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Myocyte Degeneration and Cell Death in Hibernating Human Myocardium

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Myocyte Degeneration and Cell Death in Hibernating Human Myocardium View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector JACC Vol. 27, No. ‘7 June 19964577-85 1577 MYOCARDIAL ISCHEMA Myocyte Degeneration and Cell Death in Hibernating Human Myucardium ERNST R. SCHWARZ, MD, JUTTA SCHAFER, MD,* JUERGEN VOM DAHL, MD, CARSTEN ALTEHOEFER, MD, BEATE GPOHMANN, TA,* FRiEDRICH SCHOENDUBE, MD, MS, FLORENCE H. SHEEHAN, MD.t RAINER UEBIS, MD, UDALRICH BUELL, MD, BRUNO J. MESSMER, MD, FACC, WOLFGANG SCHAPER, MD,* PETER HANRATH, MD, FACC Aachen am-l Bad Nauheim, Germany; and Seattk, Washington - --. O&etives. Tbe aim of this study wns to analyze the morpho- logic characteristics of myocyte degeneration ieadiag to replete- etai proteins titia a& aipita-actinin. Eiectroi microsc&of the q eot ftbrosis in hibernating myocardium by use of electron ceil organeiies and immunoldetochemlral aaaiysis of the eytasimi- microscopy and immunobistochemkai tecimiques. etonsbowedasimilarityintbedegweofd aiteNuone. Baekgtwmd. Data on tbe uitrastructure aad the cytoskeieton of Group 1(0 = 11) replusellted patients with ouiy aliuor atrucwai dterations, whereas group 2 (II = W) showed severe morpitkgk or deiayed tkmctionai recovery might be due to a variable degree of degeuerative cboges. Wall motion abnormalities shrewd pastup cardiomyoeyte degeneration in hiberaating mywardium. emtive improv~ets, and msdaar imaghg mealed a per&&m Me&oak In 24 patients, regionai waii motion abaonuaiities metabolism mismatch wit&out signllkmt di&- between the were analyzed by use of the cwtteriine method before and 6 f 1 PUPS. months after coronary artery bypass surgery. Preoperative tecimetium-9Pm sestamibi uptake was measured by singi~photoa emission computed tomograpay for assessing regjonat perfkufion. Fiuorinel8 Buorodeoxvvu~se uptake was measured by positron tbe siveti&of morpi&gk emission tomography to assess giwose metabolism. Transmwal nor the functionai outcome ailer revawkktbm. IBe insu4k biopsy specimeiii were taken during cownary artery bypuss dent aet ot wifqresefvatloa ia hibernating myocaniinm aiay lead surgery tkom the center of the hypocuntrac4iie aRp of the anterior toeprolyesbivcStnrttUrsidcOMDlPUoaattb~ttlrumpletePaJ wuii. detayfd reawery of function nfter rmtorntion of bioad flaw. Resuk. ‘lRe myocytes showJ varying signs of mild-to-severe (JAm Cop Cd&d 1%36;29:1599-83 degenerative changes and an increased degw of tlbrosis. Immu- -- Long-term reduction of coronary blood flow is associated with ccntiy been shown to predict recovery of regional wall motion reduced contraction and altered cellular metabolism but with and \hus maintain mykardiai viability (4,9,12-14). That con- improved or normalized regional dysfunction after successful tractile tunction can resume rather quickly (15) or can be revascularization, termed myocardiul hibernation (l-3). Im- delayed after blood flow has been restored indiites a time provement of wall motion in hibernating myocardium can be dependence of structural remodeling to rebuild energy stores achieved by coronary revascularization hy either angioplasty and cellular contractile material (16). Histologic studies are (4-7) or coronary artery bypass surgery (8 -1 I). Preoperative scarce and show moderate morphologic alterations and a slight metabolic imaging hy positron emissnn tomography has rc- increase of connectke tissue (17-U). In the present study, morphologic characteristics of myocardiai hibernation were sassed by electron microscopy and immunohistochemical techniques. MethOdS Patids. Twenty-four patients (21 men, 3 women; mean [-SD] age 60 2 8 years, range 43 to 71) underwert coronary angiography and biplane ieft ventricular angiography. Patientb prospectively recruited fulfilled the following inclusion criteria: 1578 SCHWARZ ET AL. JACC Vd. 27. No. 7 STRUCTURAl. DEGENERATtON IN tllRF.RNATtNG MYOC‘ARI~IUM ,““a’ 1996:1577-t@ 1) anterior wall motion abnormiilities; 2) stenosis (>7OQ) or occlusion of the left anterior descending coronary arlcry; 3) angina pectoris symptoms and objective clectrocardio- graphic (ECG) criteria for ischemia at rest or during exercise: 4) clinical indication for coronary revascuiarization; 5) coro- nary anatomy suitable for coronary artery bypass surgery; 6) persistent R waves in the anterior leads of the ECG; 7) absence of any history or ECG changes for previous anterior transmu- : ral infarction; 8) evidence for reduced perfusion but main- 22 tained viability of the anterior wall by nuclear imaging. B. RCA The study pro!ocol had been dpproved by the institutional Figure 1. The “polar target” of the left ventricle from apex (center ethical review board, and patients gave written informed region. I) IO base (outer