Resilience indicator traits in 3 dairy cattle breeds in Baden-Württemberg.

In recent years, research in animal breeding has increasingly focused on the topic of resilience, which is expected to continue in the future due to the need for high-yielding, healthy, and robust animals. In this context, an established approach is the calculation of resilience indicator traits with time series analyses. Examples are the variance and autocorrelation of daily milk yield in dairy cows. We applied this methodology to the German dairy cow population. Data from the 3 breeds (German Holstein, German Fleckvieh, and German Brown Swiss) were obtained, which included 13,949 lactations from 36 farms from the state Baden-Württemberg in Germany working with automatic milking systems. Using the milk yield data, the daily absolute milk yields, deviations between observed and expected daily milk yields, and relative proportions of daily milk yields in relation to lactation performance were calculated. We used the variance and autocorrelation of these data as phenotypes in our statistical analyses. We estimated a heritability of 0.047 for autocorrelation and heritabilities between 0.026 and 0.183 for variance-based indicator traits. Furthermore, significant breed differences could be observed, with a tendency of better resilience in Brown Swiss. The breed differences can be due to both genetic and environmental factors. A high value of a variance-based indicator trait indicates a low resilience. Performance traits were positively correlated with variance-based indicator traits calculated from absolute daily milk yields, but they were negatively correlated with variance-based indicators calculated from relative daily milk yields. Thus, they can be considered as different traits. Although variance-based indicators based on absolute daily milk yields were affected by the performance level, variance-based indicators based on relative daily milk yields were corrected for the performance level and also showed higher heritabilities. Thus, they seem to be more suitable for practical use. Further studies need to be conducted to calculate the correlations between resilience indicators, functional traits, and health traits.

Implementation of advanced Optimum Contribution Selection in small-scale breeding schemes: prospects and challenges in Vorderwald cattle.

Vorderwald cattle are a regional cattle breed from the Black Forest in south western Germany. In recent decades, commercial breeds have been introgressed to upgrade the breed in performance traits. On one hand, native genetic diversity of the breed should be conserved. On the other hand, moderate rates of genetic gain are needed to satisfy breeders to keep the breed. These goals are antagonistic, since the native proportion of the gene pool is negatively correlated to performance traits and the carriers of introgressed alleles are less related to the population. Thus, a standard Optimum Contribution Selection (OCS) approach would lead to reinforced selection on migrant contributions (MC). Our objective was the development of strategies for practical implementation of an OCS approach to manage the MC and native genetic diversity of regional breeds. Additionally, we examined the organisational efforts and the financial impacts on the breeding scheme of Vorderwald cattle. We chose the advanced Optimum Contribution Selection (aOCS) to manage the breed in stochastic simulations based on real pedigree data. In addition to standard OCS approaches, aOCS facilitates the management of the MC and the rate of inbreeding at native alleles. We examined two aOCS strategies. Both strategies maximised genetic gain, while strategy (I) conserved the MC in the breeding population and strategy (II) reduced the MC at a predefined annual rate. These two approaches were combined with one of three flows of replacement of sires (FoR strategies). Additionally, we compared breeding costs to clarify about the financial impact of implementing aOCS in a young sire breeding scheme. According to our results, conserving the MC in the population led to significantly (P < 0.01) higher genetic gain (1.16 ± 0.13 points/year) than reducing the MC (0.88 ± 0.10 points/year). In simulation scenarios that conserved the MC, the final value of MC was 57.6% ± 0.004, while being constraint to 58.2%. However, reducing the MC is only partially feasible based on pedigree data. Additionally, this study proves that the classical rate of inbreeding can be managed by constraining only the rate of inbreeding at native alleles within the aOCS approach. The financial comparison of the different breeding schemes proved the feasibility of implementing aOCS in Vorderwald cattle. Implementing the modelled breeding scheme would reduce costs by 1.1% compared with the actual scheme. Reduced costs were underpinned by additional genetic gain in superior simulation scenarios compared to expected genetic gain in reality (+4.85%).

