Assessment of Left Ventricular Relaxation by Doppler Echocardiography

Transcription

1 26 ssessment of Left Ventriculr Relxtion by Doppler Echocrdiogrphy Comprison of Isovolumic Relxtion Time nd Trnsmitrl Flow Velocities With Time Constnt of Isovolumic Relxtion Yngvr Myreng, MD, nd Otto. Smiseth, MD, PhD Isovolumic relxtion time (IVRT) nd events of erly trnsmitrl flow mesured by Doppler echocrdiogrphy were vlidted ginst the time constnt of left ventriculr relxtion (i-) in open-chest dogs. During incresed inotropy (by isoproterenol infusion) t constnt prelod, enhncement of relxtion ws indicted by decrese in from 48±12 (men± SD) to 33±5 msec (p=.4) with concomitnt decrese in IVRT from 74±18 to 38±8 msec (p=.3). During decresed inotropy (by proprnolol infusion) t constnt prelod, slowing of relxtion ws indicted by n increse in T from 4±8 to 51±+13 msec (p=.2) with concomitnt increse in IVRT from 71±+15 to 83+±21 msec (p<.5). significnt correltion between chnges in nd chnges in IVRT ws found (r=.66, p<.1). In contrst, when left ventriculr end-distolic pressure ws incresed from 7±2 to 24±4 mmhg t constnt inotropy, r incresed from 47±f14 to 64±25 msec (p=.3), wheres no chnge in IVRT ws observed (76±+19 nd 71±+19 msec, respectively). ortic pressure ws not significntly chnged during ny intervention, nd hert rte ws kept constnt by pcing. Pek erly trnsmitrl velocity ws unchnged by proprnolol but incresed during isoproterenol nd sline infusion (p<.1 nd p<.1, respectively). During volume loding, left tril V wve pressure ws positive predictor (p=.2) nd r ws negtive (p=.6) predictor of the flow-djusted trnsmitrl flow velocity. Thus, IVRT reflected r during chnging contrctility t constnt prelod, but not during incresing prelod. Prolongtion of IVRT s sign of slowing of relxtion during volume loding ws countercted by n erlier opening of the mitrl vlve cused by incresing tril pressure, thus leving IVRT unchnged. (Circultion 199;81: ) bnorml relxtion of the left ventricle (LV) is present in vriety of crdic diseses nd is n erly mnifesttion of LV dysfunction.1-5 The most ccepted index of LV relxtion is the time constnt of LV pressure decy (r).6 However, clcultion of r requires LV pressure recordings. ccordingly, ttempts hve been mde to ssess LV relxtion noninvsively by M-mode7 8 nd Doppler echocrdiogrphy9' nd by rdionuclide technique.11"12 Isovolumic relxtion time (IVRT), comprising the time intervl during which the principl LV pressure fll tkes plce, cn be mesured by combining phonocrdiogrphy nd M-mode echocrdiogrphy, by M-mode technique lone, or from the From the Institute for Surgicl Reserch nd Medicl Deprtment B, Rikshospitlet, University- of Oslo, Oslo, Norwy. ddress for correspondence: Dr. Yngvr Myreng, Medicl Deprtment B, Rikshospitlet, N-27 Oslo 1, Norwy. Y.M. is recipient of reserch fellowship from the Norwegin Council on Crdiovsculr Reserch. Received Februry 9, 1989; revision ccepted ugust 23, signls of vlve movements by Doppler echocrdiogrphy. We hve previously reported tht reproducible mesurements of IVRT cn be chieved by Doppler technique in ptients.13 The im of the present study ws to vlidte IVRT nd events of erly trnsmitrl filling s mesured by Doppler technique ginst r during chnging inotropy nd LV filling pressure, respectively. This ws done in n experimentl model in dogs, which llowed monitoring of the pressure determinnts of IVRT. Methods niml Preprtion The experiments were performed in 11 dogs weighing 23±2 kg (rnge, kg). nesthesi ws induced with thiopentone nd continued with intrvenous morphine injections (5-1 mg/hr) supplemented with sodium pentobrbitl s needed. The dogs were ventilted with room ir by use of Servo Ventiltor (model 9B, Siemens Elem, Stockholm, Sweden). Blood gses nd body temperture were

