Gluon fusion into Higgs pairs at NLO QCD and the top mass scheme.

We present the calculation of the full next-to-leading order (NLO) QCD corrections to Higgs boson pair production via gluon fusion at the LHC, including the exact top-mass dependence in the two-loop virtual and one-loop real corrections. This is the first independent cross-check of the NLO QCD corrections presented in the literature before. Our calculation relies on numerical integrations of Feynman integrals, stabilised with integration-by-parts and a Richardson extrapolation to the narrow width approximation. We present results for the total cross section as well as for the invariant Higgs-pair-mass distribution at the LHC, including for the first time a study of the uncertainty due to the scheme and scale choice for the top mass in the loops.

The role of COX-2 in heart pathology.

Cyclooxygenase-2 (COX-2) is a key enzyme in the production of prostaglandins, and an important anti-inflammation drug target. Recent focus has been placed on the role of COX-2 in heart function and pathology, due to the finding that specific COX-2 inhibitors significantly increased the risk of heart disease in chronic users. However, the exact role of COX-2 in cardiac physiology and disease remains controversial due to the conflicting data reported. Roughly equal numbers of reports have shown either a detrimental role or a protective role for COX-2 in heart in experimental models. Here we attempt to provide a background on the more general roles of COX-2 in pathophysiology, as well as molecular mechanisms employed to control COX-2 expression. This background provides a basis for better understanding the functional role of COX-2 in human heart pathologies, based on the results of COX-2 pharmacological inhibitor studies in humans as well as COX-2 expression in human heart disease. Furthermore, we will explore the experimental evidence implicating different intracellular molecular signaling cascades that regulate COX-2 expression in cardiomyocytes. All of this data permits a more mechanistic understanding of the published studies using pharmacological inhibitors of COX-2 in experimental models of heart pathology. Lastly, we will examine the use of genetic manipulation of COX-2 in mice as one of the future avenues in an attempt to resolve the role of COX-2 in cardiac physiology and pathology.

Serotonin-related gene expression in female monkeys with individual sensitivity to stress.

Female cynomolgus monkeys exhibit different degrees of reproductive dysfunction with moderate metabolic and psychosocial stress. In this study, the expression of four genes pivotal to serotonin neural function was assessed in monkeys previously categorized as highly stress resistant (n=3; normal menstrual cyclicity through two stress cycles), medium stress resistant (n=5; ovulatory in the first stress cycle but anovulatory in the second stress cycle), or low stress resistant (i.e. stress-sensitive; n=4; anovulatory as soon as stress is initiated). In situ hybridization and quantitative image analysis was used to measure mRNAs coding for SERT (serotonin transporter), 5HT1A autoreceptor, MAO-A and MAO-B (monoamine oxidases) at six levels of the dorsal raphe nucleus (DRN). Optical density (OD) and positive pixel area were measured with NIH Image software. In addition, serotonin neurons were immunostained and counted at three levels of the DRN. Finally, each animal was genotyped for the serotonin transporter long polymorphic region (5HTTLPR). Stress sensitive animals had lower expression of SERT mRNA in the caudal region of the DRN (P<0.04). SERT mRNA OD in the caudal DRN was positively correlated with serum progesterone during a pre-stress control cycle (P<0.0007). 5HT1A mRNA OD signal tended to decline in the stress-sensitive group, but statistical difference between averages was lacking in analysis of variance. However, 5HT1A mRNA signal was positively correlated with control cycle progesterone (P<0.009). There was significantly less MAO-A mRNA signal in the stress-sensitive group (P<0.007) and MAO-A OD was positively correlated with progesterone from a pre-stress control cycle (P<0.007). MAO-B mRNA exhibited a similar downward trend in the stress-sensitive group. MAO-B OD also correlated with control cycle progesterone (P<0.003). There were significantly fewer serotonin neurons in the stress-sensitive group. All animals contained only the long form of the 5HTTLPR. Thus, all serotonin-related mRNAs examined in the dorsal raphe to date were lower (SERT, MAO-A) or exhibited a lower trend (5HT1A, MAO-B) in the stress sensitive animals, which probably reflects the lower number of serotonin neurons present.

Mathematical characterization of three-dimensional gene expression patterns.

