BRIEF REPORTS

Dobutamine and Improvement of Regional Function in Coronary Artery Disease

and Global Left Ventricular

Assad Movahed, MD, William C. Reeves, MD, Gregory C. Rose, MD, William S. Wheeler, MD, and Stanley R. Jolly, PhD, with technical assistance from Sandra Kearney and Paula E. Barnhill

he effects of dobutamine infusion on left ventricular (LV) function in patients with coronary artery T disease(CAD) have not been completely defined. Some studies have suggestedthat dobutamine infusion can be usedto achievea significant increase in myocardial oxygen demand in the presenceof severestenosis,revealing physiologically significant ischemia.’ 3 This would be particularly desirable as an alternative to exercisestress testing becausesomepatients are unable to achievetarget heart rates due to insufficient motivation, poor physical condition or peripheral vascular disease. Studies with contrast ventriculography using postextrasystolic stimulation and epinephrine infusion have suggestedthat viable, but poorly contracting myocardium, often responds to these stimuli and can thus be differentiated from infarcted, irreversibly injured myocardium.4,5The pharmacologic profile of dobutamine as a relatively selectivep- 1 agonist6 suggeststhat dobutamine also may stimulate viable but “hibernating” myocardium.” In this report, the effectsof dobutamine infusion on global LV ejection fraction and abnormal LV regional wall motion have been assessed in 15 patients with coronary artery disease.The goal of the study was to determine whether dobutamine “stress” would induce a diminished LV ejection fraction and provoke new LV wall motion abnormalities or improve global and/or regional LV dysfunction. The protocol and consent form were approved by the Human Subjects Review Committee. Patients who had angiographically proven CAD and regional LV dysfinction were referredfor evaluation. Patients were excluded zf they had unstable angina, severe arrhythmias, valvular heart disease or systemic hypertension (defined as systolic arterial pressure of 2180 mm Hg or diastolic arterial pressure of 2 100 mm Hg). Cardiovascular drugs were continued. The electrocardiogram and blood pressure were recorded every 2 minutes. Red blood cells were labeled in vivo with 25 to 30 mCi of technetium99m after administration of a stannous agent.7 Baseline equilibrium radionuclide angiography was performed at rest in the supine position in the anterior, 45” left anterior oblique with a caudal tilt of 10 to 30” and in the 70” left anterior oblique projections. Data were acquired in the frame mode of 64 X 64 matrix, dividing the cardiac cycle into 32 equal intervals. Extrasystoles were rejected. Initially, the dobutamine dose was at 5 ng/kg/min

From the Section of Cardiology, Department of Medicine, East Carolina University School of Medicine, Greenville, North Carolina 278584354. Manuscript received November 28, 1989; revised manuscript received and accepted March 20, 1990.

and was then increased to 10 and 20 z.zg/kg/min after 5 and 18 minutes of infusion, respectively. Infusion was terminated for angina, significant arrhythmia or severe hypertension (systolic blood pressure 1230 mm Hg or diastolic pressure of 120 mm Hg). The anterior and left anterior oblique 45” equilibrium radionuclide angiograms were obtained 5 minutes after both 10 and 20 ug/ kg/min of dobutamine infusions. Regional wall motion was assessed by examination of dynamic images and global LV ejection fractions were calculated by 2 independent observers and a consensus was reached. Results are expressed as mean f standard error of the mean. Baseline and dobutamine 10 and 20 z.zg/kg/min values for hemodynamics and ej’ection fractions were compared using 2-way analysis of variance followed by Duncan’s Multiple Range test. A p value CO.05 was considered statistically significant. Baseline studies and the effects of dobutamine infusion for the 15 patients are listed in Table I along with summary statistics. Dobutamine significantly decreased the LVejection fraction in only 1 patient. Overall, dobutamine significantly increased mean LVejection fraction at infusion rates of both 10 and 20 ug/kg/min in this patient population. Nine of the 15 patients with 10 ng/ kg/min of dobutamine and 11 with 20 pg/kg/min of dobutamine infusion had clinically significant increases in the LV ejection fraction of 20.05. In addition, 8 of 11 patients with improved LV ejection fraction showed improvement of an asynergic wall region. In 1 patient, deterioration of regional wall motion was observed when the dobutamine infusion rate was increased from 10 to 20 nglkglmin. Hemodynamic effects on systolic arterial pressure and heart rate were dose-dependent while the LVejection fraction failed to increase significantly from when infusion rates were increased from 10 to 20 rig/kg/ min of dobutamine. No ventricular tachycardia was encountered. In 3 patients, additional ST-segment depression was observed, as listed in Table I. These electrocardiographic changes were observed in 1 patient with no improvement in regional and global LVfunction. One patient had 0.5 to 1.5 mm additional ST-segment depression during an infusion rate of 20 ng/kg/min of dobutamine, with an accompanying decrease of L Vejection fraction and deterioration of LV regional wall motion. The third patient with additional ST-segment depression showed improvement of regional and global LVfunction at dobutamine infusion rates of both 10 and 20 nglkglmin. Three patients who showed improved LV ejection fraction plus improvement in regional wall motion after dobutamine radionuclide angiography were referred for