2 Myreng nd Smiseth Doppler Indexes of Left Ventriculr Relxtion 261 kept within physiologic rnges. The chest ws opened through medin sternotomy, nd the pericrdium ws left open throughout the experiment. Through peripherl vessel incisions high-fidelity ctheter (Millr, Houston, Texs) nd fluid-filled reference ctheter were plced in the left ventricle. fluidfilled ctheter ws dvnced to the scending ort. In eight of the dogs, ctheter ws introduced into the left trium by mens of the left uricle; four of these dogs received fluid-filled ctheter, nd the other four dogs received Millr ctheter, which ws zero-referenced ginst the LV fluid-filled ctheter during long distses. The fluid-filled ctheters were connected to trnsducers (model E 84, SensoNor, Horten, Norwy). Both externl jugulr veins were cnnulted to llow for rpid volume infusion. The pressure trcings nd electrocrdiogrms were printed on pper t speed of 2 mm/sec by recorder (model 26 S, Gould, Clevelnd, Ohio). Sinus node function ws bolished by injection of 2% formldehyde in the frontl spect of the right tril wll to the left of nd below the superior cvl vein. Pcing electrodes were sutured to the right tril ppendge nd to the frontl spect of the interventriculr septum immeditely subjcent to the trioventriculr groove. The hert ws pced in trioventriculr sequence (trioventriculr dely, 13 msec) t rtes below 118 bets/min. Doppler Echocrdiogrphy dedicted Doppler instrument (SD-1, Vingmed Sound, Horten, Norwy) with 3-MHz probe ws used for the Doppler mesurements. During dt cquisition, the dog ws plced in the semilterl left decubitus position. The Doppler probe ws pplied mnully directly on the pex. Continuous wve mode ws used to locte the highest velocities nd, thus, to lign the ultrsound bem prllel to the flow direction, wheres pulsed wve mode ws used for recording the signls. In the mesuring depth (4-6 mm) the smple volume ws pproximtely 7 mm in dimeter nd 7 mm in length. The smple volume ws plced in the depth t which the spikes cused by mitrl vlve opening were most distinctly seen in the Doppler spectrum nd mplitude trcing; this corresponds to the tip of the mitrl vlve.14 Cre ws tken to disply distinct ortic vlve closure nd mitrl vlve opening signls simultneously. Trnsmitrl inflow velocities were visulized in the sme spectrum (Figure 1). Probe position nd ngultion were djusted to chieve optiml signls s judged from the spectrl disply nd the udible Doppler shift. ll Doppler recordings were videotped. Procedure Pressures nd Doppler signls were recorded simultneously during suspension of ventiltion for 15-3 seconds. trioventriculr sequentil pcing ws used to keep hert rte constnt (rnge, bets/min) during ech intervention. *_ m, \ kitj ' ' time (s) 2 VCIl p, MVO time E-wve FIGURE 1. Upper pnel: Recordings of trnsmitrl flow velocities from the picl pproch. Positive velocities (bove zero line) depictphsic trnsmitrl distolicflow, nd negtive velocities (below zero line) depict systolic left ventriculr outflow. Lower pnel: Line drwing demonstrting the identifiction of ortic vlve closure (VC) nd mitrl vlve opening (MVO). E-wve depicts the mximl velocity during erly inflow. In seven dogs, inotropy ws chnged by isoproterenol nd by proprnolol. fter bseline mesurements, isoproterenol ws infused intrvenously t rtes of 5, 1, nd 15,ug/kg/min, nd recordings were cquired during stedy stte t ech infusion level. LV end-distolic pressure (LVEDP) ws kept constnt by infusing sline. fter the isoproterenol infusion hd been terminted, t lest 1 minutes ws llowed for return to bseline. Then 1 mg/kg proprnolol ws injected intrvenously. LVEDP ws djusted to bseline, nd the recordings were repeted t lest 1 minutes lter. In 11 dogs, LV distolic pressure ws incresed by rpid sline infusion. Proprnolol (1 mg/kg) ws injected intrvenously t lest 1 minutes before the volume loding ws strted. Pressures nd Doppler signls were recorded t three different levels of LVEDP: less thn 1 mm Hg, mm Hg, nd greter thn 19 mm Hg. Dt nlysis nd Clcultions Doppler mesurements. The Doppler recordings were replyed from the sound trck of the videotpe. This yields high qulity Doppler signls, identicl with the rel-time recordings. On the frozen imges, -1

