(Circulation. 1995;92:756-766.)
© 1995 American Heart Association, Inc.
Articles |
Incremental Doses of Dobutamine Induce a Biphasic Response in Dysfunctional Left Ventricular Regions Subtending Coronary Stenoses
Presented in part at the 66th Scientific Sessions of the American Heart Association, Atlanta, Ga, November 8-11, 1993.
From the Division of Cardiology, Hartford Hospital, University of Connecticut, Hartford, and the Cardiac Unit, Massachusetts General Hospital, Harvard Medical School, Boston (J.V.P., M.H.C., J.T.F., A.E.W.).
Correspondence to Chunguang Chen, MD, Division of Cardiology, Hartford Hospital, 80 Seymour St, Hartford, CT 06102.
Background Dobutamine stress echocardiography has been proposed as a diagnostic tool to identify viable myocardium. How regional wall thickening responds to dobutamine in the ischemic or short-term hibernating myocardium has not been adequately defined. We hypothesized that regional wall thickening would improve initially and subsequently deteriorate with incremental doses of dobutamine in viable myocardial regions supplied by a stenotic coronary artery. This study was undertaken to determine whether this biphasic pattern of regional function characterizes the response of ischemic or hibernating myocardium to dobutamine and to explore the factors and mechanisms that determine this response.
Methods and Results Twenty-six pigs in four groups were studied: a control group (n=5) to assess the response of myocardium perfused by nonstenotic coronary artery to incremental doses of dobutamine, and three experimental groups with a left anterior descending coronary artery stenosis producing acute myocardial ischemia (n=7), short-term myocardial hibernation for 90 minutes (n=7), and short-term hibernation for 24 hours (n=7) to determine the functional and metabolic response to dobutamine under these conditions. Regional coronary flow was reduced to 40% to 60% of baseline, with significant reductions of regional wall thickening as measured by two-dimensional echocardiography and sonomicrometers. An incremental dobutamine infusion from 2.5 to 25 µg · kg-1 · min-1 increased wall thickening and coronary flow without lactate production in the control group. In the other three groups, during the incremental dobutamine infusion, regional wall thickening improved initially, from 11.4±7.5% to 19.8±11.4%, P<.01, at dobutamine doses of 2.5 to 10 (4.5±2.2) µg · min-1 · kg-1 but deteriorated subsequently to 5.0±5.8% at the maximal dose of dobutamine of 12.6±4.1 µg · min-1 · kg-1. The initial improvement of regional wall thickening was associated with a small increase in regional coronary flow (from 0.53±0.18 to 0.68±0.25 mL · min-1 · g-1 myocardium, P<.05) and with regional lactate production. High doses of dobutamine did not further increase regional coronary flow but markedly increased lactate production and induced regional myocardial acidosis (pH 7.26±0.07). The biphasic pattern of response to dobutamine was observed in each of the three experimental groups. Both peak improvement and peak deterioration occurred earlier and at lower dobutamine dose levels in the group with acute ischemia compared with the group with short-term hibernation for 24 hours (P<.05).
Conclusions A biphasic response of wall thickening to incremental dobutamine with initial improvement and subsequent deterioration is characteristic of ischemic or short-term hibernating myocardium. The initial low-dose dobutamine infusion improved wall thickening in the ischemic or hibernating myocardial region to a modest level. This initial modest improvement was transient and at the expense of metabolic deterioration of myocardial ischemia, so that at higher doses during prolonged dobutamine infusion, wall thickening deteriorated, lactate accumulated, and myocardial acidosis developed.
