Estimation of genetic trends in French Large White pigs from 1977 to 1998 for growth and carcass traits using frozen semen.

Genetic trends for growth, feed efficiency, composition, and morphometry of carcasses were estimated in a French Large White (LW) pig population using frozen semen. Two groups of pigs were produced by inseminating LW sows with either stored, frozen semen from 17 LW boars born in 1977 or with semen from 23 LW boars born in 1998. In each group, 15 males and 90 females were randomly chosen and mated to produce approximately 1,000 pigs/group. These pigs were performance tested with individual ADFI and serial BW and backfat thickness measurements, slaughtered at 105 kg of BW, and measured for carcass traits. The data were analyzed using mixed linear animal models, including the fixed effect of the experimental group (offspring of 1977 or 1998 boars), the random effect of the additive genetic value of each animal, and, when significant, the fixed effects of sex, fattening batch, and slaughterhouse, the linear regression on BW, and the random effect of the common environment of birth litter. For each trait, the genetic trend was estimated as twice the difference between the 2 experimental groups. Results showed moderately favorable trends for on-test ADG (3.7 +/- 1.3 g/d per year) and feed conversion ratio (-0.014 +/- 0.005 kg/kg per year) in spite of a tendency toward an increase in ADFI (7.6 +/- 4.7 g/yr). A strong reduction in carcass fatness (-0.35 +/- 0.07 mm/yr for carcass average backfat thickness) and a large improvement in carcass leanness (0.31 +/- 0.10 mm(2)/yr and 0.41 +/- 0.08%/yr for loin eye area and carcass muscle content, respectively) were observed. Carcass shape measurements (back and leg length, back width, muscle thickness of hind limbs) were not affected by selection. Serial measurements of BW and backfat thickness showed that the major part of the genetic gains occurred during late growth and that the reduction in the backfat layer was more pronounced in the rear than in the front part of the carcass. The use of frozen semen appears to be a powerful practice to thoroughly investigate changes attributable to selection.

Detection of quantitative trait loci for teat number and female reproductive traits in Meishan × Large White F2 pigs.

A quantitative trait locus (QTL) analysis of female reproductive data from a three-generation experimental cross between Meishan (MS) and Large White (LW) pig breeds is presented. Six F1 boars and 23 F1 sows, progeny of six LW boars and six MS sows, produced 573 F2 females and 530 F2 males. Six traits, i.e. teat number (TN), age at puberty (AP), ovulation rate (OR), weight at mating (WTM), number of viable embryos (NVE) and embryo survival (ES) at 30 days of gestation were analysed. Animals were genotyped for a total of 137 markers covering the entire porcine genome. Analyses were carried out based on interval mapping methods, using a line-cross (LC) regression and a half-full sib (HFS) maximum likelihood test. Genome-wide (GW) highly significant (P < 0.001) QTL were detected for WTM on SSC 7 and for AP on SSC 13. They explained, respectively, 14.5% and 8.9% of the trait phenotypic variance. Other GW significant (P < 0.05) QTL were detected for TN on SSC 3, 7, 8, 16 and 17, for OR on SSC 4 and 5, and for ES on SSC 9. Two additional chromosome-wide significant (P < 0.05) QTL were detected for TN, three for WTM, four for AP, three for OR, three for NVE and two for ES. With the exception of the two above-mentioned loci, the QTL explained from 1.2% to 4.6% of trait phenotypic variance. QTL alleles were in most cases not fixed in the grand-parental populations and Meishan alleles were not systematically associated with higher reproductive performance.

Genetic parameters for residual feed intake in growing pigs, with emphasis on genetic relationships with carcass and meat quality traits.