MOTIVATION: The importance of a systematic methodology for the mathematical characterization of three-dimensional gene expression patterns in embryonic development. METHODS: By combining lacunarity and multiscale fractal dimension analyses with computer-based methods of three-dimensional reconstruction, it becomes possible to extract new information from in situ hybridization studies. Lacunarity and fractality are appropriate measures for the cloud-like gene activation signals in embryonic tissues. The newly introduced multiscale method provides a natural extension of the fractal dimension concept, being capable of characterizing the fractality of geometrical patterns in terms of spatial scale. This tool can be systematically applied to three-dimensional patterns of gene expression. RESULTS: Applications are illustrated using the three-dimensional expression patterns of the myogenic marker gene Myf5 in a series of differentiating somites of a mouse embryo.

AIDA: web agents in dental treatment planning.

The objective of the AIDA project (Artificial Intelligent Dental Agents, http://aida.uni-hd.de) is the analysis of dental decision-making, the design of a computer-based decision support system, as well as the testing of the decision structure in interactions with dental experts, practicing dentists, and patients. The planning of the solution alternatives for an individual patient is based on a top-down structure for dental decision-making, aiming at a standardization of the argumentation. From a theoretical point of view, decision support can be provided only for anticipated decisions (planning). Moreover, only parts of these anticipated decisions can be supported. Accordingly, a separation of these partial aspects has to take place before one is able to build decision support systems. For prosthetic dentistry, clinicians have been shown how to use individual patient findings to sketch the possible treatment alternatives and later derive guidelines for the treatment. The planning module for fixed prostheses has already been integrated into a software agent. Planning modules for other types of prostheses are currently specified, implemented, and verified.

AIDA: Web agents to support dental treatment planning.

Dental treatment planning is highly dependent on the educational background and personal experience of the dentist and on the thoroughness with which findings are taken. The objective of research in the AIDA (Artificially Intelligent Dental Agents) project is therefore the analysis of dental decision making and the design of a decision-supportive software module to test the decision-making process and make it transparent for both dentists and patients. In the AIDA project (aida.uni-hd.de), an expert system has been set up to identify treatment alternatives with integrated decision rationale for experts, practicing dentists, and eventually also patients. It is based on a top-down structure for dental decision-making, which was developed to standardize argumentation. For prosthetic dentistry, how one uses individual patient findings to arrive at possible treatment alternatives was clarified in greater detail. The planning rules for fixed prostheses have already been integrated into a software agent. Other modules should soon specify and verify these suggestions in terms of further fields of dentistry (e.g., restorative dentistry). In the near future, AIDA will be able to deliver dentally-founded justifications for every individual decision.

Role of motility in embryonic development I: Embryo movements and amnion contractions in the chick and the influence of illumination.

This study provides a quantitative analysis of the active movements of the chick embryo and of the contractions of the amnion over the entire developmental period of 21 days. Four types of embryo movements are distinguished. The motor activity of the embryo shows two characteristic peaks, with maximum contraction frequencies on the 12th and on the 16th day. In contrast, the amnion activity is higher at earlier stages and decreases as the body activity increases. The amnion activity is largely independent of the body activity. Illumination has a strong influence on embryo movements. It is shown that increases of light intensity affect the patterns of activity of both the embryo and the amnion. While the effect of light on the embryo can be interpreted as being transmitted via the optic system, the mechanism of the amniotic response is unclear. The results suggest that the amnion itself may be sensitive to light. J. Exp. Zool. (Mol. Dev. Evol.) 291:186-194, 2001.

3D modelling of gene expression patterns.

The current genome-sequencing projects provide "word indices" of the book of life. A central post-genomic question will be how these words are three-dimensionally deployed in the generation of organism form. Gene expression studies of developing organisms contribute an increasing wealth of snapshot data on the activation of individual genes at selected locations and single moments in the developmental process. However, a comprehensive understanding of the dynamic activation of multiple genes and their functional role in controlling the 3D processes of collective cell behaviour, pattern formation and morphogenesis, requires special tools for a systematic description of spatio-temporal patterns of gene activation and the ensuing phenotypic effects. This article concentrates on new, computer-based tools for the 3D analysis of gene expression patterns in embryonic development and their use for the systematic establishment of comprehensive gene expression maps.

Computer-based three-dimensional visualization of developmental gene expression.

A broad understanding of the relationship between gene activation, pattern formation and morphogenesis will require adequate tools for three-dimensional and, perhaps four-dimensional, representation and analysis of molecular developmental processes. We present a novel, computer-based method for the 3D visualization of embryonic gene expression and morphological structures from serial sections. The information from these automatically aligned 3D reconstructions exceeds that from single-section and whole-mount visualizations of in situ hybridizations. In addition, these 3D models of gene-expression patterns can become a central component of a future developmental database designed for the collection and presentation of digitized, morphological and gene-expression data. This work is accompanied by a web site (http://www.univie.ac.at/GeneEMAC).

