Whole genome single nucleotide polymorphism associations with feed intake and feed efficiency in beef cattle.

Feed intake and efficiency are economically important traits because feed is the greatest variable cost in beef production. Feed efficiency can be measured as residual feed intake (RFI), which is the difference between actual DMI of an animal and the expected DMI based on its BW and growth rate. Feed conversion ratio (FCR) is the inverse of gross feed efficiency and is the ratio of DMI to ADG. A total of 2,633 SNP across the 29 bovine autosomes were analyzed in 464 steers sired by Angus, Charolais, or Alberta Hybrid bulls for associations with RFI. A total of 150 SNP were associated with RFI at P < 0.05 of which 23 were significant at P < 0.01. Nine of the SNP pairs show high linkage disequilibrium (r(2) > 0.80), so only 1 of the SNP pairs was used in further multiple-marker analyses. Two methods were used to create a panel of SNP that were maximally informative for RFI based on the data. In the first method, 141 unique SNP were combined in a single multivariate model and a backward elimination model was used to drop SNP until all SNP left in the model were significant at P < 0.05. The SNP had greater effects when combined in the multivariate model than when tested individually. In the second method, the estimates from the 141 SNP were used to create a sequential molecular breeding value (MBV) according to the compound covariate prediction (CCP) procedure. The sequential MBV was built by adding the estimated effects one at a time, but only keeping SNP effects in the sequential MBV if the test statistic and the proportion of variance explained were improved. Predictabilities of the 2 methods were compared by regressing RFI on a final MBV created from SNP that remained in each analytical model. The MBV from the compound covariate prediction model produced an r(2) of 0.497, whereas the multivariate model MBV had a decreased r(2) of 0.416. The significant SNP were also tested for associations with DMI and FCR. The SNP showed different combinations of associations with the 4 traits, including some that were only associated with RFI. About 9.5% of the SNP from the 2 models were within 5 cM of previously identified RFI QTL and pinpoint areas to further explore for positional candidate genes. In conclusion, this study has identified a panel of SNP with significant effects on RFI that need to be validated in an independent population and provides continued progress toward selecting markers for use in marker-assisted selection for feed efficiency in beef cattle.

Polymorphisms in positional candidate genes on BTA14 and BTA26 affect carcass quality in beef cattle.

Several studies have reported the presence of carcass quality QTL on BTA14 and BTA26, with no specific genes being conclusively linked as their cause. The aim of this study was to identify polymorphisms in genes known to affect lipid metabolism in other species and to assess their association with carcass quality traits. Two genes located on BTA14, 2,4 dienoyl CoA reductase 1 (DECR1) and core binding factor, runt domain, alpha subunit 2, translocated to 1 gene (CBFA2T1), have been previously evaluated in other species and found to contain polymorphisms influencing lipid metabolism. A gene on BTA26, fibroblast growth factor 8 (FGF8), has in recent studies been linked to several QTL affecting obesity in mice, indicating its potential for regulating adiposity in other species. Sequencing analysis identified 9 polymorphisms in DECR1, 4 in CBFA2T1, and 4 in FGF8. Multiple sequence alignment of DECR1 among cattle, humans, and mice showed that 4 of these mutations lie in conserved regions across these species. Using 464 Angus, Charolais, and crossbred animals produced associations with ultrasound marbling score (CBFA2T1, P = 0.019), ultrasound backfat (DECR1, P = 0.012), carcass backfat (FGF8, P = 0.004), and lean meat yield (FGF8, P = 0.005). Quantitative trait loci analysis including a set of previously genotyped markers on BTA14, and 1 DECR1 polymorphism resulted in several significant QTL peaks: ultrasound backfat (UBF) at 91 cM, lean meat yield at 86 cM, carcass gradefat at 15 cM, and yield grade at 87 cM, all at the P < 0.05 level. Using DECR1 as a genetic covariate removed the UBF QTL, indicating that this SNP was contributing to the variation observed in UBF. A similar analysis was performed on BTA26 using 1 of the FGF8 polymorphisms. Results showed significant peaks for lean meat yield at 2 cM and for yield grade at 25 cM, both at P < 0.01, and for carcass backfat at 25 cM (P < 0.05). Removal of FGF8 SNP in further analysis resulted in the disappearance of the carcass backfat QTL. These results suggest that polymorphisms discovered in DECR1, CBFA2T1, and FGF8 may play a role in the lipid metabolism pathway affecting carcass quality traits in beef cattle. However, further studies are needed to confirm that these polymorphisms are responsible for the differences observed in carcass quality in beef cattle.