Advanced optimum contribution selection as a tool to improve regional cattle breeds: a feasibility study for Vorderwald cattle.

In the middle of the 20th century, increasing inbreeding rates were identified as a threat to livestock breeding. Consequences include reduced fertility, fitness and phenotypic expression of lethal alleles. An important step in mitigating this inbreeding was the introduction of optimum contribution selection (OCS). OCS facilitates the simultaneous management of genetic gain and inbreeding rates. However, using a standard OCS methodology for regional breeds with historical introgression for upgrading reasons could lead to reinforced selection on introgressed genetic material since those alleles improve the rate of genetic gain and reduce the average kinship in the population. Consequently, regional breeds may become genetically extinct if a standard OCS approach is used. Thus, the advanced OCS (aOCS) approach takes introgressed genetic material into account. The major goals of this study were to (i) gather key information on the feasibility of aOCS under practical conditions of the actual breeding scheme of Vorderwald cattle, (ii) identify superior strategies for implementing the actual scheme and (iii) examine whether historical breeding decisions to increase genetic gain by introgression from commercial breeds could have been avoided by using aOCS. Stochastic simulations were designed in this study to create populations from the historical gene pool by using aOCS. Simultaneously, all practical constraints of a breeding scheme were met. Thus, the simulated populations were comparable with real data. The annual genetic gain was higher in reality (1.56) than in the simulation scenarios (1.12-1.40). The introgressed genetic material increased to 61.3% in reality but was conserved at a final value of 15.3% (±0.78) across simulations. The classical rate of inbreeding and rate of native inbreeding were constrained to 0.092% on an annual basis. This value is equal to an effective population size of 100. The observed values for rates of inbreeding were 0.082-0.087% and 0.087-0.088% for classical and native kinship, respectively. The corresponding figures in reality were 0.067% and 0.184%, respectively. This study suggests that aOCS is feasible for Vorderwald cattle. Strategies for implementation are identified. Finally, we conclude that historical breeding decisions could have been avoided by using aOCS. The genetic gain would have been reduced by at least 12.2%, but the introgressed genetic material, genetic diversity and native genetic diversity would have been more desirable for a breed under conservation.

A Novel Model to Explain Extreme Feather Pecking Behavior in Laying Hens.

Feather pecking (FP) is a serious economic and welfare problem in the domestic fowl. It has recently been shown that the distribution of FP bouts within groups is heterogeneous and contains a sub-population of extreme feather peckers (EFP). The present study proposed a novel model to detect EFP hens. A mixture of two negative binomial distributions was fitted to FP data of a F2 cross of about 960 hens, and, based on the results, a calculation of the posterior probability for each hen belonging to the EFP subgroup (pEFP) was done. The fit of the mixture distribution revealed that the EFP subgroup made up a proportion of one third of the F2 cross. The EFP birds came more frequently into pecking mood and showed higher pecking intensities compared to the remaining birds. Tonic immobility and emerge box tests were conducted at juvenile and adult age of the hens to relate fearfulness to EFP. After dichotomization, all traits were analyzed in a multivariate threshold model and a genomewide association study was performed. The new trait pEFP has a medium heritability of 0.35 and is positively correlated with the fear traits. Breeding for this new trait could be an interesting option to reduce the proportion of extreme feather peckers. An index of fear related traits might serve as a proxy to breed indirectly for pEFP. GWAS revealed that all traits are typical quantitative traits with many genes and small effects contributing to the genetic variance.

Genomic analysis of perinatal sucking reflex in German Brown Swiss calves.