circle region, 4). The upper part represents consent before participation. the anterior wall, the lcrwer part the posterior wall, with the septal lefI and the lateral wall of the left ventricle at the dght side. Regional Coronary and left ventricular ao&,rapby and regional uptake of technetium-99m sestamibi by SPEC.. and fluorine-M Iluoru- wall mation analysis. Cardiac cathelcrization was performed deoxyglucosc by positron emission tomography was exyl<ssed as by use of Judkins technique, and angiograms were recorded on percent to the rrgion of maximal perfusion (100%). For this study, only 35mm tine lilm with SO frames/s for further quantitative data in the Icfi anterior descending coronary (LAD) territory were analysis. Left ventricular angiogrlphy at baseline and at assessed with exclusion of Ihe scptal region. RCA = right coronary artery; RCX 7 circumflex artery. follow-up was obtained ia the 30” right anterior oblique and 6cp left anterior oblique view using 40 ml iopamidol (612 mg/ml) injected at 15 ml/s. Quantitative analysis of the ventriculograms, without knowledge of clinical or nuclear data fluorodcoxyglucose (Department of Radiochemistry, Nuclear in randomized order, was performed at the Cardiovascular Research Center, Juelich, Germany) were injected intrave- Training and Research Center, University of Washington, nousiy as a slow bolus. After the tracer was injected, static Seattle, Lashington. Left ventricular volume and global ejec- ungated imaging was initiated 30 tn 45 min using an ECAT tion fraction were calculated by the area length method (24). 953/15 scanner (Siemens) and lasted for 30 to 40 min. Because Regional wall motion in the distribution territory of the left of the one-block ring configuration of the scanner providing 15 anterior descending corona? artery was analyzed from the transaxial slices over a S-cm field of view, at least two adjacent right anterior oblique projection using the centerline method bed positions were necessary to cover the entire heart. Trans- and is expressed in units of standard deviation of the normal axial images were reconstructed with a Hanning filter (cutoff mean (25,26). Wall molnm was computed as the mean motion frequency 0.4) in a 64 X 64 matrii and a defined zoom factor of chords lying in the mos1 abnormally contracting region (Icft of 1.2446 to ;lbtain the same in-plane pixel size m the anterior descending coronary artery center), whcrcas wall conespondine S?ECT images. Consecutive pairs of positron motion of the remaining left anterior descending coronary emission tomographir slices were combined to achieve an artery territory was deIined aa left anterior dcxcnding coro- identical axial pixel size for positron emission tomography and nary artcry pcriphcry. SPECS imaging. Nuclrrrr irn&rg. Nuclear imaging of myocardial perfusion An&k of SEC’T imaging and posittvn emission tomo- and mclabolism followed standard promcols at our institution gaphic data. The tramaxial positron emission tomographic (27.28). Imaging was performed 2 z 2 weeks after coronary image files were converted to the str’;cturc cI’ the SPECT angiography and 2 + 2 weeks before bypass surgery. imaging files and transferred to the MuDelta sys!:m using a Single-photon emission computed tomography (SPECT). Pa- local area network. Regional Tc-99m sestamibi and F-18 tients were studied at rest after injection of 10 mCi of lluorodeoxyglucose uptake were expressed in percent of the technetium (Tc)-99m sestamibi (Cardiolite, DcPont). Imaging uptake in the region with maximal sestamibi uptake (27) (Fig. was initiated 1 to 2 h later after a light meal to reduce I). A concordant sestamibi reduction <SO% and fluorodeoxy- gastrointestinal activhy. Data were acquired using a Gamma- glucose uptake <5(14/n was defined as a scar, whereas reduced uuucs KO’l A double-head cnmora (Siemcns) equipped with a scstdmibi upldkc but preserved fbJorodeoxyglucose activity low-cncrgy all-purpou: collimator allowing a simultaneous (270%) rcprcscntcd a perfusion/metabolism mismatch (28). Ml” rotation (18(P for each camera head) with 2 X 30 steps 01 Coronary revascularizatioa. Coronary artery bypass sur- (i’ each. TranUxial slices (h.?S-mm thickness) were recon- gery was performed by use of sIandard techniquei under \trucIcd using :I Rutterw~~rth liltcr third order and a cuboff cardioplcgic condibon with internal mammary anery grafting frcyucncy of 0 5 on a MaxDelta computer 5ysIcm (Sicmcnc. to the Icft anterior deycnding u)ronary artely, Surgeons Gcrmanyl. attempud to perform complete rcvasculariition if Iechnifally Posirnm emi.uictn rc~nic*+~ A transmission an wita feasible. The interval between coronary angiography and sur- pc;formcd bcforc metabolic imaging to correcI for tissue gical revascularization WIZI 4 2 2 weeks. phoIon rt1muation u&g a retratiabk germanium-611 wurce. MydardU
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