A computational model of cardiac fibroblast signaling predicts context-dependent drivers of myofibroblast differentiation.

Cardiac fibroblasts support heart function, and aberrant fibroblast signaling can lead to fibrosis and cardiac dysfunction. Yet how signaling molecules drive myofibroblast differentiation and fibrosis in the complex signaling environment of cardiac injury remains unclear. We developed a large-scale computational model of cardiac fibroblast signaling in order to identify regulators of fibrosis under diverse signaling contexts. The model network integrates 10 signaling pathways, including 91 nodes and 134 reactions, and it correctly predicted 80% of independent previous experiments. The model predicted key fibrotic signaling regulators (e.g. reactive oxygen species, tissue growth factor ß (TGFß) receptor), whose function varied depending on the extracellular environment. We characterized how network structure relates to function, identified functional modules, and predicted cross-talk between TGFß and mechanical signaling, which was validated experimentally in adult cardiac fibroblasts. This study provides a systems framework for predicting key regulators of fibroblast signaling across diverse signaling contexts.

Sequencing of mRNA identifies re-expression of fetal splice variants in cardiac hypertrophy.

Cardiac hypertrophy has been well-characterized at the level of transcription. During cardiac hypertrophy, genes normally expressed primarily during fetal heart development are re-expressed, and this fetal gene program is believed to be a critical component of the hypertrophic process. Recently, alternative splicing of mRNA transcripts has been shown to be temporally regulated during heart development, leading us to consider whether fetal patterns of splicing also reappear during hypertrophy. We hypothesized that patterns of alternative splicing occurring during heart development are recapitulated during cardiac hypertrophy. Here we present a study of isoform expression during pressure-overload cardiac hypertrophy induced by 10 days of transverse aortic constriction (TAC) in rats and in developing fetal rat hearts compared to sham-operated adult rat hearts, using high-throughput sequencing of poly(A) tail mRNA. We find a striking degree of overlap between the isoforms expressed differentially in fetal and pressure-overloaded hearts compared to control: forty-four percent of the isoforms with significantly altered expression in TAC hearts are also expressed at significantly different levels in fetal hearts compared to control (P<0.001). The isoforms that are shared between hypertrophy and fetal heart development are significantly enriched for genes involved in cytoskeletal organization, RNA processing, developmental processes, and metabolic enzymes. Our data strongly support the concept that mRNA splicing patterns normally associated with heart development recur as part of the hypertrophic response to pressure overload. These findings suggest that cardiac hypertrophy shares post-transcriptional as well as transcriptional regulatory mechanisms with fetal heart development.

Bone marrow-derived mesenchymal stromal cells and platelet-rich plasma on a collagen matrix to improve fascial healing.

OBJECTIVE: To demonstrate improved healing of a midline laparotomy after application of mesenchymal stromal cells and platelet-rich plasma on a collagen matrix and introduce a potential cellular-based therapy for the prevention of incisional hernia formation. BACKGROUND: Up to 10 % of laparotomies are complicated by postoperative incisional hernias. Despite continuous improvements in surgical technique and technology, hernia rates have remained constant. Cell-based therapies focused on augmentation of the body's natural healing properties could reduce hernia formation. METHODS: Midline laparotomies were performed on 42 Lewis rats. Three groups were studied: (1) primary repair only, (2) primary repair with CollaTape™ (CoTa) overlay and platelet-rich plasma (PRP), and (3) primary repair with CoTa overlay and PRP and bone marrow-derived mesenchymal stromal cells (BM-MSCs). Abdominal wall fascia was recovered at 4 and 8 weeks in each group. Biomechanical testing and histological evaluation was performed. RESULTS: At 4 weeks, there was a twofold increase in tensile strength between groups 1 and 2 and a fourfold increase between groups 1 and 3 (p < 0.001). Group 3 had a 320 % increase in total energy absorption at 4 weeks compared to group 1 and a 142 % increase at 8 weeks (p < 0.001). Vascularization and collagen abundance were significantly increased in group 3 at both time points. CONCLUSION: The addition of BM-MSCs, PRP, and CoTa led to a marked improvement in abdominal wall strength and energy absorption. Histologic evaluation confirmed increased vascularity and collagen abundance consistent with the biomechanical findings. Application of this therapy may ultimately reduce incisional hernia formation.

