Cardiac amyloidosis: MR imaging findings and T1 quantification, comparison with control subjects.

In cardiac amyloidosis an interstitial deposition of amyloid fibrils causes concentric thickening of the atrial and ventricular walls. We describe the results of tissue characterization of the myocardium by T1 quantification and MRI findings in a patient with cardiac amyloidosis. The T1 time of the myocardium was elevated compared to that in individuals without amyloidosis. The T1 time of the myocardium was 1387 +/- 63 msec (mean value obtained from four measurements +/- standard deviation [SD]) in the patient with cardiac amyloidosis, while the reference value obtained from the myocardium of 10 individuals without known myocardial disease was 1083 +/- 33 msec (mean value +/- SD). In combination with other MR findings suggestive of amyloidosis, such as homogeneous thickening of the ventricular and atrial walls, thickening of the valve leaflets, restrictive filling pattern, and reduction of systolic function, T1 quantification may increase diagnostic confidence.

Transforming growth factor-beta1 downregulates beating frequency and remodeling of cultured rat adult cardiomyocytes.

We have observed increased levels of transforming growth factor-beta1 (TGF-beta1) in human hibernating myocardium (HM). Impaired ventricular function in HM is known to be restored to normal following revascularization implying that myocardial structure in HM is to a certain degree preserved. We have therefore tested whether TGF-beta1 can imitate features of HM by reducing the number and frequency of beating cells (chronotropism) and structural remodeling of cultured adult rat cardiomyocytes (ARC), thus saving substrate, energy, and oxygen. Parameters measured were cell size, protein synthesis, protein degradation, protein content, myofibrillogenesis, and chronotropism. ARC were stimulated for 6 days with sera from patients with coronary heart disease, as this period led to a maximum response of cells. An increase of 90% in cell surface area following such treatment was reduced to a 20% increase of the original size by TGF-beta1. Concomitantly, the rate of protein synthesis dropped from 3.6-fold to 2.4-fold, and myofibrillogenesis was reduced. TGF-beta1 downregulated both the number of contracting cells from 81% to 10% and the frequency from 52 to nine beats per minute. However, TGF-beta1 treatment did not reduce the augmentation of protein content (1.28-fold versus 1.25-fold) indicating that protein degradation was also inhibited. Similar results were obtained with serum from healthy volunteers. The effects of TGF-beta1 were reversible. We conclude that TGF-beta1 constrains protein turnover and beating activity in underperfused myocardium, thus mediating protection by adapting myocytes to shortages in blood supply.