Cardiac resynchronization by cardiosphere-derived stem cell transplantation in an experimental model of myocardial infarction

Michael Bonios, Connie Y. Chang, Aurelio Pinheiro, Veronica Lea Dimaano, Takahiro Higuchi, Christina Melexopoulou, Frank Bengel, John Terrovitis, Theodore P. Abraham, M. Roselle Abraham

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background: Cardiosphere-derived stem cell (CDC) transplantation can improve global left ventricular ejection fraction (LVEF) after myocardial infarction (MI). The aim of this study was to examine the effects of CDC transplantation on regional function and dyssynchrony after MI. Methods: Two million rat CDCs (n = 7) or phosphate-buffered saline (n = 7) was injected into the infarct regions of Wistar Kyoto rats. Infarct size and CDC localization were evaluated by positron emission tomography (n = 7). Two-dimensional and strain echocardiography were performed at 1 and 4 weeks after MI. LVEF, circumferential strain, and time to peak circumferential strain were measured in the basal and apical short-axis views. Dyssynchrony was defined as the maximal difference of time to peak circumferential strain of opposing segments in each short-axis view. Engraftment was measured by quantitative polymerase chain reaction. Results: Positron emission tomography revealed that infarct size was 15.4 ± 3.6% of the left ventricle and that CDCs were localized to the infarct and border zone. CDC transplantation improved mean LVEF (45 ± 8% to 52 ± 7%, P = .02), mean circumferential strain (-7 ± 2% to -10 ± 1%, P = .02), and mean dyssynchrony (45 ± 10 to 28 ± 11 m sec, P = .04) of the infarct/peri-infarct zone from 1 to 4 weeks after MI, despite CDC engraftment of only 2.4 ± 3%. In contrast, mean LVEF (48 ± 5% to 40 ± 4%, P = .03) and mean circumferential strain (-8 ± 2% to -7 ± 1%, P = .02) of the infarcted region deteriorated, with no significant change in dyssynchrony (42 ± 12 vs 46 ± 13 m sec, P = .60) in the saline group during the same time period. Change in LVEF was correlated with change in circumferential strain (r = -0.8, P = .002) and dyssynchrony (r = 0.6, P = .02) of the infarct/peri-infarct region at 4 weeks after MI. Conclusions: CDC therapy enhanced LVEF by improving circumferential strain and decreasing dyssynchrony of the infarct/peri-infarct region at 4 weeks, but not 1 week, after MI. Cellular resynchronization therapy using CDCs may be an alternative to traditional electrical cellular resynchronization therapy in post-MI dyssynchrony.

Original languageEnglish
Pages (from-to)808-814
Number of pages7
JournalJournal of the American Society of Echocardiography
Volume24
Issue number7
DOIs
Publication statusPublished - Jul 1 2011
Externally publishedYes

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Cardiac Resynchronization Therapy
Stem Cell Transplantation
Stroke Volume
Theoretical Models
Myocardial Infarction
Centers for Disease Control and Prevention (U.S.)
Stem Cells
Positron-Emission Tomography
Inbred WKY Rats
Cell- and Tissue-Based Therapy
Heart Ventricles
Echocardiography
Phosphates
Polymerase Chain Reaction
Therapeutics

Keywords

  • Dyssynchrony
  • Echocardiography
  • PET
  • Stem cells
  • Strain

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

Cardiac resynchronization by cardiosphere-derived stem cell transplantation in an experimental model of myocardial infarction. / Bonios, Michael; Chang, Connie Y.; Pinheiro, Aurelio; Dimaano, Veronica Lea; Higuchi, Takahiro; Melexopoulou, Christina; Bengel, Frank; Terrovitis, John; Abraham, Theodore P.; Abraham, M. Roselle.

In: Journal of the American Society of Echocardiography, Vol. 24, No. 7, 01.07.2011, p. 808-814.