Isotonic biaxial loading of fibroblast-populated collagen gels: a versatile, low-cost system for the study of mechanobiology.

We developed a simple, versatile system for applying a range of biaxial loads to cell-matrix constructs for the study of mechanobiology. The system consists of porous polyethylene bars that are polymerized into a square fibroblast-populated gel and loaded by freely hanging weights attached to sutures routed through a custom loading rig. The cost to manufacture each mold/loading rig pair was less than US dollars 250 and the expected life of the components is up to 10 years. Neonatal and adult cardiac fibroblasts contracted gels to a decreasing extent as external load was increased ( P=0.003) and achieved contraction forces of up to 1.4 mN per million cells. Strain distributions were reasonably homogeneous in the central region of the gel (25% of gel area), but clearly nonhomogeneous outside that central region. The primary advantages of this system are simplicity, low cost, biaxial loading, and the ability to test for a dose-response effect of mechanical load. The current disadvantages are the inability to apply cycling loading and the inhomogeneities introduced by the use of rigid loading bars.

Normalized diastolic properties after left ventricular assist result from reverse remodeling of chamber geometry.

BACKGROUND: Normalization of diastolic properties after left ventricular (LV) assist may result from a change in myocardial material properties, chamber size, or both. This study tested the hypothesis that reported normalization of LV diastolic properties is primarily due to remodeling of chamber geometry. METHODS AND RESULTS: Hearts were obtained at transplantation from 8 patients with dilated cardiomyopathy (DCM), 6 patients with DCM plus 33+/-5 days of LV assist, and 3 patients with no evidence of heart failure. LV assist normalized passive pressure-volume curves. Chamber dimensions decreased without a change in the ratio of radius to wall thickness. Midwall stress-stretch relations predicted from pressure-volume and dimension data were not different for DCM and LV assist hearts. Passive stress-stretch relations were measured in endocardial trabeculae and were not different for DCM and LV assist hearts. Myocyte size and collagen area fraction were unchanged at this brief duration of support. CONCLUSIONS: These findings are all consistent with the hypothesis that early normalization of diastolic properties after LV assist device support results from remodeling of chamber geometry, not from changes in tissue stiffness. These data emphasize the importance of geometry to ventricular mechanics and demonstrate that reduction of heart size does not necessarily produce a reduction in wall stress.

Comparison of right and left ventricular responses to left ventricular assist device support in patients with severe heart failure: a primary role of mechanical unloading underlying reverse remodeling.

BACKGROUND: Left ventricular assist devices (LVAD) reverse ventricular, myocardial, and systemic abnormalities characteristic of severe heart failure (reverse remodeling). The relative contributions of hemodynamic unloading and normalized biochemical milieu to reverse remodeling are unknown. METHODS AND RESULTS: Structural and functional characteristics were measured from 53 hearts of patients undergoing transplantation without LVAD support (medical support) and 33 hearts from patients receiving a median of 46 days of LVAD support (range, 8 to 360 days). Compared with medical support alone, patients receiving LVAD support for >/=30 days had higher central venous pressures (11+/-6 versus 8+/-5 mm Hg, P=0.04), lower pulmonary artery diastolic pressures (14+/-9 versus 21+/-9 mm Hg, P=0.01), and higher cardiac outputs (5.1+/-1.6 versus 3.7+/-1.0 L/min, P<0.001). In LVAD versus transplantation hearts, V(30) (ex vivo volume yielding ventricular pressure of 30 mm Hg) was decreased in the left ventricle (LV) (179+/-75 versus 261+/-118 mL, P=0.005) but not in the right ventricle (RV) (140+/-59 versus 148+/-52 mL, P=NS). LV myocyte diameter decreased more significantly after LVAD support (17%, P=0.05) than in the RV (11%, P=NS). Compared with transplantation, LVAD support increased normalized SERCA2a content in the LV (0.51+/-0.26 versus 1.04+/-0.34, P<0.001) but not in the RV (0.48+/-34 versus 0.67+/-0.55, P=NS). Finally, LVAD support improved force-frequency relations of isolated superfused LV trabeculae (P=0.01) but not RV trabeculae. CONCLUSIONS: Reduction of hemodynamic load is a primary factor underlying several important features of reverse remodeling. These findings do not preclude a possible primary role of neurohormonal factors underlying other facets of reverse remodeling during LVAD support.

