Abstract
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.
Highlights
Because of poor survival rate the role of right ventricular systolic dysfunction in patients with mitral valve disease is increasingly recognized
Right ventricular impairment or failure remains a challenge especially in postoperative intensive care unit. The importance of this issue can be seen in the observation, that a dysfunctional preoperative right ventricular function is associated with postoperative regurgitation, requirement of more blood transfusion, longer intensive care unit stays and hospital stays [1]
Fibers of patients with mucopolysaccharidosis behave different from those fibers, deriving from patients with mitral valve stenosis or regurgitation (Table 1)
Summary
Because of poor survival rate the role of right ventricular systolic dysfunction in patients with mitral valve disease is increasingly recognized. An early involvement of right ventricular function in mitral valve stenosis is shown by Tayyareci, who performed a study to detect early signs of right ventricular dysfunction in patients with MS [2]. Le Tourneau estimates the incidence of right ventricular impairment in patients with mitral valve regurgitation at 30% and underlines that the dysfunction mainly depends on left ventricular remodeling and septal function [3]. He emphasizes the impact of RV function as a predictor for postoperative cardiovascular survival
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