Research output: Contribution to journalArticle

Bonios, M, Chang, CY, Pinheiro, A, Dimaano, VL, Higuchi, T, Melexopoulou, C, Bengel, F, Terrovitis, J, Abraham, TP & Abraham, MR 2011, 'Cardiac resynchronization by cardiosphere-derived stem cell transplantation in an experimental model of myocardial infarction', Journal of the American Society of Echocardiography, vol. 24, no. 7, pp. 808-814. https://doi.org/10.1016/j.echo.2011.03.003
Bonios, Michael ; Chang, Connie Y. ; Pinheiro, Aurelio ; Dimaano, Veronica Lea ; Higuchi, Takahiro ; Melexopoulou, Christina ; Bengel, Frank ; Terrovitis, John ; Abraham, Theodore P. ; Abraham, M. Roselle. / Cardiac resynchronization by cardiosphere-derived stem cell transplantation in an experimental model of myocardial infarction. In: Journal of the American Society of Echocardiography. 2011 ; Vol. 24, No. 7. pp. 808-814.
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title = "Cardiac resynchronization by cardiosphere-derived stem cell transplantation in an experimental model of myocardial infarction",
abstract = "Background: Cardiosphere-derived stem cell (CDC) transplantation can improve global left ventricular ejection fraction (LVEF) after myocardial infarction (MI). The aim of this study was to examine the effects of CDC transplantation on regional function and dyssynchrony after MI. Methods: Two million rat CDCs (n = 7) or phosphate-buffered saline (n = 7) was injected into the infarct regions of Wistar Kyoto rats. Infarct size and CDC localization were evaluated by positron emission tomography (n = 7). Two-dimensional and strain echocardiography were performed at 1 and 4 weeks after MI. LVEF, circumferential strain, and time to peak circumferential strain were measured in the basal and apical short-axis views. Dyssynchrony was defined as the maximal difference of time to peak circumferential strain of opposing segments in each short-axis view. Engraftment was measured by quantitative polymerase chain reaction. Results: Positron emission tomography revealed that infarct size was 15.4 ± 3.6{\%} of the left ventricle and that CDCs were localized to the infarct and border zone. CDC transplantation improved mean LVEF (45 ± 8{\%} to 52 ± 7{\%}, P = .02), mean circumferential strain (-7 ± 2{\%} to -10 ± 1{\%}, P = .02), and mean dyssynchrony (45 ± 10 to 28 ± 11 m sec, P = .04) of the infarct/peri-infarct zone from 1 to 4 weeks after MI, despite CDC engraftment of only 2.4 ± 3{\%}. In contrast, mean LVEF (48 ± 5{\%} to 40 ± 4{\%}, P = .03) and mean circumferential strain (-8 ± 2{\%} to -7 ± 1{\%}, P = .02) of the infarcted region deteriorated, with no significant change in dyssynchrony (42 ± 12 vs 46 ± 13 m sec, P = .60) in the saline group during the same time period. Change in LVEF was correlated with change in circumferential strain (r = -0.8, P = .002) and dyssynchrony (r = 0.6, P = .02) of the infarct/peri-infarct region at 4 weeks after MI. Conclusions: CDC therapy enhanced LVEF by improving circumferential strain and decreasing dyssynchrony of the infarct/peri-infarct region at 4 weeks, but not 1 week, after MI. Cellular resynchronization therapy using CDCs may be an alternative to traditional electrical cellular resynchronization therapy in post-MI dyssynchrony.",
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author = "Michael Bonios and Chang, {Connie Y.} and Aurelio Pinheiro and Dimaano, {Veronica Lea} and Takahiro Higuchi and Christina Melexopoulou and Frank Bengel and John Terrovitis and Abraham, {Theodore P.} and Abraham, {M. Roselle}",
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T1 - Cardiac resynchronization by cardiosphere-derived stem cell transplantation in an experimental model of myocardial infarction

AU - Bonios, Michael

AU - Chang, Connie Y.

AU - Pinheiro, Aurelio

AU - Dimaano, Veronica Lea

AU - Higuchi, Takahiro

AU - Melexopoulou, Christina

AU - Bengel, Frank

AU - Terrovitis, John

AU - Abraham, Theodore P.