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TABLE

Patient 2 3 4 5 6 7 8 9 10 11 12 13 14 15 x SEM

I Effects of Dobutamine

Age (yr) &Sex 49M 31M 48M 63F 70M 40M 58M 45M 45M 54M 54F 70M 62F

Regional Improvement of Left Ventricle

+ 0 0 + 0 +

+ 0 + 0

infusion on Hemodynamics Baseline

and Ejection Fraction in Patients with Coronary Artery Disease Dobutamine

(1Opg)

Dobutamine

(2Opg)

HR

SAP

DAP

LVEF

HR

SAP

DAP

LVEF

HR.

SAP

DAP

LVEF

62 75 74 86 89 74 57 92 81 93 84 74 83 57 75 774 3

100 120 120 110 134 112 142 120 110 112 104 118 102 131 102 116 3

60 80 70 78 90 80 90 65 80 82 70 80 65 66 62 74 2

0.17 0.25 0.32 0.31 0.21 0.30 0.57 0.17 0.19 0.32 0.17 0.50 0.36 0.37 0.26 0.30 0.03

85 90 67 105 104 81 86 120 104 98 87 84 78 60 85 89+ 4

140 130 190 146 162 166 194 132 110 120 110 140 106 178 92 141+ 8

80 80 60 90 94 60 100 90 70 80 70 80 60 81 58 77 3

0.18 0.35 0.45 0.38 0.25 0.48 0.81 0.18 0.23 0.38 0.22 0.58 0.42 0.34 0.26 0.37+ 0.04

130 105 81 130 18 96 110 150 113 100 104 96 88 60 93 105+* 6

134 146 210 152 166 172 192 126 116 140 150 180 105 187 91 151+ 8

70 80 80 90 90 70 88 72 80 90 80 80 57 87 42 77 3

0.19 0.30 0.48 0.47 0.29 0.50 0.84 0.17 0.25 0.37 0.25 0.61 0.42 0.31 0.27 0.38+ 0.05

* Mean f standard error of the mean; ’ significantly different from baseline by P-way analysis of variance Duncan Mulbple Range test; f slgniflcantly ~0.05) lOpg/kg by 2.way analysis of variance.. ECG = electrocardlographlc: HR = heart rate; LVEF = left ventricular electIon fraction; SAP-DAP = systollcdlastolk arterial pressure.

coronary artery revascularization; 1 underwent coronary angioplasty and 2 had coronary artery bypass grafting. Subsequently, 2 to 4 weeks after coronary revascularization, radionuclide angiography showed recovery of regional and global LVfunction to levels seen during dobutamine infusion. One of these patients had deterioration of LV regional wall motion and global function when dobutamine dose was increasedfrom 10 to 20 pg/kg/min. In this patient, after revascularization, there was recovery of regional and global LVfunction to the level seen during the 10 ug/kg/min of dobutamine infusion.

