years. All subjects had suffered a myocardial infarction, pain in association with elevation of serum creatine

Transcription

1 The Response of Left Ventriculr Function nd Size to Atril Pcing, Volume Loding nd Afterlod Stress in Ptients with Coronry Artery Disese ROBERT SLUTSKY, M.D., JOHN WATKINS, MB., KIRK PETERSON, M.D., AND JOEL KARLINER, M.D. SUMMARY To ssess the response of left ventriculr function nd size to volume loding, tril pcing nd fterlod stress, we studied 35 ptients using equilibrium rdionuclide ngiogrphy. All subjects hd coronry hert disese, s evidenced by contrst ngiogrphy or previous myocrdil infrction. Fifteen ptients received 500 ml of norml sline given s two rpid 250ml infusions. Ejection frction incresed fter the second infusion (0.49 to 0.55, p < 0.05), s did enddistolic volume (p < 0.05), but there ws little chnge in endsystolic volume or the rtio of systolic blood pressure to endsystolic volume. Eight ptients were subjected to phenylephrine fterlod stress, with men elevtion of systolic blood pressure of 44.6 ± 12 mm Hg (p < 0.01 vs rest). Ejection frction declined (0.52 ± 0.1 to 0.41 ± 0.13,p < 0.01), enddistolic nd endsystolic volumes incresed (p t lest < 0.01), nd the rtio of systolic pressure to endsystolic volume decresed (2.31 ± 1.64 to 1.46 ± 0.67 mm Hg/mi, p < 0.05). Twelve ptients underwent tril pcing (from bets/min), resulting in decrese in ejection frction, decrese in enddistolic nd endsystolic volumes (p < 0.05) nd n increse in the pressurevolume rtio (2.00 ± 0.30 to 2.45 ± 1.02 mm Hg/ml,p < 0.05). We conclude tht ltertions in loding conditions ffect indexes of left ventriculr performnce. The ejection frction is reduced by elevtions in blood pressure nd incresed by volume infusion, but ppered reduced by tril pcing, probbly due to the offsetting chnges in hert rte nd prelod. The pressurevolume rtio did not chnge with volume loding, decresed with fterlod stress nd incresed with tril pcing. Thus, equilibrium rdionuclide ngiogrphy cn be used to ssess noninvsively the effects of physiologic nd phrmcologic interventions on left ventriculr performnce in ptients with coronry hert disese. MANIPULATIONS of hert rte,'~' ventriculr volume79 nd systemic rteril pressure2' 1012 hve direct effect on mesurements of vriety of indexes of left ventriculr performnce. Recent interest in the proposed lodindependent reltionship of endsystolic pressure nd endsystolic volume'3 14 hs led to use of the simple rtio of pek systolic blood pressure or left ventriculr pressure to endsystolic volume s mesure of left ventriculr function. To chrcterize the ventriculr response to severl welldefined physiologic nd phrmcologic interventions, including sline loding, elevtions in systemic blood pressure produced by phenylephrine nd ltertions in crdic performnce during tril pcing, we used rdionuclide ngiogrphy to study 35 ptients with coronry hert disese. In ll subjects left ventriculr ejection frction, volume nd the rtio of systolic blood pressure to endsystolic volume were nlyzed by methods vlidted in our lbortory.'4 18 To our knowledge, this noninvsive pproch hs not been used in mn; in prticulr, in subjects with coronry hert disese. From the Division of Crdiology, Deprtment of Medicine, University Hospitl nd Sn Diego Veterns Administrtion Hospitl, Sn Diego, Cliforni. Address for correspondence: Robert Slutsky, M.D., Division of Crdiology, Sn Diego Veterns Administrtion Hospitl 1 1 1A, L Joll Villge Drive, Sn Diego, Cliforni Received My 14, 1980; revision ccepted August 5, Circultion 63, No. 4, Methods Volume Loding Study Fifteen ptients constituted the study popultion, including 14 men nd one womn, men ge 54 ± 12 yers. All subjects hd suffered myocrdil infrction, defined by typicl prolonged history of chest pin in ssocition with elevtion of serum cretine kinse nd evolutionry electrocrdiogrphic chnges. Four ptients hd experienced n nterior infrction, seven n inferior infrction nd four subendocrdil infrction, s defined by their surfce ECGs t the time of infrction, n verge of 21 ± 9 months (men ± SD) before this study. On clinicl exmintion before the study, four ptients hd udible third hert sounds nd 13 hd