Up-regulation of LDL-receptor expression by LDL-immunoapheresis in patients with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is characterized by an autosomal dominantly inherited deficiency of LDL-receptor expression on the cell surface, leading to excess plasma LDL-cholesterol and severe premature atherosclerosis. In patients with heterozygous FH, a major therapeutic objective of conventional drug therapy is to stimulate maximally the residual cellular capacity to produce LDL-receptors via inhibition of endogenous cholesterol synthesis. In contrast, LDL-immunoapheresis aims at reducing the plasma LDL-cholesterol level by extracorporeal elimination of LDL particles. The present study investigates whether LDL-immunoapheresis applied in addition to conventional drug therapy is able to further stimulate residual LDL-receptor expression capacity in patients with heterozygous FH via the withdrawal of external cholesterol supply, thereby exerting a second accessory lipid lowering effect. METHODS: LDL-receptor expression--calculated by transforming mean fluorescence intensities into numbers of antibody binding sites per cell (S/C)--was determined flow-cytometrically on peripheral blood monocytes before and after LDL-apheresis. For a comparison with the maximum obtainable receptor expression capacity, in vitro stimulation experiments under completely LDL deficient conditions were performed. RESULTS: Prior to LDL-apheresis, LDL-receptor density was comparable in patients (N = 7; 2014 +/- 359 S/C) and controls (N = 10; 1782 +/- 252 S/C). Under in vitro conditions LDL-receptor expression of controls exceeded that of patients with FH by 1.6 times. Immediately after apheresis, LDL-receptor expression significantly increased to almost the same level as obtained by in vitro stimulation (3640 +/- 423 S/C and 3632 +/- 572 S/C). The LDL-receptor expression in FH subsequent to LDL-apheresis exhibited two patterns of kinetics [Type 1: maximal receptor stimulation (288 +/- 70%; P < 0.07) already during apheresis; Type 2: highest receptor density 24 hours after treatment (149 +/- 11%; P < 0.01)]. CONCLUSIONS: These results demonstrate that despite drug therapy, LDL-apheresis significantly stimulates the residual LDL-receptor expression in FH via the reduction of available extracellular cholesterol resulting in delayed reappearance of hypercholesterolemia in between treatments.

Differential expression of tumor necrosis factor receptor subtypes on leukocytes in systemic inflammatory response syndrome.

OBJECTIVE: To determine the expression of tumor necrosis factor (TNF) receptor in patients with systemic inflammatory response syndrome (SIRS). DESIGN: Prospective study. SETTING: Intensive care unit and central laboratory. PATIENTS: Blood specimens from 18 healthy volunteers (controls) and 16 patients with SIRS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using monoclonal antibodies, fluorescence labeling, and high sensitivity flow cytometry, we measured the expression of membrane TNF receptor subtypes TNF-R55 and TNF-R75 on peripheral blood leukocytes. Receptor expression is expressed as mean fluorescence intensity +/- SD (units: detection channel number). In controls, TNF-R55 was only weakly expressed (monocytes: 2.5+/-1.8; neutrophils: 0.7+/-0.8), whereas expression of TNF-R75 was higher (monocytes: 28.6+/-9.0; neutrophils: 4.8+/-1.0) and was also found on lymphocytes (on CD8+ lymphocytes: 5.7+/-1.8; CD16+: 5.5+/-1.2; CD4+: 9.7+/-3.7). In SIRS, we observed increased expression of TNF-R55 on monocytes (6.9+/-3.4, p<.001) and neutrophils (2.2+/-1.9, p<.01), as well as decreased expression of TNF-R75 on monocytes (17.3+/-13.2; p<.001). The extent of TNF-R55 up-regulation did not correlate with that of TNF-R75 down-regulation. TNF-R55 on monocytes and neutrophils strongly correlated with body temperature but not with survival, whereas monocyte TNF-R75 was considerably lower in nonsurvivors, albeit not significantly (12.3+/-7.1 vs. 23.9+/-16.7; p = .07). CONCLUSIONS: These data indicate that leukocyte TNF-R55 and TNF-R75 react differentially and probably serve different functions in SIRS, which prompts the investigation of receptor subtype-specific therapeutic approaches.

Auditory ossicle abnormalities and hearing loss in the toothless (osteopetrotic) mutation in the rat and their improvement after treatment with colony-stimulating factor-1.

