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Endogenous plasma endothelin concentrations and coronary circulation in patients with mild dilated cardiomyopathy
M Mundhenke1, B Schwartzkopff, M Köstering
1Division of Cardiology, Pneumology and Angiology, School of Medicine, Heinrich Heine University, Moorenstrabetae 5, 40225 Düsseldorf, Germany.
Insights
Patients with idiopathic dilated cardiomyopathy (IDCM) show elevated endothelin-1 (ET-1) and big endothelin (BET) plasma levels, indicating increased endothelin load. These levels correlate with functional decline and may signal a mismatch in myocardial oxygen supply and demand.
Area of Science:
- Cardiology
- Vascular Biology
- Biochemistry
Background:
- Idiopathic dilated cardiomyopathy (IDCM) is characterized by impaired cardiac function.
- Endothelin-1 (ET-1) is a potent vasoconstrictor with potential roles in cardiovascular disease.
- The role of ET-1 and its precursor big endothelin (BET) in IDCM's coronary circulation is not fully understood.
Purpose of the Study:
- To investigate the association between plasma concentrations of ET-1 and BET and the regulation of coronary circulation in patients with IDCM.
- To determine if elevated ET-1 and BET levels contribute to the pathophysiology of IDCM.
Main Methods:
- Study conducted at a tertiary referral center for cardiac diseases.
- Included 14 patients with IDCM and 5 healthy controls.
- Measured plasma ET-1 and BET concentrations from aorta and coronary sinus using radioimmunoassay.
- Assessed coronary blood flow, myocardial oxygen consumption, and coronary sinus oxygen content.
Main Results:
- Patients with IDCM exhibited significantly higher aortic concentrations of ET-1 and BET compared to controls.
- Aortic ET-1 levels positively correlated with NYHA functional class and myocardial oxygen consumption.
- Aortic ET-1 inversely correlated with coronary sinus oxygen content, which was reduced in IDCM patients.
Conclusions:
- The coronary circulation in IDCM patients is subjected to an increased endothelin burden.
- Elevated ET-1 concentrations are linked to functional deterioration in IDCM.
- A reduced coronary sinus oxygen content suggests a mismatch between coronary blood flow and metabolic demand, with ET-1 potentially marking this disequilibrium.
Objective:
To determine whether increased plasma concentrations of endothelin-1 (ET-1) and big endothelin (BET) play a role in the regulation of coronary circulation in patients with idiopathic dilated cardiomyopathy (IDCM).
Setting:
Tertiary referral centre for cardiac diseases.
Patients:
Fourteen patients (eight male/six female; mean (SD) age 59 (9) years) with IDCM (ejection fraction 36 (9)%) and five normotensive subjects (two male/three female; age 52 (7) years) serving as controls were studied.
Methods:
Functional status was classified according to New York Heart Association (NYHA) class. Endogenous ET-1 and BET plasma concentrations from the aorta and the coronary sinus were determined by radioimmunoassay. Coronary blood flow, using the inert chromatographic argon method, myocardial oxygen consumption, and coronary sinus oxygen content under basal conditions were determined.
Results:
In the aorta, mean (SD) concentrations of ET-1 (IDCM 0.76 (0.25) v controls 0.31 (0.06) fmol/ml; p = 0.002) and BET (IDCM 3.58 (1.06) v controls 2.11 (0.58) fmol/ml; p = 0.014) were increased in patients with IDCM. Aortic ET-1 concentrations correlated positively with NYHA class (r = 0. 731; p < 0.001), myocardial oxygen consumption (r = 0.749; p < 0. 001), and coronary blood flow (r = 0.645; p = 0.003), but inversely with coronary sinus oxygen content (r = -0.633; p = 0.004), which was significantly decreased in IDCM patients (IDCM 4.68 (1.05) v controls 6.70 (1.06) vol%; p = 0.003).
Conclusions:
The coronary circulation in patients with IDCM is exposed to an increased endothelin load. ET-1 concentrations correlate with functional deterioration. A decrease of the coronary sinus content of oxygen suggests a mismatch between coronary blood flow and metabolic demand. Thus, ET-1 might be a marker of a disequilibrium between myocardial oxygen demand and coronary blood flow in IDCM.