fourth hert sounds, but none hd mitrl regurgittion, pulmonry rles or elevtion of the jugulr venous pulse. Five ptients were receiving chronic orl digoxin therpy (men digoxin level 1.2 ± 0.4 ng/ml), but none ws tking ny diuretic, chronic nitrte or fblocking mediction. Ech ptient received 1520 mci of technetium 99m i.v. fter invivo lbeling of the ptient's red blood cells with stnnous pyrophosphte. After dequte intrvenous mixing, portble, singlecrystl gmm cmer ws plced over the supine ptient's thorx in the 450 left nterior oblique projection, with smll cudl tilt to mximize seprtion of the left ventricle from the left trium. A modified V, electrocrdiogrphic led ws used to gte the scintigrphic dt. Blood pressure ws tken with the id of the diphrgm of stndrd stethoscope nd Tycos cuff

2 LV RESPONSE TO STRESS/Slutsky et l. 865 dpted to Bumnometer syphgmomnometer. After bseline scintigrphic dt were obtined, 250 ml of norml sline were infused into the ptient over 35 minutes. A second resting rdionuclide study ws performed fter the first infusion. Then, n dditionl 250 ml of norml sline were infused, nd third resting scintigrphic study ws performed. All resting studies were 3 minutes in durtion. Atril Pcing Study Twelve ptients with chest pin nd ngiogrphiclly documented coronry rtery disese were included in this study. Ech ptient hd temporry bipolr Medtronic trnsvenous pcemker inserted through femorl vein nd plced ginst the lterl wll of the right trium under flouroscopic control. Thirty minutes fter the completion of stndrd crdic ctheteriztion, performed for evlution of chest pin (right nd lefthert ctheteriztion, including coronry ngiogrphy nd contrst ventriculogrphy), ech ptient underwent tril pcing t hert rtes of 80, 110 nd 130 bets/min). Three ptients developed chest pin, which ws relieved by stopping tril pcing nd dministering sublingul nitroglycerin. The rdionuclide cmer ws positioned nd dt were cquired s in the volume loding study. Ech pcing intervl ws 4 minutes, but rdionuclide dt were processed only from the lst 3 minutes of ech pcing stge. Blood pressure ws gin obtined by cuff sphygmomnometer. This group included nine men nd three women (men ge yers). One ptient hd suffered n nterior myocrdil infrction nd ws tking chronic orl digoxin. Two ptients were tking furosemide nd four were receiving chronic orl nitrte therpy, which ws stopped 8 hours before the study. Two ptients were tking orl proprnolol (60 nd 40 mg every 6 hours), which ws not given the morning of the study. Eight ptients hd significnt coronry rteril lesions (> 70% intrluminl occlusions of mjor coronry vessel) involving three vessels, three ptients hd twovessel disese, nd one ptient hd single lesion of the left nterior descending coronry rtery. The ptient who hd hd n infrction hd lrge kinetic segment, but the other ptients hd predominntly norml or hypokinetic segmentl contrction. Afterlod Stress Study Eight ptients with coronry rtery disese (four with previous myocrdil infrction nd four with ngiogrphiclly proved coronry rtery disese) underwent fterlod stress. After resting ejection frctions nd volume dt were obtined, tropine 11.5 mg) ws given to inhibit the reflex brdycrdi fter phrmcologic elevtion of blood pressure. At this point, phenylephrine (10 mg diluted in 250 ml of norml sline solution) ws infused to rise the blood pressure by 1530 mm Hg.2 Ejection frction nd volume dt were then obtined nd blood pressure ws mesured. The systolic blood pressure ws incresed by nother 1520 mm Hg nd second study ws performed. In six subjects whose systolic blood pressure ws less thn 150 mm Hg fter the second stge, third set of mesurements ws performed fter the blood pressure ws elevted by n dditionl 1520 mm Hg. No ptient developed chest pin or shortness of breth during the study. No rrhythmis or new ST chnges occurred. (A modified V, led ws monitored.) Two ptients were tking orl digoxin nd furosemide nd no ptient hd tken proprnolol or longcting nitrtes within 72 hours of the study. Agin, the rdionuclide, cmer positioning nd dt cquisition were the sme s used in the pcing nd volume infusion studies. Blood pressures were obtined with Tycos cuff dpted to Bumnometer