Autonomic organization of respirocardial function in healthy human neonates in quiet and active sleep.

BACKGROUND AND AIM: It is not known on which time scales the nonlinear respirocardial interactions occur. This work's aim is to quantitatively assess functional respirocardial organization during quiet and active sleep of healthy full-term neonates by autonomic information flow (AIF) without limitation on specific time scales. Representing respirocardial interactions on a global time scale AIF carries information on a wider scope of interdependencies than known linear and nonlinear measures described. It assesses the complexity of heart rate fluctuations (HRF) and respiratory movements (RM) and their interaction comprising both linear and nonlinear properties. Thus, we hypothesized AIF to characterize novel aspects of sleep state-dependent respirocardial interaction. METHODS: RM and ECG-derived HRF of six healthy full-term neonates were studied. We analyzed their power spectra, coherence, auto- and cross-correlation and complexity estimated on local ("next sample" prediction) and global time scales (an integral over AIF predicting for all time lags in HRF and RM). RESULTS: We found the global AIF of HRF and RM to differ significantly between active and quiet sleep in all neonates, whereas on a local time scale this applied to the HRF AIF only. HRF complexity was larger in quiet than in active sleep. Respirocardial interaction was less complex in quiet versus active sleep in the high frequency band only. CONCLUSION: Complex sleep state-related changes of respirocardial interdependencies cannot be identified completely on the local time scale. Considering the global time scale of respirocardial interactions allows a more complete physiological interpretation with regard to the underlying autonomic dynamics.

Autonomic Information Flow during awakeness, sleep, and multiple organ dysfunction syndrome assessed by mutual information function of heart rate fluctuations.

The Autonomic Information Flow (AIF) represents the complex communication within the autonomic nervous system (ANS). It can be assessed by the mutual information function (MIF) of heart rate fluctuations (HRF). AIF represented by HRF is based on several interacting physiological mechanisms operating at different time scales. Therefore one prominent time scale for HRF complexity analysis is not given a priori. MIF reflects the information flow at different time scales. This allows a more specific characterization of the complex communication leading to dynamic stability (homeostasis) of the cardiovascular-respiratory system. Three clinically relevant examples of autonomic communication, namely AIF of normals during awake state and deep sleep, and of patients with multiple organ dysfunction syndrome (MODS) were investigated. In these states MIF clearly represents and distinguishes the different communication in dependence on the time scale of information transfer. The results confirm our systems-theoretical concept that AIF, represented by MIF, characterizes the complex communication of the ANS at different time scales.

Short-term dynamics of coherence between respiratory movements, heart rate, and arterial pressure fluctuations in severe acute brain disorders.

In our previous study, healthy volunteers showed considerable short-term dynamics and patterns of the coherence of high time resolution between respiratory movements (RESP), heart rate fluctuations (HRF), and arterial blood pressure fluctuations (BPF). These are physiological indicators of autonomic short-term coordination mediated mainly by the brainstem which could be impaired in severe brain disorders. We hypothesized a direct or indirect impairment of these functions by these disorders and examined these patterns in 16 patients suffering from severe brain disorders. We calculated partial and ordinary coherence sequences and found almost the same patterns of coherence sequences as in healthy volunteers, but a distinctly reduced frequency of pattern incidence in patients (2.8+/-1.5/10 min/patient and 9.5+/-2.8/10 min/subject, P<0.05). Furthermore, there is a significantly smaller frequency of HRF-related patterns in patients with poor outcome, compared with those in patients with good outcome (1.8+/-0.8/10 min/patient and 4.5+/-2.7/10 min/patient, P<0.05). We conclude that severe brain disorders reduce physiological short-term dynamics of autonomic coordination patterns in the mean values of patients, but not in every patient.

Intrauterine growth restriction reduces nephron number and renal excretory function in newborn piglets.