Fine mapping quantitative trait loci for feed intake and feed efficiency in beef cattle.

Feed intake and feed efficiency are economically important traits in beef cattle because feed is the greatest variable cost in production. Feed efficiency can be measured as feed conversion ratio (FCR, intake per unit gain) or residual feed intake (RFI, measured as DMI corrected for BW and growth rate, and sometimes a measure of body composition, usually carcass fatness, RFI(bf)). The goal of this study was to fine map QTL for these traits in beef cattle using 2,194 markers on 24 autosomes. The animals used were from 20 half-sib families originating from Angus, Charolais, and University of Alberta Hybrid bulls. A mixed model with random sire and fixed QTL effect nested within sire was used to test each location (cM) along the chromosomes. Threshold levels were determined at the chromosome and genome levels using 20,000 permutations. In total, 4 QTL exceeded the genome-wise threshold of P < 0.001, 3 exceeded at P < 0.01, 17 at P < 0.05, and 30 achieved significance at the chromosome-wise threshold level (at least P < 0.05). No QTL were detected on BTA 8, 16, and 27 above the 5% chromosome-wise significance threshold for any of the traits. Nineteen chromosomes contained RFI QTL significant at the chromosome-wise level. The RFI(bf) QTL results were generally similar to those of RFI, the positions being similar, but occasionally differing in the level of significance. Compared with RFI, fewer QTL were detected for both FCR and DMI, 12 and 4 QTL, respectively, at the genome-wise thresholds. Some chromosomes contained FCR QTL, but not RFI QTL, but all DMI QTL were on chromosomes where RFI QTL were detected. The most significant QTL for RFI was located on BTA 3 at 82 cM (P = 7.60 x 10(-5)), for FCR on BTA 24 at 59 cM (P = 0.0002), and for DMI on BTA 7 at 54 cM (P = 1.38 x 10(-5)). The RFI QTL that showed the most consistent results with previous RFI QTL mapping studies were on BTA 1, 7, 18, and 19. The identification of these QTL provides a starting point to identify genes affecting feed intake and efficiency for use in marker-assisted selection and management.

Molecular basis for residual feed intake in beef cattle.

Feed provision is one of the greatest costs of beef production and, with the increasing costs of feed, will remain so for the foreseeable future. Improvement in efficiency has the potential to not only increase profits for cattle producers, but also to decrease the environmental footprint of beef cattle production. Both are important in addressing the challenges of increasing feed costs and land pressure. Residual feed intake (RFI) has increasingly become the measure of choice when evaluating feed efficiency in beef cattle, especially because it is independent of growth and BW. The main inhibitor to adoption of RFI remains the cost and technical difficulty in measuring the trait. This makes RFI a prime candidate for marker-assisted selection because the trait is moderately heritable and DNA or other predictive markers could be used in selection schemes. Although multiple markers have been described over several studies, no major gene affecting RFI has been found. However, a combination of genetic markers, when examined jointly, can explain a large proportion of the genetic variation. Two main barriers remain before full adoption of markers for genetic evaluation and marker-assisted selection can be implemented. First, the genetic interaction of genes affecting RFI on other traits is, as yet, not fully understood. Second the numbers of animals with high quality estimates of RFI remains small. However, current developments indicate that these challenges will soon be overcome.

Identification of polymorphisms influencing feed intake and efficiency in beef cattle.

Feed efficiency is an economically important trait in beef cattle. Net feed efficiency, measured as residual feed intake (RFI), is the difference between actual feed intake and the predicted feed intake required for maintenance and gain of the animal. SNPs that show associations with RFI may be useful quantitative trait nucleotides for marker-assisted selection. This study identified associations between SNPs underlying five RFI QTL on five bovine chromosomes (BTA2, 5, 10, 20 and 29) with measures of dry matter intake (DMI), RFI and feed conversion ratio (FCR) in beef cattle. Six SNPs were found to have effects on RFI (P < 0.05). The largest single SNP allele substitution effect for RFI was -0.25 kg/day located on BTA2. The combined effects of the SNPs found significant in this experiment explained 6.9% of the phenotypic variation of RFI. Not all the RFI SNPs showed associations with DMI and FCR even though these traits are highly correlated with RFI (r = 0.77 and r = 0.62 respectively). This shows that these SNPs may be affecting the underlying biological mechanisms of feed efficiency beyond feed intake control and weight gain efficiency. These SNPs can be used in marker-assisted selection but first it will be important to verify these effects in independent populations of cattle.