A healthy sucking reflex is essential for newborn calves to ensure sufficient colostrum intake in the first few hours postpartum. In recent decades, European Brown Swiss breeders have repeatedly reported that some calves lack the ability to consume colostrum directly after birth due to an absent sucking reflex. In this study, we collected the phenotypes of more than 5,500 German Brown Swiss calves and performed variance component estimation with sire threshold models using Markov chain Monte Carlo algorithms. The 50K (777K) genotypes of nearly 2,000 (200) calves were collected, and an imputation was performed for all 50K genotypes up to 777K. Genome-wide association studies (GWAS) for the trait sucking reflex were conducted for all 777K genotypes. Depending on the trait coding, a low heritability was estimated to range from 0.08 to 0.11. The GWAS results identified 34 trait-associated SNP on 6 different chromosomes. Post-GWAS analyses showed significant overrepresentation of Gene Ontologies for central nervous development and several regulative processes. Functional annotation clustering and pathway analysis revealed relations to lipid metabolism, immune and endocrine systems, and signal transduction. The results of this study suggest that breeding for an improved sucking reflex is possible but requires large data sets for the estimation of reliable breeding values (either large progeny testing groups or a large reference genome in a genomic selection program).

Linkage disequilibrium pattern and genome-wide association mapping for meat traits in multiple porcine F2 crosses.

In the present study, data from four F2 crosses were analysed and used to study the linkage disequilibrium (LD) structure within and across the crosses. Genome-wide association analyses (GWASes) for conductivity and dressing out meat traits were conducted using single-marker and Bayesian multi-marker models using the pooled data from all F2 crosses. Porcine F2 crosses generated from the distantly related founder breeds Wild Boar, Piétrain and Meishan, as well as from a porcine F2 cross from the closely related founder breed Piétrain and an F1 Large White × Landrace cross were pooled. A total of 2572 F2 animals were genotyped using a 62K SNP chip. The positions of the SNPs were based on genome assembly Sscrofa11.1. After post-alignment and genotype filtering, approximately 50K SNPs were usable for LD studies and GWASes. The main findings of the present study are that the breakdown of LD was faster in crosses from closely related founder breeds compared to crosses from distantly related founders. The fastest breakdown of LD was observed by pooling the data. Based on the single-marker results and LD structure, clusters and windows were built for 1-Mb intervals. For conductivity and dressing out, 183 and 191 nominal significant associations respectively and six and five clusters respectively were found. Dominance was important for conductivity, and considering dominance in GWASes improved the mapping signals. Most clear signals were found for conductivity on SSC6, 8 and 15 and for dressing out on SSC2 and 7. Considering dominance might contribute to the accuracy of genomic selection and serve as a guide for choosing mating pairs with good combining abilities. However, further research is needed to investigate if dominance is also important in crossbreed pig breeding schemes.

Estimation of relative economic weights and the marginal willingness to pay for breeding traits of Brown Swiss cattle using discrete choice experiments.

Breeding traits are usually combined in a total merit index according to their economic weights to maximize genetic gain based on economic merit. However, this maximization may not always be the aim of the selection decisions by farm managers. A discrete choice experiment was used to evaluate the importance of traits in terms of the selection decisions of farm managers operating in different environments. Six trait complexes, the semen price, the interactions between these traits, and significant characteristics of the farms were included in a conditional logit model to estimate relative economic weights and the marginal willingness to pay for all traits. Milk value, conformation/udder, and fitness were the most important traits for the farmers, and significant interactions indicated that fitness is of greater importance on organically managed farms than on conventional farms. Farm managers with an advanced education placed more weight on the milk value trait than farm managers without advanced education. On conventional farms, managers weighted the traits milk value and conformation/udder highly. The conformation/udder and fitness trait complexes were important on organic farms. A new trait called perinatal sucking behavior of newborn calves should be included in the total merit index.

Short communication: Importance of introgression for milk traits in the German Vorderwald and Hinterwald cattle.

