Coronary endothelial dysfunction precedes heart failure and reduction of coronary reserve in awake dogs

Mathias Knecht, Daniel Burkhoff, Geng Hua Yi, Sulli Popilskis, Shunichi Homma, Milton Packer, Jie Wang

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)217-227
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Volume29
Issue number1
DOIs
StatePublished - Jan 1997

Fingerprint

Heart Failure
Dogs
Nitroglycerin
Adenosine
Acetylcholine
Endothelium
Hemodynamics
Coronary Circulation
Coronary Occlusion
Microspheres
Isoproterenol
Adrenergic Agents
Canidae
Coronary Vessels
Catheters
Blood Pressure

Keywords

  • Acetylcholine
  • Coronary blood reserve
  • Coronary microembolization
  • Heart failure
  • Nitric oxide

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Coronary endothelial dysfunction precedes heart failure and reduction of coronary reserve in awake dogs. / Knecht, Mathias; Burkhoff, Daniel; Yi, Geng Hua; Popilskis, Sulli; Homma, Shunichi; Packer, Milton; Wang, Jie.

In: Journal of Molecular and Cellular Cardiology, Vol. 29, No. 1, 01.1997, p. 217-227.

Research output: Contribution to journalArticle

Knecht, Mathias ; Burkhoff, Daniel ; Yi, Geng Hua ; Popilskis, Sulli ; Homma, Shunichi ; Packer, Milton ; Wang, Jie. / Coronary endothelial dysfunction precedes heart failure and reduction of coronary reserve in awake dogs. In: Journal of Molecular and Cellular Cardiology. 1997 ; Vol. 29, No. 1. pp. 217-227.
@article{5334624687e641af9a1b50dcb67f7ac8,
title = "Coronary endothelial dysfunction precedes heart failure and reduction of coronary reserve in awake dogs",
abstract = "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.",
keywords = "Acetylcholine, Coronary blood reserve, Coronary microembolization, Heart failure, Nitric oxide",
author = "Mathias Knecht and Daniel Burkhoff and Yi, {Geng Hua} and Sulli Popilskis and Shunichi Homma and Milton Packer and Jie Wang",
year = "1997",
month = "1",
doi = "10.1006/jmcc.1996.0266",
language = "English (US)",
volume = "29",
pages = "217--227",
journal = "Journal of Molecular and Cellular Cardiology",
issn = "0022-2828",
publisher = "Academic Press Inc.",
number = "1",

}

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

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

UR - http://www.scopus.com/inward/record.url?scp=0030936291&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030936291&partnerID=8YFLogxK

U2 - 10.1006/jmcc.1996.0266

DO - 10.1006/jmcc.1996.0266

M3 - Article

C2 - 9040036

AN - SCOPUS:0030936291

VL - 29

SP - 217

EP - 227

JO - Journal of Molecular and Cellular Cardiology

JF - Journal of Molecular and Cellular Cardiology

SN - 0022-2828

IS - 1

ER -