3 262 Circultion Vol 81, No 1, Jnury 199 TBLE 1. Invsive nd Doppler Chrcteristics During Isoproterenol, Proprnolol, nd Sline Infusion Isoproterenol Proprnolol Sline infusion (gtg/kg/min) (mg/kg) (EDP, mm Hg) Control Control r (msec) ±8* * * ±17* 64±25* symptote (mm Hg) -6±4-3±7-8±3-6±6-3±4-4±2-4±2-7±1-6±4 IVRT (msec) * 43+7* 38±8* 71±15 83±21* 76±19 76±23 71±19 T (msec) ±9 72±5 69±7 71±1 7±1 73±5 78±8 E (cm/sec) 8±26 94±27* 97+26t 16±25t ±22 68±12 83±2 9±24t Dec (m/sec2) 6.3± ±2.8 6.± ± ±.7 6.3±1.9* * LVEDP (mm Hg) 7±2 8± ±2 6±2 7± ±2t 24±4t V wve (mm Hg) ±3 1±2 8±4 9±6 9±3 15+3t 3±4t ortic SBP (mm Hg) ±8 111±9 92±13 89± ±17 99±17 ortic DBP (mm Hg) ±1 45±11 45±8 5±12 59±12 58±1 62±12 ortic end-systolic BP (mm Hg) 7±2 67±11 65±17 69±16 64±15 64±16 71±8 79±12 75±6 Hert rte (bets/min) ±6 111±6 14±15 14±15 1±19 99±18 96±18 Vlues re men± 1 SD. EDP, end-distolic pressure; i, time constnt of left ventriculr isovolumic pressure fll; IVRT, isovolumic relxtion time; T, ccelertion time; E, erly trnsmitrl velocity pek; Dec, decelertion fter E; LVEDP, left ventriculr EDP; V wve, left tril V wve pressure; SBP, systolic blood pressure (BP); DBP, distolic BP. *p<.5 vs. control or EDP<1 mm Hg (sline infusion). tp<.1 vs. control or EDP<1 mm Hg (sline infusion). tp<.1 vs. EDP<1 mm Hg (sline infusion). time intervls nd velocities were mesured with clipers by use of the built-in nlysis system of SD-1. ccelertion nd decelertion between cliper positions on the disply were computed utomticlly. The spikes in the Doppler spectrum produced by the ortic vlve closure nd mitrl vlve opening were esily identified t the end of LV systolic outflow nd t the strt of mitrl inflow, respectively. The timing of vlve movements ws enhnced by Doppler mplitude trcings nd by using minimum of the compression function.15 IVRT ws mesured from the strt of the ortic vlve closure signl to the strt of the mitrl vlve opening signl (Figure 1). The erly trnsmitrl flow (E) velocity ws mesured t the pek. Lte velocities were not optimlly recorded in ll dogs becuse of the different direction of the trilly induced inflow; however, whenever recorded, the erly nd lte velocity peks were clerly seprted, even t the highest hert rtes (118 bets/min). ccelertion time ws mesured from the mitrl opening to the E velocity. Decelertion of erly inflow ws mesured between the E velocity nd point hlfwy down the following slope. t lest four consecutive bets were verged. In ddition, in ech dog three seprte Doppler recordings were performed t bseline to ssess the vrition of the Doppler prmeters. Pressures. r from minimum dp/dt to 5 mm Hg bove LVEDP ws clculted by the derivtive method s described by Crig et l.16 LVEDP ws mesured immeditely before the rpid upstroke in the LV pressure trcing. Left tril V wve pressure ws recorded in eight dogs. The systolic, distolic, nd end-systolic (dicrotic notch) ortic pressures were mesured from the ortic pressure trcing. Sttistics The results re presented s men±+1 SD. The dt were nlyzed by two-wy nlysis of vrince, Student's t test with Bonferroni correction, nd single nd multiple liner regression nlysis (lest squres). The reltive importnce of independent vribles in the multivrite nlysis ws ssessed by the stndrdized regression coefficients: The regression coefficient of ech independent vrible ws multiplied by the rtio of the stndrd devition of the independent vrible to the stndrd devition of the dependent vrible.17 Vrition between seprte recordings of Doppler prmeters ws clculted s the difference between pirs of mesurements divided by their men nd expressed s positive percent. Results The results of the Doppler nd pressure mesurements during the vrious interventions re summrized in Tble 1. Isovolumic Relxtion Time nd r Inotropic stimultion with isoproterenol induced significnt shortening of r nd concomitnt decrese in IVRT (Tble 1). Individul dt re presented in Figure 2. No significnt chnge in ortic pressure ws observed. Hert rte nd LVEDP were kept constnt during the isoproterenol infusion. Compred with bseline, incresing doses of isoproterenol (5, 1, nd 15,ug/kg/min) cused n increse in mximum LV dp/dt by 72±38, nd 14+48%, respectively.,b-drenergic blockde with proprnolol induced significnt prolongtion of r nd concomitnt increse in IVRT (Tble 1). Individul dt re

