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Endothelium-dependent dilation of the coronary microvasculature is impaired in dilated cardiomyopathy
C B Treasure1, J A Vita, D A Cox
1Department of Medicine (Cardiovascular Division), Brigham and Women's Hospital, Boston, MA 02115.
Insights
Coronary microvascular function is impaired in dilated cardiomyopathy, with reduced endothelium-dependent dilation contributing to this effect. This study investigated the role of intrinsic microvascular disease in this condition.
Area of Science:
- Cardiology
- Physiology
- Vascular Biology
Background:
- Coronary microvasculature dilator reserve is reduced in dilated cardiomyopathy.
- While factors like increased myocardial mass contribute, intrinsic microvascular disease is suspected.
- Endothelial dysfunction may play a role in impaired microvascular dilation.
Purpose of the Study:
- To test the hypothesis that impaired endothelium-dependent dilation contributes to microvascular dysfunction in dilated cardiomyopathy.
- To investigate the role of intrinsic microvascular disease in this patient population.
Main Methods:
- Infusion of acetylcholine (endothelium-dependent dilator) and adenosine (smooth muscle vasodilator) into the coronary artery.
- Measurement of coronary blood flow (CBF) using Doppler velocity catheter and angiography.
- Assessment of microvascular function by comparing responses to acetylcholine and adenosine.
Main Results:
- Cardiomyopathy patients showed no significant increase in CBF with acetylcholine, unlike controls (p < 0.0001).
- Both groups showed increased CBF with adenosine, but the response was blunted in cardiomyopathy patients (p = 0.13).
- Endothelium-dependent vasodilation accounted for a significantly smaller proportion of the maximal flow response in cardiomyopathy patients (23%) compared to controls (56%) (p < 0.01).
Conclusions:
- Endothelium-dependent microvascular dilation is significantly impaired in patients with dilated cardiomyopathy.
- This impairment suggests an intrinsic microvascular disease contributing to reduced coronary dilator reserve.
- Findings highlight the importance of endothelial function in the pathophysiology of dilated cardiomyopathy.
Abstract:
Dilator reserve of the coronary microvasculature is diminished in patients with dilated cardiomyopathy. Although increased extravascular compressive forces, tachycardia, and increased myocardial mass can explain some impairment, recent evidence suggests the possibility of intrinsic microvascular disease. We tested the hypothesis that impairment of endothelium-dependent dilation of the microvasculature could be a contributing mechanism. We infused the endothelium-dependent dilator acetylcholine (Ach) (10(-8) to 10(-6) M) and the smooth muscle vasodilator adenosine (AD) (10(-6) to 10(-4) M) into the left anterior descending coronary artery in eight patients with dilated cardiomyopathy (mean ejection fraction, 28%) and seven controls (atypical chest pain). Small vessel resistance was assessed by measuring coronary blood flow (CBF) at constant arterial pressure with a Doppler velocity catheter (corrected for cross-sectional area by angiography). With Ach, control patients increased CBF 232 +/- 40% (mean +/- SEM), whereas CBF did not significantly change in cardiomyopathy patients (41 +/- 24%) (p less than 0.0001, control vs. cardiomyopathy). With AD, control patients increased CBF 422 +/- 56% and cardiomyopathy patients increased CBF 268 +/- 43% (p = 0.13). An index of the proportion of coronary flow reserve attributable to endothelium-dependent vasodilation was obtained by standardizing each patient's Ach dose response to his maximal AD flow response. In seven control patients receiving both Ach and AD, 56 +/- 9% of the maximal AD flow response was attained with the endothelium-dependent vasodilator Ach, whereas in seven cardiomyopathy patients receiving both Ach and AD, only 23 +/- 14% of the maximal AD response was attained (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)