Polymorphisms and haplotypes in the bovine neuropeptide Y, growth hormone receptor, ghrelin, insulin-like growth factor 2, and uncoupling proteins 2 and 3 genes and their associations with measures of growth, performance, feed efficiency, and carcass merit in beef cattle.

Genes that regulate metabolism and energy partitioning have the potential to influence economically important traits in farm animals, as do polymorphisms within these genes. In the current study, SNP in the bovine neuropeptide Y (NPY), growth hormone receptor (GHR), ghrelin (GHRL), uncoupling proteins 2 and 3 (UCP2 and UCP3), IGF2, corticotrophin-releasing hormone (CRH), cocaine and amphetamine regulated transcript (CART), melanocortin-4 receptor (MC4R), proopiomelanocortin (POMC), and GH genes were evaluated for associations with growth, feed efficiency, and carcass merit in beef steers. In total, 24 SNP were evaluated for associations with these traits and haplotypes were constructed within each gene when 2 or more SNP showed significant associations. An A/G SNP located in intron 4 of the GHR gene had the largest effects on BW of the animals (dominance effect P < 0.01) and feed efficiency (allele substitution effect P < 0.05). Another A/G SNP located in the promoter region of GHR had similar effects but the haplotypes of these 2 SNP reduced the effects of the SNP located in intron 4. Three SNP in the NPY gene showed associations to marbling (P < 0.001) as well as with ADG, BW, and feed conversion ratio (FCR; P < 0.05). The combination of these 3 SNP into haplotypes generally improved the association or had a similar scale of association as each single SNP. Only 1 SNP in UCP3, an A/G SNP in intron 3, was associated with ADG (P = 0.025), partial efficiency of growth, and FCR (P < 0.01). Three SNP in UCP2 gene were in almost complete linkage disequilibrium and showed associations with lean meat yield, yield grade, DMI, and BW (P < 0.05). Haplo-types between the SNP in UCP3 and UCP2 generally reduced the associations seen individually in each SNP. An A/G SNP in the GHRL gene tended to show effects on residual feed intake, FCR, and partial efficiency of growth (P < 0.10). The IGF2 SNP most strongly affected LM area (P < 0.01), back fat, ADG, and FCR (P < 0.05). The SNP in the CART, MC4R, POMC, GH, and CRH genes did not show associations at P < 0.05 with any of the traits. Although most of the SNP that showed associations do not cause amino acid changes, these SNP could be linked to other yet to be detected causative mutations or nearby QTL. It will be very important to verify these results in other cattle populations.

Primary genome scan to identify putative quantitative trait loci for feedlot growth rate, feed intake, and feed efficiency of beef cattle.

Feed intake and feed efficiency of beef cattle are economically relevant traits. The study was conducted to identify QTL for feed intake and feed efficiency of beef cattle by using genotype information from 100 microsatellite markers and 355 SNP genotyped across 400 progeny of 20 Angus, Charolais, or Alberta Hybrid bulls. Traits analyzed include feedlot ADG, daily DMI, feed-to-gain ratio [F:G, which is the reciprocal of the efficiency of gain (G:F)], and residual feed intake (RFI). A mixed model with sire as random and QTL effects as fixed was used to generate an F-statistic profile across and within families for each trait along each chromosome, followed by empirical permutation tests to determine significance thresholds for QTL detection. Putative QTL for ADG (chromosome-wise P < 0.05) were detected across families on chromosomes 5 (130 cM), 6 (42 cM), 7 (84 cM), 11 (20 cM), 14 (74 cM), 16 (22 cM), 17 (9 cM), 18 (46 cM), 19 (53 cM), and 28 (23 cM). For DMI, putative QTL that exceeded the chromosome-wise P < 0.05 threshold were detected on chromosomes 1 (93 cM), 3 (123 cM), 15 (31 cM), 17 (81 cM), 18 (49 cM), 20 (56 cM), and 26 (69 cM) in the across-family analyses. Putative across-family QTL influencing F:G that exceeded the chromosome-wise P < 0.05 threshold were detected on chromosomes 3 (62 cM), 5 (129 cM), 7 (27 cM), 11 (16 cM), 16 (30 cM), 17 (81 cM), 22 (72 cM), 24 (55 cM), and 28 (24 cM). Putative QTL influencing RFI that exceeded the chromosome-wise P < 0.05 threshold were detected on chromosomes 1 (90 cM), 5 (129 cM), 7 (22 cM), 8 (80 cM), 12 (89 cM), 16 (41 cM), 17 (19 cM), and 26 (48 cM) in the across-family analyses. In addition, a total of 4, 6, 1, and 8 chromosomes showed suggestive evidence (chromosome-wise, P < 0.10) for putative ADG, DMI, F:G, and RFI QTL, respectively. Most of the QTL detected across families were also detected within families, although the locations across families were not necessarily the locations within families, which is likely because of differences among families in marker informativeness for the different linkage groups. The locations and direction of some of the QTL effects reported in this study suggest potentially favorable pleiotropic effects for the underlying genes. Further studies will be required to confirm these QTL in other populations so that they can be fine-mapped for potential applications in marker-assisted selection and management of beef cattle.