4 Myreng nd Smiseth Doppler Indexes of Left Ventriculr Relxtion co 6 E 4 2 Tu p=.4 IVRT p=.3 1O 8 c' 6 E 4 2 T u p=.2 IVRT p=.5, O 1 o pg. kgjmin mg kg' Isoproterenol Proprnolol FIGURE 2. Plots depicting individul observtions of the time constnt of left ventriculr isovolumic relxtion (Tu) nd isovolumic relxtion time (IVRT) during incresing doses of intrvenous isoproterenol (left pnel) nd fter proprnolol injection (right pnel). Men vlue in the respective situtions re indicted. presented in Figure 2. No significnt chnge in LVEDP or ortic pressure ws observed. Compred with bseline, proprnolol cused reduction in mximum LV dp/dt by 31+17%. During the sline infusion, which incresed LVEDP from 7±2 to 24±4 mm Hg, progressive prolongtion of r ws observed, wheres IVRT ws not ltered (Tble 1). Individul dt re presented in Figure 3. Left tril V wve pressure incresed from 9±3 to 3±4 mm Hg. ortic pressure ws not significntly chnged, nd hert rte ws kept constnt. Regression nlyses were done seprtely for the dt obtined during constnt nd incresing LVEDP. When LVEDP ws kept constnt, s during the isoproterenol nd proprnolol injections, significnt correltion between chnges in X nd chnges in E r Tu Discussion In the present niml model, IVRT s mesured by Doppler ultrsound ws found to reflect LV relxtion during constnt prelod. Chnges in the time constnt of isovolumic relxtion induced by chnging inotropy t constnt trnsmurl filling pressure nd hert rte were ccompnied by similr chnges in IVRT. During the f-drenergic phrmk) p=.3 IVRT LVEDP (mm Hg) FIGURE 3. Plots depicting individul observtions of the time constnt of left ventriculr isovolumic relxtion (Tu) nd isovolumic relxtion time (IVRT) during incresing left ventriculr end-distolic pressure (LVEDP). Men vlues t norml nd t modertely nd strongly elevted LVEDP re indicted. IVRT ws found (r=.66, p<.1); with few exceptions, the chnges were directionlly similr (Figure 4). In contrst, when LVEDP ws incresed by sline infusion, no significnt correltion between chnges in r nd chnges in IVRT existed (Figure 4). Tble 2 demonstrtes the results of the multiple regression nlysis of IVRT s the dependent vrible ginst r, left tril V wve pressure, nd pek systolic LV pressure s independent vribles (eight dogs); significnt correltion (multiple r=.66, p<.1) ws found. r ws positive predictor nd left tril V wve pressure ws negtive predictor of IVRT (p<.1 nd p =.2, respectively). LV systolic pressure ws not significntly chnged nd exerted no independent influence. Trnsmitrl Flow Prmeters nd r The E velocity incresed during isoproterenol infusion (p<.1). fter normliztion ginst control vlues in the respective dogs, wek negtive correltion with r ws found (r= -.44, p<.5). The E velocity remined unchnged during,b-drenergic blockde. ltertions of inotropy induced no significnt chnges in ccelertion or decelertion rte of erly inflow nor in left tril V wve pressure or in ortic pressure. During sline infusion, the E velocity nd decelertion rte of erly inflow incresed significntly (Tble 1) nd reflected incresed trnsmitrl flow; ccelertion ws, however, unchnged. To djust for chnges in flow, the E velocity ws normlized ginst the respective trnsmitrl velocity time integrl. Tble 2 demonstrtes the results of multiple regression nlysis of the normlized E velocity s the dependent vrible ginst left tril V wve pressure, -, nd LV systolic pressure s independent vribles; this nlysis ws performed on the vlues for the dogs in which phsic left tril pressure ws recorded during volume loding (n =8). significnt correltion (multiple r=.6, p<.1) ws found. Left tril V wve pressure ws positive predictor of the normlized E velocity (p =.2). r ws wek negtive predictor (p=.6) nd LV systolic pressure ws wek positive predictor (p=.7) of the normlized E velocity. Reproducibility No significnt difference ws found between pirs of Doppler mesurements t bseline. The percent differences between the pired mesurements of IVRT, ccelertion time, pek E velocity, nd decelertion rte of erly flow were 6±4%, 9+7%, 6+6%, nd 12+7%, respectively.