Data were collected over the first 4 generations of a divergent selection experiment for residual feed intake of Large White pigs having ad libitum access to feed. This data set was used to obtain estimates of heritability for residual feed intake and genetic correlations (r(a)) between this trait and growth, carcass, and meat quality traits. Individual feed intake of group-housed animals was measured by single-space electronic feeders. Upward and downward selection lines were maintained contemporarily, with 6 boars and 35 to 40 sows per line and generation. Numbers of records were 793 for residual feed intake (RFI1) of boar candidates for selection issued from first-parity (P1) litters and tested over a fixed BW range (35 to 95 kg) and 657 for residual feed intake (RFI2) and growth, carcass, and meat quality traits of castrated males and females issued from second-parity (P2) litters and tested from 28 to 107 kg of BW. Variance and covariance components were estimated using REML methodology applied to a series of multitrait animal models, which always included the criterion for selection as 1 of the traits. Estimates of heritability for RFI1 and RFI2 were 0.14 +/- 0.03 and 0.24 +/- 0.03, respectively, whereas the estimate of r(a) between the 2 traits was 0.91 +/- 0.08. Estimates of r(a) indicated that selection for low residual feed intake has the potential to improve feed conversion ratio and reduce daily feed intake, with minimal correlated effect for ADG of P2 animals. Estimates of r(a) between RFI2 and body composition traits of P2 animals were positive for traits related to the amount of fat depots (r(a) = 0.44 +/- 0.16 for carcass backfat thickness) and negative for carcass lean meat content (r(a) = -0.55 +/- 0.14). There was a tendency for a negative genetic correlation between RFI2 and carcass dressing percent (r(a) = -0.36 +/- 0.21). Moreover, selection for low residual feed intake is expected, through lower ultimate pH and lighter color, to decrease pork quality (r(a) = 0.77 +/- 0.14 between RFI2 and a meat quality index intended to predict the ratio of the weight of ham after curing and cooking to the weight of defatted and boneless fresh ham).

Between-breed variability of stillbirth and its relationship with sow and piglet characteristics.

Litter characteristics at birth were recorded in 4 genetic types of sows with differing maternal abilities. Eighty-two litters from F(1) Duroc x Large White sows, 651 litters from Large White sows, 63 litters from Meishan sows, and 173 litters from Laconie sows were considered. Statistical models included random effects of sow, litter, or both; fixed effects of sow genetic type, parity, birth assistance, and piglet sex, as well as gestation length, farrowing duration, piglet birth weight, and litter size as linear covariates. The quadratic components of the last 2 factors were also considered. For statistical analyses, GLM were first considered, assuming a binomial distribution of stillbirth. Hierarchical models were also fitted to the data to take into account correlations among piglets from the same litter. Model selection was performed based on deviance and deviance information criterion. Finally, standard and robust generalized estimating equations (GEE) procedures were applied to quantify the importance of each effect on a piglet's probability of stillbirth. The 5 most important factors involved were, in decreasing order (contribution of each effect to variance reduction): difference between piglet birth weight and the litter mean (2.36%), individual birth weight (2.25%), piglet sex (1.01%), farrowing duration (0.99%), and sow genetic type (0.94%). Probability of stillbirth was greater for lighter piglets, for male piglets, and for piglets from small or very large litters. Probability of stillbirth increased with sow parity number and with farrowing duration. Piglets born from Meishan sows had a lower risk of stillbirth (P < 0.0001) and were little affected by the sources of variation mentioned above compared with the 3 other sow genetic types. Standard and robust GEE approaches gave similar results despite some disequilibrium in the data set structure highlighted with the robust GEE approach.

Effects of quantitative trait loci on chromosomes 1, 2, 4, and 7 on growth, carcass, and meat quality traits in backcross Meishan x Large White pigs.