To examine the effects of intrauterine growth restriction on nephron number, renal circulation, and renal excretory functions in newborns, studies were conducted on 1-day-old anaesthetized piglets, divided into normal weight (n = 6) and intrauterine growth restricted (n = 6) piglets. Renal blood flow was measured by coloured microspheres, glomerular filtration rate was measured by inulin clearance, and osmotic clearance and fractional sodium excretion were calculated. In addition, an estimation of the nephron number was performed by counting representative glomerular numbers in microscopic sections. Newborn intrauterine growth restricted piglets exhibited a reduced glomerular filtration rate and osmotic clearance (P < 0.05), whereas renal blood flow and the filtration fraction as well as fractional sodium excretion were similar in normal weight and intrauterine growth restricted piglets. The nephron number was markedly reduced in intrauterine growth restricted piglets even if the nephron number was related to body weight (P < 0.01). There was a positive correlation between nephron number and glomerular filtration rate (r = 0.69, P < 0.05). Reduced glomerular filtration rate of newborn intrauterine growth restricted piglets is associated with a reduced nephron number. Thus, at birth, compensatory response of renal function due to nephron deficit does not exist in intrauterine growth restricted piglets.

Immunomorphological sequelae of severe brain injury induced by fluid-percussion in juvenile pigs--effects of mild hypothermia.

Severe traumatic brain injury (TBI) often leads to a bad outcome with considerable neurological deficits. Secondary brain injuries due to a rise of intracranial pressure (ICP) and global hypoxia-ischemia are critical and may be reduced in extent by mild hypothermia. A porcine animal model was used to study the effect of severe TBI, induced by fluid percussion (FP; 3.5+/-0.3 atm) in combination with a secondary insult, i.e., temporary blood loss with hypovolemic hypotension. Six-week-old juvenile pigs were subjected to this kind of severe TBI; one group was then submitted to moderate hypothermia at 32 degrees C for 6 h, starting 1 h after brain injury. Animals were killed after 24 h. TBI and hypothermia-associated alterations in the brains were investigated by immunohistochemistry with antibodies against microtubule-associated protein 2 (MAP-2) and beta-amyloid precursor protein (betaAPP). In addition, DNA fragmentation was investigated by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) method. Seven of the 13 normothermic TBI animals developed a secondary increase in ICP (TBI-NT-ICP) after an interval of several hours. None of the animals in the hypothermic trauma (TBI-HT) group exhibited a secondary ICP increase, indicating a protective effect of the treatment. TBI-HT animals showed significantly higher levels of MAP-2 immunoreactivity, lower levels of betaAPP immunoreactivity and less DNA fragmentation than the TBI-NT-ICP animals. Differences between the TBI-HT group and normothermic animals without an ICP increase (TBI-NT) were less marked. A considerable decrease in MAP-2 outside the site of TBI-FP administration was seen only in the TBI-NT-ICP animals. MAP-2 immunohistochemistry was thus a reliable marker of diffuse brain damage. Axonal injury was present in all TBI groups, indicating its special significance in neurotrauma. Thus, severe TBI caused by FP, combined with temporary blood loss, consistently produced traumatic axonal injury and focal brain damage. Mild hypothermia was able to prevent a secondary increase in ICP and its sequelae of diffuse hypoxic-ischemic brain injury. However, hypothermia did not afford protection from traumatic axonal injury.

Functional interactions within the newborn brain investigated by adaptive coherence analysis of EEG.

To assess functional cortical organization in newborns during quiet sleep we investigated instantaneous interhemispheric coherences in six healthy full-term subjects using linked ear reference and average reference. Tracé alternant was the most frequent EEG pattern during quiet sleep of these newborns and consists of burst and interburst periods. The calculation of coherence was performed by means of time-variant autoregressive models on the basis of Kalman filtering. Coherence changes simultaneously with the appearance of these burst and interburst periods. The highest level of coherence was observed during burst periods in comparison with interburst periods. The lowest level of coherence was observed just before the burst started. During burst, maximal coherence was reached at different moments--late in the low frequency band (0.5-1.5 Hz; about 3 s after the burst started) and earlier in higher frequency bands (> 2 Hz, about 2 s). Interhemispheric coherence depended on the region being investigated. A significant level of coherence could be observed over frontal, temporal and occipital regions. Our data demonstrate significant modification of interhemispheric coherence during quiet sleep of full-term newborns and, irrespective of the immaturity of the brain, these coherences differ significantly between cortical regions.

Short-term dynamics of relative coordination between respiratory movements, heart rate and arterial pressure fluctuations within the respiratory frequency range.