Osteopetrosis describes a group of skeletal metabolic diseases of heterogeneous etiology and varied severity that produces a generalized accumulation of skeletal mass, the result of reduced bone resorption. Inherited in a variety of species including humans, the most severe forms are lethal. Among common features are progressive blindness and deafness of controversial etiologies for which there are no universally effective treatments. We have studied the auditory responsiveness and auditory ossicle quantitative histomorphology and temporal bone vasculature in the toothless (tl) rat, a lethal osteopetrotic mutation with few osteoclasts, very low bone turnover, and limited angiogenesis in the axial skeleton. Compared with normal littermates, 3-week-old mutants showed significantly reduced auditory responsiveness, a hearing loss due to abnormalities in both form and tissue composition of the stapes, and little capillary sprouting in the vascular bed of the temporal bone. Treatment of mutants with colony-stimulating factor 1 (CSF-1), known to greatly reduce sclerosis in the axial skeleton, significantly improved hearing, stapedial form and tissue composition, and angiogenesis in the temporal bone. In normal rats, the stapes consisted of 89.3% bone, 9.1% mineralized cartilage, and 0.8% porosity. In osteopetrotic rats, the stapes consisted of 48.3% bone, 35.9% mineralized cartilage, and 15.9% porosity, while after CSF-1 treatment, the bone content increased to 55.2%, cartilage was decreased to 21.7%, and porosity increased to 23.0%, respectively. This is the first demonstration of an auditory abnormality in an osteopetrotic animal mutation and shows that the hearing loss in tl rats can be significantly improved following treatment with CSF-1.

Therapeutic efficiency of lipoprotein(a) reduction by low-density lipoprotein immunoapheresis.

This study was performed to investigate the effect of low-density lipoprotein (LDL) immunoapheresis on lipoprotein(a) [Lp(a)] reduction in patients with heterozygous and homozygous familial hyperlipidemia (N=16) and insufficient response to lipid-lowering agents. By desorption of approximately 5,700+/-500 mL of plasma, a mean reduction in total cholesterol of 62% (P < .001) and in LDL-cholesterol of 70% (P < .001) was achieved. Lp(a), which was elevated at study entry in seven of these patients (82.1+/-34.3 mg/dL; range, 48 to 148 mg/dL), was reduced during the initial LDL-apheresis procedure by 74.8%+/-14.1% (P < .001). Long-term apheresis treatment performed at weekly intervals resulted in an mean reduction in Lp(a) pretreatment values to 39.1+/-28.5 mg/dL (-54%; P < .001). Desorbed Lp(a) was measured at the waste of the columns for 31 apheresis treatments. Lp(a) concentration of the column waste was higher in patients with elevated serum Lp(a) pretreatment values as compared with those with Lp(a) serum values within the normal range (elevated Lp(a), 1,420+/-380 mg; without elevated Lp(a), 235+/-190 mg; P < .001). The rate of return of Lp(a) following apheresis treatment scheduled at weekly intervals was comparable to that of LDL-cholesterol.

A new episcopic method for rapid 3-D reconstruction: applications in anatomy and embryology.

The topographic relations of complex structures and the morphogenesis of organ systems can only be fully understood in their three-dimensional context. Three-dimensional (3-D) reconstruction of physically sectioned specimens has become an indispensable tool in modern anatomical and embryological research. Teaching also makes increasingly use of 3-D representations, in particular in the case of embryonic systems that undergo complicated transformations of form and shape. At present no cheap and simple technique is available that generates accurate 3-D models of sectioned objects. In this study we describe a novel technique that rapidly provides faithful 3-D models of sectioned specimens. The images are captured directly from the cutting surface of the embedding block after each sectioning and "on block" staining step. Automatic image processing generates a stack of binary images of the specimen contour. Binary images of internal structures are obtained both by automatic segmentation and manual tracing. Since these image series are inherently aligned, they can be reconstructed three-dimensionally without time-consuming alignment procedures. The quality and the flexibility of the method are demonstrated by reconstructing three kinds of specimens of different histological composition and staining contrast: a 4 mm mouse embryo together with several of its inner organs, a cavernous sinus region of a human infant, and a segment of a human carotid artery. Very short processing times and the faithful representation of complex structural arrangements recommend this technique for routine use in morphological research and for creating embryologic teaching models or 3-D embryonic staging series.

Anticytokeratins are a potential source of false-positive indirect immunofluorescence assays for C-ANCA.