AU - Abraham, M. Roselle

PY - 2011/7/1

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N2 - Background: Cardiosphere-derived stem cell (CDC) transplantation can improve global left ventricular ejection fraction (LVEF) after myocardial infarction (MI). The aim of this study was to examine the effects of CDC transplantation on regional function and dyssynchrony after MI. Methods: Two million rat CDCs (n = 7) or phosphate-buffered saline (n = 7) was injected into the infarct regions of Wistar Kyoto rats. Infarct size and CDC localization were evaluated by positron emission tomography (n = 7). Two-dimensional and strain echocardiography were performed at 1 and 4 weeks after MI. LVEF, circumferential strain, and time to peak circumferential strain were measured in the basal and apical short-axis views. Dyssynchrony was defined as the maximal difference of time to peak circumferential strain of opposing segments in each short-axis view. Engraftment was measured by quantitative polymerase chain reaction. Results: Positron emission tomography revealed that infarct size was 15.4 ± 3.6% of the left ventricle and that CDCs were localized to the infarct and border zone. CDC transplantation improved mean LVEF (45 ± 8% to 52 ± 7%, P = .02), mean circumferential strain (-7 ± 2% to -10 ± 1%, P = .02), and mean dyssynchrony (45 ± 10 to 28 ± 11 m sec, P = .04) of the infarct/peri-infarct zone from 1 to 4 weeks after MI, despite CDC engraftment of only 2.4 ± 3%. In contrast, mean LVEF (48 ± 5% to 40 ± 4%, P = .03) and mean circumferential strain (-8 ± 2% to -7 ± 1%, P = .02) of the infarcted region deteriorated, with no significant change in dyssynchrony (42 ± 12 vs 46 ± 13 m sec, P = .60) in the saline group during the same time period. Change in LVEF was correlated with change in circumferential strain (r = -0.8, P = .002) and dyssynchrony (r = 0.6, P = .02) of the infarct/peri-infarct region at 4 weeks after MI. Conclusions: CDC therapy enhanced LVEF by improving circumferential strain and decreasing dyssynchrony of the infarct/peri-infarct region at 4 weeks, but not 1 week, after MI. Cellular resynchronization therapy using CDCs may be an alternative to traditional electrical cellular resynchronization therapy in post-MI dyssynchrony.

AB - Background: Cardiosphere-derived stem cell (CDC) transplantation can improve global left ventricular ejection fraction (LVEF) after myocardial infarction (MI). The aim of this study was to examine the effects of CDC transplantation on regional function and dyssynchrony after MI. Methods: Two million rat CDCs (n = 7) or phosphate-buffered saline (n = 7) was injected into the infarct regions of Wistar Kyoto rats. Infarct size and CDC localization were evaluated by positron emission tomography (n = 7). Two-dimensional and strain echocardiography were performed at 1 and 4 weeks after MI. LVEF, circumferential strain, and time to peak circumferential strain were measured in the basal and apical short-axis views. Dyssynchrony was defined as the maximal difference of time to peak circumferential strain of opposing segments in each short-axis view. Engraftment was measured by quantitative polymerase chain reaction. Results: Positron emission tomography revealed that infarct size was 15.4 ± 3.6% of the left ventricle and that CDCs were localized to the infarct and border zone. CDC transplantation improved mean LVEF (45 ± 8% to 52 ± 7%, P = .02), mean circumferential strain (-7 ± 2% to -10 ± 1%, P = .02), and mean dyssynchrony (45 ± 10 to 28 ± 11 m sec, P = .04) of the infarct/peri-infarct zone from 1 to 4 weeks after MI, despite CDC engraftment of only 2.4 ± 3%. In contrast, mean LVEF (48 ± 5% to 40 ± 4%, P = .03) and mean circumferential strain (-8 ± 2% to -7 ± 1%, P = .02) of the infarcted region deteriorated, with no significant change in dyssynchrony (42 ± 12 vs 46 ± 13 m sec, P = .60) in the saline group during the same time period. Change in LVEF was correlated with change in circumferential strain (r = -0.8, P = .002) and dyssynchrony (r = 0.6, P = .02) of the infarct/peri-infarct region at 4 weeks after MI. Conclusions: CDC therapy enhanced LVEF by improving circumferential strain and decreasing dyssynchrony of the infarct/peri-infarct region at 4 weeks, but not 1 week, after MI. Cellular resynchronization therapy using CDCs may be an alternative to traditional electrical cellular resynchronization therapy in post-MI dyssynchrony.

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KW - Echocardiography

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