The possible linear short-term coordination between respiratory movements (RESP), heart rate fluctuations (HRF), and arterial blood pressure fluctuations (BPF) in conscious human beings has not yet been investigated because of the restricted time resolution of conventional time series analysis. At present, this short-term dynamics as an expression of relative coordination can be quantified by newly developed adaptive autoregressive modeling of time series using Kalman filtering. Thus, in 6 conscious healthy volunteers, RESP, HRF, and BPF were recorded during 10 min in the supine position, at rest and during paced breathing. A considerable part of calculated ordinary and partial coherence sequences of short-term resolution between RESP and HRF, RESP and BPF, and partially between HRF and BPF showed patterns varying in time that could be correlated to changes between gradual coordinations (coherence changing between 0.40 and 0.95). They were more seldom complete or absent. There were mostly opposite changes between partial coherence sequences RESP-HRF/BPF and RESP-BPF/HRF demonstrating competitive behavior between these coordinations. Paced breathing did not essentially affect any observed characteristics. Therefore, these coherence dynamics are not essentially dependent on voluntary breathing movements. We conclude that to a different extent these linear and changing couplings between RESP, HRF, and BPF in conscious human beings exhibit properties of short-term complete and more frequently gradual coordinations showing dynamics that can not be determined by conventional methods.

Comparison between inulin clearance and endogenous creatinine clearance in newborn normal weight and growth restricted newborn piglets.

The effect of intrauterine growth restriction (IUGR) and acute oxygen deprivation on renal plasma flow (RPF), renal excretory function (Inulin clearance and endogenous creatinine clearance) and urine flow were studied in twenty newborn piglets 12 to 27 hours old. The experiments were performed on anesthetized animals divided into normal weight piglets and intrauterine growth restricted (IUGR) piglets according to birth weights. The "normal weight" category included animals with a birth weight > 40th percentile (piglets heavier than 1220 g); the IUGR category included animals with a birth weight > 5th and < 10th percentiles (piglets with a birthweight between 733 g and 853 g). This animal model of naturally occurring growth restriction in swine gives asymmetric growth with an increase in the mean ratio of brain weight to liver weight from 1.02 to 2.02 (p < 0.01). There was only a small reduction in brain weight (11%). In contrast, the reduction in weight of liver (55%) and kidney (41%) was proportional to that in body weight (48%). Arterial blood pressure, heart rate, arterial blood gases, pH and RPF were similar in normal weight and IUGR piglets. However inulin clearance and creatinine clearance were significantly lower in the growth restricted piglets (p < 0.01). Severe hypoxia induced a moderate tachycardia, combined with pronounced metabolic acidosis and strongly reduced renal plasma flow and renal excretory function in both groups (p < 0.05). Comparison between inulin and creatinine clearances in normal weight and IUGR piglets revealed a markedly higher clearance of creatinine as of inulin at every experimental stages (p < 0.05, p < 0.01). Alterations of renal excretion due to severe hypoxia and early recovery were similar in both animal groups investigated. Regression analysis rendered a linear correlation between inulin clearance and creatinine clearance among the experimental stages for normal weight as well as IUGR piglets (p < 0.001). Thus, endogenous creatinine clearance is suggested to be a reliable indicator for renal excretory function in newborn piglets. It accurately reflects proportional effects of long-term alterations of renal function due to intrauterine growth restriction as well as acute effects of severe oxygen deprivation. However, using standard methods of plasma and urine creatinine measurement, quantitative determination of GFR by endogenous creatinine clearance is not possible.

[Cardiorespiratory desynchronization after acute myocardial infarct]. / Kardiorespiratorische Desynchronisation nach akutem Myokardinfarkt.