Our data show that dobutamine infusion of 10 and 20 pg/kg/min in patients with regional and global LV dysfunction adverselyaffected LV ejection fraction in only 1 patient. Instead, significant increasesof LV ejection fraction were observed in 11 of our 15 patients. Improved regional wall motion in asynergic regions also was observedin many patients. In all 3 casesreferred for coronary revascularization, recovery of regional and global LV function to levels achieved during dobutamine radionuclide angiography was observed.Dobutamine radionuelide angiography was not associatedwith significant adverseresponses.Additional ST-segmentdepressionswere observedin 3 patients. There is somecontroversy regarding the effect of dobutamine on cardiac function in patients with coronary artery disease.Two echocardiographic studies have used dobutamine infusion in patients with CAD who were unable to exercise.lT2The patient population in both reports was chosenfor postinfarction evaluation of residual coronary disease.In both studies, abnormal wall motion and decreasedwall thickening were observedduring dobutamine infusion. Dobutamine stresstesting was considered an alternative to exercise testing in such patients after myocardial infarction. Additionally, Freeman et al3 have describedthe use of dobutamine infusion compared to supine bicycle exercisetesting using radionuclide angiography. They concluded that incremental dobutamine 376

THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 66

ECG Changes

-

different from dobutamlne

(p

infusions were nearly equal in accuracy and sensitivity to exercise.An experimental canine study also has suggested that dobutamine infusion was associatedwith depressed regional function distal to a critical coronary stenosis.8On the basisof these reports, different results would have been expectedfrom our study. There are reports, however, supporting the present observations. Bendersky et al9 showedthat dobutamine infusion at 10 pg/kg/min improved LV function in patients with chronic heart failure due to ischemic heart disease.In their study, changesin contractile state were not evaluated directly. In all of their patients, strokevolume and stroke work indexesincreasedwhile pulmonary arterial wedge pressuretended to decreaseduring dobutarnine infusion. In 7 of the 8 patients in the study by Bendersky et aJ9 improved LV function was associated with increasedmyocardial oxygen consumption.Despite this increasedmetabolic cost, overt myocardial ischemia was observed infrequently. Rabinovitch et allo have reported that resting ejectionfraction wasincreasedin 18of the 20 CAD patients after dobutamine infusion of 5 pg/ kg/mm. Only 2 of the 20 patients in the study of Rabinovich et allo had a decreasein LV ejectionfraction and 1 of these 2 patients showed the appearanceof a new wall motion abnormality at a dobutamine infusion of 5 pg/ kg/mm. Pozenet al” studied 18 patients with CAD and congestiveheart failure during infusion of dobutaminein dosesof 2.5 to 15 pg/kg/min. In this study,improvement in 27% of the abnormally contracting segmentswas seen during dobutamine infusion. These studies and our results suggestthat the inotropic effects of p-1 adrenergic stimulation by dobutamine can improve ventricular performance in patients with CAD. Inotropic stimuli such as postextrasystolic potentiation and epinephrine infusion can produce improved regional myocardial wall motion in some patients with CAD.4 This has been attributed to “hibernating” myocardium,5 defined aspersistentlyimpaired LV function at

rest that can be restored to normal by improved blood flow or decreaseddemand. The differentiation of viable but stunned or hibernating myocardium from necrotic myocardium is desirable in deciding whether coronary artery revascularization is appropriate.5 At present, abnormal LV wall motion in regionswith preservedglucose uptake, determined with positron emission tomography, is considered to be hibernating myocardium that will recover function with revascularization.‘2 However, the availability of this test is limited by resourcesand cost. A potential alternative is delayed tomographic myocardial thallium-201 imaging to differentiate viable and nonviable myocardium.l 3This test can require delayed imaging beyond 24 hours, which presentstechnical and practical difficulties. Comparedwith thesestudies,the dobutamine test has advantages in that dobutamine is relatively cheap,easily administered,has a short half-life of 2 minutes6and is used commonly by cardiologists. Our study suggeststhat dobutamine radionuclide angiography may be an attractive alternative to other tests in detecting ischemic but viable myocardium potentially suitable for coronary artery revascularization. 1. Manncrtng D, Cripps T. Leech G. Mehta N, Valantine H. Gilmour S, Bcnnet ED The dobutamine stress test as an nlternativc to exercise testing after acute mywardial infarction. t(r Heart J /Y88;5Y;52/ -526.

2. Bcrthc C, Picrard LA, Hiernaux M. Trotteur G, Lcmpereur P. Carlier J. Kulbertus H. Predictrng the extent and location ofcoronztry wtery disease to acute myocardial infarction by cchocardiography durmg dobutamine infusion. .4n7 J Cardiol

1966;.58:1167-1172.