LV volume quantification via spatiotemporal analysis of real-time 3-D echocardiography.

This paper presents a method of four-dimensional (4-D) (3-D + Time) space-frequency analysis for directional denoising and enhancement of real-time three-dimensional (RT3D) ultrasound and quantitative measures in diagnostic cardiac ultrasound. Expansion of echocardiographic volumes is performed with complex exponential wavelet-like basis functions called brushlets. These functions offer good localization in time and frequency and decompose a signal into distinct patterns of oriented harmonics, which are invariant to intensity and contrast range. Deformable-model segmentation is carried out on denoised data after thresholding of transform coefficients. This process attenuates speckle noise while preserving cardiac structure location. The superiority of 4-D over 3-D analysis for decorrelating additive white noise and multiplicative speckle noise on a 4-D phantom volume expanding in time is demonstrated. Quantitative validation, computed for contours and volumes, is performed on in vitro balloon phantoms. Clinical applications of this spaciotemporal analysis tool are reported for six patient cases providing measures of left ventricular volumes and ejection fraction.

Chronic unloading by left ventricular assist device reverses contractile dysfunction and alters gene expression in end-stage heart failure.

BACKGROUND: Left ventricular (LV) assist devices (LVADs) can improve contractile strength and normalize characteristics of the Ca(2+) transient in myocytes isolated from failing human hearts. The purpose of the present study was to determine whether LVAD support also improves contractile strength at different frequencies of contraction (the force-frequency relationship [FFR]) of intact myocardium and alters the expression of genes encoding for proteins involved in Ca(2+) handling. METHODS AND RESULTS: The isometric FFRs of LV trabeculae isolated from 15 patients with end-stage heart failure were compared with those of 7 LVAD-supported patients and demonstrated improved contractile force at 1-Hz stimulation, with reversal of a negative FFR after LVAD implantation. In 20 failing hearts, Northern blot analysis for sarcoplasmic endoreticular Ca(2+)-ATPase subtype 2a (SERCA2a), the ryanodine receptor, and the sarcolemmal Na(+)-Ca(2+) exchanger was performed on LV tissue obtained before and after LVAD implantation. These paired data demonstrated an upregulation of all 3 genes after LVAD support. In tissue obtained from subsets of these patients, Western blot analysis was performed, and oxalate-supported Ca(2+) uptake by isolated sarcoplasmic reticular membranes was determined. Despite higher mRNA for all genes after LVAD support, only SERCA2a protein was increased. Functional significance of increased SERCA2a was confirmed by augmented Ca(2+) uptake by sarcoplasmic reticular membranes isolated from LVAD-supported hearts. CONCLUSIONS: LVAD support can improve contractile strength of intact myocardium and reverse the negative FFR associated with end-stage heart failure. The expression of genes encoding for proteins involved in Ca(2+) cycling is upregulated (reverse molecular remodeling), but only the protein content of SERCA2a is increased.

Left ventricular assist device-induced reverse ventricular remodeling.

Left ventricular assist devices provide chronic pressure and volume unloading of the dilated left ventricle in patients with end-stage heart failure. This is associated with reverse structural remodeling (normalization of the passive pressure-volume relationship), reverse molecular remodeling (increased expression of several genes involved in calcium metabolism that are down-regulated in heart failure), improved baseline contractility, and improved contractile response to increased heart rate and to beta-agonist stimulation. These findings indicate the profound degree of recovery of myocardial properties in hearts previously considered to have invincible end-stage heart failure.

The costs of rheumatoid arthritis: an international long-term view.

OBJECTIVES: To review the literature on the measurable direct and indirect costs of rheumatoid arthritis (RA) in industrialized countries from a societal perspective and to develop a template for international use. METHODS: A literature search using MEDLINE and other sources identified 153 relevant published articles, press releases, and so forth on the costs of RA and rheumatism from the major Organization for Economic Cooperation and Development (OECD) countries in English and other languages. Sixty-eight publications provide some economic data for analysis and are included in the bibliography. Twelve publications provide sufficiently detailed and robust information for inclusion in country overview tables. The concept of varied costs at different disease stages measured by years since diagnosis and Health Assessment Questionnaire (HAQ) scores is used to guide rational decisions in the allocation of scarce health care resources. RESULTS: Direct costs increase overproportionately during the course of the disease. The most important driver of direct costs is hospitalization, especially in moderate and severe RA. Costs of medication represent a comparatively small proportion of direct costs. Indirect costs caused by work disability can be substantially higher than direct costs, particularly in working-age patients. The total costs of RA to society, and the different cost components such as direct and indirect costs, are broadly comparable in industrialized countries by their order of magnitude. Major confounding factors for international comparison are different study methodologies and patient samples. CONCLUSIONS: The cost template developed in this article can be used to estimate the likely costs of RA to society for industrialized countries. It probably will underestimate indirect costs because of their incomplete coverage in the studies examined. A long-term perspective is needed for chronic diseases such as RA to assess the future effects of early interventions. Treatment in the early stages of RA that effectively reduces long-term disability has the potential to save substantial costs to society.