The prognosis of cardiac diseases can be estimated from the variability of regulation parameters of the cardiovascular system. Changes in the variability of a regulation parameter causes disturbances in the synchronisation of interacting control loops. Conclusions about the severity of the underlying functional impairment can be drawn from these disturbances. This study investigates the synchronisation of the control loops of the heart rate and respiration (cardiorespiratory synchronisation, CRS) after acute myocardial infarction. We investigated 43 patients after myocardial infarction and 27 healthy controls. To quantify the CRS the synchronisation in phase of respiration and heart rate was assessed. The heart rate variability (HRV) was also assessed. Patients after myocardial infarction have a significantly reduced HRV and CRS. There is a non-linear relationship between HRV and CRS. Patients with left ventricular enlargement and reduced left ventricular ejection fraction (< or = 45%) significantly differed from the other infarct patients and controls in CRS but not in HRV. They had a marked degree of cardiorespiratory desynchronisation and were identified by a threshold value. CRS is a measure of the interaction of respiration control and heart rate control. After myocardial infarction, a reduction of the HRV can be observed. The desynchronisation of the control loops of respiration and heart rate especially appears in large infarcts. This can be quantitatively assessed by the method presented.

Coupling of cerebral blood flow and oxygen metabolism in infant pigs during selective brain hypothermia.

Studies documenting the cerebral hemodynamic consequences of selective brain hypothermia (SBH) have yielded conflicting data. Therefore, the authors have studied the effect of SBH on the relation of cerebral blood flow (CBF) and CMRO2 in the forebrain of pigs. Selective brain hypothermia was induced in seven juvenile pigs by bicarotid perfusion of the head with extracorporally cooled blood. Cooling and stepwise rewarming of the brain to a Tbrain of 38 degrees C, 25 degrees C, 30 degrees C, and 38 degrees C at normothermic Ttrunk (38 degrees C) decreased CBF from 71 + 12 mL 100 g(-1) min(-1) at normothermia to 26+/-3 mL 100 g(-1) min(-1) and 40+/-12 mL 100 g(-1) min(-1) at a Tbrain of 25 degrees C and 30 degrees C, respectively. The decrease of CMRO2 during cooling of the brain to a Tbrain of 25 degrees C resulted in a mean Q10 of 2.8. The ratio between CBF and CMRO2 was increased at a Tbrain of 25 degrees C indicating a change in coupling of flow and metabolism. Despite this change, regional perfusion remained coupled to regional temperatures during deep cerebral hypothermia. The data demonstrate that SBH decreases CBF and oxygen metabolism to a degree comparable with the cerebrovascular and metabolic effects of systemic hypothermia. The authors conclude that, irrespective of a change in coupling of blood flow and metabolism during deep cerebral hypothermia, cerebral metabolism is a main determinant of CBF during SBH.

Altered renal function in growth-restricted newborn piglets.

The effect of intrauterine growth restriction (IUGR) on renal hemodynamics and excretory functions was studied in 76 newborn piglets 12-27 h old. The experiments were performed on anesthetized animals divided into normal-weight piglets and IUGR piglets according to their birth weight. The "normal-weight" category included animals with a birth weight >40th percentile (piglets heavier than 1,220 g); the IUGR category included animals with a birth weight >5th and <10th percentiles (piglets with a birth weight between 733 g and 853 g). Cardiac output and renal blood flow were measured by the colored microsphere technique. Urine was collected from catheters placed in the ureters. This animal model of naturally occurring growth retardation in swine gives asymmetric growth with an increase in the mean ratio of brain weight to liver weight from 1.02 to 1.85 (P<0.01). Thus there was only a small reduction in brain weight (11%). In contrast, the reduction in the weight of liver (50%) and kidney (46%) was proportional to that in body weight (46%). Heart rate, cardiac output, arterial blood gases, and pH were similar in normal-weight and IUGR piglets, but arterial blood pressure and arterial glucose content were significantly reduced in IUGR piglets (P<0.01). Moreover, IUGR piglets had higher plasma catecholamine levels (P<0.05). Renal blood flow and renal vascular resistance were similar in the normal-weight and in the IUGR groups. However, in IUGR animals, glomerular filtration rate was significantly less than in the controls (P<0.05). Normal-weight and IUGR newborn piglets reabsorbed sodium very efficiently, the fractional sodium excretion was less than 1% in both groups. We conclude that renal blood flow is maintained in relation to kidney and body weight in IUGR newborns, but that important renal excretory functions are compromised due to IUGR.

Effect of severe normocapnic hypoxia on renal function in growth-restricted newborn piglets.

