Biology of cardiac overload / Cardiac image processing and databases
I 9 8 Selective alterations in the gene expression of calcium-regulating proteins In senescent rat myocardium
P. Assayag, D. Charlemagne, J. de Leirts, F. Boucher, S. Lortet, B. Swynghedauw, S. Besse. INSERM U127 and CanSotogy hopital Bichat, Paris ; Btoenerge'tique and UPRES-CNRS 12B7, University J. Fourier, Grenoble, France Senescence, as hypertension, results in alterations of contraction and relaxation In rat hearts. Age-related impairment of the calcium handling system in myocardium has been suspected, but documented only for sarcoplasmic reticulum (SR) Ca-ATPase, while severe LV pressure overload alters the gene expression of other calcium-regulating proteins, such as ryanodlne receptor and Na-Ca exchanger. To investigate the potential implication of those proteins in age-related alterations of myocardlal mechanics, we simultaneously studied, in both 4 month (adult, n = 13) and 24 month old (senescent, n = 15) Wistar rats, the expression of genes encoding for the 3 major proteins Implicated In myocyte calcium uptake, release or extrusion. mRNA levels of SR Ca-ATPase, ryanodlne receptor and Na-Ca exchanger, expressed in normalised densitometric scores, were quantftated in left ventricle by slot blot analysis. In addition, aortic systolic blood pressure (AoSBP) and left ventricular systolic pressure (LVSP) were recorded before sacrifice using a Millar ultraminiature catheter pressure transducer. Results (data are expressed as mean ± SEM): SR Ca-ATPase mRNA levels were decreased in senescent LV as compared with adults (0.98 ± 0.05 vs 1.18 ± 0.05 respectively, p < 0.01) without any concomitant hypertension (AoSBP134 ± 5 vs 127 ± 8 mmHg; LVSP: 127 ± 7 vs 122 ± 8 mm Hg, NS) or LV hypertrophy (LV weight / Body Weight 1.83 ± 0.08 vs 1.71 ± 0.04 mg/g, NS). There was no significant change in mRNA levels of ryanocDne receptor (1.08 ± 0.08 vs 1.12 ± 0.08 in adults, NS) or Na-Ca exchanger (1.29 ± 0.06 vs 1.15 ± 0.07 In adults, NS). In conclusion, senescence selectively decreases the gene expression of SR Ca-ATPase without modifying genes encoding for other Ca-handllng proteins, in contrast to severe mechanical overload. These results suggest that SR CaATPase is the main protein Implicated in calcium handling alterations occurring during aging.
CARDIAC IMAGE P R O C E S S I N G A N D DATABASES 1106 | The surface Integration of velocity vectors technique for quantifying cardiovascular flow In vivo
JoaJdm Brandberg1, Birgltta Janerot Sjoberg 1 , Peter Wodlin 1 , Ying Sun 2 , Per Ask 2 . ' Unkoping University, Sweden;2 University of Rhode Island, USA We have designed the Surface Integration of Velocity Vectors (SIW) echocardlographlc method for angle-independent determination of cardiac flow (1). The aim of this study is to evaluate the method and to Improve the in vivo flow estimation by modifying data acquisition and by developing a computerized algorithm for S I W flow calculations. Method: Time-corrected Doppter data (Vingmed CFM 800) from an entire heart cycle was reconstructed from flow velocity data collected for consecutive heart strokes using the time delay device previously developed by us Using a combined 3.5 MHz imaging and 2 MHz ultrasound Doppler-probe (apical approach) color flow velocity information was measured from two perpendicular planes of the left ventricular inflow area. Flow was studied according to the S I W approach in a spherical transducer-centered control surface. An Incremental delay of 20 ms for each heart cycle was applied. To Improve the velocity measurements of high and low velocities, data collection was made both with a high and a tow setting of the wall-filter. These acquired data were combined at the analysis. The raw data collected was translated to an ASCII file before the actual S I W calculation, where stroke volume was obtained by Integration of the velocity information during the heart cycle. The results were compared with stroke volume determination from the aortic annulus using parastemal ultrasound 2Dimaglng for flow-area calculation and suprastemal pulsed Doppter registration for aortic flow velocity measurements. Results: The analysis was possible to automatize and velocity Information from two planes as well as different wall filters could be Implemented in the volume flow calculation. Preliminary data from stroke volume determination agrees well (8% oJfference, 67 ml by S I W versus 62 ml by the Flck equ.) Conclusions: The application of computerized S I W algorithm shows promise In patients but further improvements are planned. The method takes Into account 3D differences in flow profiles and with the modifications performed it reduces the loss of velocity Information close to the walls. [1] 1. Sun Y,P Ask, B Janerot S)fiberg, L BdenvaD, D Loyd, B Wranne A new method for determining, pulsatile volumeflowrate by surface Integration ol velocity vectors from biplane Dooptef echocardtograma. J Am CoB Cardlol 23: 239A, 1994.
