Cardiac diastolic dysfunction in conscious dogs with heart failure induced by chronic coronary microembolization

Robert M. Gill, Bonita D. Jones, Angela K. Corbly, Juan Wang, Julian C. Braz, George Sandusky, Jie Wang, Weiqun Shen

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Left ventricular (LV) diastolic dysfunction is a fundamental impairment in congestive heart failure (CHF). This study examined LV diastolic function in the canine model of CHF induced by chronic coronary embolization (CCE). Dogs were implanted with coronary catheters (both left anterior descending and circumflex arteries) for CCE and instrumented for measurement of LV pressure and dimension. Heart failure was elicited by daily intracoronary injections of microspheres (1.2 million, 90- to 120-μm diameter) for 24 ± 4 days, resulting in significant depression of cardiac systolic function. After CCE, LV maximum negative change of pressure with time (dP/dtmin) decreased by 25 ± 2% (P <0.05) and LV isovolumic relaxation constant and duration increased by 19 ± 5% and 25 ± 6%, respectively (both P <0.05), indicating an impairment of LV active relaxation, which was cardiac preload independent. LV passive viscoelastic properties were evaluated from the LV end-diastolic pressure (EDP)-volume (EDV) relationship (EDP = be α*EDV) during brief inferior vena caval occlusion and acute volume loading, while the chamber stiffness coefficient(α) increased by 62 ± 10% (P <0.05) and the stiffness constant (k) increased by 66 ± 13% after CCE. The regional myocardial diastolic stiffness in LV anterior and posterior walls was increased by 70 ± 25% and 63 ± 24% (both P <0.05), respectively, after CCE, associated with marked fibrosis, increase in collagen I and III, and enhancement of plasminogen activator inhibitor-1 (PAI-1) protein expression. Thus along with depressed LV systolic function there is significant impairment of LV diastolic relaxation and increase in chamber stiffness, with development of myocardial fibrosis and activation of PAI-1, in the canine model of CHF induced by CCE.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume291
Issue number6
DOIs
StatePublished - 2006
Externally publishedYes

Fingerprint

Heart Failure
Dogs
Plasminogen Activator Inhibitor 1
Left Ventricular Function
Canidae
Fibrosis
Replication Protein C
Blood Pressure
Venae Cavae
Left Ventricular Dysfunction
Ventricular Pressure
Microspheres
Stroke Volume
Coronary Vessels
Collagen
Catheters
Pressure
Injections

Keywords

  • Coronary embolization
  • Diastolic stiffness
  • Plasminogen activator inhibitor-1

ASJC Scopus subject areas

  • Physiology

Cite this

Cardiac diastolic dysfunction in conscious dogs with heart failure induced by chronic coronary microembolization. / Gill, Robert M.; Jones, Bonita D.; Corbly, Angela K.; Wang, Juan; Braz, Julian C.; Sandusky, George; Wang, Jie; Shen, Weiqun.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 291, No. 6, 2006.

Research output: Contribution to journalArticle

Gill, Robert M. ; Jones, Bonita D. ; Corbly, Angela K. ; Wang, Juan ; Braz, Julian C. ; Sandusky, George ; Wang, Jie ; Shen, Weiqun. / Cardiac diastolic dysfunction in conscious dogs with heart failure induced by chronic coronary microembolization. In: American Journal of Physiology - Heart and Circulatory Physiology. 2006 ; Vol. 291, No. 6.
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abstract = "Left ventricular (LV) diastolic dysfunction is a fundamental impairment in congestive heart failure (CHF). This study examined LV diastolic function in the canine model of CHF induced by chronic coronary embolization (CCE). Dogs were implanted with coronary catheters (both left anterior descending and circumflex arteries) for CCE and instrumented for measurement of LV pressure and dimension. Heart failure was elicited by daily intracoronary injections of microspheres (1.2 million, 90- to 120-μm diameter) for 24 ± 4 days, resulting in significant depression of cardiac systolic function. After CCE, LV maximum negative change of pressure with time (dP/dtmin) decreased by 25 ± 2{\%} (P <0.05) and LV isovolumic relaxation constant and duration increased by 19 ± 5{\%} and 25 ± 6{\%}, respectively (both P <0.05), indicating an impairment of LV active relaxation, which was cardiac preload independent. LV passive viscoelastic properties were evaluated from the LV end-diastolic pressure (EDP)-volume (EDV) relationship (EDP = be α*EDV) during brief inferior vena caval occlusion and acute volume loading, while the chamber stiffness coefficient(α) increased by 62 ± 10{\%} (P <0.05) and the stiffness constant (k) increased by 66 ± 13{\%} after CCE. The regional myocardial diastolic stiffness in LV anterior and posterior walls was increased by 70 ± 25{\%} and 63 ± 24{\%} (both P <0.05), respectively, after CCE, associated with marked fibrosis, increase in collagen I and III, and enhancement of plasminogen activator inhibitor-1 (PAI-1) protein expression. Thus along with depressed LV systolic function there is significant impairment of LV diastolic relaxation and increase in chamber stiffness, with development of myocardial fibrosis and activation of PAI-1, in the canine model of CHF induced by CCE.",
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AB - Left ventricular (LV) diastolic dysfunction is a fundamental impairment in congestive heart failure (CHF). This study examined LV diastolic function in the canine model of CHF induced by chronic coronary embolization (CCE). Dogs were implanted with coronary catheters (both left anterior descending and circumflex arteries) for CCE and instrumented for measurement of LV pressure and dimension. Heart failure was elicited by daily intracoronary injections of microspheres (1.2 million, 90- to 120-μm diameter) for 24 ± 4 days, resulting in significant depression of cardiac systolic function. After CCE, LV maximum negative change of pressure with time (dP/dtmin) decreased by 25 ± 2% (P <0.05) and LV isovolumic relaxation constant and duration increased by 19 ± 5% and 25 ± 6%, respectively (both P <0.05), indicating an impairment of LV active relaxation, which was cardiac preload independent. LV passive viscoelastic properties were evaluated from the LV end-diastolic pressure (EDP)-volume (EDV) relationship (EDP = be α*EDV) during brief inferior vena caval occlusion and acute volume loading, while the chamber stiffness coefficient(α) increased by 62 ± 10% (P <0.05) and the stiffness constant (k) increased by 66 ± 13% after CCE. The regional myocardial diastolic stiffness in LV anterior and posterior walls was increased by 70 ± 25% and 63 ± 24% (both P <0.05), respectively, after CCE, associated with marked fibrosis, increase in collagen I and III, and enhancement of plasminogen activator inhibitor-1 (PAI-1) protein expression. Thus along with depressed LV systolic function there is significant impairment of LV diastolic relaxation and increase in chamber stiffness, with development of myocardial fibrosis and activation of PAI-1, in the canine model of CHF induced by CCE.

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