Structural and mechanical factors influencing infarct scar collagen organization.

Although large collagen fibers in myocardial infarct scar are highly organized, little is known about mechanisms controlling this organization. The preexisting extracellular matrix may act as a scaffold along which fibroblasts migrate. Conversely, deformation within the ischemic area could guide fibroblasts so new collagen is oriented to counteract the stretch. To investigate these potential mechanisms, we infarcted three groups of pigs. Group 1 served as infarct controls. Group 2 had the endocardium slit longitudinally to alter local systolic deformation. Group 3 had a plug sectioned from ischemic tissue and rotated 90 degrees. The slit altered systolic deformation in the infarcted tissue, changing circumferential strain from expansion to compression and increasing radial strain and shears and the variability of collagen fiber angles but not the mean angle. In the plug pigs, when deformation, matrix orientation, and continuity are altered in the infarct area, the result is complete disarray in the organization of collagen within the infarct scar.

Frequency-dependence of myocardial energetics in failing human myocardium as quantified by a new method for the measurement of oxygen consumption in muscle strip preparations.

Diastolic dysfunction at high heart rates may be associated with increased myocardial energy consumption. Frequency-dependent changes of isometric force and oxygen consumption (MVO2) were investigated in strip preparations from endstage failing human hearts exhibiting various degrees of diastolic dysfunction. MVO2 was determined by a new method which was validated. When stimulation rate was increased from 40 to 200 min-1 (n=7), developed force decreased from 16.5+/-4.3 to 7.9+/-2.9 mN/mm2 (P<0.01), diastolic force increased from 15.9+/-3.2 to 22.0+/-3.0 mN/mm2 (P<0.01), and total MVO2 increased from 2.6+/-0.6 to 4.7+/-0.9 ml/min/100 g (P<0.025). Resting MVO2 and resting force were 1.8+/-0.4 ml/min/100 g and 15.9+/-3.0 mN/mm2, respectively. After addition of 30 mm 2,3-butanedione monoxime (BDM) to inhibit crossbridges, resting MVO2 and resting force decreased by 46% (P<0.05) and 15% (P<0.01), respectively, indicating the presence of active force generation in unstimulated failing human myocardium. In each muscle preparation, there was a significant correlation between force-time integral (FTI) and total MVO2 (r=0.96+/-0.01). The strength of these correlations did not vary with the contribution of diastolic FTI to total FTI. The ratio of activity related MVO2 to developed FTI, an inverse index of the economy of contraction, increased depending on the rise of diastolic FTI at higher stimulation rates. In conclusion, in failing human myocardium, diastolic force development is occurring at the same energy expenditure as systolic force generation. Therefore, in muscle preparations with disturbed diastolic function economy of contraction decreases with higher stimulation rates, depending on the rise of diastolic force.

Functional implications of myocardial scar structure.

During healing after myocardial infarction, scar collagen content and stiffness do not correlate. We studied regional mechanics and both area fraction and orientation of large collagen fibers 3 wk after coronary ligation in the pig. During passive inflation of isolated, arrested hearts, the scar tissue demonstrated significantly less circumferential strain but similar longitudinal and radial deformation in comparison with noninfarcted regions of the same hearts. The observed selective resistance to circumferential deformation was consistent with the finding that most of the large collagen fibers in the scar were oriented within 30 degrees of the local circumferential axis. Furthermore, data from a previous study indicate that during ventricular systole these scars resist circumferential stretching, whereas they deform similarly to noninfarcted myocardium in the longitudinal and radial directions. We conclude that large collagen fiber structure is an important determinant of scar mechanical properties and that scar anisotropy allows the scar to resist circumferential stretching while deforming compatibly with adjacent noninfarcted myocardium in the longitudinal and radial directions.