9 9 | Nitric oxide synttiase Inhibition does not restore the depressed contraction of myocytes from failing human ventricle
Sian E. Harding, Crispin H. Davles, Philip A. Poole-Wilson. National Heart and Lung Institute, Imperial College, London, UK The contraction of single ventricular myocytes isolated from failing human heart Is depressed compared to those from oon-falJIrM subjects. It has been shown that nitric oxide (NO) synthesis is Induced In faffing ventricular myocardium. In guinea-pigs with septic shock, where induction of NO synthesis Is widespread, NO synthase inhibitors can reverse the depression of contraction seen fn single ventricular myocytes; We bave-therelota -attempted lo oaxatsa the decreased contractility of myocytes from falling human heart with these compounds. Myocytes were isolated from the ventricular myocardium of patients with end-stage failure due to Ischaemic or Idlopathic dilated cardiomyopathies: no qualitative difference was seen between these aetiologies In any of the findings reported here. Cells were stimulated at 02 Hz in Krebs-Henselett solution with 1 mM Ca 2 *: basal contraction amplitude (% cell shortening) was 2.8 ± 0.5%, n = 7 patients. Supervision with 0.1 mM L-NMMA for 10 mln did not significantly increase amplitude, which was a maximum of 3.0 ± 0.5% within this time. The contrastien deficit was more evident at high stimulation frequencies. Myocytes from non-failing hearts had an amplitude of 2.7 ± 0.4% at 6.2 Hz, which increased to 3.9 ± 0.7% at 1 Hz (n = 9, P < 0.05), while the corresponding figures for failing were 2.1 ± 0.2% at 0.2 Hz and 1.8 ± 0 . 3 % at 1 Hz(n = 11). Application of 0.1 mM L-NMMA to cells from 3 falling hearts did not restore the positive inotroptc effect of frequency (ampttude 1.9 ± 0.4% at 0.2 Hz and 1.8 ± 0.4% at 1 Hz). We conclude that blockade of NO synthesis does not restore the depressed contraction of myocytes from the failing human heart.
1107 Echocardlographic tissue characterization In heart transplantation: does it help In rejection diagnosis?
E. Ueback, R. Koch, I. Hardouin, R. Hetzer. German Heart Institute Berlin, Augustenburger Platz 1, 13353 Berlin, Germany The aim of this study was to assess whether texture classification of echocardlograprilc Images can Iitiprove the diagnostic ability of echocardiography for detecting cardiac rejection. During echocardlographic examination, short axis image was on-line digitized. Fdowing, a region of interest (ROI) was manually placed in the anteroseptal segment of myocardium. The texture of the ROI was then characterized by 51 parameters, describing features of Its histogram, co-occurrence and runlength matrices and tts power spectrum. For classification purpose, we chose a neural network of the type "back-propagation", composed of three layers with 51,60 and two neurons. As learning set, 100 echocardlograms were used with known cflagnosts of rejection or no rejection, confirmee1 by eiapsy. The neural net was able to recognize the whole learning set and therefore could be used for further classification of following echocardlographic Images. This method was then applied for the classification of 165 echocardiograms acquired In 18 patients after heart transplantation. After each echocardiographic examination, texture statistics were computed. Their classification through the neural network were compared with the clinical diagnosis obtained from all other nonlnvasive monitoring procedures and from endomyocardlal biopsy. The sensitivity of texture classification for recognition of cardiac rejection was 96% and the specificity 84%. We conclude that cardiac rejection can be recognized by echocardiographlc tissue characterization. Thus a new procedure for rejection monitoring Is available which, in combination with other nonirrvasJve methods, can be appHed cltnlcalfy.
