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Experimental Impact of Mucopolysaccharidosis on Right Atrial Contractile Capacity of Skinned Fibers

Constanze Bening, Ahmad Abugameh, Nicole Stumpf, Christian-Friedrich Vahl and Uwe Mehlhorn

Objective: Mucopolysaccharidosis is a group of inherited lysosomal storage disorders caused by the absence of an enzyme, contributing to the degradation of the Glycosaminoglycans (GAG). To evaluate if storage of GAGs affects the contractile capacity, we compared the contractile performance of patients with and without MPS in a skinned fiber model.

Methods: Right auricle tissue from 12 patients (4 MPS, 8 Non-MPS) undergoing cardiac operation for Mitral Valve Stenosis (MS) or Mitral Valve Regurgitation (MR) was harvested prior to implementation of extracorporal Circulation (ECC). The trabeculae are resected from the right auricle; the tissue was dissected down to small bundles of fibers. They were chemically skinned by removal of cell membrane-dependent properties to gain the actin-myosinformation. These bundles are dissected in single fiber stripes. The fibers were exposed to a gradual increase of calcium concentration (pCa) and the corresponding force was measured and recorded.

Results: 1.) pCa-force development was significant lower in fibers with MPS (p max 2.2 ± 0.1 mN) than in fibers with MS (3.4 ± 0.7 mN, p 0.03) or MR (4.6 ± 0.9 mN, p 0.04). 2.) The pCa-force values of fibers with mitral valve stenosis and regurgitation did not differ significantly at single steps of calcium concentration among each other (p 0.3). 3.) Fibers with MR developed significant more force at almost all steps of calcium concentration than those with MPS (p 0.02) 4.) Fibers with MS developed only once significant more force compared to MPS fibers: pCa 5.5: 1.6 mN vs. 0.3 mN, p 0.02. 5.) Calcium sensitivity is similar in patients with MPS and MR (pCa 4.5), but different in patients with MS (pCa 5).

Conclusion: Patients with MPS develop significantly less force at similar calcium concentrations compared to patients with a mitral valve stenosis or regurgitation. We suggest that impairment of the contractile apparatus due to the accumulation of GAGs leads to early onset left ventricular hypertrophy and diastolic dysfunction limiting the ventricular filling. This stands in opposition to patients with mitral valve regurgitation with volume overload due to incomplete valve closure.