The subject of the present study was to analyze the influence of genetic introgression on milk yield performance of the German local Vorderwald and Hinterwald cattle breeds. Deviations of milk yield, fat yield, and protein yield of cows as well as pedigree information were analyzed. A sire model was used to estimate genetic trend and effects of the migrant breeds. Migrant contributions to Vorderwald cattle were high and have been rising even in the recent past. The effects of these breeds on milk yield performance were positive. Montbéliarde cattle not only had the largest effect on milk production of Vorderwald cattle but also the highest genetic contribution to this breed. Genetic introgression with Montbéliarde continued until recently. This suggests that introgression of high-yielding breeds is still a preferred method for genetic improvement of local breeds, even though it diminishes their value for conservation. Hence, the current population management has too little focus on the preservation of genetic uniqueness. In comparison, migrant breed contributions to the Hinterwald cattle, a breed with a unique phenotype and an own niche, were moderate and almost constant over the time. For the Hinterwald cattle, no significant effect of migrant breeds could be detected, which suggests that population management has different priorities in different endangered breeds. We conclude that not only the registration of animals from local breeds but also the breeding programs themselves should be supported and need to be controlled.

Estimation of ancestral inbreeding effects on stillbirth, calving ease and birthweight in German Holstein dairy cattle.

In this study, the effect of different measurements of ancestral inbreeding on birthweight, calving ease and stillbirth were analysed. Three models were used to estimate the effect of ancestral inbreeding, and the estimated regression coefficient of phenotypic data on different measurements of ancestral inbreeding was used to quantify the effect of ancestral inbreeding. The first model included only one measurement of inbreeding, whereas the second model included the classical inbreeding coefficients and one alternative inbreeding coefficient. The third model included the classical inbreeding coefficients, the interaction between classical inbreeding and ancestral inbreeding, and the classical inbreeding coefficients of the dam. Phenotypic data for this study were collected from February 1998 to December 2008 on three large commercial milk farms. During this time, 36,477 calving events were recorded. All calves were weighed after birth, and 8.08% of the calves died within 48 h after calving. Calving ease was recorded on a scale between 1 and 4 (1 = easy birth, 4 = surgery), and 69.95, 20.91, 8.92 and 0.21% of the calvings were scored with 1, 2, 3 and 4, respectively. The average inbreeding coefficient of inbred animals was 0.03, and average ancestral inbreeding coefficients were 0.08 and 0.01, depending on how ancestral inbreeding was calculated. Approximately 26% of classically non-inbred animals showed ancestral inbreeding. Correlations between different inbreeding coefficients ranged between 0.46 and 0.99. No significant effect of ancestral inbreeding was found for calving ease, because the number of animals with reasonable high level of ancestral inbreeding was too low. Significant effects of ancestral inbreeding were estimated for birthweight and stillbirth. Unfavourable effects of ancestral inbreeding were observed for birthweight. However, favourable purging effects were estimated for stillbirth, indicating that purging could be partly beneficial for genetic improvement of stillbirth.

The contribution of migrant breeds to the genetic gain of beef traits of German Vorderwald and Hinterwald cattle.

During the past decades, migrant contributions have accumulated in many local breeds. Cross-breeding was carried out to mitigate the risk of inbreeding depression and to improve the performance of local breeds. However, breeding activities for local breeds were not as intensive and target oriented as for popular high-yielding breeds. Therefore, even if performance improved, the gap between the performance of local and popular breeds increased for many traits. Furthermore, the genetic originality of local breeds declined due to the increasing contributions of migrant breeds. This study examined the importance of migrant breed influences for the realization of breeding progress of beef traits of German Vorderwald and Hinterwald cattle. The results show that there is a high amount of migrant contributions and their effects on performance are substantial for most traits. The effect of the French cattle breed Montbéliard (p-value 0.014) on daily gain of Vorderwald bulls at test station was positive. The effects of Vorderwald ancestors (p-value for daily gain 0.007 and p-value for net gain 0.004) were positive for both traits under consideration in the population of Hinterwald cattle. Additionally, the effect of remaining breeds (p-value 0.030) on net gain of Hinterwald cattle in the field was also positive. The estimated effect of Fleckvieh ancestors on net gain of Hinterwald cattle was even larger but not significant. Breeding values adjusted for the effects of the migrant breeds showed little genetic trend.