Radiotherapy, toxicity and dosimetry of copper-64-TETA-octreotide in tumor-bearing rats.

UNLABELLED: The efficacy of 64Cu [T1/2 = 12.7 hr; beta+ (0.655 MeV; 19%); beta- (0.573 MeV; 40%)] as a radioisotope for radiotherapy has been recently established. Here we demonstrate that 64Cu-1,4,8,11 -tetraazacyclotetradecane-N,N',N",N'''-tetraacetic acid (TETA)-octreotide, a somatostatin receptor ligand, inhibits the growth of CA20948 rat pancreatic tumors in Lewis rats at doses that cause minimal toxicity. METHODS: Tumor-bearing rats were administered a single 15 mCi (555 MBq) dose, a fractionated dose of 15 mCi given in 2-3 doses over 2-8 days, or control agents of buffer, unlabeled octreotide or 64Cu-labeled TETA. In certain experiments, blood was removed at times from 4-23 days post-treatment, and a complete blood count along with blood chemistry analyses were obtained. RESULTS: Tumor-growth inhibition was significantly greater in rats injected with a single 15 mCi dose than in rats injected with control agents (p < 0.05). Dose fractionation in two doses, either 1 or 2 days apart, induced significantly increased tumor-growth inhibition compared with rats given a single dose (p < 0.05). The only toxicity observed in treated rats was a decrease in the white blood cell count. This drop was more pronounced in rats treated with a single dose compared with those treated with a fractionated dose. Human absorbed doses of 64Cu-TETA-octreotide to normal organs were estimated from biodistribution data in Lewis rats, and these data indicate that radiotherapy with 64Cu-TETA-octreotide in humans would be feasible. CONCLUSION: Copper-64-TETA-octreotide is a promising radiopharmaceutical for targeted radiotherapy of somatostatin receptor-positive tumors.

Synthesis, in vivo evaluation and PET study of a carbon-11-labeled neuronal nitric oxide synthase (nNOS) inhibitor S-methyl-L-thiocitrulline.

UNLABELLED: Reports have implicated neuronal nitric oxide synthetase (nNOS) in the pathological effects of neurodegenerative diseases. S-Methyl-L-thiocitrulline (MTICU), a potent and selective nNOS inhibitor (Ki = 1.2 nM), was chosen as our initial target molecule for positron emitter labeling as a potential nNOS tracer. We report the synthesis, biological evaluation and primate brain images of S-[11C]methyl-L-thiocitrulline ([I11C]MTICU). METHODS: The two-step synthesis of [11C]MTICU consisted of the S-alkylation of alpha-N-Boc-L-thiocitrulline t-butyl ester with [11C]Mel followed by TFA hydrolysis and HPLC purification. The final product was obtained within 50 min (yield = 9.1%-12.5%, based on [11C]Mel S.A. = 27-680 Ci/mmol at end of synthesis). The lipophilicity of [11C]MTICU was determined by octanol/water partition coefficient (LogP). Blood stability of this tracer in vitro and in vivo was measured by HPLC analysis. Biodistribution using female Sprague-Dawley rats was performed, including examination of uptake in cerebellum and olfactory bulb (high nNOS) as well as cortex and brain stem (low nNOS). Carbon-11-MTICU was administered to a female baboon and brain images were obtained using a Siemens ECAT EXACT scanner for determination of brain regional uptake and blood-brain barrier permeability. RESULTS: At 30 min postinjection, [11C]MTICU remained 64% intact in vivo and 95% intact in vitro. Lipophilicity estimation gave Log p = 1.08 +/- 0.08 (n = 6). The brain (0.11% ID/g)-to-blood (0.20% ID/g) ratio was 1:2 at 30 min postinjection. Uptake in the cerebellum was 20% higher than in either the cortex or the brain stem (p < 0.05). Blockage using 1 mg/kg MTICU reduced uptake in the cerebellum and the cortex by 22%, but did not affect the brain stem. PET imaging showed that [11C]MTICU brain uptake, corrected for blood volume, was stable from 10 min to 1 hr at approximately 0.4% ID/organ. PET images of a baboon brain showed increased uptake in the region of the olfactory bulb compared to uniform biodistribution in the rest of the brain. CONCLUSION: The [11C]MTICU is a tracer that is potentially useful in determining nNOS levels in vivo.