5 264 Circultion Vol 81, No 1, Jnury 199 Constnt LVEDP Incresing LVEDP C ) cn c c C) y= x ^ ^ SEE=23% /- r=.66; p<.1 Isoproterenol: Proprnolol: Chnge in Tu (%;) C7) X} u' I * E X Chnge in Tu (%) FIGURE 4. Plots depicting percent chnge in the time constnt of left ventriculr isovolumic relxtion (Tu) versus percent chnge in isovolumic relxtion time (IVRT) during constnt left ventriculr end-distolic pressure (LVEDP) (left pnel) nd during incresing LVEDP (right pnel). cologicl interventions, end-systolic ortic pressure ws unchnged, nd LV filling pressure ws kept constnt. However, during incresing prelod, chnges in IVRT did not prllel the prolongtion of i. Since IVRT is mesured s the time intervl between ortic vlve closure nd mitrl vlve opening, determinnts of the vlve movements will lso influence IVRT. Therefore, together with the rte of LV pressure fll, end-systolic ortic pressure s well s left tril pressure constitute the determinnts of IVRT. Multivrite nlysis of dt cquired during incresing volume lod showed direct reltion between IVRT nd r, wheres n inverse reltion between left tril V wve pressure nd IVRT existed. Thus, progressive rise in left tril pressure would tend to cuse n erlier opening of the mitrl vlve,18 which explins why IVRT remined unchnged despite the pprent slowing of relxtion during sline infusion s indicted by r. decline in end-systolic ortic pressure could hve similr effect, but no such chnge ws observed in the present study. LV relxtion is not complete t the strt of the distolic filling period,19,2 nd vrition of relxtion rte would be expected to influence the erly trioventriculr pressure grdient21 nd, hence, the E velocity. Despite unchnged left tril pressure, we TBLE 2. Results of Multiple Regression nlysis found n incresed E velocity during isoproterenol infusion. This could be relted to the inverse reltion between the E velocity nd i. During sline infusion, multivrite nlysis reveled tht left tril V wve pressure ws stronger predictor of the E velocity thn r (Tble 2). These findings re consistent with the study of Choong et l,22 who in ddition demonstrted tht incresing fterlod (pek LV systolic pressure) ws ssocited with decline in the E velocity. In pprent contrst to the ltter, wek tendency (p=.71) towrd n increse in the E velocity by incresing LV systolic pressure ws found in the present study. However, this finding probbly reflects rndom vrition of the dt, becuse no significnt chnge in LV systolic pressure ws observed. In ccordnce with Ishid et l,23 who showed tht IVRT corresponded with the time constnt of LV relxtion but tht the ccelertion time ws not meningful index of erly filling dynmics, we found no consistent chnges in ccelertion time during ny intervention. The incresed decelertion rte during volume loding probbly reflects incresed trnsmitrl flow with more rpid trioventriculr pressure equliztion. The derivtive method of clculting r16 ws used s the reference method for mesurement of LV relxtion. This method ccounts for LV pressure Dependent Independent Regression Stndrdized regression vrible vrible coefficient coefficient p IVRT r V wve LVP E r V wve LVP The reltive importnce of the independent vribles ws ssessed by the stndrdized regression coefficients.'7 IVRT, isovolumic relxtion time; r, time constnt of left ventriculr (LV) isovolumic pressure fll; V wve, left tril V wve pressure; LVP, LV systolic pressure; E, pek erly trnsmitrl velocity.