Genome-wide association analysis for growth, muscularity and meat quality in Piétrain pigs.

Improvement in growth and meat quality is one of the main objectives in sire line pig breeding programmes. Mapping quantitative trait loci for these traits using experimental crosses and a linkage-based approach has been performed frequently in the past. The Piétrain breed often was involved as a founder breed to establish the experimental crosses. This breed was selected for muscularity and leanness but shows relatively poor meat quality. It is frequently used as a sire line breed. With the advent of genome-wide and dense SNP chips in pig genomic research, it is possible to also conduct genome-wide association studies within the Piétrain breed. In this study, around 500 progeny-tested sires were genotyped with 60k SNPs. Data filtering showed that around 48k SNPs were useable in this sample. These SNPs were used to conduct a genome-wide association study for growth, muscularity and meat quality traits. Because it is known that a mutation in the RYR1 gene located on chromosome 6 shows a major effect on meat quality, this mutation was included in the models. Single-marker and multimarker association analyses were performed. The results revealed between zero and eight significant associations per trait with P < 5 × 10(-5) . Of special interest are SNPs located on SSC6, SSC10 and SSC15.

Identification and characterization of hierarchical structures in dog breeding schemes, a novel method applied to the Norfolk Terrier.

Popular sires, a limited population size, and the founder event are widely considered the main reasons for the low genetic diversity observed in many dog breeds. However, these factors have had only a small role in the historic decrease in diversity observed in the Norfolk Terrier breed. We show that the decrease in this breed has been mainly due to large, popular kennels. Dogs from these kennels have, on average, larger genetic contributions to subsequent generations than others. A test for the presence of a popular kennel effect is proposed and applied (P < 0.001). These kennels were found to be the same as nuclei of selection existing in other livestock species. This result revealed a hierarchical structure of dog breeding schemes, with an asymmetric gene flow predominantly from the nuclei toward the main population. Possible reasons for this structure and implications for future population management are discussed. The main reason is probably that the breed type was established by large, popular kennels and that small kennel breeders used their stud dogs to benefit from the achievements of the popular kennels. Many kennels, however, were unable to make their own substantial genetic contributions to the breed.

Pedigree analysis for conservation of genetic diversity and purging.

We present an approach to describe and evaluate changes in genetic diversity and to calculate bounds for improvement. This pedigree-based analysis was applied to the Kromfohrländer dog (FCI Gr9 Sec10). Pedigrees trace back to the foundation of the breed and were available for 5527 individuals. Based on this dataset the population structure and historical bottlenecks were studied. Distributions of allele frequencies were estimated by Monte Carlo simulation. To monitor changes in mating systems throughout the breeding history, the homozygosity of alleles was compared with their expectations in Hardy-Weinberg equilibrium. Different breeding lines were identified by hierarchical cluster analysis and were characterized by ancestor contributions. Our calculations showed that the founder event in 1945 was followed by two bottlenecks. One was caused by strong selection in a very small population, and the other was triggered by rigorous disease management. The necessary amount of purging that arised due to the bottlenecks was also discussed.

Dobutamine maintains intestinal villus blood flow during normotensive endotoxemia: an intravital microscopic study in the rat.

