Cardiac diastolic dysfunction in conscious dogs with heart failure induced by chronic coronary microembolization.
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-microm diameter) for 24 +/- 4 days, resulting in significant depression of cardiac systolic function. After CCE, LV maximum negative change of pressure with time (dP/dt(min)) 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(alpha*EDV)) during brief inferior vena caval occlusion and acute volume loading, while the chamber stiffness coefficient (alpha) 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.
Gill
Robert M
RM
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
Jones
Bonita D
BD
Corbly
Angela K
AK
Wang
Juan
J
Braz
Julian C
JC
Sandusky
George E
GE
Wang
Jie
J
Shen
Weiqun
W
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D004617:Embolism / Q000150:complications*; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D006333:Heart Failure / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000503:physiopathology; D008863:Microspheres; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000503:physiopathology*
D017395:Plasminogen Activator Inhibitor 1; D003094:Collagen