Current practices of preoperative bowel preparation among North American colorectal surgeons.

In North America, the rate of infections following colorectal surgery decreased after the introduction of oral antibiotic bowel preparation against colonic microflora. Eight hundred eight board-certified colorectal surgeons were surveyed for their current bowel preparation practices before elective procedures. The 471 responders (58%) all use mechanical preparation: oral polyethylene glycol solution (70.9% of the respondents), oral sodium phosphate solution with or without bisacodyl (28.4%), and "traditional" methods of dietary restriction, cathartics, and enemas (28.4%). Most surgeons (86.5%) add oral and parenteral antibiotics to the regimen; 11.5% add only parenteral antibiotics, 1.1% add only oral antibiotics, and 0.9% add no antibiotics. Generally (77.8% of cases), oral neomycin and erythromycin or metronidazole are combined with a perioperative parenteral antibiotic. Most individuals start the preparation as outpatients the day before surgery, and the parenteral drugs are added to the regimen 1-2 hours before the procedure. The use of outpatient bowel preparation is increasing; however, patient selection is critical, and education is needed to reduce the rate of complications.

Enhanced regional deformation at the anterior papillary muscle insertion site after chordal transsection.

BACKGROUND: Clinical and experimental studies of mitral valve replacement have shown a depression of ventricular function after chordal transsection; most recent studies have proposed that this is secondary to a depression of local function near the papillary muscle insertion site. However, there is no direct experimental evidence for changes in local fiber shortening in the wall of the left ventricle overlying the papillary muscle. Accordingly, we investigated the effect of chordal transsection on left ventricular shape and on three-dimensional regional deformation of the myocardium near the insertion of the anterior papillary muscle. METHODS AND RESULTS: In six open-chest dogs, two sets of three transmural columns of radiopaque markers were implanted in the anterior wall, one set at the tip of the papillary muscle (basal) and one at the site of papillary muscle fiber insertion (apical). A Björk-Shiley mitral valve was placed in the left atrium adjacent to the native valve. Markers were then tracked with biplane cineradiography, and deformation was quantified with the use of finite strain analysis. Chordal transection resulted in reduced left ventricular end-systolic pressure and slowed relaxation. After chordal transsection, outward displacement of the ventricular wall and transverse shearing deformation were observed in the area of the papillary muscle during isovolumic contraction. Circumferential and radial strains during ejection were maintained at our basal site and enhanced on our apical site. CONCLUSIONS: Chordal transsection led to enhanced local shortening and wall thickening and regional strain nonuniformity. These results indicate that chordal transsection induces an unloading of myocardium at the papillary muscle insertion site and that the resulting heterogeneity of regional function is the mechanism for the reduced global function and slowed ventricular relaxation.

Depressed regional deformation near anterior papillary muscle.

The role of the papillary muscle in left ventricular function has received new attention. We hypothesized that regional mechanics of the left ventricular wall near the anterior papillary muscle are influenced by the papillary muscle insertion. We therefore studied three-dimensional regional mechanics in and near the anterior papillary muscle in anesthetized, open-chest dogs, using implanted radiopaque markers and biplane cineradiography. In seven dogs, deformation differed little between an anterior papillary muscle insertion site (PMA) and a more basal site (PMB) overlying the anterior papillary muscle. However, local shortening and wall thickening were depressed in both locations relative to anterior free wall sites (FWA, FWB) studied in five additional dogs. A distinct structural border was observed at the junction between the myocardial wall and anterior papillary muscle, which may preclude the use of homogeneous strain in that region. Data from within the anterior papillary muscle indicated that uniaxial measurements in the papillary muscle are extremely sensitive to the orientation of the measurement axis, possibly explaining the variety of papillary muscle shortening patterns reported by previous investigators.

Impaired subendocardial function in tachycardia-induced cardiac failure.