Antibodies to neutrophil cytoplasmic antigens (ANCA) targeted toward granule enzymes have been recognized as a valuable diagnostic tool in the detection of Wegener's granulomatosis and systemic vasculitides. However, the most commonly used method of detection, the indirect immunofluorescence assay, is prone to false-positive results due to antibodies of different pathological significance either targeted to, or cross-reacting with, similarly distributed epitopes. Using double immunofluorescence, the present study demonstrates that anticytokeratin antibodies are able to produce false-positive C-ANCA immunofluorescence assays. In addition, a case of natural appearance of cytokeratin-reactive antibodies causing a false-positive "pseudo-ANCA" staining pattern in a patient presenting with sepsis is reported. Since the expression of cytokeratins is almost exclusively confined to epithelial cells, the most plausible explanation for both phenomena is a crossreaction of anticytokeratin antibodies with granule associated epitopes. Due to the natural appearance of anticytokeratin antibodies in association with a variety of other pathologic entities, it is of crucial importance for the diagnostic significance of the C-ANCA immunofluorescence assay to exclude anticytokeratin caused false-positive results. It is shown that supplementary indirect immunofluorescence tests performed on cultured human epithelial cells readily distinguish anticytokeratin caused "pseudo-ANCA" from true C-ANCA.

External marker-based automatic congruencing: a new method of 3D reconstruction from serial sections.

BACKGROUND: Computer-based three-dimensional (3D) visualizations reconstructed from sectional images represent a valuable tool in biomedical research and medical diagnosis. Particularly with those imaging techniques that provide virtual sections, such as CT, MRI, and CLSM, 3D reconstructions have become routine. Reconstructions from physical sections, such as those used in histological preparations, have not experienced an equivalent breakthrough, due to inherent shortcomings in sectional preparation that impede automated image-processing and reconstruction. The increased use of molecular techniques in morphological research, however, generates an overwhelming amount of 3D molecular information, stored within series of physical sections. This valuable information can be fully appreciated and interpreted only through an adequate method of 3D visualization. METHODS AND RESULTS: In this paper we present a new method for a reliable and largely automated 3D reconstruction from physically sectioned material. The 'EMAC' concept (External Marker-based Automatic Congruencing) successfully approaches the three major obstacles to automated 3D reconstruction from serial physical sections: misalignment, distortion, and staining variation. It utilizes the objectivity of external markers for realignment of the sectional images and for geometric correction of distortion. A self-adapting dynamic thresholding technique compensates for artifactual staining variation and automatically selects the desired object contours. CONCLUSIONS: Implemented on a low-cost hardware platform, EMAC provides a fast and efficient tool that largely facilitates the use of computer-based 3D visualization for the analysis of complex structural, molecular, and genetic information in morphological research. Due to its conceptual versatility, EMAC can be easily adapted for a broad range of tasks, including all modern molecular-staining techniques, such as immunohistochemistry and in situ hybridization.

Anatomical compartments of the parasellar region: adipose tissue bodies represent intracranial continuations of extracranial spaces.

The cavernous sinus is traditionally described as a single anatomical compartment that contains cranial nerves, blood vessels, and connective tissue. A detailed analysis of 45 infant and 4 fetal parasellar regions shows that this view must be modified. The spatial arrangement, the topographic relations, and the expansion of the adipose and connective tissue spaces were analysed and reconstructed 3-dimensionally on a computer. It is shown that 3 different anatomical compartments, which are strictly demarcated by connective tissue, compose the parasellar region of infants. Two represent intracranial continuations of extracranial tissue spaces. The 3rd compartment corresponds to the so-called 'cavernous sinus' of the adult. Each of the 3 compartments contains characteristic adipose tissue bodies. Because the cavernous sinus represents only one compartment of the area, we propose to use the term 'parasellar region' to designate the entire anatomical region on either side of the sella turcica.

Toward a new reference method for the leukocyte five-part differential.