Cardiac image processing and databases
1108 | Should the ACC guidelines for digital coronary anglography be modified?
Sigmund Sittrer, Rolf D6rr, Gunnar ZincDer, Hotger MQtillng, Thomas Dlebel. Dr. MOIier Hospital, Munich, Germany According to the ACC/ACR/NEMA guidelines, the film for coronary angiography should be replaced by digital technology with recordable CD (CD-R). The recommended lossless data compression (JPEG 2:1) results In a data flow of approx. 3 MB/s. This data flow, however, prevents viewing angiograms in real time directly from CD-R, even with the latest "high-speed* CD-player technology. Data have to be time consumingly copied first to hard disk. We therefore assessed in a prospective, randomized and blinded study with 1440 evaluations whether higher JPEG-compresslon rates actually alter clinically relevant Information. Angiograms using lossless compression as the reference were classified as follows:
Ouatty Better Equal Good Acceptable Unacceptable Digital compression rates 5 1 12 42 90 36 0 6.1 2 41 106 31 0 71 1 27 101 51 0 9.1 1 29 106 44 0 11.1 1 2B 102 49 0 14.1 1 22 97 60 0 221 0 17 76 84 3 43:1 0 1 1 25 153
(ODBC) communication driver are installed for easier use of x-base-standard databases. Analogue-digital signal converting and linking with central net is applied for most sophisticated diagnostic equipment Decision making support software (measured parameter limits based, Bayes theorem based and full expert-system (MedExperr*) is incorporated. ES is used in years 1995-86. Goal: any relevant patient information (diagnostic or therapeutic) is available or any link from diagnostic related groups (DRG) is affordable. Simulation and predicting of all potentially risky or advantageous Interventions, decisions or interconnections are possible. During the use of such one complete Information system with ES, the complication rate and cost of invasive and surgical intervention Is decreased. Some of data for the period 1993-96 are represented In table:
Procedure: CATH - contrast media usage (ml)* CATH - catheter changes/procedure* CATH - X-ray scopy duration (min)* Post-CATH ICUmosptal stay (days)' EfcB - mean number of speefcnena" EMS - hemopertcanSum" EMB-atrialflbrilatkMi" EMB - ventricular tachycardy"* EMB-AVbtock 3 degree" Before ES 160 4.7 57 0.7/3.8 6.1 4 (0.62%) 2(0.31%) 2(031%) 1 (0 16%) During ES 135 4.3 49 0.5/3.3 7.6 0 0 1(0 9%) 0
Conclusions: Since a compression rate of 7:1 does not lead to a visible deterioration of digital coronary angiograms and would allow reviewing them In real-time from CD-R, a modification of the ACC/ACR/NEMA guidelines should be considered.
