Tumour necrosis factor-alpha in diastolic dysfunction.

Background: Active relaxation develops as a result of sequestration of calcium into the sarcoplasmic reticulum, and is controlled mainly by sarcoplasmic reticulum calcium ATPase (SERCA) and phospholamban.Tumour necrosis factor-alpha (TNF-alpha) downregulates both of these proteins, so it may play a role in the development of abnormal relaxation. However, a possible relationship between TNF-alpha and diastolic dysfunction has not been sufficiently evaluated in vivo. We investigated whether circulating levels of TNF-alpha increased in patients with relaxation abnormality.

Methods: Forty hypertensive patients with normal left ventricular systolic function were enrolled in the study. Age-adjusted values of echocardiographically measured mitral inflow velocities, E-wave deceleration time and isovolemic relaxation time were used to define normal and abnormal relaxation. Twenty of the patients (mean age 59.2 +/- 10.6) had a relaxation abnormality (group I), and the twenty other patients (mean age 45.9 +/- 7.9) had a normal diastolic function (group II). TNF-alpha levels were measured by ELISA.

Results: There were no significant differences between the two groups in terms of interventricular septal thickness, posterior wall thickness, left ventricular mass, ejection fraction, plasma creatinin level, and medication. Patients with a relaxation abnormality were older than those with a normal diastolic function (p < 0.001). TNF-alpha levels were similar in both groups (62.1 +/- 46.0 pg/ml for group I, and 48.7 +/- 51.4 pg/ml for group II, p = 0.089).

Conclusion: In this preliminary study, we demonstrated that TNF-alpha levels did not increase in patients with a relaxation abnormality. However, we think that a possible relationship between TNF-alpha and diastolic dysfunction should be clarified by further studies involving a larger number of patients with a wider spectrum of diastolic dysfunction.