposes an oxidative stress leading to decreased T-cell acivity. Received: 1 September 1997 / Accepted: 22 May 1998     

早期灌喂母源粪菌对新生仔猪肠道菌群发育的影响

【目的】粪菌移植(fecal microbiota transplantation,FMT)作为一种治疗手段,已在人类肠道疾病治疗中有较多应用,但在干预新生仔猪肠道菌群上的研究未见报道。本文旨在研究早期母源粪菌移植对新生仔猪肠道菌群发育的影响。【方法】选取一窝12头杜长大新生仔猪,随机分为粪菌处理组(feces treatment,FT)和对照组(control,CO)。FT组仔猪出生后1–5 d每日灌注母源粪菌接种液,CO组灌注等量生理盐水。于1、3、5、7、10、14、18和22日龄采集仔猪粪样,Miseq高通量测序分析仔猪粪便菌群。【结果】灌喂母源粪菌有增加仔猪肠道菌群丰富度的趋势;主坐标分析显示,两组仔猪粪样菌群结构簇并未分开,并在18和22日龄时靠近母猪粪样菌群结构簇;随日龄增加,两组仔猪肠道中的变形菌门丰度均显著降低,而厚壁菌门的丰度显著增加,且从10日龄起拟杆菌门和厚壁菌门之和约为90%;与对照组相比,灌喂母源粪菌增加了10日龄时Escherichia-Shigella的丰度,而降低了18日龄时该菌属的丰富度,18日龄时肠球菌属和普氏菌属的丰度则显著增加。【结论】1–3日龄口服灌喂母源粪菌液并不能影响仔猪肠道菌群的定殖,这一阶段主要受母体微生物结构的影响;灌喂粪菌液对仔猪肠道菌群定殖的影响最多持续10–14 d;而且仔猪在22 d左右,肠道菌群结构逐渐趋同于母猪肠道菌群。     

Accelerated contractile function and improved fatigue resistance of calf muscles in newborn piglets with IUGR

Asymmetrical intrauterine growth restriction is denoted by disproportional reduction of muscle mass compared with body weight reduction. However, effects on contractile function or tissue development of skeletal muscles were not studied until now. Therefore, isometric force output of serial-stimulated hindlimb plantar flexors was measured in thiopental-anesthetized normal weight (NW) and intrauterine growth-restricted (IUGR) 1-day-old piglets under conditions of normal, reduced (aortic cross clamping), and reestablished (clamp release) blood supply (measured by colored microspheres technique). Furthermore, muscle fiber type distribution was determined after histochemical staining, specific muscle force of the plantar flexors [quotient from absolute force divided by muscle mass (N/g)] was calculated, and glycogen content and morphometric data of the investigated muscles were estimated. Regional blood flow of hindlimb muscles was similar in NW (6 +/- 2 ml. min(-1). 100 g(-1)) and IUGR piglets (8 +/- 1 ml. min(-1). 100 g(-1)). Isometric muscle contractions induced a marked increase in regional blood flow of 4.1-fold in NW and 5-fold in stimulated hindlimb muscles of IUGR piglets (baseline blood flow). Specific force of NW piglet muscles (5.2 +/- 0.2 N/g) was significantly lower than IUGR piglet muscles (6.1 +/- 0.6 N/g; P < 0.05). Isometric muscle contractions (NW: 32.7 +/- 4.7 N; IUGR: 21.7 +/- 4.0 N) resulted in a higher rate of force decrease in the calf muscles of NW animals compared with IUGR piglets (8 +/- 2 vs. 3 +/- 1%; P < 0. 01). Functional restoration of contractile performance after hindlimb recirculation was nearly complete in IUGR piglets (98 +/- 1%), whereas in NW piglets a deficit of 9 +/- 3% was found (P < 0. 01). Muscle fiber type estimation revealed an increased proportion of type I fibers in flexor digitalis superficialis and gastrocnemius medialis in IUGR piglets (P < 0.05). These data clearly indicate that contractile function is accelerated in newborn IUGR piglets.