Effects of antibodies obtained from patients with dilated cardiomyopathy on the function of isolated rat hearts

Abstract

Cardiac autoantibodies may play a pathophysiological role in cardiac dysfunction of patients suffering from dilated cardiomyopathy (DCM). Immunoadsorption (IA), which removes antibodies from patients' plasma, may consequently improve cardiac function in DCM. The functional effects of DCM antibodies are only partly understood. DCM patients (n = 10) were treated with IA by application of antibody columns directed against human immunoglobulin (Ig). IA was also performed with plasma taken from 10 healthy donors (controls). The antibodies eliminated and purified by IA were collected and dialysed. Rat hearts were isolated and perfused retrogradely via the aorta in Langendorff mode. During constant-pressure and constant-volume perfusion of the hearts, the influence of diluted antibodies on contractility, relaxation, and on coronary perfusion was analysed. Antibodies obtained from controls had no effect on contractility and relaxation of isolated perfused hearts during constant-pressure and constant-volume perfusion. In contrast, during constant-pressure perfusion, collected DCM antibodies caused immediate and dose-related reduction of contractility (dLVP/dtmax: dilution -1:32 = -7.1 +/- 1.1%; dilution -1:2 = -20.1 +/- 2.1%; P < 0.001) and diastolic relaxation (dLVP/dtmin: dilution -1:32 = -11.1 +/- 1.5%; dilution -1:2 = -23.9 +/- 2.2%; P < 0.001). The heart rate did not change significantly in either group. The effects of DCM antibodies on contractility and relaxation remained detectable during constant-volume perfusion. The observed reduction of contractility and diastolic relaxation was accompanied by impairment of coronary perfusion. In the rat heart, antibodies obtained from DCM patients may impair contractility and relaxation, and thereby probably also coronary perfusion.