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Defective endothelium-mediated control of coronary circulation in conscious dogs after heart failure
Insights
Heart failure in dogs impairs coronary endothelial function, reducing nitric oxide production. This study found that endothelium-mediated control of the coronary circulation was depressed, likely due to decreased nitric oxide.
Area of Science:
- Cardiovascular Physiology
- Heart Failure Pathophysiology
- Endothelial Function Research
Background:
- Pacing-induced heart failure is a model to study cardiac dysfunction.
- Coronary endothelial function plays a critical role in regulating blood flow.
- Alterations in endothelial function contribute to heart failure progression.
Purpose of the Study:
- To investigate changes in coronary endothelial function following pacing-induced heart failure in dogs.
- To determine the role of nitric oxide in endothelial dysfunction during heart failure.
Main Methods:
- Conscious dogs underwent 4 weeks of left ventricular pacing to induce heart failure.
- Systemic hemodynamics, coronary artery diameter, and blood flow were measured.
- Vessel-mediated dilations and nitrite production from isolated vessels were assessed.
Main Results:
- Heart failure was characterized by reduced arterial pressure, increased atrial pressure, and depressed cardiac function.
- Coronary artery dilation to acetylcholine and arachidonic acid was attenuated.
- Nitrite production from coronary arteries and microvessels was significantly reduced in failing hearts.
Conclusions:
- Coronary endothelial function is depressed in pacing-induced heart failure.
- Reduced nitric oxide production is a key factor in this endothelial dysfunction.
- Endothelium-derived relaxing factor (nitric oxide) deficiency contributes to impaired coronary circulation during heart failure.
Abstract:
The goal of this study was to determine whether coronary endothelial function was altered after pacing-induced heart failure in conscious dogs. Fourteen mongrel dogs were chronically instrumented for measurements of systemic hemodynamics, left circumflex coronary artery diameter (CD) and blood flow, and for left ventricular pacing for 4 wk. Heart failure developed during this pacing regimen and was characterized by a significant reduction in arterial pressure, an increase in left atrial pressure, a resting tachycardia, a depression of left ventricular dP/dt to isoproterenol injection, a significant reduction of the slope of the end-systolic pressure-diameter relationship, and all of the characteristic clinical signs. During heart failure, the dilation of CD after release of a brief coronary artery occlusion, acetylcholine, and arachidonic acid was attenuated, whereas prostaglandin (PG) I2- and nitroglycerin-induced dilations of CD were unchanged. The coronary blood flow responses to occlusion, acetylcholine, and nitroglycerin were depressed, but not to PG. Large coronary arteries and microvessels were isolated from normal and failing hearts. Both isolated large coronary arteries and microvessels from failing hearts produced significantly less nitrite, the immediate metabolite of nitric oxide in aqueous solution, than those of normal hearts. Thus endothelium-mediated control of the coronary circulation was depressed during heart failure. A decrease in the production of nitric oxide-endothelium-derived relaxing factor was most likely responsible for this depression.