6 Myreng nd Smiseth Doppler Indexes of Left Ventriculr Relxtion 265 decy towrd nonzero symptote. lthough the pericrdium ws open during the experiments, some externl pressure my hve resulted from contct with the Doppler probe, chest wll, lungs, nd fluid in the thorcic cvity. The observed chnges in r during the isoproterenol nd proprnolol interventions reflect chnging inotropy nd re in ccordnce with previous knowledge.6,2425 Like others2326 we found significnt increse in r when LV distolic pressure ws incresed by blood volume expnsion. However, the incresed r during volume loding might be due to incresed LV fterlod (systolic wll stress) rther thn increse in prelod per se.27 The dvntge of the present niml model is tht it llowed control of severl of the hemodynmic determinnts of LV distolic function. limittion of the model is, however, the rther extensive chest surgery nd the bsence of the physiologic influence of the lungs nd the pericrdium. Therefore, the present dt should be interpreted with cre, nd the findings my not be redily extrpolted to other situtions. Furthermore, the pcing protocol my hve cused some synchrony of relxtion, lthough plcing the electrode high on the septum probbly provided more physiologic trnsmission of the electricl impulse thn conventionl right ventriculr picl pcing. Dedicted Doppler offers high sensitivity nd precision for velocity mesurements nd prevents bis due to concomitnt imging.28 Becuse the pericrdium ws open during the experiments, the mitrl orifice my hve become dilted when filling pressure ws elevted. Thus, the E velocity my not hve reflected the true trnsmitrl volume trnsport, in prticulr during sline infusion. Clcultion of flow rther thn mesurement of pek velocity might hve improved the possibility of detecting relxtionrelted chnges in erly distolic filling prmeters. This problem ws prtly overcome by djusting the E velocity ccording to the trnsmitrl velocity time integrl. Mesurement of mitrl flow re would hve introduced significnt mesurement error, nd this might hve incresed vribility substntilly. Despite the limittions inherent in the present experimentl study, the clinicl implictions of our findings re importnt. Tking the dvntge of noninvsive methods into considertion, IVRT ssessed by Doppler echocrdiogrphy ppers to be useful prmeter of LV relxtion nd is more relible thn indirect indexes derived from the trnsmitrl Doppler velocity curve. However, IVRT is influenced by its pressure determinnts nd is not vlid s relxtion prmeter when they re significntly chnged. This limittion reduces the pplicbility of IVRT in clinicl prctice. Referepces 1. Hirot Y: clinicl study of left ventriculr relxtion. Circultion 198;62: Brutsert DL, Rdemkers FE, Sys SU: Triple control of relxtion: Implictions in crdic disese. Circultion 1983; 69: Eichhorn P, Grimm J, Koch R, Hess, Crroll J, Kryenbuehl HP: Left ventriculr relxtion in ptients with left ventriculr hypertrophy secondry to ortic vlve disese. Circultion 1982;65: roesty JM, McKy RG, Heller GV, Royl HD, ls V, Grossmn W: Simultneous ssessment of left ventriculr systolic nd distolic dysfunction during pcing-induced ischemi. Circultion 1985;71: Nkmur Y, Ssym S, Nonogi H, Miyzki S, Fujit M, Kihr Y, Konishi T, Kwi C: Effects of pcing-induced ischemi on erly left ventriculr filling nd regionl myocrdil dynmics nd their modifiction by nifedipine. Circultion 1987;76: Weiss JL, Frederiksen JW, Weisfeldt ML: Hemodynmic determinnts of the time-course of fll in cnine left ventriculr pressure. J Clin Invest 1976;58: Upton MT, Gibson DG, Brown DJ: Echocrdiogrphic ssessment of bnorml left ventriculr relxtion in mn. Br Hert J 1978;38: Hnrth