The aim of this work was to estimate whether genetic dissection of QTL on chromosomes 1, 2, 4, and 7, detected in an F2 Meishan x Large White population, can be achieved with a recombinant back-cross progeny test approach. For this purpose, a first generation of backcross (BC1) was produced by using frozen semen of F1 Large White x Meishan boars with Large White females. Four BC1 boars were selected because of their heterozygosity for at least 1 of the 4 regions. The BC1 boars were crossed with Large White sows, and the resulting BC2 offspring were measured for several growth and body composition traits. Contrary to the F2 animals, BC2 animals were also measured for meat quality traits in adductor, gluteus superficialis (GS), longissimus dorsi, and biceps femoris (BF) muscles. Each BC1 boar was tested for a total of 39 traits and for the 4 regions with statistical interval mapping analyses. The QTL effects obtained in BC1 families showed some differences compared with those described in F1 families. However, we confirmed QTL effects for growth in the SW1301-SW2512 markers interval on chromosome 1 and also for body composition in the SW1828-SW2512 markers interval on chromosome 1, in the SW2443-SWR783 markers interval on chromosome 2, and in the SW1369-SW632 markers interval on chromosome 7. In addition, we detected new QTL for growth traits on chromosome 2 and for meat quality traits on chromosomes 1 and 2. Growth of animals from weaning to the end of the test was influenced by the IGF2 gene region on chromosome 2. Concerning meat quality, ultimate pH of adductor, longissimus dorsi, and BF were affected by the interval delimited by UMNP3000 and SW2512 markers on chromosome 1, and a* of GS, L* of BF, and water-holding capacity of GS were affected by QTL located between marker loci SW2443 and SWR783 on chromosome 2. Recombinant progeny testing appeared to be a suitable strategy for the genetic dissection of the QTL investigated.

Exclusion of the swine leukocyte antigens as candidate region and reduction of the position interval for the Sus scrofa chromosome 7 QTL affecting growth and fatness.

Pig chromosome 7 (SSC 7) has been shown to be rich in QTL affecting performance and quality traits. Most studies mapped the QTL close to the swine leukocyte antigens (SLA), which has a large effect on adaptability and natural selection. Previous comparative mapping studies suggested that the 15-cM region limited by markers LRA1 (mapped at 55 cM) and S0102 (mapped at 70 cM) contains hundreds of genes. To decrease the number of candidate genes, we improved the mapping resolution with a genetic chromosome dissection through a backcross recombinant progeny test program between Meishan (MS) and European (EU; i.e., Large White or Landrace) breeds. Three first-generation backcross--(EU x MS) x EU--and two second-generation backcross--([EU x MS] x EU) x EU--sires carrying a recombination in the QTL mapping interval were progeny-tested (i.e., measured for a total of 44 growth, fatness, carcass and meat quality traits). Progeny family size varied from 29 to 119 pigs. Animals were genotyped for markers covering the region of interest. Progeny-test results allowed the QTL interval to be decreased from 15 to 20 cM down to 10 cM, and even less than 6 cM if we assumed that the EU pigs used in this study share only one QTL allele. Except for a putative QTL affecting some carcass composition traits, the SLA is excluded as a candidate region, suggesting that it might be possible to apply a marker-assisted selection strategy for this QTL, while controlling SLA allele diversity. The strong QTL effects remaining in animals with only 12.5% (issued from first-generation backcross boars) and 6.25% (issued from second-generation back-cross boars) Meishan genetic background shows that epistatic interactions are likely to be limited. Finally, the QTL does not have strong effects on meat quality traits.

Genetic linkage mapping of quantitative trait loci for behavioral and neuroendocrine stress response traits in pigs.