CATH - right » left cathetsrizaton + ventricutography + coronarography f" total 6610 patients, 4800 before, 1810 during ES use); EM8 = EndoMyocanfial Biopsy (*• total 752 patients (from 1985.), 640 patients before, 112 during ES use)
1111 [ A World Wide Web-accessible two-dimensional gel electrophoresis database for human heart proteins 1109 | Detection and visualization of non-concentric coronary stenoses by a model-based correlation method
S. Krass, R. Brennecke, T. Voigtiander, H.-J. Rupprecht, J. Meyer. 2nd Medical Clinic, University Mainz, Germany The assessment of the severity of coronary stenoses Is restricted due to the limited number of angiographic projection planes during cardiac examination. When examining geometries of coronary stenoses, many of them are not detectable due to narrowing but only due to the haziness In anglographic Images or in intracoronary ultrasound (ICUS) Images. ICUS Is still limited to very few Indications The goal of this study was to develop and to evaluate a model-based correlation (MBC) method for the detection and visualization of coronary stenoses which are not recognizable In angtograms. Methods: Anglographic Images of coronary arteries were simulated using pre-lnterventlonal ICUS Images of 20 patients with non-concentric coronary stenoses. From these, those projections were chosen which snowed minimal luminal narrowing. These angiographic images were examined by two observers to determine whether coronary stenoses are visually detectable. All images were analysed using the MBC algorithm. This algorithm compared the line profiles of the coronary arteries with the reference line profile of an Ideal circular vessel assuming the same diameter as the coronary artery. The reference line profile was produced by a computer simulation of the anglegraphic imaging process. The correlation function of coronary line profile and reference profile was displayed. In addition, the difference between coronary and reference profile was visualized by color coding and by 3D display. Results: By the visual examination, In nine out of twenty anglographic images no coronary stenoses have been detected, whereas the correlation functions of coronary line profiles and reference profiles were significantly (p < 0.01) reduced In 18 cases. Both visualization methods allowed to detect the pathologic geometry of the coronary arteries. Conclusion: The MBC algorithm Is able to detect and visualize pathologic coronary geometries which are not recognizable in angiograms. This new tool for the diagnosis of coronary heart disease, together with conventional quantitative coronary angfography, can reduce discrepancies between ICUS and angiographlc diagnosis. K.P. Plelssner, S. Sander, H. Oswald, V. Regitz-Zagrosek, E. Fleck. Dept. Internal Medicine, Cardiology/Anglology, Vlrchow-Klinikum of the Humboldt University and German Heart Institute Berlin, Germany The World Wide Web (WWW) allows the transmission of multimedia) information over the Internet Thus, the WWW provides the possibility to publish own data on human myocandlal proteins obtained by two-dimensional gel electrophoresis in an immediate and attractive way. Therefore, the WWW-eccessibJe database •HEART-2DPAGE1 was developed. Methods: A 2-D gel protein database represents a combination of gel images and descriptive Information for the proteins. The proteins are described by several categories as protein name, molecular mass, isoelectrical point, amlno acid composition, methods of identification, accession number to protein sequence databases, comments, gene name, etc. For a user-friendly application of the database the representation of silver stained gel images, interactive viewing capabilities as magnification of gel regions and the presentation of the position of proteins have to be considered during the construction. Our database allows the retrieval of descriptive information on proteins listed in tables or interactively by mouse-clicking on a protein spot within a gel image. Using the protein name the position of the protein on the gel is marked. Additionally, one can search for protein name or substrings. The creation of clickable spots overlaid by crosses was carried out by the use of the "mapedlf-program, the graphics library "gd" and the client/server principles of the HTML-language for the WWW. Especially, the interactive viewing capabilities are realized by several PERL-scripts and C-programs using the Common Gateway Interface (CGI) mode. The accession number enables WWW-links to protein sequence databases to obtain detailed functional and structural descriptions. Results: The database considers that some human heart proteins are chamber-specific (atrial, ventricular). The descriptive Information of nearly 50 protein spots for each heart chamber Is retrievable. Using the Mr/pl axis given on the entire gel Image the approximate molecular mass and rsoelectrical point of nearly 1500 protein spots can be obtained. The database Is referenced in the WORLD-2DPAGE of the ExPASy molecular biology server and can be accessed at the Uniform Resource Locator http://www.ctiemie.fuberUn.d8/user/pleiss. Conclusion: A WWW-accessible gel protein database was created as a comfortable and user-friendly method of information exchange between laboratories dealing with human myocardial proteins.
110 Cardiology (Internal diseases) database and expert
system for risk predicting of invasive cardiac intervention
S. SrrJc, i- Karadzic, R. Jung, M. Stajnlc, D. Benc, D. DebeljacW, A. StojSIc, D. ivkov-Saponja, N. Secen, D. StojSc. Institute for Cardiovascular Diseases, Clinic of Cardiology, University of Novi Sad, Yugoslavia In our Institute (Cardiology clinic: 2100 cathetertzations/year and CartBosurgery cflntc: 1500 open heart surgery/year), we projected and installed one complete hospital information system with patient arid hospital management and decision making support-expert system (ES). Modified and expanded international classifications of cSseases (ICD 10), procedures (ICP) and drugs (ATC) are used. On 2-processor PC-s, Unix System V and Windows* with Relational Data Bases Management System (RDBMS) and Open Data Base Connectivity