Comparison of four bifunctional chelates for radiolabeling monoclonal antibodies with copper radioisotopes: biodistribution and metabolism.

The bifunctional chelating agents (BFCs), 6-[p-(bromoacetamido)benzyl]-1,4,8,11-tetraazacyclotetradecane-1,4 ,8, 11-tetraacetic acid (BAT), 6-[p-(isothiocyanato)benzyl]-1,4,8, 11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid (SCN-TETA), 4-[(1,4,8,11-tetraazacyclotetradec-1-yl)methyl]benzoic acid (CPTA), and 1-[(1,4, 7,10,13-pentaazacyclopentadec-1-yl)methyl]benzoic acid (PCBA), were synthesized and conjugated to the anti-colorectal monoclonal antibody (mAB), 1A3, and antibody fragments, 1A3-F(ab')2, for radiolabeling with 64,67CU and comparison in animal models. In vivo metabolism studies were carried out in liver and kidneys in order to correlate the nature of the metabolites formed to the uptake and retention of the radiolabel in each organ. Animal biodistribution studies were performed in Golden Syrian hamsters bearing the GW39 human colon cancer tumors and in normal Sprague-Dawley rats. All conjugates showed good tumor uptake in hamsters. Biodistribution in rats showed that 64CU-BAT-2IT-1A3 had the lowest liver and kidney uptake of the intact 1A3 conjugates (p < 0.03), whereas in hamsters, there were no significant differences in liver and kidney uptake between the four intact BFC-1A3 conjugates. Tumor-bearing hamsters injected with 64CU-CPTA-1A3-F(ab')2 and 64CU-PCBA-1A3-F(ab')2 had from 3 to 7 times greater uptake in the kidneys than hamsters given 64CU-labeled BAT and SCN-TETA 1A3-F(ab')2 conjugates, while rats injected with 64Cu-CPTA-1A3-F(ab')2 and 64Cu-PCBA-1A3-F(ab')2 had nearly twice the uptake. The in vivo metabolism of the mAbs 1A3 and 1A3-F(ab')2 radiolabeled with 67Cu through the SCN-TETA, CPTA, and PCBA BFCs was investigated by excising the livers and kidneys of normal rats from 1-5 days post-injection of the radiolabeled conjugates. Liver and kidney homogenates were analyzed by size exclusion chromatography and thin layer chromatography (TLC). The size exclusion chromatography data showed that all of the 67Cu-labeled 1A3-F(ab')2 conjugates were > 85% degraded in the kidneys to small molecular weight metabolites by 1 day post-injection. In contrast, in the liver at 1 day post-injection, greater than 70% of the 67Cu-labeled 1A3 conjugates were unmetabolized. By day 5, a 35 kDa peak appeared in the liver of rats injected with the 67 Cu-labeled 1A3 conjugates, possibly due to transchelation of the 67Cu to proteins. Superoxide dismutase chromatographically elutes at the same retention time as this 67Cu-labeled metabolite. The TLC data indicate that the low molecular weight metabolite (< 5 kDa) of both 67Cu-CPTA-1A3 and 67Cu-CPTA-1A3-F(ab')2 conjugates co-chromatographed with a 67Cu-CPTA-epsilon-lysine standard. Our data suggest that chelate charge and lipophilicity play a large role in kidney retention of 64/67Cu-labeled BFC-1A3-F(ab')2 conjugates, while transchelation of the copper label appears to be the major factor for liver accumulation of 64/67Cu-labeled BFC-1A3 conjugates.