A QTL analysis of behavioral and neuroendocrine responses to a "novel environment" stress was conducted in a three-generation experimental cross between Meishan and Large White pig breeds. A total of 186 F2 males and 182 F2 females were studied for their behavioral and neuroendocrine reactivity to a novel environment test at 6 wk of age. Locomotion, vocalization, and defecation rate, as well as exploration time, were measured for 10 min. Blood samples were taken immediately before and after the test to measure plasma levels of ACTH, cortisol, and glucose. Animals were typed for a total of 137 markers covering the entire porcine genome. Analyses were performed using two interval mapping methods: a line-cross regression method, where founder lines were assumed to be fixed for different QTL alleles, and a half-/full-sib maximum likelihood method where allele substitution effects were estimated within each half-/full-sib family. Both methods revealed a highly significant gene effect for poststress cortisol level (P < 0.001) and a significant effect for basal cortisol level (P < 0.05) at the end of the q arm of chromosome 7, explaining, respectively, 20% and 7% of the phenotypic variance. Meishan alleles are associated with higher cortisol levels and are partially dominant (for poststress levels) over Large White alleles. Other significant gene effects on biological measures were detected on chromosomes 1 and 17 (ACTH response to stress), 3, 5, and 8 (glucose levels). The SSC 17 QTL explains 12% of the phenotypic variance of poststress ACTH levels, with a suggestive evidence of imprinting effects. Meishan alleles are associated with lower poststress ACTH levels. Gene effects of low amplitude only were found for behavioral reactivity traits. Considering the effects of stress neuroendocrine systems on energy fluxes and protein deposition, and the importance of stress reactivity for meat quality and animal welfare, these results open new perspectives for pig selection.

Detection of quantitative trait loci for growth and fatness in pigs.

A quantitative trait locus (QTL) analysis of growth and fatness data from a three-generation experimental cross between Meishan (MS) and Large White (LW) pig breeds is presented. Six boars and 23 F1 sows, the progeny of six LW boars and six MS sows, produced 530 F2 males and 573 F2 females. Nine growth traits, i.e. body weight at birth and at 3, 10, 13, 17 and 22 weeks of age, average daily gain from birth to 3 weeks, from 3 to 10 weeks and from 10 to 22 weeks of age, as well as backfat thickness at 13, 17 and 22 weeks of age and at 40 and 60 kg live weight were analysed. Animals were typed for a total of 137 markers covering the entire porcine genome. Analyses were performed using two interval mapping methods: a line-cross (LC) regression method where founder lines were assumed to be fixed for different QTL alleles and a half-/full-sib (HFS) maximum likelihood method where allele substitution effects were estimated within each half-/full-sib family. Both methods revealed highly significant gene effects for growth on chromosomes 1, 4 and 7 and for backfat thickness on chromosomes 1, 4, 5, 7 and X, and significant gene effects on chromosome 6 for growth and backfat thickness. Suggestive QTLs were also revealed by both methods on chromosomes 2 and 3 for growth and 2 for backfat thickness. Significant gene effects were detected for growth on chromosomes 11, 13, 14, 16 and 18 and for backfat thickness on chromosome 8, 10, 13 and 14. LW alleles were associated with high growth rate and low backfat thickness, except for those of chromosome 7 and to a lesser extent early-growth alleles on chromosomes 1 and 2 and backfat thickness alleles on chromosome 6.

Intranasal midazolam in piglets: pharmacodynamics (0.2 vs 0.4 mg/kg) and pharmacokinetics (0.4 mg/kg) with bioavailability determination.

Intranasal midazolam was studied in two series of piglets: series 1, n = 20 (18 +/- 3 kg), a randomized double blind pharmacodynamic study to compare doses of 0.2 mg/kg and 0.4 mg/kg; series 2, n = 9 (42 +/- 8 kg), a pharmacokinetic study with a 0.4 mg/kg dose administered either intravenously (i.v.) or intranasally (i.n.) in a cross-over protocol with a one-week wash-out period between each. In series 1, midazolam caused significant anxiolysis and sedation within 3 to 4 min, without a significant difference between 0.2 and 0.4 mg/kg doses for any of the studied parameters. In series 2, after intranasal midazolam administration of 0.4 mg/kg, plasma concentrations attained a maximum (Cmax) of 0.13 +/- 0.04 mg/l at 5 min (median Tmax) and remained higher than 0.04 mg/l until 60 min. The bioavailability factor (F) in this study was F = 0.64 +/- 0.17 by the intranasal route. The terminal half-life (T1/2 lambda z) = 145 +/- 138 min was comparable with the i.v. administration half-life (158 +/- 127 min). In conclusion, optimal intranasal midazolam dose in piglets was 0.2 mg/kg, which procures rapid and reliable sedation, adapted to laboratory piglets.

