TY - JOUR
T1 - Coronary endothelial dysfunction precedes heart failure and reduction of coronary reserve in awake dogs
AU - Knecht, Mathias
AU - Burkhoff, Daniel
AU - Yi, Geng Hua
AU - Popilskis, Sulli
AU - Homma, Shunichi
AU - Packer, Milton
AU - Wang, Jie
N1 - Funding Information:
This work was supported in part by a Grant-In-Aid from the American Heart Association (National Center) and a grant from NIH HLBI R29 (HL51885-01). JW and DB were Investigator of the American Heart Association and supported in part by In-vestigatorship from AHA, New York City Affiliate. Additional support was provided by the Whitaker Foundation.
PY - 1997/1
Y1 - 1997/1
N2 - Endothelial dysfunction in coronary circulation is well documented in heart failure (HF). However, whether this dysfunction is a consequence of heart failure or precedes the development of HF remains unknown. To determine endothelium-dependent regulation in the remote coronary vasculature in a canine coronary microembolization-induced HF model, seven dogs were chronically instrumented for measurement of systemic hemodynamics, for selective coronary microembolization via an implanted coronary catheter and for measurement of corollary blood flow in the non-embolized coronary artery. Microembolizations were performed daily until hemodynamic and echocardiographic measurements showed HF. The responses of coronary blood flow to acetylcholine (0.25, 0.5, 5, 10 μg/kg), nitroglycerine (0.2, 0.8, 5, 25 μg/kg), adenosine (0.25, 0.5, 2, 5 μmol/kg) and brief coronary occlusions (5, 10, 15, 20, 30 s) were examined. Although no signs of HF developed and the responses of coronary blood flow to nitroglycerine, adenosine and occlusions were not altered, the response to acetylcholine was selectively reduced after 1 week of embolization (275,000 ± 55,000 microspheres). Resting coronary flow increased from 21.3 ± 1.4 ml/min in control state to 27.7 ± 3.5 ml/min (P < 0.001). As HF developed, characterized by an elevated left ventricular end-diastolic pressure (6.4 ± 1.6 v 16 ± 1.6 mmHg, P < 0.001), a decreased area election fraction (54 ± 5 v 36 ± 5% P < 0.05) and a reduced β-adrenergic response to isoproterenol, the responses of coronary blood flow to acetylcholine, nitroglycerine, adenosine and occlusions were consistently depressed. Resting coronary blood flow was decreased to 15.4 ± 2.7 ml/min (P < 0.01). Our results indicate, that there is a selectively impaired endothelium-mediated dilator capacity of the resistance coronary vasculature before the development of HF and a reduction of the coronary flow reserve.
AB - Endothelial dysfunction in coronary circulation is well documented in heart failure (HF). However, whether this dysfunction is a consequence of heart failure or precedes the development of HF remains unknown. To determine endothelium-dependent regulation in the remote coronary vasculature in a canine coronary microembolization-induced HF model, seven dogs were chronically instrumented for measurement of systemic hemodynamics, for selective coronary microembolization via an implanted coronary catheter and for measurement of corollary blood flow in the non-embolized coronary artery. Microembolizations were performed daily until hemodynamic and echocardiographic measurements showed HF. The responses of coronary blood flow to acetylcholine (0.25, 0.5, 5, 10 μg/kg), nitroglycerine (0.2, 0.8, 5, 25 μg/kg), adenosine (0.25, 0.5, 2, 5 μmol/kg) and brief coronary occlusions (5, 10, 15, 20, 30 s) were examined. Although no signs of HF developed and the responses of coronary blood flow to nitroglycerine, adenosine and occlusions were not altered, the response to acetylcholine was selectively reduced after 1 week of embolization (275,000 ± 55,000 microspheres). Resting coronary flow increased from 21.3 ± 1.4 ml/min in control state to 27.7 ± 3.5 ml/min (P < 0.001). As HF developed, characterized by an elevated left ventricular end-diastolic pressure (6.4 ± 1.6 v 16 ± 1.6 mmHg, P < 0.001), a decreased area election fraction (54 ± 5 v 36 ± 5% P < 0.05) and a reduced β-adrenergic response to isoproterenol, the responses of coronary blood flow to acetylcholine, nitroglycerine, adenosine and occlusions were consistently depressed. Resting coronary blood flow was decreased to 15.4 ± 2.7 ml/min (P < 0.01). Our results indicate, that there is a selectively impaired endothelium-mediated dilator capacity of the resistance coronary vasculature before the development of HF and a reduction of the coronary flow reserve.
KW - Acetylcholine
KW - Coronary blood reserve
KW - Coronary microembolization
KW - Heart failure
KW - Nitric oxide
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U2 - 10.1006/jmcc.1996.0266
DO - 10.1006/jmcc.1996.0266
M3 - Article
C2 - 9040036
AN - SCOPUS:0030936291
SN - 0022-2828
VL - 29
SP - 217
EP - 227
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 1
ER -