A flow cytometric method performing a five-part leukocyte differential based on three-color staining with anti-CD45-fluorescein isothiocyanate (FITC), anti-CD-14-phycoerythrin (PE)/Cy5, and a cocktail of PE-labeled anti-CD2, anti-CD16, and anti-HLA-DR antibodies was evaluated. Results obtained by using three different sample preparation procedures and two different flow cytometers were compared with those of a 1,000-cell manual differential for evaluation of accuracy. We observed excellent correlations with the manual differential for all leukocyte subclasses and even higher correlations between the different flow cytometric methods. Flow cytometric basophil results were identical to the manual counts, regardless of which sample preparation technique or flow cytometer was used. Therefore, we propose our flow cytometric method as the first acceptable automated reference method for basophil counting. The flow cytometric results for the other leukocyte subclasses were apparently influenced by the sample preparation, which could not be explained by cell loss during washing steps. Moreover, a small influence of the flow cytometer was also observed. Assessing the influence of sample storage, we found only minimal changes within 24 h. In establishing reference values, high precision of flow cytometric results facilitated detection of a significantly higher monocyte count for males (relative count: 7.08 +/- 1.73% vs. 6.44 +/- 1.33%, P < 0.05; absolute count: 0.536 +/- 0.181 x 10(9)/liter vs. 0.456 +/- 139 x 10(9)/liter, P < 0.01). Our data indicate that monoclonal antibody-based flow cytometry is a highly suitable reference method for the five-part differential: It also shows, however, that studies will have to put more emphasis on methodological issues to define a method that shows a high interlaboratory reproducibility.

Dynamic three-dimensional imaging of the mitral valve and left ventricle by rapid sonomicrometry array localization.

OBJECTIVES: The first objective was to develop a quantitative method for tracking the three-dimensional geometry of the mitral valve. The second was to determine the complex interrelationships of various components of the mitral valve in vivo. METHODS AND RESULTS: Sixteen sonomicrometry transducers were placed around the mitral vale anulus, at the tips and bases of both papillary muscles, at the ventricular apex, across the ventricular epicardial short axis, and on the anterior chest wall before and during cardiopulmonary bypass in eight anesthetized sheep. Animals were studied later on 17 occasions. Reproducibility of derived chord lengths and three-dimensional coordinates from sonomicrometry array localization, longevity of transducer signals, and the dynamics of the mitral valve and left ventricle were studied. Reproducibility of distance measurements averages 1.6%; Procrustes analysis of three-dimensional arrays of coordinate locations predicts an average error of 2.2 mm. Duration of serial sonomicrometry array localization signals ranges between 60 and 151 days (mean 114 days). Sonomicrometry array localization demonstrates the saddle-shaped mitral anulus, its minimal orifice area immediately before end-diastole, and uneven, apical descent during systole. Papillary muscles shorten only 3.0 to 3.5 mm. Sonomicrometry array localization demonstrates nonuniform torsion of papillary muscle transducers around a longitudinal axis and shows rotation of papillary muscular bases toward each other during systole. CONCLUSION: Tagging of ventricular structures in experimental animals by sonomicrometry array localization images is highly reproducible and suitable for serial observations. In sheep the method provides unique, quantitative information regarding the interrelationship of mitral valvular and left ventricular structures throughout the cardiac cycle.

Triiodothyronine optimizes sheep ventriculoarterial coupling for work efficiency.

BACKGROUND: Triiodothyronine (T3) administration after cardiopulmonary bypass has been shown to significantly improve cardiac performance. The present study was undertaken to elucidate the effects of T3, when administered as an intravenous bolus, on both cardiac energetics and stroke work-oxygen utilization (EW/LVVO2) efficiency. METHODS: In both unstressed and stressed hearts, energetics were evaluated at baseline and 2 hours after intervention in an in vivo sheep preparation. In the first group (n = 5) sheep received saline vehicle. In the second group (n = 9) sheep received an intravenous bolus of 1.2 micrograms/kg of T3. In the third group (n = 7) sheep received a 2-hour intravenous infusion of dobutamine at a rate of 5 micrograms/kg/min. RESULTS: In the unstressed heart, T3 improved cardiac function at no cost in oxygen consumption by decreasing afterload and hence improved EW/LVVO2 efficiency. In contrast, dobutamine improved unstressed cardiac function by increasing contractility at the cost of increased oxygen consumption and thus decreased EW/LVVO2 efficiency. Triiodothyronine optimized ventriculoarterial coupling for efficiency, but dobutamine optimized coupling for maximal work. In the stressed heart, T3 again improved EW/LVVO2 efficiency, but dobutamine had the opposite effect. CONCLUSIONS: The bolus administration of T3 improves unstressed cardiac performance through optimization of ventriculoarterial coupling for EW/LVVO2 efficiency, primarily through vasodilation. Triiodothyronine also increases efficiency in the stressed heart. This study supports the use of T3 in cardiac operations to improve cardiac performance with no cost in oxygen consumption characteristic of inotropic agents.