Comparison between the three porcine RN genotypes for growth, carcass composition and meat quality traits.

A three-step experimental design has been carried out to add evidence about the existence of the RN gene, with two segregating alleles RN- and rn+, having major effects on meat quality in pigs, to estimate its effects on production traits and to map the RN locus. In the present article, the experimental population and sampling procedures are described and discussed, and effects of the three RN genotypes on growth and carcass traits are presented. The RN genotype had no major effect on growth performance and killing out percentage. Variables pertaining to carcass tissue composition showed that the RN- allele is associated with leaner carcasses (about 1 s.d. effect without dominance for back fat thickness, 0.5 s.d. effect with dominance for weights of joints). Muscle glycolytic potential (GP) was considerably higher in RN- carriers, with a maximum of a 6.85 s.d. effect for the live longissimus muscle GP. Physico-chemical characteristics of meat were also influenced by the RN genotype in a dominant way, ultimate pH differing by about 2 s.d. between homozygous genotypes and meat colour by about 1 s.d. Technological quality was also affected, with a 1 s.d. decrease in technological yield for RN- carriers. The RN genotype had a more limited effect on eating quality. On the whole, the identity between the acid meat condition and the RN- allele effect is clearly demonstrated (higher muscle GP, lower ultimate pH, paler meat and lower protein content), and the unfavourable relationship between GP and carcass lean to fat ratio is confirmed.

Influence of the three RN genotypes on chemical composition, enzyme activities, and myofiber characteristics of porcine skeletal muscle.

An experiment was conducted to evaluate the effects of the RN genotype on skeletal muscle characteristics in pigs sharing otherwise the same polygenic background. Animals were genotyped for RN on the basis of RTN (Rendement Technologique Napole) records using segregation analysis methods. Samples of longissimus (L) and semispinalis capitis (S) muscles were taken from 39 rn+/rn+, 38 RN-/rn+ and 37 RN-/RN- pigs slaughtered at 108 +/- 8.6 kg live weight. Activities of lactate dehydrogenase (LDH), citrate synthase (CS), and beta-hydroxy-acyl-coenzyme A dehydrogenase (HAD) were measured on both muscles to assess glycolytic, oxidative, and lipid beta-oxidation capacities, respectively. Histological examinations and chemical analyses were performed on L muscle. The energetic metabolism of the white L muscle was more oxidative in RN-/RN- than in rn+/rn+ pigs, as shown by increased CS and HAD activities (P < .001), decreased LDH activity (P < .001), larger cross-sectional area of IIA (P < .05) and IIB-red (P < .05) fibers, higher relative area of IIA fibers ( P < .05), and lower relative area of IIB-white fibers (P < .001). No significant difference was found between heterozygous and homozygous carriers of the RN- allele, except for CS activity, which was lower in RN-/rn+ than in RN-/RN- pigs. In L muscle, the RN- allele led to a large increase in glycolytic potential (+3.5 phenotypic SD between homozygotes) and lightness (+.7 SD), and a decrease in ultimate pH, dry matter, and protein contents (-1.7 to -2 phenotypic SD for these three traits), with an almost completely dominant effect. No differences were found between genotypes for intramuscular fat and hydroxyproline contents. In the red S muscle, the presence of RN- had no influence on enzyme activities. These results indicate that the RN genotype greatly influences compositional and histochemical traits and metabolic enzyme activities in a muscle type-dependent manner, with a completely or incompletely dominant effect of the RN- allele.

Behavior and pituitary-adrenal function in large white and Meishan pigs.

