Incremental doses of dobutamine induce a biphasic response in dysfunctional left ventricular regions subtending coronary stenoses

Chunguang Chen, Li Li, Liang Long Chen, Jose V. Prada, Ming Hui Chen, John T. Fallon, Arthur E. Weyman, David Waters, Linda Gillam

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

Background: Dobutamine stress echocardiographic 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% 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 the 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.

Original languageEnglish (US)
Pages (from-to)756-766
Number of pages11
JournalCirculation
Volume92
Issue number4
DOIs
StatePublished - Aug 15 1995
Externally publishedYes

Fingerprint

Dobutamine
Coronary Stenosis
Myocardium
Lactic Acid
Hibernation
Acidosis
Myocardial Ischemia
Coronary Vessels
Myocardial Stunning
Control Groups

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Chen, Chunguang ; Li, Li ; Chen, Liang Long ; Prada, Jose V. ; Chen, Ming Hui ; Fallon, John T. ; Weyman, Arthur E. ; Waters, David ; Gillam, Linda. / Incremental doses of dobutamine induce a biphasic response in dysfunctional left ventricular regions subtending coronary stenoses. In: Circulation. 1995 ; Vol. 92, No. 4. pp. 756-766.
@article{c7b6b2728b4d4e91b5d1caed5afd2552,
title = "Incremental doses of dobutamine induce a biphasic response in dysfunctional left ventricular regions subtending coronary stenoses",
abstract = "Background: Dobutamine stress echocardiographic 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{\%} 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 the 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.",
author = "Chunguang Chen and Li Li and Chen, {Liang Long} and Prada, {Jose V.} and Chen, {Ming Hui} and Fallon, {John T.} and Weyman, {Arthur E.} and David Waters and Linda Gillam",
year = "1995",
month = "8",
day = "15",
doi = "10.1161/01.CIR.92.4.756",
language = "English (US)",
volume = "92",
pages = "756--766",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

Incremental doses of dobutamine induce a biphasic response in dysfunctional left ventricular regions subtending coronary stenoses. / Chen, Chunguang; Li, Li; Chen, Liang Long; Prada, Jose V.; Chen, Ming Hui; Fallon, John T.; Weyman, Arthur E.; Waters, David; Gillam, Linda.

In: Circulation, Vol. 92, No. 4, 15.08.1995, p. 756-766.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Incremental doses of dobutamine induce a biphasic response in dysfunctional left ventricular regions subtending coronary stenoses

AU - Chen, Chunguang

AU - Li, Li

AU - Chen, Liang Long

AU - Prada, Jose V.

AU - Chen, Ming Hui

AU - Fallon, John T.

AU - Weyman, Arthur E.

AU - Waters, David

AU - Gillam, Linda

PY - 1995/8/15

Y1 - 1995/8/15

N2 - Background: Dobutamine stress echocardiographic 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% 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 the 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.

AB - Background: Dobutamine stress echocardiographic 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% 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 the 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.

UR - http://www.scopus.com/inward/record.url?scp=0029120024&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029120024&partnerID=8YFLogxK

U2 - 10.1161/01.CIR.92.4.756

DO - 10.1161/01.CIR.92.4.756

M3 - Article

VL - 92

SP - 756

EP - 766

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 4

ER -