To examine the effects of intrauterine growth restriction and acute severe oxygen deprivation on renal blood flow (RBF), renovascular resistance (RVR), and renal excretory functions in newborns, studies were conducted on 1-day-old anesthetized piglets divided into groups of normal weight (NW, n = 14) and intrauterine growth-restricted (IUGR, n = 14) animals. Physiological parameters, RBF, RVR, and urinary flow, were similar in NW and IUGR piglets, but glomerular filtration rate (GFR) and filtration fraction were significantly less in IUGR animals (P < 0.05). An induced 1-h severe hypoxia (arterial PO(2) = 19 +/- 4 mmHg) resulted in, for both groups, a pronounced metabolic acidosis, strongly reduced RBF, and increased fractional sodium excretion (FSE; P < 0.05) with a less-pronounced increase of RVR and arterial catecolamines in IUGR piglets. Of significance was a smaller decrease in RBF for IUGR piglets (P < 0.05). Early recovery showed a transient period of diuresis with increased osmotic clearance and elevated FSE in both groups (P < 0.05). However, GFR and renal O(2) delivery remained reduced in NW piglets (P < 0.05). We conclude that, in newborn IUGR piglets, RBF is maintained, although GFR is compromised. Severe hypoxemia induces similar alterations of renal excretion in newborn piglets. However, the less-pronounced RBF reduction during hypoxemia indicates an improved adaptation of newborn IUGR piglets on periods of severely disturbed oxygenation. Furthermore, newborn piglets reestablish the ability for urine concentration and adequate sodium reabsorption early after reoxygenation so that a sustained acute renal failure was prevented.

Reduced muscle vascular resistance in intrauterine growth restricted newborn piglets.

It has been shown that asymmetrical intrauterine growth restriction is denoted by disproportional reduction of muscle mass compared to body weight reduction. However, the effects of IUGR on regional vascular resistance and blood flow of skeletal muscles and their contractile function have not been studied until now. Therefore, muscle blood flow (MBF) and isometric force output of serial stimulated hindlimb plantar flexors was measured in thiopental -anesthetized normal weight (NW; n = 9) and intrauterine growth restricted (IUGR; n = 9) one-day-old piglets. Additionally, muscle vascular resistance (MVR) and thyroid hormones were estimated. MBF was found to be markedly increased in IUGR piglets by 36% with a concomitant MVR reduction of 37% (p < 0.05). Isometric force of the plantar flexors was considerably higher in NW than in IUGR piglets (p < 0.05). However, amount of muscle fatigue was more pronounced in NW piglets (9.1+/-2.8%) than was in IUGR piglets (3.7+/-2.3%) (p < 0.05). Furthermore, specific tension of NW muscles (18.8+/-0.7 N/cm2) was significantly lower than for IUGR muscles (21.2+/-0.9 N/cm2) (P<0.05). IUGR newborn piglets exhibited increased plasma levels of thyroxine (T4) (p < 0.05), whereas triiodothyronine (T3) showed similar values in both animal groups. These data clearly indicate that muscle hemodynamics and contractile function are more developed in newborn IUGR piglets. Furthermore it is suggested that the improved tolerance to fatigue during isometric contractions may indicate an increased oxidative capacity of calf muscles due to intrauterine growth restriction.

Relations between early prespike magnetic field changes, interictal discharges, and return to basal activity in the neocortex of rabbits.

To evaluate possible prespike field synchronizations, its relation to both interictal discharges and postspike return to baseline, penicillin-induced cortical interictal discharges were recorded in anaesthetized rabbits by magnetoencephalography (MEG) and electrocorticography (EcoG). Statistical parameters of spatial (global field power (GFP)) and temporal properties (Z-parameter) of field synchronization were calculated. In our previous report, three types of prespike field synchronization were found before the onset of interictal spike. We report here that the continuous and fluctuating, but not the abrupt prespike increases, were more often associated with a spike and wave pattern of interictal discharge than with a spike alone. Furthermore, the postspike return of these statistical parameters shows the same three patterns as the prespike field synchronizations, but in the inverse time sequence. More often than not pre- and postspike pattern were of the same type. The results suggest an influence of prespike field synchronization upon interictal discharge and subsequent field return dynamics.

Effect of mild hypothermia on cerebral oxygen uptake during gradual cerebral perfusion pressure decrease in piglets.

