Relation of tissue Doppler-derived myocardial velocities to serum levels and myocardial gene expression of tumor necrosis factor-alpha and inducible nitric oxide synthase in patients with ischemic cardiomyopathy having coronary artery bypass grafting.

We evaluated the relation of segmental and annular tissue Doppler (TD) velocities to serum levels and myocardial gene expression of tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide (NOS2) in humans. Seven patients with coronary artery disease underwent echocardiographic examination including TD imaging, along with transmural endomyocardial biopsies (2 biopsies per patient for a total of 14 specimens) at the time of bypass surgery. The specimens were analyzed for the number of mRNA copies of TNF-alpha and NOS2. In addition, serum levels of TNF-alpha and nitrite were determined before and after surgery. Normal segments (n = 7) had fewer numbers of mRNA copies of both TNF-alpha (54.6 vs 6.5, p = 0.002) and NOS2 (3,093 +/- 486 vs 661 +/- 259, p <0.001) than dysfunctional segments (n = 7). Peak systolic velocity (Sm) (13.3 +/- 1.4 vs 4.9 +/- 1.6 cm/s, p = 0.002) and early diastolic velocity (Em) (16.5 +/- 2.7 vs 8.8 +/- 1.3 cm/s, p = 0.02) were significantly higher in normal segments. A significant correlation was present among Em, Sm, and the number of mRNA copies of TNF-alpha and NOS2 at baseline and during infusion of dobutamine (r range -0.72 to -0.92, p <0.01 for all). Likewise, significant relations were present between the changes in serum cytokine levels and changes in the mitral annulus diastolic velocity, E/Ea ratio, and end-diastolic wall stress (r range 0.75 to 0.88, p </=0.05 for all). In conclusion, Sm and Em are strongly dependent on the regional levels of cytokine gene expression, which are known to have negative inotropic and lusitropic effects when overexpressed.