Six-wk-old piglets of both sexes from European Large White (LW, n = 36) and Chinese Meishan (MS, n = 24) breeds were individually exposed to a novel environment, a stressful stimulation. Behavioral and pituitary-adrenal reactivity were investigated. When compared with LW, MS pigs displayed low locomotion (18.5 +/- 2.2 vs. 41.0 +/- 3.8 squares crossed/10 min; P < 0.0001), and defecation scores (0.58 +/- 0.15 vs. 4.86 +/- 0.37 fecal boli; P < 0.0001). Basal concentrations of cortisol were higher in MS (96.1 +/- 1.1 vs. 44.9 +/- 1.1 ng/ml; P < 0.0001), although no differences between breeds were found in basal concentrations of adrenocorticotropic hormone (ACTH). In response to novel environment exposure, the ACTH increase was greater in LW than in MS, but the cortisol response was not different on a log scale. To further investigate the pituitary-adrenal differences between the two breeds, the 24-hr profile of ACTH and cortisol plasma concentrations, a corticotropin-releasing factor (CRF) and a coupled dexamethasone-ACTH test were studied. Five castrated male 9-wk-old piglets from each breed were fitted surgically with a jugular vein catheter. A classic marked circadian rhythm of cortisol and a weak nycthemeral variation of ACTH were found. Cortisol concentrations were approximately twice higher in MS exclusively during the early light phase (from 0800-1200 hr) of the cycle, but no significant interbreed difference was found in the circadian rhythm of ACTH. Administration of CRF (1 microgram/kg iv) induced the same significant increase in plasma ACTH and cortisol concentrations in both breeds. Administration of ACTH (10 micrograms/kg i.v.) increased significantly cortisol concentrations and revealed no difference in plasma cortisol response to ACTH. These data suggest that the hypercortisolism of MS pigs is of adrenal origin, and related to extrapituitary factors that control the adrenal sensitivity during the light phase of the diurnal cycle.

Trimetazidine reverses deleterious effects of ischemia-reperfusion in the isolated perfused pig kidney model.

BACKGROUND: Delayed graft function has remained an important complication after renal transplantation. METHODS: The purpose of this study was to evaluate Euro-Collins (EC) plus trimetazidine (TMZ) in comparison with standard EC solution after 24- or 48-hour cold storage. The normothermic isolated perfused pig kidney technique combined with proton nuclear magnetic spectroscopy was used. RESULTS: The study verified that TMZ plus EC had a beneficial preservation effect over EC in terms of better perfusate flow rate at both 24 and 48 h (p < 0.01 and p < 0.001, respectively). In addition, TMZ also was beneficial in terms of increased glomerular filtration rate, better proximal tubular functions, and less tubular injury markers. Lipid peroxidation, evaluated by malondialdehyde renal tissue levels, was decreased in kidney homogenates preserved with TMZ, particularly after 48-hour cold storage. Citrate excretion which reflects a better intracellular pH regulation was detected in urine from kidneys preserved with TMZ. Histological data paralleled findings of the above when comparing cellular injury factors such as vacuolization, necrosis, tubular structure, and interstitial edema. CONCLUSION: These results indicate that, under the conditions of our experiments, the addition of TMZ to EC solution increased the preservation quality of kidneys particularly after prolonged cold ischemia.

Lipid peroxidation after cold storage and normothermic reperfusion: the effect of trimetazidine.

Ischemia reperfusion injury is still a leading cause of early graft dysfunction after transplantation. Trimetazidine (TMZ) has been postulated to be protective against renal damage from oxygen free radicals. The aim of this study was to assess the effect TMZ during cold storage (CS) and normothermic reperfusion in an isolated perfused pig kidney model. Three groups were studied: control group, immediately perfused (G0), 48 h CS in Euro-Collins solution (G1), and 48 h CS in Euro-Collins solution plus TMZ (G2). Glomerular filtration rate (GFR) and fractional sodium reabsorption (FRNa+) were calculated during reperfusion from urine and perfusate samples. Lipid peroxidation was determined by the renal tissue level of Schiff bases (SB) and malondialdehyde (MDA) after reperfusion. A histological evaluation was performed after reperfusion. Renal function was significantly improved and lipid peroxidation reduced after preservation in Euro-Collins solution plus TMZ. Functional data were closely related to histological damage. In conclusion, TMZ is a useful protective agent against renal damage induced by CS.