In vitro and in vivo evaluation of copper-64-octreotide conjugates.

UNLABELLED: Copper-64 (T1/2 = 12.8 hr) is a reactor-produced radionuclide that has applications in both nuclear medicine imaging by PET and radiotherapy. Octreotide, a somatostatin receptor ligand, has been conjugated with TETA and CPTA, labeled with 64Cu, evaluated both in vitro and in vivo and compared to 111In-DTPA-D-Phe1-octreotide. METHODS: The carboxylic acid moieties on the T bifunctional chelates were conjugated to the N-terminal amine of D-Phe using the linking agents hydroxybenzotriazol (HOBT) and diisopropylcarbodiimide (DIC). Receptor binding assays on all three radiolabeled octreotide conjugates were accomplished in AtT20 mouse pituitary carcinoma cell membranes. In vivo biodistribution was performed using normal Sprague-Dawley rats and Lewis rats carrying a somatostatin receptor-positive rat pancreatic tumor. RESULTS: The binding affinities of 64Cu-CPTA-D-Phe1-octreotide and 64Cu-TETA-D-Phe1-octreotide in AtT20 cell membranes were both greater than 111In-DTPA-D-Phe1-octreotide (Kd, 78.5 pM, 314 pM and 3.28 nM, respectively). In normal rats, 64Cu-CPTA-D-Phe1-octreotide was localized primarily in the liver. Copper-64-TETA-D-Phe1-octreotide, similar to 111In-DTPA-D-Phe1-octreotide, had moderate uptake in the kidneys; the hepatobiliary uptake was negligible. In rats bearing CA 20948 pancreatic tumors, both 64Cu-CPTA-D-Phe1-octreotide and 64Cu-TETA-D-Phe1-octreotide had uptake in tumors comparable to better than 111In-DTPA-D-Phe1-octreotide. CONCLUSION: Of the two 64Cu-labeled octreotide conjugates evaluated, 64Cu-CPTA-D-Phe1-octreotide has the highest affinity for the somatostatin receptor; however, the clearance was hepatobiliary with slow excretion. Copper-64-TETA-D-Phe1-octreotide binds to the somatostatin receptor with five times the affinity of 111In-octreotide, has desirable clearance properties (renal clearance with rapid excretion) and is a potential agent for PET imaging of somatostatin receptors.

Medical intensive care: indications, interventions, and outcomes.

To evaluate current practices regarding intensive-care units (ICU's), we collected data on 2693 consecutive admissions to a medical ICU during a two-year period and studied indications for admission, specific interventions, costs, and outcomes. The need for noninvasive monitoring rather than immediate major interventions prompted 77 per cent of the admissions. Only 10 per cent of monitored patients had subsequent indications for major interventions. The 23 per cent who required immediate interventions accounted for disproportionate shares of total charges (37 per cent) and deaths during hospitalization (58 per cent). Demographic and diagnostic data indicate that the aged and chronically ill have become the principal consumers of intensive care. Overall mortality during hospitalization was 10 per cent; cumulative mortality during follow-up study (mean duration, 15 months) was 25 per cent. We conclude that identification of sensitive predictors of complications and specific predictors of mortality can lead to more efficient and effective ICU practices.

The course of patients with suspected myocardial infarction. The identification of low-risk patients for early transfer from intensive care.

The hospital course of all patients admitted to a medical intensive-care unit (ICU) with suspected myocardial infarction was reviewed to test the feasibility of identifying patients suitable for earlier transfer from the ICU. Three hundred sixty patients admitted after presentation with uncomplicated chest pain could be stratified into three risk groups within 24 hours of admission to the ICU. One hundred sixty-eight patients (47 per cent), who were without major complications, elevation of total serum creatine phosphokinase, or electrocardiographic evidence of transmural infarction during the first day, could be designated "low-risk" patients. Three per cent of the low-risk patients subsequently met clinical criteria for infarction, 2 percent had late complications in the ICU, and none died. Rates of infarction, late complications in the ICU, and mortality in the hospital were significantly higher for patients at intermediate and high risk. Identification of low-risk patients for whom early transfer may be routinely indicated is feasible and could reduce by 55 per cent the total number of days that such patients spend in the ICU.