PURPOSE: The gut plays a pivotal role in sepsis. Intestinal hypoperfusion with subsequent ischemia leads to translocation of endotoxin. Dobutamine has been demonstrated to increase mesenteric blood flow during endotoxic shock; however, its effects on mucosal blood flow especially in intestinal villi is not known. Therefore, we investigated its influence on the blood flow and the arteriolar diameters in intestinal villi in a model of normotensive endotoxemia. MATERIALS AND METHODS: Twenty-one male Wistar rats were divided into three groups: (1) control, saline; (2) endotoxin, endotoxin 1.5 mg/kg during 60 minutes; and (3) dobutamine, endotoxin 1.5 mg/kg (60 minutes) and dobutamine 2.5 micrograms/kg/min during 120 minutes. Villus blood flow and arteriolar diameters were determined at 0 minutes, 60 minutes, and 120 minutes in each group using intravital microscopy. RESULTS: Villus blood flow was constant in the control group, significantly reduced at 120 minutes in the endotoxin group (120 minutes, 55.1 +/- 7.4%), and remained at baseline values in the dobutamine group. The arteriolar diameters remained constant in the control and the dobutamine groups, but they were significantly reduced in the endotoxin group at 120 minutes (7.8 +/- 0.2 to 6.5 +/- 0.7 micron). CONCLUSION: Our results indicate that in rats with normotensive endotoxemia, arteriolar diameters and blood flow in intestinal villi were reduced. Dobutamine prevented arteriolar constriction and maintained villus blood flow at preendotoxemic values.

Dopexamine maintains intestinal villus blood flow during endotoxemia in rats.

OBJECTIVE: To determine the influence of dopexamine, a synthetic catecholamine ligand for dopaminergic and beta 2-adrenergic receptors, on alterations of the intestinal villus microcirculation in a model of normotensive endotoxemia. DESIGN: Randomized, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Twenty-one male Wistar rats. INTERVENTIONS: Rats were treated with a continuous infusion of dopexamine (2.5 micrograms/kg/min; N = 7; group A) or 0.9% saline (n = 7; group B) during a study period of 120 mins. Both groups were given endotoxin (Escherichia coli lipopolysaccharide; 1.5 mg/kg Iv) over 60 mins. Animals in the control group (n = 7; group C) received a volume-equivalent infusion of 0.9% saline. Total volume substitution in all groups was 15 mL/kg/hr. MEASUREMENTS AND MAIN RESULTS: Blood flow in the intestinal villi of the distal ileum was determined using in vivo videomicroscopy at baseline, and 60 and 120 mins after the endotoxin challenge. These blood flow determinations were done by an observer who was unaware of the previous treatment of the animals. In addition, mean arterial pressure was monitored at baseline, and 15, 30, 45, 60, 75, 90, 105, and 120 mins later. The administration of 1.5 mg/kg endotoxin alone (group B) resulted in a reduction of the intestinal villus blood flow to 74.8 +/- 9.5% of baseline after 60 mins, and to 61.1 +/- 8.5% of baseline after 120 mins (baseline: 7.4 +/- 0.6 nL/min; 60 mins: 5.3 +/- 0.8 nL/min; 120 mins: 4.4 +/- 0.5 nL/min; p < .05). This reduction of blood flow was associated with a decrease in the arteriolar diameters by 13.8 +/- 2.5% after 60 mins, and by 17.1 +/- 4.3% after 120 mins (p < .05 vs. baseline). In contrast, villus blood flow in the dopexamine group (group A) did not show statistically significant changes during the entire study period, despite the administration of endotoxin (baseline: 8.2 +/- 0.6 nL/min; 60 mins: 7.3 +/- 0.8 nL/min; 120 mins: 7.8 +/- 0.5 nL/min). No vasoconstriction of the villus arterioles was noted in this group. In control animals (group C), the blood flow (baseline: 8.1 +/- 1.6 nL/min; 60 mins: 7.6 +/- 1.4 nL/min: 120 mins: 7.8 +/- 1.4 nL/min) and the arteriolar diameters remained unchanged throughout the observation period. Mean arterial pressure did not differ between groups: it remained unaltered in all groups during the entire study period. CONCLUSIONS: Dopexamine maintains intestinal villus arterial perfusion and prevents the vasoconstriction in villus arterioles during early normotensive endotoxemia. Therefore, further studies in critically ill patients will have to determine whether the early prophylactic use of dopexamine can limit ischemia and prevent the development of multiple organ failure.

Effect of low-dose dopamine on intestinal villus microcirculation during normotensive endotoxaemia in rats.