Effects of trimetazidine on lipid peroxidation and phosphorus metabolites during cold storage and reperfusion of isolated perfused rat kidneys.

This study was undertaken to evaluate the effect of trimetazidine (TMZ) during cold storage (CS) and the consequence during normothermic reperfusion in an isolated perfused rat kidney model (IPK). IPK was used to assess the rate of perfusion flow, the ratio of ATP to inorganic phosphate (ATP/Pi) as a reflection of the energetic status during reperfusion, intracellular pH (pHi), tissue water content and malondialdehyde (MDA) tissue levels in four different preservation solutions after 48-hr preservation at 4 degreesC and 2-hr reperfusion at 37.5 degreesC: EuroCollins (EC), University of Wisconsin (UW), EC plus TMZ (10(-)6 M) (EC + TMZ) and UW plus TMZ (10(-)6 M) (UW + TMZ). When TMZ was added to the preservation solutions, perfusion flow rate (PFR) was significantly improved during reperfusion. Tissue water content, which reflected tissue edema, was significantly lower in TMZ groups than in groups without TMZ during both CS and reperfusion conditions. In TMZ groups, ATP/Pi ratio was also significantly improved during CS and reperfusion. In addition, TMZ lowered the pHi both during preservation and after reperfusion. MDA renal tissue level significantly decreased with TMZ both during the preservation period and after reperfusion. These overall results strongly suggested that TMZ contributes to renal protection from cold ischemia-reperfusion injury in this IPK model, especially when TMZ was added to UW solution and during prolonged hypothermic ischemia.

Trimetazidine prevents renal injury in the isolated perfused pig kidney exposed to prolonged cold ischemia.

BACKGROUND: Ischemia caused by cold storage (CS) and reperfusion of the kidney is often responsible for delayed graft function after transplantation. Significant attention has been focused on the cascade of events involved in ischemia-reperfusion injury, with the objective of identifying drugs to ameliorate the functional damage that occurs. METHODS: The purpose of this study was to evaluate the renal function of isolated perfused pig kidneys after 48 hr of CS with Euro-Collins (EC) solution plus trimetazidine (EC+TMZ), standard EC solution, or University of Wisconsin (UW) solution. Normothermic isolated perfused pig kidneys were randomized into five experimental groups: (A) control group (cold flush with cold heparinized saline and immediately reperfused; n=6); (B) cold flush with cold heparinized saline with TMZ (10(-6) M), n=6; (C) 48 hr of CS with EC and reperfusion (n=8); (D) 48 hr of CS with EC+TMZ alone and reperfusion (n=8); (E) 48 hr of CS with UW and reperfusion (n=8). Proton nuclear magnetic resonance spectroscopy and biochemical studies were performed for the functional evaluation during reperfusion. Lipid peroxidation was also determined. Histological examination (optical and electron microscopy) was performed after CS and reperfusion. RESULTS: Using TMZ, the renal perfusate flow rate as well as the glomerular filtration rate and proximal tubular function were significantly improved. This improvement of renal function during reperfusion was correlated with a less significant cellular and interstitial edema. In addition, tubular injury markers were significantly lower in the group preserved with EC+TMZ, and TMZ reduced lipid peroxidation dramatically during reperfusion. CONCLUSIONS: The addition of TMZ to the EC solution increased the preservation quality and renal tubular function, and gave protection from reperfusion injury better than EC alone or UW. These results strongly suggest that TMZ has a cytoprotective effect and may therefore be useful for kidney preservation.