P, Mthey DG, Siegert R, Bleifeld W: Left ventriculr relxtion nd filling pttern in different forms of left ventriculr hypertrophy: n echocrdiogrphic study. m J Crdiol 198;45: Kitbtke, Inoue M, so M, Tnouchi J, Msuym T, be H, Morit H, Send S, Mtsuo H: Trnsmitrl blood flow reflecting distolic behviour of the left ventricle in helth nd disese: study by pulsed Doppler technique. Jpn Circ J 1982;46: Lbovitz J, Person C: Evlution of left ventriculr distolic function: Clinicl relevnce nd recent Doppler echocrdiogrphic insights. m Hert J 1987;114: Bonow RO, Bchrch SL, Green MV, Kent KM, Rosing DR, Lipson LC, Leon MB, Epstein SE: Impired left ventriculr distolic filling in ptients with coronry rtery disese: ssessment with rdionuclide ngiogrphy. Circultion 1981; 64: Reduto L, Wickemeyer WJ, Young JB, Del Ventur L, Reid JW, Gleser DH, Quinones M, Miller RR: Left ventriculr distolic performnce t rest nd during exercise in ptients with coronry rtery disese: ssessment with firstpss rdionuclide ngiogrphy. Circultion 1981;63: Myreng Y, Ihlen H: Reproducibility of trnsmitrl flow velocity prmeters mesured by pulsed Doppler echocrdiogrphy. J Crdiovsc Ultrson 1988;7: Zhng Y, Nitter-Huge S, Ihlen H, Myhre E: Doppler echocrdiogrphic mesurement of crdic output using the mitrl orifice method. Br Hert J 1985;53: Htle L, ngelsen B: Doppler ultrsound in crdiology: Physicl principles nd clinicl pplictions, ed 2. Phildelphi, Le & Febiger, 1985, pp Crig WE, Murgo JP, Psipoulrides : Evlution of time course of left ventriculr isovolumic relxtion in humns, in Grossmnn W, Lorell BH (eds): Distolic Relxtion of the Hert. Boston, Mrtinus Nijhoff Publishing, 1988, pp Norusis MJ: SPSSY Introductory Sttistics Guide. Chicgo, SPSS, 1983, pp 138, Weisfeldt ML, Scully HE, Frederiksen JW, Rubenstein JJ, Pohost GM, Beierholm E, Bello G, Dggett WM: Hemodynmic determinnts of mximum negtive dp/dt nd periods of distole. m J Physiol 1974;227: Fioretti P, Brower RW, Meester GT, Seeruys PW: Interction of left ventriculr relxtion nd filling during erly distole in humn subjects. m J Crdiol 198;46: Psipoulrides, Mirsky I, Hess OM, Grimm J, Kryenbuehl HP: Myocrdil relxtion nd pssive distolic properties in mn. Circultion 1986;74: Yellin EL, Sonnenblick EH, Frter RWM: Dynmic determinnts of left ventriculr filling: n overview, in Bn J, rntzenius C, Yellin EL (eds): Crdic Dynmics. The Hgue/Boston/London, Mrtinus Nijhoff Publishers, 198, pp

7 266 Circultion Vol 81, No 1, Jnury Choong CY, bscl VM, Thoms JD, Guerrero JL, McGlew S, Weymn E: Combined influence of ventriculr loding nd relxtion on the trnsmitrl flow velocity profile in dogs mesured by Doppler echocrdiogrphy. Circultion 1988; 78: Ishid Y, Meisner JS, Tsujiok K, Gllo JI, Yorn C, Frter RWM, Yellin EL: Left ventriculr filling dynmics: Influence of left ventriculr relxtion nd left tril pressure. Circultion 1986;74: Mord M, Rolett EL: Relxing effects of ctecholmines on mmmlin hert. J Physiol (Lond) 1972;224: Gsch WH, Blustein S, ndris CW, Donhue RP, vitll B: Myocrdil relxtion. II. Hemodynmic determinnts of rte of left ventriculr isovolumic pressure decline. m J Physiol 198;239:H1-H6 26. Rff GL, Glntz S: Volume loding slows left ventriculr isovolumic relxtion rte: Evidence of lod-dependent relxtion in the intct dog hert. Circ Res 1981;48: Gsch WH, Zile MR, Blustein S, Bing OHL: Loding conditions nd left ventriculr relxtion, in Grossmnn W, Lorell BH (eds): Distolic Relxtion of the Hert. Boston, Mrtinus Nijhoff Publishing, 1988, pp Htle L, ngelsen B: Doppler Ultrsound in Crdiology: Physicl Principles nd Clinicl pplictions, ed 2. Phildelphi, Le & Febiger, 1985, pp KEY WORDS * distole * isoproterenol * proprnolol