OBJECTIVE: To study the effect of mild hypothermia on cerebral oxygen metabolism and brain function in piglets during reduced cerebral blood flow because of gradual reduction of the effective cerebral perfusion pressure (CPP). DESIGN: Comparison of two randomized treatment groups: normothermic group (NT; n = 7) and hypothermic group (HT; n = 7). SETTING: Work was conducted in the research laboratory of the Institute for Pathophysiology, Friedrich Schiller University, Jena, Germany. SUBJECTS: Fourteen piglets (14 days old) of mixed German domestic breed. INTERVENTION: Animals were anesthetized and mechanically ventilated. An epidural balloon was gradually inflated to increase intracranial pressure to 25 mm Hg, 35 mm Hg, and 45 mm Hg every 30 mins at adjusted mean arterial blood pressures. After determination of baseline CPP (NT, 79+/-14 mm Hg; HT, 84+/-9 mm Hg), CPP was reduced to approximately 70%, 50%, and 30% of baseline (NT, 38.1+/-0.5 degrees C; HT, 31.7+/-0.5 degrees C). MEASUREMENTS AND MAIN RESULTS: Every 25 mins after the gradual CPP reductions. Mild hypothermia induced a reduction of the cerebral metabolic rate of oxygen (CMRO2) to 50%+/-15% of baseline values (baseline values, 352+/-99 micromol x 100 g(-1) x min(-1)) (p < .05). Moreover, the electrocorticogram was altered to a pattern of reduced delta activity (p < .05) but unchanged higher frequency activity. The cerebral oxygen balance in HT animals remained improved until CPP reduction to 50%, indicated by a reduced cerebral arteriovenous difference of oxygen but elevated brain tissue Po2 (p < .05). Further CPP reduction gave rise to a strong CMRO2 reduction (NT, 19+/-21%; HT, 15+/-15%; p < .05). However, the high-frequency band of electrocorticogram was less reduced in hypothermic animals (p < .05). CONCLUSIONS: Mild whole body hypothermia improves cerebral oxygen balance by reduction of brain energy demand in juvenile piglets. The improvement of brain oxygen availability continues during a mild to moderate CPP decrease. A loss of the difference in CMRO2 between the hypothermic and normothermic piglets together with the fact that brain electrical activity was less suppressed under hypothermia during severe cerebral blood flow reduction indicates that hypothermic protection may involve some other mechanisms than reduction of brain oxidative metabolism.

Relation between brain tissue pO2 and dopamine synthesis of basal ganglia--a 18FDOPA-PET study in newborn piglets.

Perinatal hypoxic-ischemic cerebral injury is a major determinant of neurologic morbidity and mortality in the neonatal period and later in childhood. There is evidence that the dopaminergic system is sensitive to oxygen deprivation. However, the respective enzyme activities have yet not been measured in the living neonatal brain. In this study, we have used 18F-labelled 6-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) together with positron emission tomography (PET) to estimate the activity of the aromatic amino acid decarboxylase (AADC), the ultimate enzyme in the synthesis of dopamine, in the brain of newborn piglets under normoxic and moderate asphyxial conditions. The study was performed on 8 newborn piglets (2-5 days old). In each piglet PET studies were performed under control conditions and during 2-hour asphyxia. Simultaneously, brain tissue pO2 was recorded, cerebral blood flow (CBF) was measured with colored microspheres and cerebral metabolic rate of oxygen (CMRO2) was determined. Asphyxia was induced by lowering the inspired fraction of oxygen from 0.35 to 0.10 and adding about 6% CO2 to the inspired gas. Asphyxia elicited a more than 3-fold increase of the CBF (p < 0.01) so that CMRO2 remained unchanged throughout the asphyxial period. Despite this, brain tissue pO2 was reduced from 19 +/- 4 mm Hg to 6 +/- 3 mm Hg (p < 0.01). Blood-brain transfer of FDOPA as well as permeability-surface area product (PS) from striatum were unchanged. Striatal synthesis rate of fluoro-dopamine from FDOPA (k3) was, however, significantly increased (p < 0.01). This increase of the AADC activity is associated with reduced brain tissue pO2. Asphyxia-induced CBF increase impedes an alteration of brain oxidative metabolism.

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.