Hypoperfusion of the gut mucosa is thought to be a factor in the development of gut barrier failure during sepsis and septic shock. Dopamine stimulates DA-1 receptors which mediate regional vasodilatation in the gut. Therefore, we have investigated the effect of low-dose dopamine (3 micrograms kg-1 min-1) on the intestinal villus microcirculation during endotoxaemia in a rat model of normotensive endotoxaemia, using in vivo videomicroscopy. Blood flow in and the diameters of central villus arterioles were measured before, immediately after and 60 min after a 1-h continuous infusion of endotoxin 1.5 mg/kg body weight. After baseline measurements were obtained, rats received either an infusion of 0.9% saline (group A; n = 7) or a volume-equivalent infusion of dopamine 3 micrograms kg-1 min-1 (group B; n = 7) throughout the study. Control animals (group C; n = 7) received no endotoxin or dopamine. In group A, villus blood flow (mean baseline 8.4 (SEM 0.9) nl min-1) decreased by 29.7 (8.9)% to 5.9 (0.9) nl min-1 immediately after endotoxin challenge and by a total of 43.1 (7.3)% to 4.7 (0.7) nl min-1 after another 60 min. Simultaneously, villus arteriolar diameters decreased from 7.8 (0.2) to 6.9 (0.3) microns and to 6.5 (0.3) microns, respectively. In group B, villus blood flow (baseline 8.7 (0.4) nl min-1) was unchanged immediately after the 1-h infusion of endotoxin (8.3 (0.4) nl min-1). However, another 60 min later blood flow decreased by 28.8 (8.0)% to 6.1 (0.7) nl min-1. In contrast with group A, the diameters of the central villus arterioles were unchanged despite administration of endotoxin (7.9 (0.2) microns; 8.1 (0.4) microns; 8.2 (0.5) microns). In group C, there were no changes in villus blood flow or arteriolar diameters throughout the study. Our results indicated that low-dose dopamine did not prevent, but delayed and attenuated, the decrease in intestinal villus blood during normotensive endotoxaemia.

Effect of endotoxemia on intestinal villus microcirculation in rats.

Intestinal mucosal hypoperfusion with subsequent ischemia during endotoxemia might cause a breakdown of the gut barrier with translocation of bacteria and their toxins into the systemic circulation, thus maintaining a "gut-derived" septic state. The aim of this study was to investigate the influence of endotoxin on the microcirculation of intestinal villi, which represent the most vulnerable part of the mucosa. The changes in blood flow and in the diameters of the central villus arterioles located in the distal ileum were monitored in control rats without lipopolysaccharide (LPS) exposure (n=7), and in rats receiving 1.5 mg/kg b.w. LPS (n=7) or 15 mg/kg b.w. LPS (n=7) over 60 min. The blood flow and the arteriolar diameters were determined using in vivo videomicroscopy at baseline, and 60 min and 120 min later. In control animals, no change in blood flow and arteriolar diameters were observed during the entire experiment. Administration of 1.5 mg/kg b.w. LPS reduced the blood flow to 69.5 +/- 9.0% of the baseline value at the end of the study period. This decrease in blood flow was associated with a decrease in the villus arteriolar diameters by 17.4 +/- 2.5% from the baseline values. In animals exposed to 15 mg/kg b.w. LPS, the decrease in villus blood flow at 60 min was 64.8 +/- 10.9% of baseline, and at 120 min 66.9 +/- 12.6% of baseline. The diameters of the villus arterioles were reduced by 11.5 +/- 2.4% and 15.1 +/- 1.7%, respectively. In the control group and in the 1.5-mg/kg LPS group, the mean arterial blood pressure did not change during the entire study period. In the 15-mg/kg LPS group, the mean arterial pressure tended to decrease after 60 min. These data suggest a reduction of villus blood flow due to vasoconstriction in the central villus arterioles during normotensive endotoxmia, which might represent the mechanism for the mucosal ischemia observed in critically ill patients.