Key Words: dobutamine • echocardiography • myocardium • ischemia
This article has been cited by other articles:
 |
|
 |
|
  D. Mannheim, D. Versari, E. Daghini, M. Gossl, O. Galili, A. Chade, V. S. Rajkumar, E. L. Ritman, L. O. Lerman, and A. Lerman Impaired myocardial perfusion reserve in experimental hypercholesterolemia is independent of myocardial neovascularization Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2449 - H2458. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L A Pierard and P Lancellotti Determinants of persistent negative T waves and early versus late T wave normalisation after acute myocardial infarction Heart, August 1, 2005; 91(8): 1008 - 1012. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Heusch, R. Schulz, and S. H. Rahimtoola Myocardial hibernation: a delicate balance Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H984 - H999. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Leung, W. H. Bellows, and D. Pastor Does Intraoperative Evaluation of Left Ventricular Contractile Reserve Predict Myocardial Viability? A Clinical Study Using Dobutamine Stress Echocardiography in Patients Undergoing Coronary Artery Bypass Graft Surgery Anesth. Analg., September 1, 2004; 99(3): 647 - 654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Bito, F. R. Heinzel, F. Weidemann, C. Dommke, J. van der Velden, E. Verbeken, P. Claus, B. Bijnens, I. De Scheerder, G. J.M. Stienen, et al. Cellular Mechanisms of Contractile Dysfunction in Hibernating Myocardium Circ. Res., April 2, 2004; 94(6): 794 - 801. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Thompson, D. Bergstrome, and J. L. Parlow Limitations of preoperative dobutamine stress echocardiography in identifying severe left main coronary artery stenosis: a report of two cases and a brief review: [Les limites de l'echocardiographie d'effort preoperatoire avec dobutamine dans l'identification d'une stenose du tronc de l'artere coronaire gauche : observation de deux cas et breve revue] Can J Anesth, November 1, 2003; 50(9): 933 - 939. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Lancellotti, E. P. Hoffer, and L. A. Pierard Detection and clinical usefulness of a biphasic response during exercise echocardiography early after myocardial infarction J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1142 - 1147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Ceconi, G. La Canna, O. Alfieri, A. Cargnoni, G. Coletti, S. Curello, M. Zogno, G. Parrinello, S. H. Rahimtoola, and R. Ferrari Revascularization of hibernating myocardium. Rate of metabolic and functional recovery and occurrence of oxidative stress Eur. Heart J., December 1, 2002; 23(23): 1877 - 1885. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. J Malm, G. Suzuki, J. M Canty Jr., and J. A Fallavollita Variability of contractile reserve in hibernating myocardium: dependence on the method of inotropic stimulation Cardiovasc Res, December 1, 2002; 56(3): 422 - 432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. O. Bonetti, S. H. Wilson, M. Rodriguez-Porcel, D. R. Holmes Jr, L. O. Lerman, and A. Lerman Simvastatin preserves myocardial perfusion and coronary microvascular permeability in experimental hypercholesterolemia independent of lipid lowering J. Am. Coll. Cardiol., August 7, 2002; 40(3): 546 - 554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Fallavollita, M. Logue, and J. M. Canty Jr. Coronary patency and its relation to contractile reserve in hibernating myocardium Cardiovasc Res, July 1, 2002; 55(1): 131 - 140. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. B. Chin, G. Esposito, and D. L. Kraitchman Myocardial Contractile Reserve and Perfusion Defect Severity with Rest and Stress Dobutamine 99mTc-Sestamibi SPECT in Canine Stunning and Subendocardial Infarction J. Nucl. Med., April 1, 2002; 43(4): 540 - 550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F Piscione, P Perrone-Filardi, G De Luca, M Prastaro, C Indolfi, P Golino, S Dellegrottaglie, and M Chiariello Low dose dobutamine echocardiography for predicting functional recovery after coronary revascularisation Heart, December 1, 2001; 86(6): 679 - 686. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Schulz, H. Post, T. Neumann, P. Gres, H. Luss, and G. Heusch Progressive loss of perfusion-contraction matching during sustained moderate ischemia in pigs Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H1945 - H1953. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Casey and P. G. Arthur Hibernation in Noncontracting Mammalian Cardiomyocytes Circulation, December 19, 2000; 102(25): 3124 - 3129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R Schulz and G Heusch Hibernating myocardium Heart, December 1, 2000; 84(6): 587 - 594. [Full Text]
|
|
|
|
|
|
D Pagano, J N Townend, D V Parums, R S Bonser, and P G Camici Hibernating myocardium: morphological correlates of inotropic stimulation and glucose uptake Heart, April 1, 2000; 83(4): 456 - 461. [Abstract] [Full Text]
|
|
|
|
|
|