sphygmomnometer nd stndrd stethoscope with the diphrgm plced over the right brchil rtery. Rdionuclide Dt Processing Dt recording nd processing were performed using generl nucler medicine computer (Medicl Dt Systems, PAD). Severl hundred hert bets were integrted during the cquisition period to construct multiple, identiclly phsed composite imges. The RR intervl from ech crdic cycle ws divided into 28 equl time frmes. Usully, counts could be ccumulted within the left ventriculr region of interest t enddistole (counts corrected for bckground ctivity). A left ventriculr timectivity curve ws generted from rectngulr region of interest plced round the ventricle t enddistole. An edgedetection lgorithm using secondderivtive count rte chnge s well s simple count rte threshold outlines the ventricle in ech frme during the crdic cycle. An utomticlly ssigned bckground region of interest ws locted outside the lower left qudrnt of the left ventricle in the endsystolic frme to correct for noncrdic ctivity. A composite left ventriculr volume curve ws then produced. Ejection frction ws clculted s: EF = EDC ESC EDC where EDC = bckgroundcorrected enddistolic counts nd ESC = bckgroundcorrected endsystolic counts. In recent study from this lbortory involving 76 ptients who underwent both rdionuclide nd contrst ventriculogrphy, this method hd n excellent correltion (r = 0.93), nd interobserver, introbserver nd seril vribility were ll less thn 0.04 ejection frction units.'8 Left ventriculr endsystolic nd enddistolic volumes were clculted using previously described method.',16, 118 Briefly, the counts t the enddistolic nd endsystolic dt point were corrected for frme time, the totl number of processed hert bets nd

3 866 CIRCULATION VOL 63, No 4, APRIL 1981 blood rdioctivity obtined from 4ml blood smple drwn t the midpoint of ech study. Whole blood ws used to clculte the rdioctivity "concentrtion," rther thn plsm s previously described, to enble the use of redcelllbeled rdionuclides. This modifiction of our originl technique lso provided rbitrry volume units tht correlted well with contrst ventriculogrphy (r > 0.91).11 Absolute volumes were obtined from the lestsqures fit liner regression reltionship between the rdionuclide volume units nd contrst volumes.17 The seril vribility (hour by hour) of ventriculr volumes in eight ptients studied four times over 4 hours ws ±7.5% using these techniques. Ejection frction vribility on n hourly bsis ws 0.03 ± 0.02 ejection frction units."8 Introbserver vribility, interobserver vribility, seril vribility in counts/ cycles hs been reported on number of occsions nd found to be less thn 4% To obtin noninvsive representtion of the rtio of the pek systolic pressure to endsystolic volume, systolic blood pressure nd rdionuclide endsystolic volume were used. We hve shown tht this noninvsive rtio correltes well (r > 0.92) with the rtio of pek systolic left ventriculr pressure to endsystolic volume determined ngiogrphiclly14 nd tht the vribility of this rtio is less thn 5%. In tht study, s well s in the present study, ptients with systemic hypertension or peripherl vsculr disese (s evidenced by clinicl exmintion of the peripherl pulses) were excluded. Sttisticl Anlysis All seril dt points were evluted by performing repetedmesures nlysis of vrince20 or when pproprite, t test for unpired dt. Liner correltions were performed using lestsqures liner fit. Dt re men ± SD unless otherwise stted. Results Volume Infusion Study No ptient developed dditionl clinicl symptoms of congestive hert filure. signs or Vitl Signs The men hert rte in this study group declined from 77.3 ± 13 to 72.3 ± 12 bets/min (p < 0.05) fter the complete infusion of 500 ml of sline. The hert rte response in ech ptient vried widely, from n increse in 10 bets/min to decline of 11 bets/min. The systolic blood pressure incresed slightly (118.3 ± 6.3 to 123 ± 7.1 mm Hg,p < 0.05), lthough the distolic pressure did not chnge significntly (74.6 ± 5.3 to 73.2 ± 5 mm Hg). The intermedite determintions for hert nd blood pressure (fter 250 ml of sline) were not significntly different from bseline. Hemodynmic Results The resting left ventriculr ejection frction ws 0.49 ± 0.12 t rest, 0.50 ± 0.12 fter 250 ml of sline LUi LL~ 0 C) cr_ U J C), Uj =,UJ W WC) CDcn r.60 _.50 _.40 h * p<. 