Effects of beta-blockade and atropine on ischemic responses in left ventricular regions subtending coronary stenosis during dobutamine stress echocardiography.
OBJECTIVE
This study was designed to examine the effects of a beta-adrenergic blocking agent on the ischemic response to dobutamine stress and to determine the degree to which these effects can be abolished by the addition of atropine.


BACKGROUND
Whether beta-blockade affects the sensitivity of dobutamine stress echocardiography for the diagnosis of coronary artery disease has been controversial.


METHODS
In nine pigs, a left anterior descending coronary artery stenosis was created to reduce flow reserve (maximal/rest flow) to 1.1 to 1.9 without baseline regional wall motion abnormalities. This corresponded to a 50% to 90% diameter stenosis. Wall thickening was measured using epicardial echocardiography. Regional lactate production and coronary venous pH were monitored from an adjacent cardiac vein. A standard protocol of dobutamine stress echocardiography was first performed. After normalization of the ischemic abnormalities elicited with this infusion, esmolol was infused at 50 micrograms/kg body weight per min and the dobutamine test was repeated, with 1.0 mg of atropine added at the maximal dobutamine dose.


RESULTS
Without esmolol, dobutamine stress induced myocardial ischemia with a reduction in regional wall thickening and lactate production in all nine pigs. Multiple regression analysis revealed that coronary flow per heartbeat (p < 0.01) and lactate production (p < 0.05) independently correlated with regional wall thickening during dobutamine stress. The beta-blocker significantly reduced heart rate and regional oxygen consumption and altered the relation between coronary flow per heartbeat and regional wall thickening (p < 0.05) during dobutamine stress. Esmolol prevented dobutamine-induced ischemia (lactate production and wall motion abnormalities) in seven of nine pigs. The addition of atropine induced lactate production and a reduction in wall thickening in five of seven pigs in which ischemia had been prevented by beta-blockade. However, lactate production was higher and regional venous pH was lower with the baseline dobutamine infusion than with that performed after esmolol with atropine added at the maximal dobutamine dose (p < 0.05).


CONCLUSIONS
A correlation between regional wall thickening and coronary flow per heartbeat was demonstrated during baseline dobutamine stress. Beta-blockade shifted this relation so that dobutamine stress-induced myocardial ischemia was attenuated. The mechanisms by which beta-blockade prevents dobutamine-induced ischemia appeared to be mainly through decreases in heart rate and rate of rise in left ventricular pressure, improvement of regional coronary flow per heartbeat and attenuation of regional ischemic lactate production. Adding atropine in conventional doses enhanced the ability of dobutamine stress to induce myocardial ischemia but did not completely abolish the effects of beta-blockade on either the severity of dobutamine-induced wall thickening abnormalities or regional metabolic disturbances.
Chen
L
L
Department of Medicine, Hartford Hospital, University of Connecticut School of Medicine 06102, USA.
Ma
L
L
de Prada
V A
VA
Chen
M
M
Feng
Y J
YJ
Waters
D
D
Gillam
L
L
Chen
C
C
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D002316:Cardiotonic Agents; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000503:physiopathology; D004280:Dobutamine; D004452:Echocardiography; D019344:Lactic Acid / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D015588:Observer Variation; D010101:Oxygen Consumption / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013552:Swine; D016277:Ventricular Function, Left / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D002316:Cardiotonic Agents; D011412:Propanolamines; D019344:Lactic Acid; D004280:Dobutamine; D001285:Atropine; C036604:esmolol