B. Shivalkar, W. Flameng, M. Szilard, S. Pislaru, M. Borgers, and J. Vanhaecke Repeated stunning precedes myocardial hibernation in progressive multiple coronary artery obstruction J. Am. Coll. Cardiol., December 1, 1999; 34(7): 2126 - 2136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. G. Hundley, C. A. Hamilton, M. S. Thomas, D. M. Herrington, T. B. Salido, D. W. Kitzman, W. C. Little, and K. M. Link Utility of Fast Cine Magnetic Resonance Imaging and Display for the Detection of Myocardial Ischemia in Patients Not Well Suited for Second Harmonic Stress Echocardiography Circulation, October 19, 1999; 100(16): 1697 - 1702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. P. Hoffer, W. Dewe, C. Celentano, and L. A. Pierard Low-level exercise echocardiography detects contractile reserve and predicts reversible dysfunction after acute myocardial infarction: Comparison with low-dose dobutamine echocardiography J. Am. Coll. Cardiol., October 1, 1999; 34(4): 989 - 997. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. A. Chaudhry, J. T. Tauke, R. S. Alessandrini, G. Vardi, M. A. Parker, and R. O. Bonow Prognostic implications of myocardial contractile reserve in patients with coronary artery disease and left ventricular dysfunction J. Am. Coll. Cardiol., September 1, 1999; 34(3): 730 - 738. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. HEUSCH Hibernating Myocardium Physiol Rev, October 1, 1998; 78(4): 1055 - 1085. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Kudej, B. Ghaleh, N. Sato, Y.-T. Shen, S. P. Bishop, and S. F. Vatner Ineffective Perfusion-Contraction Matching in Conscious, Chronically Instrumented Pigs With an Extended Period of Coronary Stenosis Circ. Res., June 15, 1998; 82(11): 1199 - 1205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D Pagano, R S Bonser, J N Townend, F Ordoubadi, R Lorenzoni, and P G Camici Predictive value of dobutamine echocardiography and positron emission tomography in identifying hibernating myocardium in patients with postischaemic heart failure Heart, March 1, 1998; 79(3): 281 - 288. [Abstract] [Full Text]
|
|
|
|
|
|
L. Ma, L. Chen, L. Gillam, D. D Waters, and C. Chen Nitroglycerin Enhances the Ability of Dobutamine Stress Echocardiography to Detect Hibernating Myocardium Circulation, December 2, 1997; 96(11): 3992 - 4001. [Abstract] [Full Text]
|
|
|
|
|
|
G. Heusch, R. Ferrari, D. J Hearse, T. J.C Ruigrok, and R. Schulz 'Myocardial hibernation'--questions and controversies Cardiovasc Res, December 1, 1997; 36(3): 301 - 309. [Full Text] [PDF]
|
|
|
|
|
|
M. F. Meza, S. Ramee, T. Collins, D. Stapleton, R. V. Milani, J. P. Murgo, and J. Cheirif Knowledge of Perfusion and Contractile Reserve Improves the Predictive Value of Recovery of Regional Myocardial Function Postrevascularization : A Study Using the Combination of Myocardial Contrast Echocardiography and Dobutamine Echocardiography Circulation, November 18, 1997; 96(10): 3459 - 3465. [Abstract] [Full Text]
|
|
|
|
|
|
H. H. Lee, V. G. Davila-Roman, P. A. Ludbrook, M. Courtois, J. F. Walsh, D. A. Delano, P. J. Rubin, and R. J. Gropler Dependency of Contractile Reserve on Myocardial Blood Flow : Implications for the Assessment of Myocardial Viability With Dobutamine Stress Echocardiography Circulation, November 4, 1997; 96(9): 2884 - 2891. [Abstract] [Full Text]
|
|
|
|
|
|
P. G. Camici, W. Wijns, M. Borgers, R. De Silva, R. Ferrari, J. Knuuti, A. A. Lammertsma, A. J. Liedtke, G. Paternostro, and S. F. Vatner Pathophysiological Mechanisms of Chronic Reversible Left Ventricular Dysfunction due to Coronary Artery Disease (Hibernating Myocardium) Circulation, November 4, 1997; 96(9): 3205 - 3214. [Full Text]
|
|
|
|
 |
|
 K. Bouki and A. Kranidis In Response: Reply to Drs. Pontillo and Capezzuto Angiology, October 1, 1997; 48(10): 932 - 932. [PDF]
|
|
|
|
|
|
J.-L. J. Vanoverschelde, W. Wijns, M. Borgers, G. Heyndrickx, C. Depre, W. Flameng, and J. A. Melin Chronic Myocardial Hibernation in Humans: From Bedside to Bench Circulation, April 1, 1997; 95(7): 1961 - 1971. [Full Text]
|
|
|
|
|
|
U. Qureshi, S. F. Nagueh, I. Afridi, P. Vaduganathan, A. Blaustein, M. S. Verani, W. L. Winters, and W. A. Zoghbi Dobutamine Echocardiography and Quantitative Rest-Redistribution 201Tl Tomography in Myocardial Hibernation: Relation of Contractile Reserve to 201Tl Uptake and Comparative Prediction of Recovery of Function Circulation, February 4, 1997; 95(3): 626 - 635. [Abstract] [Full Text]
|
|
|
|
|
|
S. H. Rahimtoola Hibernating Myocardium Has Reduced Blood Flow at Rest That Increases With Low-Dose Dobutamine Circulation, December 15, 1996; 94(12): 3055 - 3061. [Full Text]
|
|
|
|
|
|
R. O. Bonow Identification of Viable Myocardium Circulation, December 1, 1996; 94(11): 2674 - 2680. [Full Text]
|
|
|
|
|
|
C. Chen, L. Chen, J. T. Fallon, L. Ma, L. Li, L. Bow, D. Knibbs, R. McKay, L. D. Gillam, and D. D. Waters Functional and Structural Alterations With 24-Hour Myocardial Hibernation and Recovery After Reperfusion: A Pig Model of Myocardial Hibernation Circulation, August 1, 1996; 94(3): 507 - 516. [Abstract] [Full Text]
|
|