0 vs Control 0 0 2~ ~ w w I~~~~~~~1 6~~~~~~~~ * Control * 250 ml 500 ml FIGURE 1. The effects of n infusion of 250 ml of sline followed by second 250mi infusion re shown. Ejection frction incresed significntly, with little chnge in the rtio of systolic blood pressure to endsystolic volume. were infused (p = NS) nd incresed to 0.55 ± 0.12 fter totl of 500 ml of sline ws infused (n increse of 12%, p < 0.05 vs bseline). The rtio of systolic blood pressure to endsystolic volume incresed slightly but not significntly (1.73 ± 0.95 mm Hg/ml t rest, 1.76 ± 0.86 mm Hg/ml fter 250 ml of sline nd 1.80 ± 0.94 mm Hg/mI fter 500 ml of sline were infused) (fig. 1). Figure 2 illustrtes the chnges in left ventriculr size. Enddistolic volume incresed from 150 i 47 ml t rest to 165 ± 52 ml (10% increse) fter the 500ml infusion (p < 0.05). The intermedite enddistolic volume ws not significntly different from the resting vlue. The endsystolic volume did not chnge fter the sline infusion (78 ± 41 ml t rest to 77 ± 39 ml, nd finlly, 77 i 40 ml). Thus, stroke volume incresed, from 72 ± 26 ml to 88 ± 33 ml (p < 0.05), s did crdic output, from 5.56 i 1.1 to 6.36 ± 1.4 1/min (p < 0.05). Atril Pcing Study All 12 subjects underwent right tril pcing t sequentil hert rtes of 80, 110 nd 130 bets/min. Three subjects developed ngin pectoris during the pek pcing rte in ssocition with. 1 mm ST r,

4 LV RESPONSE TO STRESS/Slutsky et l. 867 E 1 =3 C, CD z CS 260 r *~~~~~~~~~~ p,<,.05 vs Con7trol 0 2 C) LU LU. C3.70 k.60 I.50 I.401 *p<.05 vs 80 C WI C), cn ui ' J ~~ 9 ~ 0~~~~~~~ 1 Control 250 ml 500 ml FIGURE 2. With sline infusion, enddistolic volume nd stroke volume incresed significntly, with little chnge in endsystolic volume. segment depression on modified V6 electrocrdiogrphic led. The other nine ptients hd neither pin nor electrocrdiogrphic chnges. Systolic blood pressure did not chnge in these ptients, but in the three subjects who developed ngin, systolic pressure declined by men of 10 mm Hg compred with resting levels. The ejection frction declined from t pced rte of 80 bets/min to 0.55 ± 0.09 t 1 = 10 bets/min (p NS) nd to 0.52 ± 0.04 t 130 bets/min (p < 0.05 vs bseline) (fig. 3). Ptients who developed ngin showed decline in ejection frction, but this response did not clerly seprte them from the ptients who did not develop ngin, four of whom lso hd decresed ejection frctions. Interestingly, ll pinfree ptients incresed their pressurevolume rtio, while those with pin showed mrked decline (fig. 3). The volume response is shown in figure 4. Enddistolic volume declined from ml t 80 bets/min to 136 ± 9 ml t 110 bets/min (p < 0.05) to ml t 130 bets/min (p < 0.01 vs bseline). Most subjects showed continul decline in enddistolic volume t ech pced rte. When ngin resulted, enddistolic volume ctully incresed. Similr results were seen for endsystolic volume in both nginl nd nonnginl ptients. Stroke volume decresed by 39% (p < 0.01), but the response ws similr in nginl nd nonnginl ptients. Crdic output ws unchnged t ech pced rte. LLI CR LJJ cj CD D DO 0 2> J C clu) M _ 1F I I l l m A PACED RATE FIGURE 3. The ejection frction ndpressurevolume rtio response re shown t tril pcing rtes of 80, 110 nd 130 bets/min. Note the increse in the pressurevolume rtio, except when ngin intervened. The men ejection frction grdully declined, nd ngin did not clerly lter the response. Phenylephrine Infusion Study All subjects hd n increse in systolic blood pressure of t lest 30 mm Hg (men increse of 44.6 ± 11.9 mm Hg, rnge 3370 mm Hg). Hert rte did not decrese more thn 4 bets/min (fter mg of i.v. tropine) fter the infusion ws initited. No ptient developed clinicl evidence of pulmonry congestion nd none complined of chest pin. No subject developed rrhythmis, STsegment depression or ny other physicl complint. Ejection frction (bseline obtined fter tropine infusion) decresed from men of 0.52 ± 0.18 to 0.41 ± 0.13 (p < 0.01) t the pek blood pressure. The pressurevolume rtio lso declined from 2.31 ± 1.64 to 1.46 ± 0.67 mm Hg/ml (p < 0.05; fig. 5). Simultneously, there were increses in enddistolic volume (men increse 64 ± 36 ml, from to 218 ± 70 ml, p < 0.001), endsystolic volume (men increse 49 ± 21 ml, from 79 ± 46 to 128 ± 56 ml, p < 0.005), nd stroke volume (14 ± 23 ml, from 76 ± 26 to 90 ± 27 ml, p < 0.05). The reltionship between