Chronic rapid ventricular pacing (CRVP) in many experimental models induces ventricular dilatation, reduced ejection fraction, and symptomatic congestive heart failure. We have investigated transmural mechanical function in the left ventricular (LV) wall of five Hanford miniature swine before and after CRVP-induced failure. Three columns of radiopaque markers 1 mm in diameter were implanted in the anterior LV wall through a median sternotomy. A pair of LV pacing wires were sutured into the myocardium, a pneumatic cuff was placed around the inferior vena cava (IVC), and two fluid-filled Silastic catheters were implanted into the LV apex. Two weeks after surgery, the pigs were suspended awake in a sling, and markers were tracked with biplane cineradiography. The hearts were paced for 3 wk (225-240 beats/min), and the study was repeated with the pacemaker off. Saline infusion and IVC occlusion were used to vary LV end-diastolic pressure (EDP) so control-to-failure comparisons could be made at matched LV EDPs. End-systolic strains in the circumferential (E11), longitudinal (E22), and transmural (E33) directions were quantified using finite element methods. There was a significant reduction in E11 and E33 for the subendocardium: in E11, from -0.27 to -0.18; in E33, from 0.83 to 0.46. There were no significant changes in subendocardial E22 or in any of the outer wall normal strains. These results indicate that CRVP causes substantial reduction of subendocardial, but not subepicardial, function; taken together with previous data indicating subendocardial hypoperfusion, these results support the contention that an imbalance between blood flow and oxygen demand plays a role in the etiology of heart failure in this model.

Prophylaxis in bowel surgery.

The busy colon and rectal surgeon deals daily with a sea of bacteria. Using good surgical judgment as well as time-honored techniques and innovative equipment the postoperative results are generally good. The role that appropriately administered efficacious antibiotics play in this scenario should not be underestimated and can only be realized when historical controls are evaluated. The results of these studies of antibiotic bowel preparation suggest that many different approaches may be equally effective in reducing infection after elective colonic resection. Certain features, however, appear to be common to most of the studies. 1 Oral antibiotic regimens with both aerobic and anaerobic activity (e.g., neomycin/erythromycin base) were used. 2 The oral agents were given in limited doses the day before operation. 3 Addition of systemic antibiotic agents without broad-spectrum coverage to the oral regimen generally did not improve the results. 4 Use of broad-spectrum parenteral antibiotic agents alone was associated with a lower infection rate than the use of systemic agents having only limited coverage. 5 Addition of a broad-spectrum parenteral antibiotic to the oral antibiotics may further reduce the postoperative infection rate. 6 Parenteral or oral antibiotics should be administered only for short periods of time during the perioperative period. Since the general acceptance of the approach outlined above, infection rates have decreased and the number of clinical studies reported has drastically decreased. The authors do feel, however, that there is a need for further study to outline possible benefits of other appropriate regimens (34).

Scar remodeling and transmural deformation after infarction in the pig.

BACKGROUND: Changes in stress and tissue material properties have been proposed as important mechanical factors that may influence infarct expansion and subsequent healing. Because such changes will be reflected by alterations in the finite deformation of the tissue, we examined the direction and magnitude of myocardial deformation after coronary ligation in the pig. METHODS AND RESULTS: Gold beads were implanted in the left ventricular free wall of five pigs. After ligation of the coronary supply to the region containing the markers, we used biplane cineradiography to reconstruct the three-dimensional deformations of the myocardium during single cardiac cycles as well as the remodeling deformations that occurred over time. Deformations were studied at 1 and 3 weeks after infarction. The analysis of single cardiac cycles revealed permanent loss of systolic shortening immediately after ligation. However, significant passive systolic wall thickening (P < .001) and large shears were observed at 3 weeks in regions composed almost entirely of collagen. The analysis of remodeling deformations at 1 week revealed infarct expansion with a predominant axis that varied widely. At 3 weeks, a 30% to 60% reduction in local tissue volume was measured in the infarct region, with the principal direction of scar shrinkage nearly circumferential in all animals (range, -2 degrees to 35 degrees). CONCLUSIONS: We conclude that infarct expansion and scar shrinkage may be controlled by different factors. In addition, we conclude that measurement of systolic wall thickening alone is not always adequate to assess postinfarction regional contractile function.

The relevance of pressure-sensitive paint to aerodynamic research.

Aerodynamic tests are designed to give information about the performance of a model when subjected to an airflow. The introduction of pressure sensitive paint provides a new method for obtaining the pressure distribution on the surface of wind-tunnel models. A paint, the luminescence of which is dependent on air pressure, is applied to the surface of the model and the pressure distribution is obtained from the image produced. This paper gives an explanation of this technique, a résumé of possible applications and some results from research performed at DRA Bedford.