High resolution mechanical function in the intact porcine heart: mechanical effects of pacemaker location

Azeloglu, Evren U.; Yun, Yang; Saltman, Adam E.; Krukenkamp, Irvin B.; Chiang, Fu‐Pen; Chen, Weiliam; Gaudette, Glenn R.

doi:10.1016/j.jbiomech.2004.12.018

Cited by 8 publications

(4 citation statements)

References 21 publications

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“…The frequency of cellular contraction was quantified from bright-field images (see Supplemental Fig. 1) by applying a fast-Fourier transform to the time course of axial cell displacement, determined using a published phase correlation algorithm (4). The convolution of the AFM indentation frequency (f AFM) and the myocyte pulse rate (fcell) created a response signal with a third envelope frequency (fenvelope) equal to the magnitude of the difference between the two input frequencies,…”

Section: Methodsmentioning

confidence: 99%

Cross-bridge cycling gives rise to spatiotemporal heterogeneity of dynamic subcellular mechanics in cardiac myocytes probed with atomic force microscopy

Azeloglu

Costa

2010

American Journal of Physiology-Heart and Circulatory Physiology

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To study how the dynamic subcellular mechanical properties of the heart relate to the fundamental underlying process of actin-myosin cross-bridge cycling, we developed a novel atomic force microscope elastography technique for mapping spatiotemporal stiffness of isolated, spontaneously beating neonatal rat cardiomyocytes. Cells were indented repeatedly at a rate close but unequal to their contractile frequency. The resultant changes in pointwise apparent elastic modulus cycled at a predictable envelope frequency between a systolic value of 26.2 +/- 5.1 kPa and a diastolic value of 7.8 +/- 4.1 kPa at a representative depth of 400 nm. In cells probed along their major axis, spatiotemporal changes in systolic stiffness displayed a heterogeneous pattern, reflecting the banded sarcomeric structure of underlying myofibrils. Treatment with blebbistatin eliminated contractile activity and resulted in a uniform apparent modulus of 6.5 +/- 4.8 kPa. This study represents the first quantitative dynamic mechanical mapping of beating cardiomyocytes. The technique provides a means of probing the micromechanical effects of disease processes and pharmacological treatments on beating cardiomyocytes, providing new insights and relating subcellular cardiac structure and function.

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Section: Methodsmentioning

confidence: 99%

Cross-bridge cycling gives rise to spatiotemporal heterogeneity of dynamic subcellular mechanics in cardiac myocytes probed with atomic force microscopy

Azeloglu

Costa

2010

American Journal of Physiology-Heart and Circulatory Physiology

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“…The regional function was determined by high-density mapping (HDM) as described in detail elsewhere (2,4,8). This method allows for the accurate determination of deformation within a well-defined area.…”

Section: Methodsmentioning

confidence: 99%

Enhanced recovery of mechanical function in the canine heart by seeding an extracellular matrix patch with mesenchymal stem cells committed to a cardiac lineage

Potapova¹,

Doronin²,

Kelly³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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The need to regenerate tissue is paramount, especially for the heart that lacks the ability to regenerate after injury. The urinary bladder extracellular matrix (ECM), when used to repair a right ventricular defect, successfully regenerated some mechanical function. The objective of the current study was to determine whether the regenerative effect of ECM could be improved by seeding the patch with human mesenchymal stem cells (hMSCs) enhanced to differentiate down a cardiac linage. hMSCs were used to form three-dimensional spheroids. The expression of cardiac proteins was determined in cells exposed to the spheroid formation and compared with nonmanipulated hMSCs. To determine whether functional calcium channels were present, the cells were patch clamped. To evaluate the ability of these cells to regenerate mechanical function, the spheroids were seeded on ECM and then implanted into the canine heart to repair a full-thickness right ventricular defect. As a result, many of the cells spreading from the spheroids expressed cardiac-specific proteins, including sarcomeric alpha-actinin, cardiotin, and atrial natriuretic peptide, as well as the cell cycle markers cyclin D1 and proliferating cell nuclear antigen. A calcium current similar in amplitude to that of ventricular myocytes was present in 16% of the cells. The cardiogenic cell-seeded scaffolds increased the regional mechanical function in the canine heart compared with the unmanipulated hMSC-seeded scaffolds. In addition, the cells prelabeled with fluorescent markers demonstrated myocyte-specific actinin staining with sarcomere spacing similar to that of normal myocytes. In conclusion, the spheroid-derived cells express cardiac-specific proteins and demonstrate a calcium current similar to adult ventricular myocytes. When these cells are implanted into the canine heart, some of these cells appear striated and mechanical function is improved compared with the unmanipulated hMSCs. Further investigation will be required to determine whether the increased mechanical function is due to a differentiation of the cardiogenic cells to myocytes or to other effects.

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“…This technique utilizes markers affixed to the epicardial surface, which are then imaged by one or more cameras. The markers themselves can be of different compositions such as adhesive paper [25], suture [26] or reflective micro-particles [27]. The use of one camera prevents the tracking of fully three-dimensional material points; in this case the projection of these points onto the plane of the camera is used instead.…”

Section: Intact Heart Mechanicsmentioning

confidence: 99%

Use of larger species such as dog and pig as model systems to study cardiac disease

Coppola

Omens

2008

Drug Discovery Today: Disease Models

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High resolution mechanical function in the intact porcine heart: mechanical effects of pacemaker location

Cited by 8 publications

References 21 publications

Cross-bridge cycling gives rise to spatiotemporal heterogeneity of dynamic subcellular mechanics in cardiac myocytes probed with atomic force microscopy

Cross-bridge cycling gives rise to spatiotemporal heterogeneity of dynamic subcellular mechanics in cardiac myocytes probed with atomic force microscopy

Enhanced recovery of mechanical function in the canine heart by seeding an extracellular matrix patch with mesenchymal stem cells committed to a cardiac lineage

Use of larger species such as dog and pig as model systems to study cardiac disease

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