5 868 CIRCULATION VOL 63, No 4, APRIL 1981 C, 230 _ ii110 CS 80 E 140 p<.05 vs 80 *u **P<.0l vs O E _ ~80 CO 60 * ch40 LU CO, PACED RATE FIGURE 4. Enddistolic volume declined with pcing, s did endsystolic nd stroke volume. With ngin, both enddistolic volume nd endsystolic incresed. systolic blood pressure nd endsystemic volume ws liner, with ll r vlues (fig. 6). W C C, p Discussion The influence of sequentilly induced, cute ltertions in prelod, fterlod nd hert rte on noninvsive mesurements of left ventriculr performnce hve received little systemtic study in ptients with coronry hert disese, prtly becuse of difficulties in the seril noninvsive evlution of ptients with synchronous regionl ventriculr contrction. Becuse recent dvnces in rdionuclide imging hve fcilitted the evlution of left ventriculr function nd size without use of geometric ssumptions regrding crdic chmber shpe,'5 these vribles cn be serilly evluted in ptients with coronry hert disese. In this study, we evluted the response of left ventriculr ejection frction nd volumes to tril pcing, volume infusion nd fterlod stress. Similrly, becuse of the recent interest in the slope nd simple rtio of the endsystolic pressurevolume reltionship,13' 14, 2126 we lso investigted the response of systolic blood pressure/endsystolic volume. In niml studies, volume infusion produces in Li U. =... G _ C C C O, W U).90 r * *s _~~~~ A 0~~~~~~ I Control 1 0 II~~~~~~~~ CHANGE IN SYSTOLIC BLOOD PRESSURE (mmhg) FIGURE 5. The response of ejection frction nd the rtio ofsystolic blood pressure to endsystolic volume to elevtion in blood pressure. Both of these vribles declined with incresing systemic pressure. creses in hert rte (depending on the rpidity of the infusion) long with smll increses in ejection phse nd isovolumic phse indexes of left ventriculr performnce.9' 27 In our ptients, hert rte declined slightly but not significntly (lthough severl ptients showed increses of up to 10 bets/min) with increses in enddistolic volume (10%), stroke volume (22%) nd crdic output (13%). A "Binbridge" response ws not seen in these subjects, probbly becuse of the modest mount of volume infused. When more fluid hs been dministered, hert rte increses hve been reported, lthough usully in subjects under generl nesthesi.28 The ejection frction incresed significntly (12%), while the rtio of systolic blood pressure to endsystolic volume showed n increse tht ws not sttisticlly significnt. The response of enddistolic volume nd endsystolic volume ws similr to the niml dt reported by Krliner et l.28 Recent work by Ricci et l.30 hs shown tht in conscious mn, increses in hert rte represent positive inotropic stimulus, independent of other fctors influencing ventricul/r performnce, such s utonomic influences. They found tht the velocity of circumferentil shortening incresed linerly with the increse in pced hert rte. Similr dt were found in norml subjects by DeMri et l.' In the ltter study, however, frctionl shortening declined, while velocity indexes incresed. In the present study, tril pcing induced reduction in enddistolic, endsystolic nd

6 4 4=. C E co CJ Lu LU _ C_ cn UJ. 2 C) SF jmk=~~~~~~~~ LV RESPONSE TO STRESS/Slutsky et l. 869 rphy in evluting these ptients. We hve previously shown the excellent correltion between the rtio of systolic blood pressure to endsystolic volume determined by rdionuclide techniques nd the rtio of pek left ventriculr systolic pressure to endsystolic volume determined by contrst ngiogrphy.'4 Using this noninvsive technique in the present study nd ltering systolic pressure by infusing phenylephrine, we found tht the reltionship between endsystolic volume nd systolic blood pressure is liner in ptients with coronry hert disese. During phenylephrine infusion, enddistolic volume, endsystolic volume nd often stroke volume increse, but the ejection frction nd the