Effects of cytokines on the contractility of cultured cardiac myocytes.

Cardiac impairment is a major complication in immunotherapy. In order to investigate whether the cardiac complications are due to directly cardiodepressant cytokine effects, the contractility of heart cells in culture under immune mediator exposition was studied. The beat frequency and inotropy of spontaneously contracting cultured cardiac myocytes was determined in a microscope perfusion system equipped with computer image analysis devices. Under control conditions, the perfused cardiac myocytes were rhythmically and synchronously beating for many hours. Perfusion with the cytokines (IL-1, IL-2, IL-3, TNF) induced arrhythmias resulting in a complete cessation of spontaneous contractions and a severe loss of myocyte inotropy. The effects were concentration-dependent and reversible. Our results indicate a direct toxic interference of the interleukins and TNF with the contractile function of cultured cardiac myocytes.