3. Freem2.c ML, Pa!nc R. h:ssoh J. Bathes WE, Eastman G, Virupannavar S. Loeb HS, Kaplan E. A comparison of dobutamine infusion and supine bicycle exercise for radionuclide cardiac stress testing. C/in Nucl Med 1984;9:251-258. 4. Horn HR. Teichholz LE, Cohn TF, Ilerman MV, Gorlin R. Augmentation of LV contraction pattern in coronary artery disease by an inotropic catecholarnine: the epinephrme ventriculogram. Circulation 1974;49-1063-1071. 5. Rahimtoola SH. The hibernatmg myocardium ,4w Nparr J /YRY;1/7:2/1220.

6. Tuttle RR, Mills J. Dobutamine, development of a new catecholamine to selectively increase cardiac contractihty. c‘irc Key lY75;36~lRS-lY6. 7. Pave1 DG, Zimmer AM, Patterson VN. In Go labeling of red blood cells with 99mTc: a new approach to blood pool visualizrtion. J Nucl Mzd 1977:/8.X5312.

8. McCillem MJ, DeBwe SF, Friedman HZ, Mancint GBJ. The effects of dopamme and dobutamine on regional function in the presence of rigid coronary stehoses and subcritical impairments of reactive hyperemia. Am Hemt J 198x:1/5:970-977.

9. Bendersky R. ChatterJee K, Parmley WW. Brundage BH, Ports TA. Dobutamine in chronic ischemic heart failure: alterations in LV function and coronary hemodynamica. Am J Cm-diol lY81;48:554~558 10. Rabmovitch MA, Kalff V, Chan W. Schork A, Gross MD, Vogel Rh, Thrall JH, Pitt B. The effect of dobutamine on exercise performance in patients with symptomatic ischemic heart disease. Am Hearr J /YX4;107:8/-85. 11. Poren RG, DiBianco R. Katz RJ, Bortz R, IMyerburg RJ, Fletcher RD Mywardial metabolic and hemodynamic effects of dobutaminc in heart failure complicating coronary artery discasc. Circulation lYXI;63~127Y-l2X5. 12. Tillisch J, Brunken R, Marshall R, Schwaiger M, Mandclkern M. Phelps M. Schelbert HR. Reversibility of cardiac-wall motion abnormalities predicted by positron tomography. IV .%gl J Med IY86;3/4:884-8R8. 13. Kiat H, Berman DS, Maddaht J, Yang LD. Van Train K. Roranski A, Friedman J. Late reversibility of tomographic myocnrdial thalliun-201 defects 1463 an accurate marker of mywardial viability. J.Ac‘C /YXH;/2-1456

Semiselective Angiography of the Internal Preparation for Coronary Bypass Surgery

Mammary

Arteries

as a

Rudolf Krijne, MD, Mario C.-H.K. Deng, MD, Karl-Wilhelm Heinrich, MD, Hermann Sons, MD, and Arno Krian, MD

changesin the subclavian and internal mammary arteries among our patients, we performed semiselectiveangiography on both mammary arteries during cardiac cathegrafting. Angiography of the mammary arteries before terization in candidates for bypass surgery. One hundredfive consecutive patients (87 men and I8 bypasssurgery is considered to be superfluous because they are rarely affected by atherosclerosis.’ There are, women) aged 35 to 80 years (median 58) were studied. however, no data on how often an internal mammary Sixty-fiuepatients (62%) had 3-vessel disease, 25 (24%) artery graft is intraoperatively rejected becauseof insuffi- had 2-vessel disease and 15 (14%) had I -vessel disease. cient sluggishflow due to atherosclerosis.Early postoper- In all patients semiselective angiography of both mamative graft failure is said to be mainly related to technical mary arteries, performed with a standard 5Fr right Juderrors.?,3To establish the frequency of atherosclerotic kins diagnostic catheter, complemented the coronary arnternal mammary artery grafting in coronary artery Itency bypasssurgery has resulted in increasedlong-term paand improved survival compared to venous bypass

From trum West script

the Departments of Cardiology and Cardiac Surgery, HerzzenKaiser Wilhelm Krankenhaus, Gerrickstrasse 21,410O Duisburg, Germany. Manuscript received February 9, 1990; revised manureceived and accepted March 26, 1990.

tery procedure. Ten ml of undiluted contrast medium was injected manually with the catheter tip as near as possible to the origin of the internal mammary artery. Only posteroanterior views were used, documented on 35-mm cinefilm. Significant atherosclerosis was defined as a diameter reduction of 150%. In 13 patients the imaging quality of the right mammary artery was insuf-

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