rtio of systolic pressure to endsystolic volume declined in equl proportions. I We conclude tht the rtio of systolic pressure to endsystolic volume is useful index of left ventriculr function tht ppers reltively independent of prelod but is predictbly dependent on fterlod. We hve lso presented model for the nlysis of the pressurevolume reltionship tht cn be esily performed noninvsively using systolic blood pressure nd equilibrium rdionuclide ngiogrphy. Similr to the niml dt presented by others, this reltionship is liner in ptients with coronry hert disese. Finlly, equilibrium rdionuclide ngiogrphy cn be used to evlute vriety of phrmcologic nd physiologic interventions in ptients with coronry hert disese. CHANGE IN SYSTOLIC BLOOD PRESSURE (mmhg) FIGURE 6. Enddistolic, endsystolic nd stroke volumes incresed with phenylephrine stress. The reltionship between systolic blood pressure nd endsystolic volume ws liner (r > 0.91, men r = 0.95) over lrge rnge of pressures nd volumes. stroke volumes, with little chnge in crdic output or systolic pressure. The rtio of systolic blood pressure to endsystolic volume incresed by 23%, but the ejection frction declined by 10%. Only three ptients developed ngin (ll in ssocition with ST depression), nd in ll three of them, the rtio of systolic blood pressure to endsystolic rtio declined during pin. Our dt suggest tht the chnge in ejection frction lone during tril pcing does not reflect chnges in contrctile stte, similr to conclusions reched by DeMri et l.' However, the chnges in the pressurevolume rtio response ppers to correspond to findings in both clinicl" 30 nd niml studies.3' In the ltter study, Mhler et l.33 demonstrted increses in dp/dt with tril pcing, which ws not ltered by f blockde. As hert rte incresed, so did dp/dt. The responses of left ventriculr function nd size to fterlod stress hve been nlyzed in series of clinicl studies involving ptients with symmetric ventriculr contrction nd norml subjects The linerity of the reltionship of systolic blood pressure nd endsystolic volume hs been exmined in only one study,26 nd the constncy of the pressurevolume rtio hs never been studied. Additionlly, ptients with coronry hert disese were excluded becuse of the inherent limittions of Mmode echocrdiog References 1. DeMri A, Neumn A, Schubrt P, Lee G, Mson D: Systemtic correltion of crdic chmber size nd ventriculr performnce determined with echocrdiogrphy nd ltertions in hert rte in norml persons. Am J Crdiol 43: 1, Hirshleifer J, Crwford M, O'Rourke R, Krliner J: Influence of cute ltertions in hert rte nd systemic rteril pressure on echocrdiogrphic mesures of left ventriculr performnce in norml subjects. Circultion 52: 835, Kryenbuhl HP, Schoenbeck M, Rotishuser W, Wirz P: Abnorml segmentl contrction velocity in coronry rtery disese produced by isometric exercise nd tril pcing. Am J Crdiol 35: 794, Noble M, Wyler J, Milne M, Trenchrd D, Guz A: Effect of chnges in hert rte on left ventriculr performnce in conscious dogs. Circ Res 24: 285, Dwyer E: Left ventriculr pressurevolume ltertions nd regionl disorders of contrction during myocrdil ischemi induced by tril pcing. Circultion 42: 1111, Psternc A, Gorlin R, Sonnenblick E, Hft J, Kemp H: Abnormlities of ventriculr motion induced by tril pcing in coronry rtery disese. Circultion 45: 1195, Ross J Jr: Afterlod mismtch nd prelod reserve: conceptul frmework for the nlysis of ventriculr function. Prog Crdiovsc Dis 43: 255, Burns J, Covell J, Ross J Jr: The mechnics of isotonic left ventriculr contrction. Am J Physiol 224: 725, Mhler F, Ross J Jr, O'Rourke R, Covell J: Effects of chnges on prelod fterlod nd inotropic stte on ejection nd isovolumic phse mesures of contrctility in 17 conscious dogs. Am J Crdiol 35: 676, Ross J Jr, Brunwld E: The study of left ventriculr function in mn by incresing resistnce to ventriculr ejection with ngiotensin. Circultion 29: 739, Bolen J, Lopes M, Hrrison D, Aldermn E: Anlysis of left ventriculr function in response to fterlod chnges in ptients with mitrl stenosis. Circultion 52: 894, Pyne R. Horwitz L, Mullins C: Comprison of isometric exer

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