Tumour necrosis factor-alpha in diastolic dysfunction

Abstract

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-a) downregulates both of these proteins, so it may play a role in the development of abnormal relaxation. However, a possible relationship between TNF-a and diastolic dysfunction has not been sufficiently evaluated in vivo.We investigated whether circulating levels of TNF-a 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-a 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-a 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-a levels did not increase in patients with a relaxation abnormality. However, we think that a possible relationship between TNF-a and diastolic dysfunction should be clarified by further studies involving a larger number of patients with a wider spectrum of diastolic dysfunction.

Key Words:

• tumour necrosis factor-alpha
• diastolic dysfunction
• abnormal relaxation