High-frequency ultrasound detection of the temporal evolution ofprotein cross linking in myocardial tissue

摘要

The progressive increase in stiffening of the myocardiumnassociated with the aging process and abetted by comorbid conditionsnsuch as diabetes may be linked to an excessive number of collagen crossnlinks within the myocardial extra-cellular matrix. To determine whethernultrasound can delineate changes in the physical properties of heartntissue undergoing cross linking, the authors employed a model in whichnincreased cross linking was induced by treating rat myocardial tissuenwith specific chemical fixatives. Rat hearts (n=5 each group) werenarrested at end-diastole, insonified (30 to 50 MHz) fresh within a fewnminutes of excision in a phosphate buffered solution, placed in anfixative (10% formalin or 2.5% glutaraldehyde) and insonified atn30-minute intervals thereafter for 24 hours. Ultrasonic attenuationnincreased in tissues cross linked with formalin (maximal change:n27.2±3.4 dB/cm) and glutaraldehyde (maximal change:n40.2±5.6 dB/cm) over a 24-hour period. The frequency dependencenof the attenuation coefficient increased as a function of the extent ofncollagen cross links in formalin (maximal change: 0.8±0.3ndB/cm-MHz) and glutaraldehyde (maximal change: 0.9±0.6ndB/cm-MHz). This study represents the first time that the precise timencourse of myocardial protein cross linking in situ has beenncharacterized by using real time monitoring, and the physiologic effectnhas been delineated on microscopic material properties